CLINICAL

PSYCHOPHARMACOLOGY
made
ridiculously
Edition 4
simple

John Preston, Psy.D.

James Johnson, M.D.
 CLINICAL PSYCHOPHARMACOLOGY

made
ridiculously
simple

John Preston, Psy.D.

University of California, Davis, Medical School
California School of Professional Psychology
Sacramento, California

James Johnson, M.D.

Kaiser Medical Center
Department of Psychiatry
South Sacramento, California
Copyright © 1990, 1991, 1993, 1994, 1995, 1997, 1998, 2000, 2001 by MedMaster

All rights reserved. This book is protected by copyright. Np part of it may be

reproduced, stored in a retrieval system, or transmitted in any form by any
means, electronic, mechanical, photocopying, recording or otherwise, without
written permission from the copyright owner.

ISBN #0-940780-44-5

Made in the United States of America

Published by
MedMaster, Inc.
P.O. Box 640028
Miami, Fla. 33164
 Contents

Preface .. vii

Chapter 1 General Principles .

Chapter 2 Depression. 2

Chapter 3 Bipolar Illness . 18

Chapter 4 Anxiety Disorders . 25

Chapter 5 Psychotic Disorders. 36

Chapter 6 Miscellaneous Disorders . 46

Chapter 7 Non-Response and “Breakthrough Symptoms”

Algorithms. 53

Chapter 8 Case Examples. 55

Appendix A History and Personal Data Questionnaire . 68

Appendix B Special Cautions When Taking MAO Inhibitors 70

References . 72

Index . 73
 Preface
This brief book provides an overview of clinical psychopharmacology. Suc¬
cessful medical treatment of emotional and mental disorders depends on two
factors: a thorough knowledge of psychotropic medications and an accurate
diagnosis. Both issues are addressed in this book in a practical and concise format.
To the best of our knowledge, recommended doses for medications listed in
this book are accurate. However, they are not meant to serve as a guide for
prescription of medications. Physicians, please check the manufacturer’s prod¬
uct information sheet or the Physicians’ Desk Reference for any changes in
dosage schedule or contraindications.
We wish to express our appreciation to the following people who have re¬
viewed this book and made a number of helpful suggestions: John H. Greist,
M.D., Donald Klein, M.D., Glen Hakanson, M.D., and Patrick Donlon. M.D.
Many thanks to Michelle Riekstins for her help in the preparation of the manu¬
script and to our editor. Dr. Stephen Goldberg, for many helpful suggestions.
 Chapter 1 General Principles

BIOLOGY vs. PSYCHOLOGY

For many years a debate raged in psychiatry with regard to the etiology and treat¬
ment of major mental disorders. Two opposing camps emerged: biological psy¬
chiatry, whose devotees held that psychiatric disorders had an organic basis; and
psychologically oriented psychiatry, probably best represented by the psycho¬
dynamic movement, whose converts focused on the role of current emotional
stressors, early childhood traumas, interpersonal problems, and intrapsychic con¬
flict as causal agents in the development of psychiatric symptomatology. Although
these polar views still exist, in recent years there has been an emerging view that
encompasses both psychological and physiological factors in the etiology and
treatment of many psychiatric disorders. In many, if not most, mental disorders it
is helpful to think of a continuum or spectrum. Almost all mental disorders usually
represent heterogeneous syndromes.
When one talks about depression, for instance, it is important to realize that de¬
pression can present in a number of different ways and may have diverse etiolo¬
gies. In some instances the cause may be purely psychological, e.g.. a reaction to
losing a job, death of a loved one, a significant rejection, etc. Likew ise. symptoms
may be largely psychological, e.g., feelings of low self-esteem and sadness. In
other cases the picture is one of a pure biological disorder which has little or
no connection to environmental precipitants. but rather involves an endogenous
neurochemical malfunction. In addition to psychological symptoms, the resulting
symptoms may include a host of somatic symptoms, such as sleep disturbance and
weight loss. Clearly, in some individuals there is an interplay ol environmen¬
tal/psychological factors and biochemical dysfunctions. The question "Is this a
psychological or biological problem?" is overly simplistic. Rather, one must ask.
"To what extent is this disorder due to psychological factors and to what extent is
it due to a biochemical disturbance?" The answer to this question is extremely im
portant in guiding treatment decisions. Most purely psychological problems are
not helped by medication treatment. On the other hand, most biologically based
psychiatric disorders require medication treatment.
In this book we hope to provide key diagnostic guidelines to help the clinician
pinpoint the diagnosis and develop a realistic treatment plan.

I
 Chapter 2 Depression

DIAGNOSIS

Major Clinical Features and Differential Diagnosis

It is important to distinguish between (1) reactive sadness, (2) grief, (3) med¬
ical illness and medications that cause depressive symptoms, and (4) clinical de¬
pression. The first two are painful but normal emotional reactions and usually do
not require treatment. These four syndromes may be distinguished by the follow¬
ing characteristics:

1. Reactive Sadness. The emotional reaction stems from a relatively minor

event. It is transient (a few hours to a few days) and rarely interferes with
functioning.

2. Grief. This is a normal response to a major interpersonal loss (such as the

death of a loved one or marital separation/divorce). This process can be
tremendously painful and is much more prolonged than reactive sadness.
Grief differs from clinical depression in three ways:

a. Despite intense sadness, there is no significant loss of self-esteem.

b. The patient clearly relates the sadness to the loss. There may be active
mourning and pining for the loved one; the painful feelings “make
sense.”

c. Grief work (i.e., mourning) and time are often the major ingredients
necessary for emotional healing.

3. Medical Illnesses and Medications That Can Cause Depression. Certain

medical disorders (see Figure 1) can at times result in biochemical changes
that affect central neurotransmitters, thereby triggering serious depressive re¬
actions. Likewise, some medications can cause depression as a side effect
(see Figure 2). Please note that minor tranquilizers may cause or exacerbate
depression by depleting serotonin, which is a key neurotransmitter implicated
in some types of depression. A very frequent treatment mistake is for the
physician to be impressed by the more obvious symptoms of anxiety or agita¬
tion, to fail to recognize an underlying depression, and to prescribe a benzodi-
azepine/minor tranquilizer. The result is often some initial calming, but after
a week or two the depression worsens. If the basic disorder is depression, but
 with coexisting anxiety symptoms, it is important to treat the depression.
With appropriate treatment for the depression, the anxiety symptoms will
generally subside.
When the basic cause of depression is one of the illnesses listed in Figure 1
or a side effect of medication, the primary focus should be on treating the core
illness or switching medications. When such interventions are carried out, the
depression will usually lift.

Figure 1

COMMON DISORDERS THAT MAY CAUSE DEPRESSION

■ Addison’s disease ■ Influenza

■ AIDS ■ Malignancies (cancer)
■ Anemia ■ Malnutrition
■ Asthma ■ Menopause
■ Chronic Fatigue Syndromes ■ Multiple sclerosis
■ Chronic infection (mononucleosis, TB) ■ Post-partum hormonal changes
■ Chronic pain ■ Prophyria
■ Congestive heart failure ■ Premenstrual syndrome
■ Cushing’s disease ■ Rheumatoid arthritis
■ Diabetes ■ Syphilis
■ Hyperthyroidism ■ Systemic lupus erythematosis
■ Hypothyroidism ■ Uremia
■ Infectious Hepatitis ■ Ulcerative colitis

4. Clinical Depression. This is a pathological process characterized as follows:

a. Depressed mood (sadness or emptiness) is often continuous and pcr\ asivc.

b. There is increasing impairment of normal functioning (work, school, and

intimate relationships).

c. There is an irrational or exaggerated erosion of self-esteem.

d. There is a dramatic and specific change in vegetative patterns (e.g.,

sleep, appetite, sex drive, etc.) and the appearance of nonspecific physical
complaints.

e. In contrast to grief, the patient is often puzzled as to why he is depressed.

3
 4
Figure 2

DRUGS THAT MAY CAUSE DEPRESSION

TYPE GENERIC NAME BRAND NAME

Antihypertensives reserpine Serpasil. Ser-Ap-Es, Sandril

(for high blood propranolol Inderal
pressure) hydrochloride
methyldopa Aldomet
guanethidine sulfate Ismelin sulfate
clonidine Catapres
hydrochloride
hydralazine Apresoline hydrochloride
hydrochloride
Corticosteroids and cortisone acetate Cortonc
other Hormones estrogen Evex. Menrium, Femest
progesterone Lipo-Lutin, Progestasert,
Proluton
A ntiparkinson Drugs levodopa and carbidopa Sinemet
levodopa Dopar, Larodopa
amantadine Symmetrel
hydrochloride
Antianxiety Drugs diazepam Valium
and others (see Figure 21)
Birth Control Pills progesterone estrogen Various Brands
Alcohol wine, beer, spirits Various Brands

Target Symptoms

All types of depression tend to share certain universal symptoms (see Figure 3).
Disorders that reflect a basic biochemical dysfunction present with both the uni¬
versal symptoms and \he physiological symptoms, listed below: (See Figure 4).

ANTIDEPRESSANT MEDICATION

When Do You Prescribe Antidepressants?

The most important guideline for prescribing antidepressant medication is

whether or not there are sustained physiological symptoms, as outlined below

4
 Figure 3

SYMPTOMS COMMON TO ALL DEPRESSIONS

■ Mood of sadness, despair, emptiness

■. Anhedonia (loss of the ability to experience pleasure)1
■ Low self-esteem
■ Apathy, low motivation, and social withdrawal
■ Excessive emotional sensitivity
■ Negative, pessimistic thinking
■ Irritability and low frustration tolerance
■ Suicidal ideas

'Note: Some degree of decreased capacity for pleasure may be seen in all types of depression. In de¬
pressions that involve a biochemical disturbance, this loss of ability to experience pleasure can be¬
come so pronounced that the patient has almost no moments of joy or pleasure. Such people are said
to have a “non-reactive mood." which means that they are unable to temporarily get out of their de¬
pressed mood.

Figure 4

VEGETATIVE/PHYSIOLOGICAL SYMPTOMS REFLECTING

A BIOCHEMICAL DYSFUNCTION
(TARGET SYMPTOMS FOR MEDICATION TREATMENT)

■ Sleep disturbance (early morning awakening, decreased sleep efficiency,

frequent awakenings throughout the night,' occasionally hypersomnia:
excessive sleeping)
■ Appetite disturbance (decreased or increased, with accompanying weight
loss or gain)
■ Fatigue
■ Decreased sex drive
■ Restlessness, agitation, or psychomotor retardation
■ Diurnal variations in mood (usually feeling worse in the morning)
■ Impaired concentration and forgetfulness
■ Pronounced anhedonia (total loss of the ability to experience pleasure)

'Note: Initial insomnia (difficulty in falling asleep) may be seen *ith depression but is n«H diagnostic
of a major depressive disorder. Initial insomnia can be seen in anyone experiencing stress in general
Initial insomnia alone is more characteristic of anxiety disorders than of depression

5
(see Figure 4). Occasional disturbances of sleep or appetite, for instance, do not
warrant medication treatment. Flowever, if there is continuing weight loss,
marked fatigue each day, and poor sleep most nights, antidepressants are indi¬
cated. In the Appendix we have included a brief symptom checklist that can be
used to quickly assess a host of psychiatric symptoms. Depressive symptoms are
included under Section A. Additionally, those patients who are depressed and are
judged to be poor psychotherapy candidates (e.g., lower intelligence, not psy¬
chologically minded, or refuse psychotherapy) should be considered for a trial on
antidepressants.

Choosing Medication

Antidepressant medications fall into two primary groups: (1) typical antide¬
pressants, and (2) MAO inhibitors. The choice of medications is determined
largely by the side effect profile (see Figure 5). The side effects of antidepressant
medications often result in serious compliance problems, although some side ef¬
fects can at times be clinically useful (e.g., sedation for patients with marked ag¬
itation or severe sleep disturbances).
If medications are indicated, first assess the patient’s motor state. An agitated,
restless patient may do better with a more sedating antidepressant, and a more
lethargic, fatigued patient may do better with a less sedating antidepressant. (See
Figure 5).
Second, consider the special problems that the patient may have. Some med¬
ications have selective effects. (See Figure 7).

Prescribing Treatment

Antidepressant medications are generally started at a low dosage and gradually

titrated up. The most common mistake made by family physicians is to under-
medicate. Although there are exceptions, generally a patient (ages 15-55) must
receive a dose that is within the therapeutic range (see Figure 5). (Doses for those
over 55 are often somewhat lower.) As an example, a typical start-up regime for
desipramine would be 25 mg. qhs for 2 days. This should be increased by 25 mg
every 2-3 days as long as side effects are minimal, until the patient reaches a solid
therapeutic level, i.e., at least 150 mg q.d. Often it takes from 10-14 days to reach
a dosage that is within the therapeutic range. Faster increases may result in side
effects and compliance problems. Slower increases prolong the suffering caused
by the depression. With selective serotonin re-uptake inhibitors (SSRIs: fluoxe¬
tine, sertraline, paroxetine) often the starting dose (20 mg., 50 mg., 20 mg., re¬
spectively) is the dose that is therapeutic. Increases in dose can be made if there
is a failure to show a positive response after 4-5 weeks of treatment. Note: If pa¬
tient had first episode prior to 18. is experiencing a recurrent episode, and/or has
been depressed for more than two months, often requires 4-6 weeks to show first
signs of clinical response.

6
 Figure 5

ANTIDEPRESSANT MEDICATIONS

USUAL
DAILY
NAMES DOSAGE ACH
GENERIC BRAND RANGE SEDATION EFFECTS'

TYPICAL ANTIDEPRESSANTS
imipramine Tofranil 150-300 mg mid mid
desipramine Norpramin 150-300 mg low low
amitriptyline Elavil 150-300 mg high high
nortriptyline Aventyl, Pamelor 75-125 mg mid mid
protriptyline Vivactil 15-40 mg low mid
trimipramine Surmontil 100-300 mg high mid
doxepin Sinequan. Adapin 150-300 mg high mid
maprotiline Ludiomil 150-225 mg mid low
amoxapine Asendin 150-400 mg mid low
trazodone Desyrel2 150-400 mg mid none
fluoxetine Prozac 20-80 mg low none
bupropion Wellbutrin2 200-450 mg low none
bupropion, S.R. Wellbutrin, S.R. 150-300 mg low none
sertraline Zoloft 50—2(X) mg low none
paroxetine Paxil 20-50 mg low low
venlafaxine Effexor 75-375 mg low none
venlafaxine, X.R. Effexor, X.R. 75-350 mg low none
nefazodone Serzone2 100-500 mg mid low
fluvoxamine Luvox 50-300 mg low low
mirtazapine Remeron 15-45 mg mid mid
citalopram Celexa 10-60 mg low none
reboxetine Vestra 4-8 mg low none

MAO INHIBITORS3
phenelzine Nardil 30-90 mg low none
tranylcypromine Parnate 20-60 mg low none
isocarboxazid Marplan 10-40 mg low none

'ACII EFFECTS (anticholinergic side effects) include dry mouth. conMipution. difficulty in urinating,
and blurry vision. Can cause confusion and memory disturbances m the elderly 01 brain itainted
patient.
-’Due to short half-life, requires divided dosing
'Require strict adherence to dietary and medication regimen
Note: prescribe maprotiline and bupropion to patients with history of sei/utes only ss ith great caution

7
 Figure 6

DECISION TREE FOR DIAGNOSIS

AND TREATMENT OF DEPRESSION - 4

The treatment of major depression involves three phases:

Acute Treatment: Begins with the first dose and extends until the patient is
asymptomatic (in good case scenarios, this may be from 6-8 weeks).

Continuation Treatment: To avoid acute relapse, it is strongly suggested that

patients continue treatment for a minimum of six months beyond the acute phase.

8
 Figure 6 (cont.)

DECISION TREE: TREATMENT OF DEPRESSION - II

Phase of Treatment

Rapid
ACUTE Delayed Response No Response
Responders
-i-
(2-4 wk. I'* Sxi) (4-8 wk. I** Sxlxi) 0 Check compliance
i 0 Check substance abuse

until
asymptomatic

0 Augment
a. Lithium
b. Tj
c. 2nd antidepressant
d. buspirone
e. stimulants

Conti nualion Minimum of 6 months at same dose, once patient is asymptomatic.

Only proceed to next phase if patient has remained asymptomatic for
six months

Main lenance
—1
- I'1 episode: gradually discontinue
I 2 episode: gradually discontinue <2)
I- 3“ or subsequent episodes: life-long maintenance dose

Footnotes:
1. Patients with (he following characteristics may ultimately be good responders, but take longer to
achieve first signs of symptomatic improvement: current episode has been ongoing for more than
three months and the symptoms are severe.
2. If a second episode and these risk factors are present, may consider life-long treatment: first episode
was prior to the age of 18. family history of mood disorders. intcr-cpisodc the patient was not eu-
thymic (i.e. did not fully recover from first episode).
3. This decision tree is based on results from the Texas Medication Algorithm Project (IWH). Note
that the general concepts from the project arc addressed in this decision tree, however the particu¬
lar graphics above were developed by the authors of this book.

Also, recent studies indicate that the patient should be maintained on the same
dose used during the acute phase.

Maintenance Treatment: Relapse prevention is an important aspect of treat¬

ment. especially in those patients judged to have recurrent episodes (or at risk for

9
 Figure 7

SPECIAL PROBLEMS AND MEDICATIONS OF CHOICE

THE PROBLEM DRUGS OF CHOICE

1. Highsuicideri.sk1 1. trazodone, fluoxetine, sertraline,

paroxetine, bupropion, venlafaxine
2. Concurrent depression and 2. phenelzine, imipramine, fluoxetine
panic attacks paroxetine
3. Chronic pain with or without 3. amitriptyline, doxepin
depression
4. Weight gain on other 4. fluoxetine, bupropion, sertraline,
antidepressants paroxetine
5. Sensitivity to anticholinergic 5. trazodone, fluoxetine, phenelzine,
side effects tranylcypromine, bupropion,
sertraline, reboxetine, citalopram
6. Orthostatic hypotension 6. nortriptyline, bupropion, sertraline
7. Sexual dysfunction 7. bupropion, nefazodone, citalopram

'Note: Many antidepressants are quite toxic when taken in overdose. Extreme caution should be ex
ereised in prescribing to high-risk suicidal patients.

recurrence).* Continued (lifelong) treatment provides the best outcome for such
individuals. The following guidelines are offered:

1. First Episode: at the end of the continuation phase, gradually reduce the dose
(over a period of 2-4 weeks) and, assuming no return of depressive symptoms,
discontinue. Educate the patient to be alert to any signs of recurrence (e.g.,
poor sleep, fatigue, etc.) and should this occur, contact the treating doctor as
soon as possible to reinstigate treatment.

2. Second Episode:

a. With “Risk Factors" which include: family history of mood disorders, first
episode occurring prior to the age of 18. and/or most recent episode has severe
symptoms: Recommend life-long medication treatment to prevent recurrence.

b. Without "Risk Factorsgradually discontinue medications.

3. Third or later episodes. Recommend life-long medication treatment.

Note: 50-65** of patients w ith major depression w ill experience either chronic or recurrent, episodic
depressions.

10
What to Expect

Neuro-researchers have hypothesized that many of the primary symptoms of

clinical depression are caused by a dysregulation of certain neurotransmitters
(e.g., norepinephrine, dopamine, and/or serotonin). Antidepressant medications
are able to restore normal neuronal functioning in key limbic structures in the
brain. It is very important to note, however, that these drugs do not act rapidly. It
generally requires 10 to 21 days of treatment for symptoms to improve. This is a
crucial point. Many, if not most, depressed patients become easily discouraged
if there is no relief in a few days. Such patients often discontinue medications
prematurely.

Side Effects

Probably owing to their tremendous feelings of hopelessness and pessimism,

depressed patients are especially prone to discontinuing treatment prematurely.
This is often the case when they encounter side effects which typically emerge
long before the therapeutic effects are realized. Thus, choosing medications that
are low in side effects is an important rule of thumb. Fortunately, most newer gen¬
eration antidepressants have a far better side effect profile than older generation
tricyclics. Side effects certainly account for treatment failures, however it should
be noted that other factors also contribute to treatment drop-outs (see figure S). It
is likely that many drop-outs are due to the prolonged time before the onset of
symptomatic improvement (i.e. 2-6 weeks) and tremendous pessimism that is a
cardinal feature of depression.

Figure H

Treatment drop-outs during the first two months

Of treatment: Primary Care Setting:

Prescriptions are never taken by the patient

(not filled at the pharmacy) 8%
Drop-out in first two weeks 44%

Drop-out in first four weeks 68%

Drop-outs due to side effects

First six weeks of treatment

Placebo 3-7%
Tricyclics 25-30%
New generation antidepressants 9-21%

II
Side Effect Management Considerations: SSRIs

SSRIs are often prescribed for depression owing to their effectiveness and rela¬
tively low incidence of side effects. Recently, two later-onset side effects (gener¬
ally seen 4-6 months into treatment) have been noted, and may occur in from
20-35% of patients. These side effects are a common reason for patient-initiated
discontinuation or poor compliance, and are side effects patients seldom report
(thus, it is important for the physician to inquire). The side effects include sexual
dysfunction (especially inorgasmia) and/or decreased spontaneity and apathy. This
last side effect may be spotted by reports by the patient that “I’m feeling depressed
again.” However, on closer inspection most depressive symptoms continue to be
in remission. Rather, the patient is experiencing either a loss of motivation or a
decreased sense of emotional aliveness (sometimes including an inability to cry.)
These side-effects can often be successfully managed by the pharmacologic
solutions indicated below:

Figure 9

PROBLEM TREATMENT OPTION

■ Inorgasmia ■ Reduce SSRI dose, or

■ Add buspirone 10-20 mg. b.i.d., or
■ Add cyproheptadine 4-12 mg., p.r.n.
■ Apathy, decreased spontaneity ■ Reduce SSRI dose, or
■ Add bupropion (start low: e.g., 75 mg.
b.i.d. and do not exceed 225 mg. q.d.)

Common Treatment Errors To Avoid

• Under-dosing
• Poor compliance
• Co-morbid substance abuse (if not detected, can result in treatment failure
of antidepressants. This is a very common reason for inadequate medication
response).
• Using benzodiazepines to treat depression (can increase depressive symp¬
toms and may lead to drug dependence/abuse)
• Premature discontinuation

KEY POINTS TO COMMUNICATE TO PATIENTS

In prescribing antidepressant medication, patient education is especially im¬

portant. Listed below are the key points to communicate to patients starting on
antidepressants.
1. Onset of clinical action generally takes 10-21 days. It will take this long for
you to notice a reduction of symptoms.

2. Symptomatic improvement is usually seen primarily in the physiological

symptoms (Figure 4). Many of the other symptoms (e.g.. depressed mood, low
self-esteem, etc.) may respond only partially to medication treatment. These
medications are not “happy pills"; they do not totally erase feelings of sadness
or emptiness.

3. The best barometers of early medication response generally include improved

sleep, less daytime fatigue, and some improvement in emotional control (e.g.. less
frequent crying spells or better frustration tolerance). The physician may need to
inquire specifically about these symptoms because many depressed people will
say “I’m no better," despite the fact that there is symptomatic improvement.

4. There may be side effects. However, side effects can most often be managed
by dosage adjustment or by switching to another medication.

5. Total length of treatment varies considerably for individuals. Typically, it may

take 4-8 weeks for the major depressive symptoms to subside. It is very im¬
portant not to discontinue treatment at this point. The relapse rate can be as
high as 80%. The general rule of thumb is to continue treatment for a period
of 6 months beyond the point of symptomatic improvement and then gradually
to reduce the dose. Should symptoms return during this medication-reduction
phase of treatment, the dosage should again be increased. Medication should
be continued for 4-6 weeks before another trial on lower doses. Occasionally,
a person may need to be on long-term chronic medication management.

6. Antidepressants are not addictive.

7. You should not drink alcohol when taking antidepressants. Alcohol can block
the effects of the antidepressants (although, in clinical practice, many physi¬
cians will allow patients on antidepressants to have an occasional drink, but
not in excess of one per day).

Treatment-Resistant Depressions

Generally it is best to start with a typical antidepressant. It is necessary to treat

at adequate doses; most treatment failures are due to inadequate doses. Unless side
effects are intolerable or a person is a high risk patient (sec I’rrcauiions. pg. 16).
standard practice is to push the dose to the upper level o! the therapeutic range un
til symptomatic improvement is attained. If a patient is on a high dose lor a pe¬
riod of 3-4 weeks without symptomatic improvement it is unlikely that
improvement will occur. A second strategy that often produces positive results is
to add a low dose of lithium (600 to 900 mg. per day) to the antidepressant. AI airly
large number of non-respondents do benefit from lithium augmentation Should
this fail, then a change in the antidepressant medication is in order.

13
 The next step generally is to switch to another typical antidepressant. The
choice is guided by two factors: side effect profiles and neurotransmitter action.
There is some evidence to suggest that there exist three basic neurochemicals that
may be affected in major depressive disorder: norepinephrine/dopaminc and sero¬
tonin. The various antidepressant medications have different effects on these three
neurochemical systems (sec Figure 10). Some arc considered to have broad spec¬
trum effects (“shotguns”) and others are more selective (“bullets”). The disad¬
vantage in choosing a broad spectrum drug is that they typically have more
troublesome side effects. If your first unsuccessful drug was serotonergic, then the
second choice should be a medication targeting norepinephrine or dopamine.

Figure 10

SELECTIVE ACTION OF ANTIDEPRESSANT MEDICATIONS

MONOAMINE
GENERIC BRAND NOREPINEPHRINE SEROTONIN OXIDASE DOPAMINE

imipramine Tofranil ++ +++ 0 0

desipramine Norpramin + + + ++ 0 0 0
amitriptyline Elavil + ++++ 0 0
nortriptyline Aventyl. Panic lor +++ ++ 0 0
protriptyline Vi vac-til1" ++++ + 0 0

(rimipramine Surmontil'" ++ ++ 0 0
doxcpin Sinequan. Adapin'" +++ ++ 0 0
maprotiline Ludiomil + + + ++ 0 0 0
amoxapinc Asendin ++++ + 0 0

venlafaxine Effexor ++ +++ 0 +

trazodone Desyrel 0 +++++ 0 0

fluoxetine Prozac 0 +++++ 0 0
pamxetine Paxil + +++++ 0 0

sertraline Zoloft 0 +++++ 0 0

bupropion Wellbutnn'’' +++ 0 0 ++
nefa/odone Serzone + ++++ 0 0

fluvoxamine Luvox 0 +++++ 0 0

ntirtazapine Remeron +++ ++ + 0 0

citalopram Cclexa 0 +++++ 0 0

rcboxetine Vestra ++++ + 0 0 0

phenelzine Nardil'" +++ +++ +++++ +++

tranylcypromine PamatC" +++ +++ +++++ +++

isocarboxazid Marplan " +++ +++ + +++ + +++

'"Uncertain, but likely effects.

'’’Atypical antidepressant Uncertain effects
" MAOIs increase NE. 5-MT. and DA

14
 What if this fails too? A fourth strategy is to switch to mirtazanine. venlafax-
ine, or to an MAO inhibitor. Treatment is described below. The final option is elec-
trocovulsive therapy (ECT) which is a highly effective, albeit costly, form of
treatment for depression.

Note that the clinician must wait 2 weeks after discontinuing typical antide¬
pressants before beginning an MAOI. and six weeks after discontinuing fluoxetine
before a switch to an MAOI. Failure to do so may result in very serious, life-threat¬
ening drug interactions.

Dysthymia

Dysthmia is a type of mild, chronic depressive disorder characterized by the fol¬

lowing symptoms (which are present almost every day over a period of 2 + years):

• Daytime fatigue
• Negative, pessimistic thinking
• Low self-esteem
• Low motivation, loss of enthusiasm
• Decreased capacity for joy

Evidence from a number of recent studies suggests that 50-55# of patients

with dysthymia can respond favorably to a trial on anti-depressant medications.
MAOIs and SSRIs appear to be more effective than tricyclics in treating dys¬
thymia (Klein, 1995).

Seasonal Affective Disorder (S.A.D.)

Decreased exposure to photic stimulation has been strongly implicated in cases

of S.A.D. This is often a factor in people who work at night, live in geographic
areas with significant cloud cover and/or pollution, and in northern climes (North¬
ern hemisphere) during winter months. A full discussion of S.A.D. is beyond the
scope of this book, but physicians should be aware of this common clinical con¬
dition. Treatment for S.A.D. includes antidepressants (current hypotheses suggest
that S.A.D. may be closely tied to serotinergic dysfunction and thus. SSRIs may
be medications of choice). Additionally, increased bright light exposure has been
shown to be effective (either by use of commercially available light boxes or by-
encouraging patients to spend a minimum of one hour per day outside ... of
course, without sunglasses).
For a detailed discussion of S.A.D.. please see Winter Blues by N E. Rosenthal.
Guilford Press, N.Y. (1993).

Pre-menstrual Dysphoric Disorder (P.D.D.)

Approximately 5c/< of women experience severe mood changes premenstruall>

This disorder is characterized by the tremendous regularity ot mood symptoms

15
 4.
(depression, irritability or anxiety) seen for a few days prior to ovulation. Serolin-
ergic dysregulation has been implicated and treatment with SSRIs is often a suc¬
cessful strategy. Currently, there is some debate whether or not it is necessary to
treat P.D.D. continuously (i.e., all month-long) or on a P.R.N. basis. All other types
of depression require chronic treatment, however, some women with P.D.D. may
respond to P.R.N. dosing only during the symptomatic time of the month.

Psychotic Depressions

Psychotic symptoms may be seen in cases of unipolar depression and bipolar

disorder, and occur also in the context of postpartum and menopausal depressions.
They usually manifest with severe vegetative symptoms, delusions (especially so¬
matic delusions, extreme beliefs regarding worthlessness, and paranoid thinking)
and occasionally, auditory hallucinations.
Antidepressants alone or antipsychotics alone are generally ineffective. Almost al¬
ways the treatment of choice includes a combination of antidepressants and anti¬
psychotics. Electroconvulsive therapy (E.C.T.) may be both necessary and effective
in more severe cases. Finally, please keep in mind that these patients are very high risk
for suicide. Referral to a psychiatrist and possibly hospitalization are recommended.

Precautions: Tricyclic Antidepressants

The following patients should either not be treated or treated cautiously with tri¬
cyclics: immediate post-MI patients, epileptics, patients with narrow-angle glaucoma,
and pregnant women. The physician should consult package inserts and the Physi¬
cians'Desk Reference for more details regarding precautions and contradictions.

Precautions: Selective Serotonin Reuptake Inhibitors

Drug-drug interactions can sometimes be dangerous. SSRIs should be used

cautiously with the following medications (Figure 11):

Figure II

■ MAO Inhibitors—never use with SSRIs (very dangerous/fatal)

■ Diet pills, e.g., fenfluramine
■ Non-sedating antihistamines, e.g., Hismanal (can be fatal)
■ Tricyclic antidepressants (may increase TCA levels)
■ Lithium (may increase lithium levels)
■ Carbamazepine (may increase carbamazepine levels)
■ St. John's Wort (may be dangerous)

Non-: this list is not exhaustive, but includes common drug-drug interactions

16
MAO Inhibitors

Three commonly used MAOIs, phenelzine, isocarboxazid, and tranyl¬

cypromine have been shown to be as effective as tricyclics in a number of stud¬
ies. However, shortly after their introduction into the United States in the 1950s
there were reports of severe reactions in some patients, which resulted in great
concern in the medical community. The drugs interact with certain medications
(sympathomimetic amines) and with certain foods (containing tyramine. a natural
byproduct of bacterial fermentation processes, found in many cheeses, some
wines and beers, and foods such as chopped liver, broad beans, chocolate, snails,
etc.). (See Appendix B.) The interaction resulted in a severe hypertensive crisis,
which for a number of patients was fatal. So for many years these medications
were abandoned because doctors viewed them as unsafe. However, especially in
Europe, doctors recognized that these drugs had clinical utility and could be safely
used if certain dietary restrictions were followed. In fact, in Europe during the past
30 years the MAOIs have probably been used as much as the tricyclics.
Just recently the MAOIs have been rediscovered by American medicine and are
now enjoying a renaissance for several reasons. First, it dietary restrictions are ob¬
served, these drugs are actually safer than the tricyclics and have fewer side ef¬
fects. Secondly, they have been found to work in many patients who do not
respond to tricyclics. And Finally, some studies indicate that MAOIs may be the
drug of choice for some types of affective disorders including atypical depressions
presenting primarily with anxiety and phobic symptoms, masked depression (c.g„
hypochondriasis), and dysthymia.
Otherwise, guidelines for treatment and clinical response arc similar to those
previously described for the tricyclics. (See pages 4-13.) The one exception is the
important dietary/medication restrictions that must be observed (see Appendix B.
patient handout for specific restrictions).

Notes on Over-the-Counter Products

Two OTC products have some research support for treatment ol depression: St.
John’s Wort (mild depressions) and SAM-e (mild-to-moderate depressions). Both
appear to have favorable side effect profiles and safety (although St. John's Wort
should not be co-administcred with MAOIs or SSRIs). Studies are now in
progress at NIMH and final conclusions regarding efficacy and safety should
await the outcome of these investigations.

Hooks to Recommend to Patients

1. Preston, J. (1996). You Can Heat Depression: .4 Guide to prevention and Re

covery (second edition). Impact Publishers. PO. Box 1094. San I uis Obispo.
CA 93406.
2. Griest. J. and Jefferson. J. (19X4). Dtp res\ion and Its Treatment. Warner Books

17
 Chapter 3 Bipolar Illness

DIAGNOSIS

Major Clinical Features and Differential Diagnosis

The diagnosis of a bipolar disorder is based in two sources of data: the current
clinical picture (depression or mania) and a clear history of both manic and depres¬
sive episodes. The depressive episodes may range from minor to major depressive
syndromes as outlined in Chapter 2. Manic episodes typically are described as
either full blown or less intense manic episodes, referred to as hypomania.
It is important to rule out medical causes of bipolar illness. (See Figures I and
2 in Chapter 2 and Figures 12 and 13.)

Figure 12

COMMON DISORDERS THAT MAY CAUSE MANIA

■ Brain tumors Metabolic changes associated with

■ CNS syphilis hemodialysis

■ Delirium (due to various causes) Metastatic squamous adenocarcinoma

■ Encephalitis Multiple sclerosis

■ Influenza Q fever

Figure 13

DRUGS THAT MAY CAUSE MANIA

■ amphetamines
■ bromides
■ cocaine
■ antidepressants
■ isoniazid
■ procarbazine
■ steroids

is
 Several classification schemes for bipolar disorders have been proposed by var¬
ious authors. The three most clinically useful classifications are outlined below:

A. BIPOLAR / V5. BIPOLAR II

1. Bipolar / This disorder fits the more classic description of bipolar illness
with clearly recognized episodes of depression and mania.

2. Bipolar II This disorder presents with obvious episodes of depression; but

the manic phases of the illness are often less intense, unrecognized, and thus
not reported by the patient. If you inquire about manic episodes, the patient
will give the impression that none have occurred. The best ways to diagnose
such conditions are either to witness a hypomanic episode clinically or to
carefully inquire about the history. In particular, if hypomanic episodes are
suspected, the most important question to ask is, “Have you ever had a pe¬
riod of time when you didn't need as much sleep?” A decreased need for
sleep and a lack of daytime fatigue are red flags for hypomania.

B. TYPICAL BIPOLAR vs. RAPID CYCLING BIPOLAR DISORDERS

In the more typical bipolar patient, depressive and manic episodes last for several
weeks to several months, often with periods of normal mood occurring between
periods of depression and mania. When there are two or more episodes of both
depression and mania, (e.g., depression-mania-depression-mania) within a year,
this is referred to as “rapid cycling” (APA. 1987, p. 225). Sometimes rapid cyclers
can dramatically switch moods from week to week or even day to day.

C. DYSPHORIC MANIA (or MIXED MANIA)

This is a diagnostic term which describes patients that have concurrent manic and
depressive symptoms (e.g., increased activity, pressured speech, suicidal ideas,
and feelings of worthlessness).

The subclassifications of Bipolar I and Bipolar II. typical vs. rapid cycling, and
dysphoric mania are important because they have different treatment implications.

Target Symptoms

The target symptoms vary depending on the current phase ol the illness Major
depressive symptoms are listed in Chapter 2 (Figures 3 and 4). Manic episodes
are identified by the following clinical features (see Figure 14).

MEDICATIONS USED TO TREAT BIPOLAR ILLNESS

When Do You Prescribe Medications?

Treatment of bipolar disorders has two goals. The lust goal is the reduction ol
current symptoms, and the second is the prevention of relapse Bipolar disorders

\<i
 Figure 14

SYMPTOMS OF MANIA'

■ A pronounced and persistent mood of euphoria (elevated or expansive mood)

or irritability and at least three of the following:
■ Grandiosity or elevated self-esteem
■ Decreased need for sleep
■ Rapid, pressured speech (Often these people are hard, if not impossible, to
interrupt.)
■ Racing thoughts
■ Distraetibility
■ Increased activity or psychomotor agitation
■ Behavior that reflects expansiveness (lacking restraint in emotional
expression) and poor judgment, such as increased sexual promiscuity,
gambling, buying sprees, giving away money, etc.

'Adapted from APA. 1987 (with permission), p. 217. Also see Questions 13-16 on the History and
Personal Data Questionnaire (Appendix A.).

are invariably recurring and thus prophylactic treatment is warranted. Strong ev¬
idence indicates that failure to continue treatment can and often leads not only to
relapse, but to a progressively worsening condition. Subsequent episodes tend to
become more and more severe and can. at times, become treatment refractory.

Choosing Medication

The primary medication used to treat this disorder is lithium. However a num¬
ber of other drugs have been found to be effective as adjuncts or alternatives to
lithium. We will describe standard treatment with lithium and then comment on
the role of other medications.
Lithium has two primary effects: It stabilizes mood, and in many instances it
can prevent relapse (or at least lessen the intensity of subsequent episodes) if treat¬
ment is on an ongoing basis. Lithium seems to be somewhat more effective in pre¬
venting relapse of mania rather than depression.

Prescribing Treatment

The treatment of bipolar disorders can be quite complex. Generally a referral

to a specialist is recommended.
If the presenting pluise is a manic episode. Often, especially if the patient is
quite agitated, out of control or psychotic, the initial plan is to begin treatment
with hath lithium and an antipsychotic medication. The antipsychotics seem to

2»
improve behavioral control more rapidly. With lithium, the patient may require 10
days to show a clinical response. Once mood has been stabilized, the antipsychotic
may be phased out. Alternatively, high potency benzodiazepines can be used in
place of antipsychotics (e.g., clonazepam).
Treatment is initiated after necessary lab tests are conducted (see Figure 16.)
Generally the starting dose is 600 or 900 mg./day given in divided doses. The ther¬
apeutic range and toxic range of lithium are very close to one another. Thus it is
necessary to gradually increase the dose while carefully monitoring blood levels.
Most patients must reach a level between 1.0 and 1.2 mEq/L. Not infrequently the
level may need to be higher to obtain symptomatic improvement (1.2 to 1.6). but
on these higher levels, side effects are more common and compliance is poorer.
On occasion, patients may need and tolerate blood levels up to 2.0 mEq/L. How¬
ever, there is increased risk of toxicity at such doses. Generally, daily doses range
from 1200-3000 mg. Once mood is adequately stabilized, the dose can be lowered
somewhat (0.8-1.0 mEq/L) for maintenance treatment.
If the presenting phase is a depressive episode. Because lithium is less effective
as an antidepressant, many times, for a patient seen during a depressive phase,
treatment is initiated with an antidepressant in combination with lithium. One risk

Figure 15

DECISION TREE FOR TREATMENT OF BIPOLAR DISORDERS

21
in administering an antidepressant to a bipolar patient is that the drug may precip¬
itate an acute shift into mania. Bupropion appears to be the antidepressant least
likely to cause a shift into mania. After the depressive episode has resolved, lithium
can be used to prevent relapse. Antidepressant treatment is described in Chapter 2,
and lithium treatment is the same as previously outlined for a manic episode.

Side Effects of Lithium and Signs of Toxicity

Major side effects include nausea, diarrhea, vomiting, fine hand tremor, seda¬
tion. muscular weakness, polyuria, polydypsia. edema, weight gain and a dry
mouth. Adverse effects from chronic use may include leukocytosis (reversible
upon discontinuation of lithium), hypothyroidism and goiter, acne, psoriasis, ter-
atogenesis (first trimester, although the risk is low), nephrogenic diabetes in¬
sipidus (reversible), and kidney damage.
Signs of toxicity include lethargy, ataxia, slurred speech, tinnitus, severe nau¬
sea/vomiting, tremor, arrhythmias, hypotension, seizures, shock, delirium, coma,
and even death. Since the toxic range is near to the therapeutic range, blood lev¬
els and adverse effects must be monitored closely. In addition, a number of other
clinical lab tests should be conducted at the beginning of treatment and periodi¬
cally thereafter (see Figure 16).

Figure 16

CLINICAL LAB TESTS FOR PATIENTS TAKING LITHIUM

■ NA (Sodium) ■ Creatinine
■ Ca (Calcium) ■ Urinalysis
■ P (Phosphorus) ■ Complete CBC
■ EKG ■ Thyroid battery (with TSH)

Listed below are the key points that should be communicated to patients start¬
ing treatment with lithium.

KEY POINTS TO COMMUNICATE TO PATIENTS

1. Lithium is a medication that treats your current emotional problem and will
also be helpful in preventing relapse. So it will be important to continue with
treatment after the current episode is resolved.

2. Since the therapeutic and toxic dosage ranges are so close, we must monitor
your blood level closely. This will be done more frequently at first and every
several months thereafter. Never increase your dose without first consulting
with your physician.
3. Lithium is not addictive.

4. Many side effects can be reduced/minimized by taking divided doses or may

subside as treatment progresses.

5. Bipolar disorders often run in families. Any relatives that have pronounced
mood swings should be alerted to the possibility of a treatable condition and
the need for professional evaluation. (The yield on this maneuver is high, since
medical awareness of bipolar disorder is still low, especially with milder
forms, and family history is impressively often positive for this disorder.)

6. You and your family need to be aware that this is a biological disorder, not a
moral defect or a character flaw. When severe, you may not always be able to
control your behavior, necessitating that practical steps be taken to protect all
concerned from poor judgment during episodes.

7. Many self-help groups have been developed to provide support for bipolar pa¬
tients and their families. In this community, the local self-help group is_.
and you can find out more information by calling_.

Common Treatment Errors to Avoid

• Lithium: very toxic thus warrants close monitoring (especially in suicidal

patients. Note: suicides occur frequently not only in depressed but also
manic patients)
• Poor compliance
• Discontinuation: note: bipolar patients need life-long treatment to avoid re¬
lapse. Patient or physician-initiated discontinuation can and dtvs result in fre¬
quent relapses. And, subsequent episodes often are more severe and may
become treatment-resistant.

Specialized Treatments for Subtypes of Bipolar Disorder

In addition to standard lithium treatment, many researchers and clinicians have

suggested treatment options for certain bipolar subtypes (see Figure 17).

Figure 17

SPECIALIZED TREATMENTS FOR SUBTYPES OF

BIPOLAR DISORDERS

SUBTYPE MEDICATION ALTERNATIVES

Bipolar II MAO inhibitors

Rapid Cyclers Carbamazcpine (Tegretol i

Dysphoric Mania Divalproex tDepakote)

23
Newer Treatment Alternatives

For treatment refractory patients, the following medications can be used (as sole
agents or to augment standard treatments): anticonvulsants: Lamictal (lamotri-
gine), Neurontin (gabapentin), or Klonopin (clonazepam); high doses of T? (e.g.
150-200 micrograms) for rapid cycling; the calcium channel blocker verapamil.
In clinical practice, only 33% of patients remain on monotherapy; i.e. combina¬
tion/augmentation is frequently required (e.g. lithium and divalproex).
For details on newer treatment approaches see the following:

Practice Guidelines for Treatment of Patients with Bi-Polar Disorder.

Supplement to the American Journal of Psychiatry', December. 1994: American

Psychiatric Press: 1-800-368-5777.

Books to Recommend to Patients

1. Fieve. R. (1975). Mood Swings, Bantam Books.

2. Lithium and Manic Depression: A Guide, Lithium Information Center, Univ.

of Wisconsin, (1989).

24
 Chapter 4 Anxiety Disorders

DIAGNOSIS

Major Clinical Features and Differential Diagnosis

Six different anxiety disorders are seen in clinical practice. An accurate diag¬
nosis is important as the treatments vary. There is no one treatment appropriate
for all anxiety disorders. It is important to distinguish between the following:
(1) generalized anxiety disorder (G.A.D.), (2) stress related anxiety. (3) panic
disorder, (4) social phobias, (5) medical illnesses presenting with anxiety symp¬
toms, and (6) anxiety symptoms as a part of a primary mental disorder (e.g.. de¬
pression, schizophrenia).
Before outlining the main features of each disorder, it is necessary to define
two terms: panic attacks and anxiety symptoms. Panic attacks are very brief but
extremely intense surges of anxiety. The major differences between a panic
attack and more generalized anxiety symptoms are differences in the onset, dura¬
tion, and intensity. Panic attacks often “come out of the blue" (i.e.. not necessar¬
ily provoked by stress), they come on suddenly (the full attack reaching its peak
in from one-to-ten minutes), are extremely intense, last from 1-30 minutes, and
then subside. The patient feels as if he will actually die or go cra/y. We arc not
talking about uneasiness; we are talking about full-blown panic. The person may
continue to feel nervous or upset for several hours, but the attack itself lasts only
a matter of minutes. If a patient says, 4Tvc had a continuous panic attack for the
past three days,” he may be having intense anxiety symptoms, but not a true
panic attack. In other anxiety disorders, anxiety symptoms can be very unpleas¬
ant, but arc much less intense; they also can be prolonged or generalized (i.e..
present most of the day and last from days to years). The distinction between
“symptoms” and “attacks" is very important when it comes to treatment. Please
refer to Figure 18.
The six anxiety syndromes can be distinguished by the following charac¬
teristics:

1. Generalized Anxiety Disorder. The key here is lonyterm. low level, fairly
continuous anxiety. Patients with this disorder may have no specific current
life stressors. To them, daily living provokes anxiety. Such people are chronic

Noic: Obsessive-Compulsive disorder and I’oM-irau malic sticss disorder arc discussed hi Chapin b

25
 Figure 18

SYMPTOMS OF ANXIETY'

■ Trembling, feeling shaky, restlessness, muscle tension

■ Shortness of breath, smothering sensation
■ Tachycardia (rapid heartbeat)
■ Sweating and cold hands and feet
■ Lightheadedness and dizziness
■ Paresthesias (tingling of the skin)
■ Diarrhea and/or frequent urination
■ Feelings of unreality (derealization)
■ Initial insomnia (difficulty falling asleep)
■ Impaired attention and concentration
■ Nervousness, edginess, or tension

'Adapted from APA. 1987 (with permission), p. 253.

worriers, always ‘what-if-ing" (e.g„ “What if I get fired?" “What if my check

bounces?" “What if my wife leaves me?”).

2. Stress-related Anxiety. The patient with this disorder typically functions well.
However, the anxiety symptoms have recently emerged in the face of major
life stresses (e.g., a serious family illness, a marital separation, etc.).

3. Panic Disorder. This is characterized by repeated episodes of full-blown panic,

as described in the discussion of panic attacks. Often phobias will also develop.

4. Social Phobias. Anxiety is experienced only when the person is in social/in¬

terpersonal settings, e.g., public speaking, asking someone out for a date, so¬
cial gatherings.

5. Medical Illnesses, and Medications Presenting with Anxiety Symptoms. Cer¬

tain diseases/conditions can at times result in biochemical changes that pro¬
duce anxiety symptoms. If someone complains of nervousness or anxiety,
it should never be assumed that it is simply an emotional disorder until medi¬
cal causes have been ruled out (Figure 19). Likewise, a number of medica¬
tions and over-the-counter products can cause pronounced anxiety symptoms
(Figure 20).

6. Anxiety as a Part of a Primary Mental Disorder. Anxiety frequently accompa¬

nies many mental disorders (e.g., depression, schizophrenia, organic brain syn¬
dromes. substance abuse).

26
 Figure 19

COMMON DISORDERS THAT MAY CAUSE ANXIETY

■ Adrenal tumor ■ Hyperthyroidism

■ Alcoholism ■ Meniere’s disease (early stages)
■ CNS degenerative diseases ■ Parathyroid disease
■ Cushing's disease ■ Post-concussion syndrome
■ Coronary insufficiency ■ Premenstrual syndrome
■ Delirium1 ■ Mitral valve prolapse2
■ Hypoglycemia

'Delirium can occur as a result of many toxic/metabolic conditions and often produces anxiety and
agitation.
:The mitral valve prolapse probably does not cause anxiety, but it has been found that MVP and anx¬
iety disorders often coexist. This may be due to some underlying common genetic factor.

Figure 20

DRUGS THAT MAY CAUSE ANXIETY

■ Amphetamines
■ Asthma medications
■ Caffeine
■ CNS depressants (withdrawal)
■ Cocaine
■ Nasal decongestants
■ Steroids

ANTIANXIETY MEDICATION* TREATMENT

When Do You Prescribe Antianxiety Medications?

Treatment differs depending on the diagnosis, so each disorder will be ad¬

dressed separately.

I. Generalized Anxiety Disorder (G.A.D.). Many physicians have tried to treat

this disorder with benzodiazepines. This presents two problems: (I) In the long

•Also referred to as minor tranquilizers, anxiolytics, and ben/odia/cpincs These term* Mill be used
interchangeably.

27
 run, such treatment is often not very effective. (2) Patients can develop toler¬
ance/dependence problems with chronic benzodiazepine use. Many clinicians
think that G.A.D. is primarily a psychological (not biological) disorder and
recommend psychotherapy. However, recently a new* drug, buspirone hy¬
drochloride, has been shown to be effective in treating some G.A.D. patients.
An added feature of this medication is that patients do not develop dependence
or tolerance. Other minor tranquilizers are usually not indicated in the treat¬
ment of G.A.D.

2. Stress-related anxiety. Minor tranquilizers are very helpful in reducing anxiety

symptoms (especially insomnia and restlessness) which accompany acute sit¬
uational stress. The most important issue to consider is whether or not the stress
is acute and likely to be of short duration. Antianxiety medications should only
be used for a period of 1-4 weeks. If it is clear that this is just one in a series
of chronic life crises, it is probably best not to prescribe benzodiazepines.

3. Panic disorder. One isolated panic attack is generally insufficient evidence of

true panic disorder. However, four or more true attacks within a period of one
month suggest panic disorder. Look for spontaneous attacks (most “come out
of the blue") episodes that last a matter of minutes (not hours or days). Many
patients with other types of disorders say they have panic attacks but on close
inspection, many do not.

4. Social phobias. Generally, social phobias are not treated medically but with
psychotherapy and behavioral approaches. In some cases beta blockers or MAO
inhibitors or serotonin antidepressants (c.g. paroxetine) have been helpful.

5. Medical illnesses/medications causing anxiety symptoms. In almost all in¬

stances, the treatment of choice is to treat the primary medical illness or to dis¬
continue the offending drug. Be cautious in stopping certain drugs; for instance,
if a patient stops drinking coffee abruptly, he may have significant w ithdrawal
symptoms which mimic anxiety. Such drugs must be gradually withdrawn.

6. Anxiety symptoms as a part of another primary mental disorder. Treat the pri¬
mary disorder. Minor tranquilizers arc usually not indicated.

Choosing a Medication

Antianxiety medications fall into five groups (see Figure 21). The primary
choice of medication is based on the diagnosis. Secondarily, one should consider
certain problematic side effects such as sedation and rapidity of absorption (rapid
absorption may be associated with a euphoric “rush").

Prescribing Treatment

I. Generalized Anxiety Disorder. Buspirone is the medication of choice. Unlike

the benzodiazepines, buspirone is slow acting. It often requires 2-6 weeks of

2K
 treuiment before symptomatic improvement. The major problem encountered
with this medication is premature discontinuation by the patient. Patients of¬
ten expect quick results from medications. It is important to educate the pa¬
tient about onset of action. Buspirone can be effective in treating many
symptoms of G.A.D., but it does not seem to decrease panic attacks. Buspirone
must be taken every day; it is not a medication that is taken only when the pa¬
tient feels anxious. Recently, a number of clinicians have also reported that
serotinergic antidepressants (SSRls) may be beneficial in treating G.A.D. If
patients fail to respond to buspirone or SSRls. if symptoms are severe, and if
there is no history of alcohol or other substance abuse, benzodiazepines can
be used to treat G.A.D.

2. Stress-Related Anxiety. All benzodiazepines are effective in treating acute

stress-induced anxiety. (See Figure 21). The most important considerations in
choosing a medication have to do with side effects and medication half life.
The most common side effect is sedation. Intense restlessness or agitation may
require a more sedating drug; however, in most instances it is better to use low
sedation benzodiazepines to reduce daytime anxiety. Of course many anxious
patients will present with a sleep disturbance. Insomnia will be addressed be¬
low. A second side effect is the so-called euphoric “rush" secondary to the peak
in blood level of medication. Such a peak creates a good deal of sedation and
can be useful if the goal is to induce sleep, but the euphoric experience can lead
to abuse. In addiction-prone individuals it is best to choose a drug that avoids
or minimizes this effect. Finally the half life of a medication is an important
variable when it comes to discontinuing the drug. Those medications listed that
have a shorter half life may need to be discontinued very gradually so as to
avoid withdrawal symptoms.
Dosage ranges vary widely as seen in Figure 21. However, a typical start¬
ing dose of lorazepam, for instance, is 0.5 mg. b.i.d. or t.i.d. Such a dose should
be increased every three days as needed until a final range of 2-6 mg./day is
achieved. The goal is to provide some symptomatic relief over a period of from
1-4 weeks. Should a person still experience significant anxiety alter this pc
riod of time, a reassessment of the diagnosis is in order.
It has long been held that long term use of benzodiazepines is contraindi¬
cated. Although this is often true, it is not always the case. Investigations into
chronic benzodiazepine use have shed new light on this clinical practice
Uhlenhuth. et al. (1988, p. 161) report that "... many patients continue to de¬
rive benefit from long-term treatment w ith benzodiazepines; and ... attitudes
strongly against the use of these drugs may be depriving many anxious patients
of appropriate treatment.” The key is to monitor closely for signs of increasing
dosage, especially as the patient may be increasing dosage without medical ad
vice. If in doubt, don't hesitate to get a blood level and to share your concents
openly with the patient. Addiction to benzodiazepines that arise in the Course
of the treatment of anxiety should be treated for what it is; an occasional and
serious side effect. Always discontinue benzodiazepines gradually (c.g . it the
 Figure 21

ANTIANXIETY MEDICATIONS

Medication
- Usual Daily Rapidity of Vt Life
Disorder Generic Brand Dosage Range Absorption (Hours)

1. G.A.D. buspirone BuSpar 5-40 mg. ♦ 2-8

SSRIs'"

2. Stress-Related
Anxiety diazepam Valium 5-40 mg. +++++ 20-50
chlordiazepoxide Librium 15-100 mg. +++ 5-30
oxazepam Serax 30-120 mg. ++ 5-20
clorazepate Tranxene 15-60 mg. ++++ 30-100
lorazepam Ativan 2-6 mg. +++ 10-15
prazepam Centrax 20-60 mg. + 30-100
alprazolam Xanax .25-4 mg. +++ 6-20
clonazepam Klonopin .5-4 mg. + 80

3. Panic Disorder alprazolam Xanax .25-8 mg. +++ 6-20

clonazepam Klonopin .5-4 mg + 80
antidepressants"'
MAO Inhibitors'1'

4. Social Phobia propranolol Inderal 20-80mg.

MAO Inhibitors'1'

5. Stress-Related
Initial
Insomnia'2' flurazepam Dalmane 15-30 mg. +++++ 40-250’'
temazepam Restoril 15-30 mg. +++++ 10-20
triazolam Halcion .25-.5 mg. +++++ 2-3
quazepam Doral 7.5-15 mg. +++++ 39
zolpidem Ambien 5-10 mg. ++++ 2-3
estazolam Prosom 2-4 mg. +++++ 10-24
zaleplon Sonata 5-10 mg. +++++ 1-2

“'See Chapter 2, Figure 5.

<2’lnitial insomnia: difficulty falling asleep.
'’’Active metabolite (norflurazepam)

patient takes 1.5 mg. of alprazolam, q.d., then each week the daily dose should
be reduced by 0.25 mg. This slow taper is especially important with short half-
life benzodiazepines).

3. Stress-Induced Insomnia. Benzodiazepine sedative-hypnotics can be a safe

and effective treatment for transient initial insomnia. (Recall that middle in¬
somnia and early morning awakening are more indicative of depression and
therefore should not be treated with benzodiazepines). Again, in most cases
treatment is initiated only if the insomnia is precipitated by recent environ¬
mental stress and is not a chronic problem. Chronic insomnia is extremely hard

30
 to treat. Note that the newer drug zolpidem tartrate is not a benzodiazepine and
studies to-date show that dependence is less likely with this medication. For
this reason, it may be a safe alternative in individuals with a substance abuse
history. Typical dosages for the various sedatives are listed in Figure 21.

4. Panic Disorder. The treatment of panic disorder has two discrete phases.

Phase 0;i?;'Eliminate or reduce the frequency or intensity of the panic attacks

with antipanic drugs. There are three main groups of antipanic drugs. Let’s dis¬
cuss the pros and cons of each.

a. High potency benzodiazepines and like compounds (e.g., alprazolam and

clonazepam)

Pros. Very effective. It works quickly, often within days. It also reduces an¬
ticipatory anxiety.

Cons. Although some patients respond to low doses (0.25 mg t.i.d.), most
require much larger doses (3-8 mg/day for alprazolam, 2-4 mg/day for
clonazepam), and at these higher doses, sedation is a very common prob¬
lem. With prolonged use, tolerance can develop. Very gradual discontinua¬
tion is required to avoid withdrawal symptoms.

b. Antidepressants: tricyclics and selective serotonin re-uptake inhibitors

(SSRIs).

Pros. Effective in reducing attacks. Can treat concurrent depression. Can

be used for prolonged periods of time without risk of tolerance/dependence.

Cons. Side effects (see Chapter 2) and delayed onset of action (2-4 w eeks
before symptomatic improvement). Treat in the same way and same dosage
levels as you would use to treat depression. Some patients experience an
initial increase in panic attacks; these are usually managed well w ith short
term use of a benzodiazepine, as necessary. (Note: bupropion is one anti¬
depressant that apparently is not effective in treating panic attacks).

c. MAO Inhibitors

Pros. Very effective. Can treat concurrent depression. Can be used for pro¬
longed periods of time without risk of tolcrancc/depcndence.

Cons. Delayed onset of action (2-4 weeks) and medical ion/d ietary restric¬
tions as outlined in Chapter 2. As with typical antidepressants, treat as you
would treat depression.

Phase Two. Patients not only have the attacks, but develop significant antici¬
patory anxiety, phobias, and avoidance (a strong urge to avoid situations in
which they have experienced prior panic attacks, e.g.. to avoid crowded stores
or driving on freeways). These problems frequently do not spontaneously re
mit when the panic attacks are eliminated. People continue to have intense
worries that "It could happen again.** Phase two involves gradual reexposure
to feared situations. So if a person is afraid of having an attack at the grtwery

31
 store, he must gradually approach the feared situation. Only by repeated ex¬
posure to the situation and by a series of experiences without panic will the pa¬
tient’s anticipatory anxiety and avoidance diminish. The keys to successful
graded reexposure are (1) to first effectively control or reduce attacks with
medication and then (2) to have the patient very gradually face the phobic sit¬
uation. To be effective, exposures should last from 60-90 minutes.
The duration of the underlying biochemical dysfunction is quite variable.
Some people may be treated medically for six months and gradually with¬
drawn from medication. Others may need years of continued treatment. (Most
patients are treated for 18-24 months.) Like depression, the strategy with any
of the antipanic drugs is to achieve symptomatic relief and then continue to
treat for 6 months. At that point, a medication-reduction trial may be initiated.
If necessary, treatment can be resumed if panic symptoms reemerge.

5. Social Phobias. In most cases psychotherapy is the treatment of choice. Psy¬

chotropic medications have been used, however, in two types of social phobia.
Some social phobics are extremely sensitive to rejection and this is why they
are fearful of social interactions. Some new research and clinical data indicate
that these patients may benefit from MAO inhibitors or SSRIs. A second type
of phobia, stage fright/public speaking phobia, has been successfully treated
by beta blockers such as propanolol (usually 20-40 mg., 1 hour prior to per¬
forming). Beta blockers do not eliminate the centrally mediated, subjective
sense of anxiety, but do quite effectively reduce many peripheral somatic
symptoms of anxiety, e.g., tachycardia, trembling.

Common Treatment Errors to Avoid

• Prescribing benzodiazepines to a patient with a personal or family history of

substance abuse (high risk of abusing the benzodiazepine). Watch for patient
requests for higher and higher doses.
• “Cold turkey” discontinuation or rapid taper of benzodiazepines (can result in
significant withdrawal symptoms. 1-3 month gradual taper advised).
• Misdiagnosis: failure to recognize depression or an emerging psychotic ill¬
ness and treating with benzodiazepines (can worsen depression and fail to
treat psychosis).
• Over sedation with benzodiazepines in the treatment of day-time anxiety.
• Benzodiazepines in treating elderly patients can cause cognitive impairment
and contribute to unsteady gait and falls. Use with caution.

IN EVERY CASE, REMEMBER

Some degree of stress and anxiety is a common part of normal, daily living.
Medication treatment should only be initiated if symptoms are significantly in¬
tense and severely interfere with normal functioning.

32
 When you prescribe any kind of medication to control anxiety, it is essential to
discuss the following key points with the patient:

KEY POINTS TO COMMUNICATE TO PATIENTS

Generalized Anxiety Disorder

1. If buspirone or SSRIs are prescribed, you should expect that it will take from
2-6 weeks to notice symptomatic improvement. Daily doses are required. This
is not a medication that you take only as needed.
2. Often medication treatment is not enough and psychotherapy, stress manage¬
ment, relaxation training, and biofeedback are helpful adjuncts to medical
treatment.

Stress-Related Anxiety
1. The following analogy is helpful. Pain killers can reduce suffering when
you have a toothache, but at some point you must fix or pull the tooth.
Likewise, minor tranquilizers do not cure people, but they temporarily re¬
duce suffering. You must do something to alter the basic source of stress
if lasting recovery is to be achieved. Minor tranquilizers are only for short¬
term use.
2. Do not abruptly discontinue minor tranquilizers, especially if they have been
taken daily for several weeks. Cold-turkey discontinuation can result in with-
drawal syndromes (many withdrawal symptoms are almost identical to symp¬
toms of anxiety).
3. Do not drink any kind of alcohol if you are taking a minor tranquilizer.

Panic Disorder
1. There is strong evidence that panic disorder is a biochemical dysfunction,
not a psychological disorder. It can often be very successfully treated with
medications.
2. Medication must be taken each day. The treatment is prophylactic and not a
medication that you only lake as needed.
3. The medication treats only the panic attacks. Once these are adequately con
trolled, you will need to enter Phase Two of treatment (graded reexposure) to
deal with anticipatory anxiety and avoidance. In many cases this is best done
with the help of a therapist familiar with behavioral techniques.
4. If MAO inhibitors are used, you must understand the dietary and medication
restrictions and sign a consent form.
5. If alprazolam or clonazepam are used, you must never abruptly discontinue n
(medication reduction should be done gradually, generally 0.25 to 0.5 nig. |vr
day per week).
6. If treated by antidepressants or MAOIs. it may take 2 4 weeks before you no
lice symptomatic changes.

33
 Figure 22

DECISION TREE FOR DIAGNOSIS AND TREATMENT OF ANXIETY

plus

Psychotherapy

Social Phobias
1. If medication is used (MAOI, SSRI, or beta blockers), this must be accompa¬
nied by exposure (i.e., you must be willing to enter certain social situations and
test out the water).
2. Psychotherapy is also indicated.

34
Books to Recommend to Patients

Beckfield, D. (1994). Master Your Panic, Impact Publishers, San Luis Obispo, CA.

Sheehan, D. (1983). The Anxiety Disease, Bantam Books.

Greist, J., Jeffe.rson, J., and Marks, J. (1986). Anxiety and Its Treatment, Warner
Books.

35
 «

Chapter 5 Psychotic Disorders

DIAGNOSIS

Major Clinical Features and Differential Diagnosis

For practical purposes three major psychotic disorders are described: (I) Schizo¬
phrenia (and schizophrenic-like disorders), (2) psychotic mood disorders, and
(3) psychosis associated with neurological conditions.
Before discussing differential diagnosis, let's first briefly define psychosis.
Psychosis is not an illness; it is a symptom associated with a number of disorders.
The hallmark of psychosis is impaired reality testing (impaired ability to perceive
reality). The loss of contact with reality can take many forms: severe confusional
states, delusions (bizarre, unrealistic thoughts), hallucinations, and marked im¬
pairment in judgement and reasoning. Having psychotic symptoms does not in
itself imply a specific etiology; causes are varied. The three groups of psychotic
disorders mentioned above are distinguished by the following characteristics:

1. Schizophrenia. Schizophrenia is generally a recurring illness; people diag¬

nosed as schizophrenic are prone to repeated psychotic episodes. It is helpful
to think about three types of schizophrenia:

a. Positive Symptom Schizophrenia. This type of schizophrenia is also re¬

ferred to as dopaminergic schizophrenia because of its presumed etiology:
a hyperactive dopamine system. Positive systems are active, florid delu¬
sions and hallucinations: agitation and emotional dyscontrol. There are
two subtypes:

1. Schizophreniform disorder (Brief psychotic reaction). This disorder

looks like schizophrenia but remits quicker and often does not recur.

2. Schizophrenia, per se. This is a recurring or chronic disorder.

b. Negative Symptom Schizophrenia. This is a neuro-developmental disorder.

Negative symptoms include: Hat affect, anhedonia (inability to experience
pleasure), marked social aloofness/withdrawal, and the absence of florid
delusions and hallucinations. Negative symptom schizophrenia tends to
have an earlier and more insidious onset. As children, these people were of¬
ten seen as weird and aloof.

2. Psychotic Mood Disorders. Both mania and depression can present with poor
reality testing and other psychotic symptoms.

36
3. Psychosis Associated with Neurological Conditions. Many acute metabolic and
toxic states can result in a delirium. Head injury occasionally produces transient
psychotic behavior and a number of degenerative diseases (e.g., Alzheimer's)
can produce periods of agitated confusion. Detailed description of psycho-
pharmacologic treatment of various neurological conditions is beyond the
scope of this book. However, it is very important to distinguish such conditions
from schizophrenia and mood disorders. A brief mental status exam can be
helpful. It should include a test of short term memory, as well as tests for ori¬
entation and naming. Most neurologically based disorders that present with
psychotic symptoms will also show gross impairment in recent/short-tcrm
memory; these abilities are relatively intact in schizophrenia. Damage to Wer¬
nicke’s area (superior temporal lobe) can occasionally result in what looks like
a schizophrenic reaction (language and thinking are grossly impaired). Wer¬
nicke’s patients have a terrible time naming objects; people with schizophrenia
and mood disorders do not. See the Four Minute Neurological Exam (in the
MedMaster Series) for more hints on conducting a brief neurological exam.
Figure 23 lists medical illnesses that may produce psychotic symptoms, and
Figure 24 lists medications that may result in psychotic reactions.

NOTE: The treatment of mood disorders that present with psychotic symptoms
primarily involves treating the depression (antidepressants or ECT) and adding
antipsychotics to control the psychotic symptoms. Since much of this has been
covered previously (Chapters 2 and 3), the focus of the following sections will be
on treating schizophrenia.

Figure 23

COMMON DISEASES AND DISORDERS THAT MAY

CAUSE PSYCHOSIS

■ Addison’s disease ■ Multiple sclerosis

■ CNS infections ■ Myxedema

■ CNS neoplasms ■ Pancreatitis

■ CNS trauma ■ Pellagra

■ Cushing’s disease ■ Pernicious anemia

■ Delirium1 ■ Porphyria

■ Dementias2 ■ Systemic lupus crytheinatosis

■ Folic acid deficiency ■ Temporal lobe epilepsy

■ Huntington’s chorea ■ Thyrotoxicosis

'Any number of toxic/mctabolic stales may result in delirium

-’Any number of dementing conditions te g . Alzheimer's disease) may result in psych**ik symptoms

37
 Figure 24

COMMON DRUGS THAT MAY CAUSE PSYCHOSIS

■ Sympalhomimetics (e.g., cocaine and “crack,” a form of almost pure

cocaine, many over-the-counter cold medications)
■ Antiinflamatory drugs (e.g., steroids)
■ Anticholinergic drugs (e.g., antiparkinsonian drugs)
■ Hallucinogenic drugs (e.g., LSD)
■ L-Dopa (in schizophrenic patients)

NOTE: Older persons are often on centrally acting drugs and have less ability to tolerate their toxic
effects.

Target Symptoms

It is helpful to subdivide scizophrenic symptoms into four categories: positive

symptoms, disorganization symptoms, characterological traits, and negative
symptoms. (See Figure 25.)

Figure 25

SCHIZOPHRENIC SYMPTOMS

POSITIVE SYMPTOMS NEGATIVE SYMPTOMS

■ Delusions and impaired thinking ■ Flat or blunted affect
■ Hallucinations ■ Poverty of thought (i.e., few or no
■ Confusion and impaired judgement thoughts and concrete thinking)

■ Severe anxiety, agitation, and ■ Emptiness and anhedonia (no joy)

emotional dyscontrol ■ Psychomotor retardation/inactivity
■ Blunting of perception (e.g.,
insensitivity to pain)

DISORGANIZATION CHARACTEROLOGICAL
SYMPTOMS TRAITS
■ Incoherent speech ■ Social isolation and sense of
■ Bizarre behavior alienation

■ Extreme confusion ■ Low self-esteem

■ Social skills deficits
ANTIPSYCHOTIC MEDICATION

When Do You Prescribe Antipsychotic Medication?

Although many general practitioners treat anxiety and depressive disorders,

most patients presenting with psychotic symptoms should be referred to a psy¬
chiatrist. Thesd patients are often hard to treat. Many psychotic patients can be
treated on an outpatient basis; however, hospitalization is often necessary.
Antipsychotic medications (also referred to as neuroleptics or major tranquiliz¬
ers) should be started when the early signs of psychosis appear, since many times
a more florid psychotic episode can be averted with appropriate early intervention.
Positive symptoms and disorganization symptoms are the primary target
symptoms for treatment by antipsychotic medications. Such drugs do little to
affect characterological traits or negative symptoms (with some exceptions. See
page 44).

Choosing a Medication

All antipsychotic medications are equally effective in their ability to reduce

positive symptoms. The choice of medication is dictated almost exclusively by
the side effect profile. For a list of antipsychotic medications, see Figure 26.
Antipsychotic medications have three primary side effects which must be taken
into consideration: sedation, anticholinergic (ACH), and extrapyramidal (EPS)
effects.
Before choosing a medication, assess the patient’s motor state. Psychotic reac¬
tions that present with marked agitation may require more sedating drugs. Use less
sedating drugs for psychoses with pronounced psychomotor retardation and with¬
drawal. This is a general rule of thumb, but there are exceptions.
Consider anticholinergic and EPS side effects. The most common cause for re¬
lapse is poor compliance or premature discontinuation because of unpleasant side
effects. The key to successful treatment rests on how well you handle side effects.

Extrapyramidal Side Effects. There are four classes of EPS:

1. Parkinson-like Side Effects. These include muscular rigidity, flat affect (mask¬
like facial expression), tremor, and bradykincsia (slowed motor responses).
These symptoms need to be distinguished from the flat affect and withdrawal
often seen as primary symptoms of schizophrenia. Parkinson-like side effects
are often diminished by the administration of anticholinergic agents (eg., ben/o
tropine. trihexylphenidyl. or amantadine).

2. Akathisia. This is an uncontrolled sense of inner restlessness. Akathisia must

be distinguished from anxiety. Often, a physician may mistake it lor anxiety
and increase the dose of antipsychotic, only to see a worsening ot the restless
ness. Akathisia can be partially alleviated by anticholinergic agents. Other
 Figure 26

ANTIPSYCHOTIC MEDICATIONS

DOSAGE ACH
GENERIC BRAND RANGE'" SEDATION EPS12' EFFECTS'" EQUIVALENCE'4’

Low Potencv

chlorpromazine Thorazine 50-1500 mg High ++ ++++ 100 mg

thioridazine Mellaril 150-800 mg High + +++++ 1 (X) mg

clozapine Clozaril 300-900 mg High 0 +++++ 50 mg

mesoridazine Serentil 50-500 mg High + +++++ 50 mg

quetiapine Seroquel 150-400 mg High + + 50 mg

High Potency

molindone Moban 20-225 mg Low +++ +++ 10 mg

perphena/ine Trilafon 8-60 mg Mid ++++ ++ 10 mg

loxapine Loxitane 50-250 mg Low +++ ++ 10 mg

trifluoperazine Stelazine 10-40 mg Low ++ ++ ++ 5 mg

fluphenazine Prolixin'5' 3-45 mg Low +++++ ++ 2 mg

thiothixene Navane 10-60 mg Low ++++ ++ 5 mg

haloperidol Haldol15’ 2-40 mg Low +++++ + 2 mg

olanzapine Zyprexa 5-20 mg Mid + + 2 mg

pimozide Orap 1—10 mg Low + ++++ + 2 mg

risperidone Risperdal 4-16 mg Low + + 2 mg

ziprasidone Zeldox 60-160 mg Low + ++ 10 mg

11'Usual daily oral dosage

,2’Acute: Parkinson’s dystonias, akathisia. Does not reflect risk for tardive dyskinesia. All neuroleptics may
cause tardive dyskinesia, except clozapine.
•’'Anticholinergic Side Effects: dry mouth, constipation, urinary retention, and blurry vision.
14'Dose required to achieve efficacy of 100 mg chlorpromazine.
•’’Available in time-released IM format.

drugs, however, are often more successful. These include diphenhydramine,

propranolol, or minor tranquilizers, such as lorazepam.

3. Acute Dystonias. These are muscle spasms and prolonged muscular con¬
tractions, usually of the head and neck. These can be resolved quickly with
intramuscular anticholinergic agents, or treated prophytactically with oral
anticholinergics.

4. Tardive Dyskinesia (TD). TD is generally a late onset EPS. This is a very seri¬
ous and often irreversible effect of antipsychotic medication treatment. It af¬
fects about one out of 25 people treated for a period one year, and by seven

40
 years of continuous treatment, it affects one in four. Symptoms include invol¬
untary sucking and smacking movements of the mouth and lips, and can in¬
clude chorea in the trunk and extremeties. Although various drugs have been
used to reduce TD symptoms (e.g., baclofen, sodium valporate, lecithin, and
benzodiazephines), there is no true cure. Treatment starts with stopping the
medication. Initial worsening of the dyskinesia is expected, as the drug not
only causes'the syndrome but also tends to mask it. Be patient, for months if
necessary, and TD will often remit. But control of severe psychosis usually out¬
weighs the problem of TD. All patients receiving antipsychotics must sign an
informed consent form which explains the risks of TD.

Anticholinergic Side Effects. These are the same as described in Chapter 2 on

depression.

The Relationship Betw een Side Effects. Anticholinergic agents reduce EPS. You
may coadminister neuroleptics and anticholinergics, or you may use certain anti-

DRUG CLASSES SIDE EFFECTS

(See Figure 26) Sedation ACH EPS

Low Potency High High Low

High Potency Low Low High
Please see Figure 26 for a more detailed outline of antipsychotic side
effects.

psychotics which have anticholinergic metabolites. The chart above is a simple

way to remember how the various side effects relate to one another.
Several potentially serious additional side affects can occur \s ith antipsychotic
medications, including agranulocytosis, impaired temperature regulations and
thus increased risk of heat stroke or hypothermia, and neuroleptic malignant syn¬
drome (a very rare syndrome that presents with fever, extrapyramidal rigidity,
severe autonomic dysfunction and in some cases death, l or a detailed review ol
this syndrome, sec Pearlman, 1986). For these reasons, treatment of psychotic dis
orders is often more appropriately carried out by a psychiatrist

Prescribing Treatment and What to Expect

Antipsychotic medications arc generally started at low to moderate doses and

titrated up until there is reduction in the more disruptive aspects ol the psychotic

41
reaction, e.g.. agitation* (NOTE: Some clinicians recommend “rapid neuroleptiza-
tion," i.e.. very high initial doses of neuroleptics. This treatment approach is con¬
troversial and not recommended). Divided doses may be helpful initially; however,
after a few days, a switch to a once-a-day bedtime dose is advisable. Dosage ranges
are extremely broad and vary considerably from patient to patient. In outpatient
practice, an initial starting dose might be haloperidol 2 mg./day or with chlorpro-
mazine, 100 mg./day. Inpatients are often treated at higher initial doses. See Figure
26 for dosage ranges. Antipsychotic medications must be taken each day.
Symptomatic improvement initially is seen as a decrease in arousal, emotional
dyscontrol. and agitation. Poor reality testing, hallucinations, and disordered
thinking may take much longer to respond. In many chronic schizophrenics, these
latter symptoms may take a number of weeks to respond.
Assuming a good response, how long do you continue to treat? If the psychotic
episode is a first episode, the rule of thumb is to decrease to a maintenance dose
and continue to treat for one year. If the episode is a repeated episode, will prob¬
ably be best to treat for two to three years before a medication-free trial is initi¬
ated. Always, owing to the risk of TD, one should treat at the lowest possible dose
that provides symptomatic relief.

KEY POINTS TO COMMUNICATE TO PATIENTS

1. It is important to describe side effects to patients, especially akathisia. This side

effect can be extremely unpleasant, yet often it is not spontaneously reported
by patients. If it occurs and is not treated, this will greatly increase the risk of
noncompliance, as well as increasing the patient’s suffering. So tell patients,
“You may notice an inner feeling of restlessness or nervousness. If you do,
please tell me. Do not just discontinue the medication. Most side effects can
be treated.”

2. Schizophrenia is a relapsing disorder and it is extremely important to keep

taking medication even if things seem fine. Premature discontinuation is the
primary cause of relapse.

3. The total length of treatment is likely to be at least one year and often longer
for more chronic schizophrenia.

4. Antipsychotic medications are not addictive.

5. You should avoid prolonged exposure to high temperatures and sunlight (some
antipsychotics have photosensitivity as a side effect).

6. Avoid amphetamines, cocaine, and L-Dopa because these drugs almost alw ays
exacerbate psychoses.

7. You and your relatives need to know about the risk of TD (and sign appropri¬
ate consent forms.)

42
 Figure 27

DECISION TREE FOR DIAGNOSIS AND TREATMENT

OF PSYCHOSIS

Note: Due to favorable side effects, atypical antipsychotic* arc advised (unless lonjr - acting
IM antipsychotics arc warranted).

43
 %

Treatment-Resistent Schizophrenic Disorders

There are three main reasons why schizophrenic patients may not respond to
antipsychotic medication:

1. Poor compliance. Often this is due to the unpleasant side effects. Many times
patient education and proper medical management of side effects resolve the
problem. Sometimes, patients simply forget to take their medication. In such
cases, treatment with time-released intramuscular forms of antipsychotics can
be helpful. Additionally, involving the family in treatment can significantly en¬
hance compliance.

2. Inadequate doses. Blood levels can be monitored and doses increased as

indicated.

3. Negative symptom schizophrenics may have a different underlying patho¬

physiology and often do not respond well to traditional antipsychotics. These
patients are hard to treat.

Several, newer antipsychotic medications have shown promise in treating the

negative (as well as positive) symptoms of schizophrenia. The first is clozapine —
(brand name Clozaril). Clozapine became available in the United States in 1990.
This medication is considered to be an atypical antipsychotic agent; its pharma¬
cologic profile is different than other existing antipsychotics. The first important
feature is that initial trials show it to be effective in treating many schizophrenic
patients who have failed to respond to standard antipsychotic drugs. This includes
a number of patients that presented with negative symptoms (as well as other
treatment-resistant schizophrenics). The second important and unique feature is
the virtual lack of acute extrapyramidal symptoms and few reported cases of tar¬
dive dyskinesia. This medication does have two significant potential side effects:
(1) The incidence of clozapine-induced agranulocytosis (a potentially fatal blood
dyscrasia) is between 1 and 2%, as compared to the incidence seen in other anti¬
psychotics (about 0.1%). This problem, however, is proving to be avoidable
through a mandatory hematological monitoring program (weekly medication
dispensing occurs only if the patient’s white blood cell count is normal). Since
implementing this program, there have been no fatalities in the 15 cases of
clozapine-related agranulocytosis reported in the United States. If there is a low
WBC count, medication is immediately discontinued and, to date, all such cases
have been reversible. (2) A second troublesome side effect is a fairly high inci¬
dence of seizures (about 1-2% at low doses and 5% at higher doses). Despite these
problematic features, clozapine appears to represent an important breakthrough in
the management of otherwise treatment-resistant schizophrenic disorders.
The newest additions to the “atypical" list are risperidone, olanzapine, queti-
apine, and ziprasidone. providing additional options for treating both positive and
negative psychotic symptoms with a much more benign side effect profile w hen
compared to standard antipsychotics. These medications do not have the high in¬
cidence of agranulocytosis seen w ith clozapine.

44
Common Treatment Errors to Avoid

• Akathisia (extreme inner sense of restlessness) is a very common side effect

that is quite uncomfortable and a primary cause for patient-initiated discon¬
tinuation. Remarkably, many schizophrenic patients will not spontaneously
complain of this side effect, but simply discontinue. It is therefore important
to inquire specifically about the presence of akathisia during follow-up visits
• Be especially watchful for early signs of tardive dyskinesia. Early signs can
be elicited by having the patient lay his/her arms on lap while seated, ex¬
tending the fingers in a relaxed, downward position over the knees. Note: for
the presence of spontaneous, purposeless, jerking movements of the fingers
• Antipsychotics often produce significant emotional blunting and apathy or
Parkinsonian symptoms which may be mis-identified as negative symptoms
(in such cases, raising the dose will likely exacerbate the side effects)

Books to Recommend to Patients and Their Families

Torrey, E.F. (1983). Surviving Schizophrenia: A Family Manual. Harper and

-Row Publishers.

Mueser, K. and Gingerich, S. (1994). Coping with Schizophrenia: A Guide for

Families, New Harbinger, Oakland.

45
 *

Chapter 6 Miscellaneous Disorders

In this chapter we would like to briefly discuss six additional disorders for
which psychotropic medications can be useful.

OBSESSIVE-COMPULSIVE DISORDER

Major Clinical Features

The major features of this disorder are recurring obsessions (persistent, intru¬
sive, troublesome thoughts or impulses that are recognized by the patient as sense¬
less) and/or compulsions (repetitive behaviors or rituals enacted in response to an
obsession, e.g., repeatedly checking to see if doors are locked, compulsive hand
washing, or counting). In order to meet the criteria for obsessive compulsive dis¬
order. the obsessions and/or compulsions must create significant distress or be
time consuming enough to interfere with normal routines (APA, 1987).

Medication Treatment

Treatments of choice include the use of serotinergic antidepressants (see be¬

low) often in combination with behavior therapy. Without behavior therapy, re¬
lapse is likely with discontinuation. Thus, chronic medication treatment is
generally necessary.

Figure 28

NAME
Generic Brand Dose Range Sedation ACH Effects

clomipramine Anafranil 150-300 mg Hi Hi

fluoxetine Prozac'1 > 20-80 mg Low None
sertraline Zoloft"1 50-200 mg Low None
paroxetine Paxil'" 20-50 mg Low Low
fluvoxamine Luvox 50-300 mg Low Low
citalopram Celexa 10-60 mg Low None

'"often higher doses are required to control obsessive-compulsive sy mptoms than the doses generally
used to treat depression.

46
BORDERLINE PERSONALITY DISORDER

Major Clinical Features

Borderline personality disorders constitute a very heterogeneous group of in¬

dividuals that suffer from long-term emotional instability. As a group they are
characterized by the following features: a pattern of chaotic, unstable relation¬
ships, significant emotional lability, impulsiveness (e.g.. self-mutilation, suicide
attempts, substance abuse, very poor frustration tolerance, sexual promiscuity).
anger control problems (e.g. pronounced irritability, temper tantrums, etc.), a ten¬
dency to develop significant bouts of anxiety and depression, and chronic feelings
of emptiness. Some borderline patients can develop transient psychotic symptoms
(that usually remit within hours to days). These patients are prone to any number
of major psychiatric syndromes in addition to what is a very stable, chronic pat¬
tern of maladaptive functioning in life.

Medication Treatment

Although there is increasing data to suggest an underlying biologic cause in

some of these patients, it is generally felt that the basic disorder is an outgrow th
of significant early, maladaptive psychological development. Psychotropic med¬
ications in no way treat the basic personality disorder, however, medications can
be used to treat particular target symptoms. The literature is sparse on the phar¬
macologic treatment of borderline disorders. However, clinical case reports and a
handful of empirical studies are beginning to provide some helpful guidelines for
pharmacologic treatment.
Not all borderline patients are alike, and for treatment purposes, the following
subgroups can be delineated to provide guidelines for choosing medications. The
subgroups are defined by the presence of a dominant symptom picture. Note: in¬
vestigators to date have found that minor tranquilizers generally are not indicated
in the treatment of borderline personality disorder. These patients often experi¬
ence an increased degree of emotional dyscontrol/disinhibition with minor trail
quilizers, and are at high risk for abusing such drugs.
For more information, the reader is referred to the following review articles and
book:

Cowdry, R. W. and Gardner. I). L. (1988). “Pharmacotherapy of Borderline Per

sonality Disorder.” Archives of General Psychiatry. Vol. 45. pill 119

Cornelius. J. R.. et al. (1991). **A Preliminary Trial of Fluoxetine in Refractory

Borderline Patients.” Journal of Clinical Psychopharmacology. Vol. II. No 2.
p. 116-120.

Preston. J. D. (1997). Short-term Therapy for Borderline Personality Disorders.

New Harbinger Publications. Oakland. ( A.

47
 Figure 29

SUBGROUPS DRUGS OF CHOICE

1. Impulsivity/Angcr Control Serotonergic antidepressants, e.g.

Problems fluoxetine, sertraline
2. Schizotypal (peculiar thinking, Low doses of antipsychotic
transient psychosis) medications e.g. 1 mg. haloperidol,
25-50 mg thioridazine, 1 mg. risperidone
3. Extreme sensitiv ity to rejection/ Serotonergic antidepressants
being alone
4. Emotional instability Lithium, divalproex

ATTENTION DEFICIT DISORDER1

Attention deficit disorder (ADD)2 affects between 3-5% of children. It is now

widely held that this disorder is largely due to a neurochemical disturbance (likely
involving dysregulation of dopamine and/or norepinephrine in the reticular sys¬
tem and frontal cortex).
Recent longitudinal/follow-up studies indicate that as many as 70% of ADD
children continue to exhibit symptoms well into adolescence and adult life, thus
suggesting that potentially 2-3% of the adult population experience ADD symp¬
toms. The major symptoms of ADD are outlined in Figure 30.
With age and maturation 30% of ADD kids “grow out of it" and exhibit no on¬
going symptoms. The remaining 70% tend to see a gradual reduction in restless¬
ness and “hyperactivity” although other core ADD symptoms remain.
ADD kids and teenagers often encounter considerable social/peer rejection and
academic failure. Self-esteem problems and frank clinical depression are not un¬
common. Rates of substance abuse in ////treated ADD adolescents are high (prob¬
ably best seen as an attempt to medicate-away feelings of sadness and inadequacy).
The discussion of pharmacologic treatment of ADD with children and young
teens is beyond the scope of this book (the reader is referred to an excellent text
by Green, 1991). Older adolescent and adult ADD clients can be very successfully
treated with psychotropic medications (success rates approaching 90%).
The mainstay of pharmacologic treatment of ADD is the use of stimulants (Sec
Figure 31). Please note that the three fast-acting stimulants listed (methylpheni-
date, amphetamine, and dextroamphetamine) can become drugs of abuse in those
predisposed to chemical dependency. Thus caution should be exercised in treating
patients with a substance abuse history. (Note: studies of ADD children, adoles¬
cents and adults without a personal or family history of substance abuse, show no

11 'Adapted from Preston. Lucas and O'Neal. 1995.

'-'Also referred to as Attention Dcficil/Hyperaclivity Disorder (Al)HI)).
 Figure 30

SYMPTOMS OF ADD

■ Impulsivity, e.g. acting before thinking, quick responses, poor judgement

■ Impaired abilities for attention and concentration; distractibility
■ Difficulties organizing tasks and activities
■ Restlessness and “hyperactivity”
■ Impaired emotional controls
■ Associated features:
Learning disabilities
Low self-esteem

tendency to abuse these stimulant drugs.) And the abuse potential does not occur
with pemoline or the antidepressants listed in Figure 31.
Because ADD (in adults) is almost always a life-long condition, prolonged
medication treatment is the rule rather than the exception.

AGGRESSION

Major Clinical Features

Marked aggression (including irritability, hostility, violence), whether chronic

or episodic, is seen in a number of psychiatric and neurologic disorders, includ¬
ing those listed in Figure 32.

Figure 31

MEDICATIONS USED TO TREAT ADD

GENERIC BRAND DAILY DOSES

Stimulants
methylphenidate Ritalin 5-50 mg.
mcthylphenidate Concerta 18-36 mg.
methylphenidate Metadate 10-40 mg.
dextroamphetamine Dexedrine 5-40 mg.
pemoline Cylert 37.5-112.5 mg.
d- and l-amphetamine Adderall 5-40 mg.
Antidepressants
imipramine Tofranil 75-300 mg.
buproprion, SR Wellbutrin. SR 150-300 mg.

49
 Figure 32

PSYCHIATRIC DISORDERS PRESENTING WITH SYMPTOMS

OF AGGRESSION '

■ A.D.D. ■ Iatrogenic, e.g. steroid use

■ Anti-Social Personality Disorder ■ Mania
■ Borderline Personality Disorder ■ Mental Retardation
■ Conduct Disorder ■ Paranoid Disorder
■ Delirium ■ Post-concussion syndrome
■ Dementias ■ Schizophrenia
■ Depression ■ Substance use disorders
■ Explosive Disorder ■ Temporal lobe epilepsy

In most cases, the preferred strategy is to treat the primary disorder (e.g. use of
antipsychotics with schizophrenics). Beyond this, certain medication treatment op¬
tions exist (See Figure 33). However, it is important to note that no single treatment
for aggressive behavior has been devised that has a high rate of success. The clini¬
cian must consider side effects of all potential agents and then proceed w ith a sys¬
tematic trial of available medications until one proves to be helpful. Regretfully,
severe aggression continues to be a target symptom that is very difficult to treat.

Figure 33

MEDICATION OPTIONS IN THE TREATMENT OF AGGRESSION

■ Anticonvulsants (e.g. carbamazepine)

■ Antipsychotics
■ Beta blockers (e.g. propranolol)
■ Buspirone
■ Clonidine
■ Lithium
■ SSRIs

EATING DISORDERS

Eating disorders are generally categorized as follows: bulimia (periodic binge

eating following by purging) and anorexia nervosa (intense fear of becoming fat
and a refusal to maintain healthy, age-appropriate body weight).

5()
 Unfortunately, anorexia nervosa, which can often be a life-threatening illness,
has a poor response rate to a host of standard psychotopic medications. It has been
treated experimentally with the opiate antagonist, naltrexone. Because it is po¬
tentially a very severe disorder, a referral to a psychiatrist or a specialized eating
disorders program is almost always warranted.
Bulimia, however, often is responsive to treatment with antidepressants (even
in the absence of depressive symptoms). The clinician should treat bulimia much
in the same way as he/she treats depression (i.e., with regard to dosing, length of
treatment, etc.). It is important to note that bupropion should be used with caution
due to a tendency for a higher rate of medication-induced seizures in bulimic pa¬
tients (seen with standard formulations, not sustained release).
A final note of caution: with the popularity of new diet medications (e.g. fen¬
fluramine) be sure not to co-administer these medications w ith either SSRIs or
MAOIs; drug-drug interactions are potentially dangerous.

POST-TRAUMATIC STRESS DISORDER

Post-traumatic stress disorder (P.T.S.D.) may be seen in the aftermath of re¬

cently occurring severe stressful events or can present in a chronic form which
continues for many years after traumatic experiences (the latter is often seen in in¬
dividuals who experienced very severe abuse as children). The symptoms of
P.T.S.D. vary, and can include the following: generalized anxiety, panic attacks,
depression, transient psychotic symptoms, intrusive symptoms (intense unwanted
memories, flashbacks or nightmares) and states of emotional numbness.
The treatment of choice for P.T.S.D. is psychotherapy. Psychotropic medication
treatment may be helpful in reducing certain target symptoms (treatments for
panic and depressive symptoms follow general guidelines for these conditions).
Additionally, three symptoms of P.T.S.D. warrant specific comments.
Transient psychotic symptoms often respond to a short course of anti¬
psychotic agents. Often, the doses required are somewhat lower than that gener¬
ally required to treat schizophrenia. Intrusive symptoms have been treated with
a host of psychiatric medications. To date, the best outcomes are achieved
with SSRI antidepressants. It should be noted that often high doses may be re¬
quired (e.g. 60-80 mg fluoxetine or 2(X) mg. sertraline). Although no specific
medication targets emotional numbing, often once intrusive symptoms arc di¬
minished, there is a corresponding decrease in the frequency and intensity
of numbness (and related symptoms such as dissociation, depersonalization and
derealization).

Books to Recommend to Patients and T heir Families

Obsess i ve-Compu Isive

Rapoport. J. L. (1989). The Hoy Who Couldn 't Stop Washing. Signet: New York

51
Sleketee, G. and White, K. (1990). When Once is Not Enough: Help for Obses¬
sive-Compulsives. New Harbinger, Oakland, CA.

ADI)
Parker, H. C. (1988). The ADD: Hyperactivity Workbook. Impact Publications,
Manassus, VA.

Borderline Personality Disorder

Kreisman, J., and Krauss, H. (1988). / Hate You—Don't Leave Me: Understand¬
ing Borderline Personality Disorder, Price Stern: New York.

Mason, P. and Kreger. R. (1998). Stop Walking On Eggshells. New Harbinger,

Oakland, CA.

Aggression
Potter-Efron. R. (1989). Angry All the Tune, New Harbinger, Oakland, CA.

Eating Disorders
Sandbek, T. (1993). The Deadly Diet: Recovering from Anorexia and Bulimia
(Second Edition), New Harbinger, Oakland, CA.

Post-traumatic Stress Disorder

Matsakis, A. (1992). / Can't Get Over It: A Handbook for Trauma Survivors, New
Harbinger, Oakland, CA.

A General Reference for Clients to Help Them Understand the Process of Psy¬
chotherapy and the Role of Medications
Preston, J., Varzos, N., and Liebert, D. (2000). Make Every Session Count. New
Harbinger, Oakland, CA.

52
 Chapter 7 Non-Response and “Breakthrough
Symptoms’’ Algorithms

When the diagnosis is made and treatment initiated, if there is a failure to respond
to treatment then the following algorithm can provide a strategy for re-evaluation:

NON-RESPONSE CHECKLIST

1. Re-evaluate the initial diagnosis

2. Rule out co-existing medical illness

3. Rule out substance abuse (which often interferes with the metabolism of psy¬
chotropic medications and/or exacerbates psychiatric symptoms)

4. Rule out medication induced psychiatric symptoms (e.g. antihypertensives

causing depression)

5. Has there been an adequate trial? This always assumes:

a. Adequate dose (may necessitate monitoring blood levels)

b. Adequate duration of time (remember, most psychotropics require several

weeks of treatment before the onset of symptom reduction)

c. Compliance (notoriously poor among psychiatric patients). Monitor side

effects.

6. Rule out drug-drug interactions that may affect pharmacokinetics

7. Psychological and psychosocial issues are not being adequately addressed (re¬
fer for psychotherapy)

8. The patient may be on the wrong class of medications and/or require

augmentation.

Not infrequently a patient has a positive initial response to treatment and later
experiences a return of symptoms. In such instances the clinician can assess the
following:

53
UNEXPLAINED RELAPSE CHECKLIST

1. Recent onset or increase in substance use/abuse

2. Sleep disturbance has become more pronounced due to increased stress, phys¬
ical pain, and/or substance use (e.g. caffeine). Sleep deprivation always in¬
creases psychiatric symptoms.

3. Failure to comply with medication treatment

4. Significant increases in psychosocial stressors

5. Changes in underlying metabolic factors and/or neurobiologic changes (e.g.

impaired hepatic or renal functioning, recent head injury, menopause)

6. Tolerance for the psychotropic medication may have developed (although this
is rare).

7. Rule out an underlying medical disorder.

54
 Chapter 8 Case Examples

In this chapter we will present a number of case examples which illustrate com¬
monly encountered clinical issues and problems (with suggested solutions and
strategies). Although general principles are helpful in initiating treatment, in a real
sense each case is unique and somewhat of an experiment. Accurate diagnostic
assessment and a review of the patient’s personal and health status (e.g.. age. med¬
ical problems, prescription drugs being taken, etc.) will certainly help determine
initial psychotropic medication choices. However, beyond this starting point, the
clinician must track patient response closely to monitor for compliance, side ef¬
fect problems and eventual symptomatic improvement.
In managed care, HMO, and family practice settings, compliance problems
abound. This is due to four common factors: a) inadequate patient education re¬
garding the medication, b) the emergence of side effects and c) the frequent prob¬
lems of demoralization and feelings of hopelessness (i.c.. many psychiatric
patients come to the clinician in a state of despair and pessimism. When psychi¬
atric medications do not rapidly provide symptom improvement or unpleasant
side effects occur, many patients abruptly stop taking medications or drop out of
treatment), and d) general aversion to/fear of taking medications, especially psy¬
chiatric medications, for a variety of psychosocially and philosophically based
reasons, which the patient often will not share spontaneously. Frequently such pa¬
tients deteriorate and re-emerge later either in a more severe psychological state,
or are seen and treated for a host of stress-related somatic symptoms.
It is our opinion that somewhat more time spent initially in diagnosis and treat¬
ment followup can contribute significantly to successful treatment outcomes.
Hopefully this chapter will highlight common treatment complications and sug¬
gested action strategies.
In the treatment of anxiety and depressive disorders, the “rule of threes’ seems to
apply. About one-third of patients are fairly uncomplicated and can be treated suc¬
cessfully with psychotropic medications, brief supportive counseling and the sup¬
port offered by social networks (family, friends, churches, support groups). A second
third of patients are more challenging. These people experience medication-related
problems (e.g., side effect problems, inadequate response to standard regimens or
failure to respond to first-line medications) and/or are in need ot more intensive psy
chotherapy where treatment by a professional therapist is indicated 'let despite
these added challenges, this group can generally lx* managed quite successfully.'

•Noli-: In ihc United Stales, lamily practice and other non-psychiatric physicians trc.it tin- m.i|.wit> ■»!
people seckmj! help tor depressive anil ansicty disorders, writing hW of all prev option for aniulc
pressants and of all prescriptions lor aniiansictv medications.

55
The remaining third are significantly more difficult to treat and most often must have
medications managed by a psychiatrist as well as being involved in psychotherapy.
The treatment of bipolar and psychotic disorders is considerably more difficult
owing to three factors: a) these severe mental Illnesses often require inpatient
treatment, b) the medications used can have more problematic and serious side ef¬
fects (often requiring more monitoring of the patient's medical status) and c) the
medication regimen often is more complicated. For these reasons, although some
relatively uncomplicated and treatment-responsive bipolar and psychotic patients
can be and are treated in family practice settings, a referral to a psychiatrist is usu¬
ally necessary.

CASE A: A Case of Major Depression

Background and Presenting Problems: Mr. E. is a 62 year old retired draftsman.

He has suffered for 20+ years from rather severe arthritis. He takes over-the-
counter pain medication and currently is on no prescribed medication. Beyond the
arthritis. Mr. E. is in good health. Characterologically, he can be seen as a rigid,
obsessional man who has had few close friends aside from business colleagues
and his wife of 35 years. He is a stamp collector and since his retirement two years
ago he has become progressively isolated and withdrawn.
Mr. E. comes to you complaining of problems with his “nerves” and insomnia.
His grooming is adequate, but he appears to be quite fatigued. He reports that
problems have developed over the past three months ever since his wife confessed
to having a “one night fling” with an old boyfriend while she was visiting rela¬
tives out of town. She promises that the affair is not on-going, but he worries al¬
most constantly about her “leaving me” and harbors significant anger towards her.
Mr. E’s symptoms include: irritability, an almost total loss of the capacity for
experiencing pleasure, fatigue, an inner sense of restlessness, a 15 pound weight
loss over the past three months, suicidal ideas, loss of libido and a sleep distur¬
bance (restless sleep almost every night and early-morning awakening 5 nights
out of 7 during the past six weeks).
Diagnosis Issues: The initial impressions are that Mr. E. has a major depression.
(Because of no previous episodes of depression or mania, it is considered to be a
single-episode, unipolar depression.) Although clearly this depression is “reac¬
tive" (i.e., in response to a significant psychosocial stressor), the symptom picture
reveals the presence of physiological symptoms (see pg. 5) which suggest a neuro¬
chemical dysregulation and indicate that he is a candidate for antidepressants.
Initial Medication Treatment Issues and Decisions: Although Mr. E. reports an
inner sense of restlessness, he is quite fatigued and his overall motor slate is re¬
tarded. Thus it makes sense to choose a more stimulating antidepressant. You
choose fluoxetine. Mr. E. is prescribed a 10 mg. q.d. dose, is given proper patient
education underscoring two points: a) the medication will take 2-4 weeks to yield
symptomatic improvement and he needs to be patient and take the medicine as
prescribed, and b) be sure to call if he notices any significant side effects. (He is

56
told the most common side effects which may occur with this medication.) After
one week you increase the dose to 20 mg. q.d. Two days later. Mr. E. calls to say
that he is feeling “jittery.” You instruct him to reduce the dose to 10 mg. q.d. for
a week. You ask him to touch base with you by phone in the next day or so. Upon
follow-up. the jitteriness has disappeared and he reports no other side effects. Af¬
ter a week on 10 mg. q.d., he is instructed again to increase to 20 mg. q.d.: he does
so this time without noticeable side effects.
Points to Underscore:

• Minor side effect problems are common with all antidepressants, and most
can be managed by dosage adjustment. As patients tolerate lower doses, the
doctor can then gradually titrate the dose up into the therapeutic range.
• Patient education and close doctor-patient communication arc the keys to ini¬
tiating treatment dealing with early emergent problems.

Course of Treatment: Let’s consider three possible outcomes.

Scenario One: By day 18 of treatment, now on 20 mg. q.d. for nine days.
Mr. E. begins to report less daytime fatigue, somewhat better sleep and reduced
irritability. He continues on the same dose, and by day 40 almost all major de¬
pressive symptoms have resolved. He still has on-going issues with his wife (for
which they are in couples counseling with their minister), but core depressive
symptoms are resolved. You instruct Mr. E. to continue on the antidepressant at
the same dose for an additional six months before discontinuing (a highly recom¬
mended strategy to reduce the likelihood of acute relapse). The medication is dis¬
continued six months later and he remains asymptomatic.
Scenario Two: By day 30 Mr. E. reports only a slight improvement in his sleep,
but otherwise remains quite depressed. At this point it is very important to ask or
review a number of key questions:

• Is he taking the medication as prescribed?

• Is he abusing alcohol or illicit drugs? (Concurrent and often unreported alco¬
hol abuse is a very common reason for inadequate response to antidepressants.)
• Have psychosocial stressors increased?
• Although he reported that, aside from arthritis, his general health status \sas
good, could there be an undiagnosed medical condition contributing to his de¬
pressive symptoms (e.g.. hypothyroidism)? An old saying is "Dogs can have
fleas and ticks”; always consider the possibility ol symptoms related to life
stressors anil coexisting medical conditions.

If all questions have been addressed and none of these factors ap|x\ir to Iv con
tributing to his lack of response, the next step will be to increase the medication
dose (if and only if Mr. E. tolerates side effects).
In this scenario we will assume that he di>es tolerate an increase to 40 mg. q d
of fluoxetine. After seven days on the new dose, he begins to respond positively.

57
Within a few weeks, all depressive symptoms resolve. He is then maintained on
the same 40 mg. tj.d. dose for six months before discontinuation.
Scenario Three: As above, after an increase to 40 mg. q.d.. Mr. E. fails to show
clinical improvement. He is maintained on the dose for two*weeks. You decide
to increase again to 60 mg., but after two weeks there is still little improvement.
At this point there are two options: a) augment or b) switch to a different class of
medication.
Scenario Three - A: You decide to add lithium 300 mg. b.i.d to the fluoxetine and
within a week. Mr. E. begins to show the first signs of symptomatic improvement.
Scenario Three - li: Mr. E. either cannot tolerate lithium or fails the augmenta¬
tion trial. You decide to sw itch to another class of antidepressant. MAO inhibitors
and fluoxetine can be very toxic in combination, and a consultation with your local
pharmacist revealed that fluoxetine can remain in a person’s system for six weeks
(owing to a long half-life). Thus you decide to switch to bupropion, SR. (Since flu¬
oxetine is a serotonergic drug, the most reasonable choice for second-line treatment
is an antidepressant that affects norepinephrine.) You allow for a one week no-drug
wash out and then start bupropion, SR. beginning with a low dose, 100 mg. q.d.
In order to avoid or minimize initial side effect problems, it is advisable to start
with low doses, gradually titrating up every 4 days, as tolerated by the patient.
The dose of bupropion. SR is gradually increased during the first week until it
reaches the therapeutic range (i.e., 150 mg) (Note: since Mr. E. is 62 years old,
general metabolic activity, as with most older people, is slowed in the liver, and
thus may benefit from lower doses, e.g., 100 mg. q.d. However, almost w ithout
exception, younger and middle-aged adults require doses within the therapeutic
range (see page 7). As doses are increased, the clinician always monitors two vari¬
ables: signs of clinical improvement and side effects. In the scenario, Mr. E. was
able to reach a dose of 150 mg. of bupropion, SR by day 7, tolerating the med¬
ication well. By day 14 he began to respond.
Had he failed the 150 mg. trial, several options still exist:

• Progressively increase the dose of bupropion, SR up to a maximum of 300

mg. q.d. (if necessary and if tolerated).
• Take a bupropion, SR blood level to assure that it is within the therapeutic
range.
• Augment with lithium.
• Switch classes of medications to either an MAO inhibitor (after an appropri¬
ate 2 week wash out of bupropion) or the antidepressant, venlafaxine.
• Electroconvulsive therapy is a final option if all other treatments fail and/or
if his condition deteriorates and suicidal impulses intensify.

Throughout treatment the clinician should continue to monitor for the presence
of alcohol use/abuse, medical problems, and the use of other prescription drugs.
And it is always important to consider psychotherapy as an important aspect of
treatment, especially in cases such as that of Mr. E.. where psychosocial and in¬
terpersonal issues play such an important role in the genesis of his depression.

58
CASE B: A Case of Bipolar Illness

Mr. M. is a 22 year-old college student brought to you by his parents after a

two-week history of marked change in his usual behavior. At first, he began stay¬
ing up later and getting up earlier. Although his parents assumed he was studying
for his impending final examinations, they were puzzled by his high energy and
enthusiasm in’the morning since he was usually a slow starter, especially if he
did not get a good night’s sleep. Concern began when they discovered that he was
not, in fact, studying at all. but was working on a new computer program that
would make him a millionaire. He was vague on details and brushed aside objec¬
tions that he had little knowledge of computer equipment and became irritable and
demanding when they questioned the wisdom and reality of this behavior. He had
always been a reasonable and somewhat conservative individual. In addition, he
seemed to talk incessantly and without any interest in input from others, although
attempted input by others would often send him off on a tangential line of dis¬
course. Concern turned to alarm, anger and embarrassment when he made inap¬
propriate sexual comments to one of his mother’s friends who had come to visit.
The patient came for a consultation only with the firm insistence of his parents,
and only to make them happy since he felt nothing was wrong with his behavior.
A history confirms the patient’s prior apparent excellent adjustment without
psychiatric consultation and a negative recent physical exam and full chemistry
screen prior to his tryout for a baseball team.
The patient denies drug use, and his parents had found no evidence of drug use.
A urine screen for drugs of abuse is obtained and confirms no drugs.
An uncle had had several episodes of erratic and irresponsible behavior, lead¬
ing to financial problems and divorce, but he was the black sheep of the family and
was a heavy abuser of alcohol, which the family had blamed for his misfortunes.
At this point the family practitioner should remind himself or herself of the fol¬
lowing points:

• The diagnosis of manic or hypomanic stales is relatively easy as it is dramatic

and unlikely to be confused with other conditions provided drug abuse is
ruled out, especially stimulants.
• Bipolar disorder is often complicated in its long term course by associated
difficulties, especially of a psychosocial nature, and drug regimens for cer¬
tain variant forms of the illness. It is. therefore, usually best left to the care ol
a psychiatrist. This is especially true if the illness has been present lor some
time, is rapidly cycling, or if the patient is on other medications.
• The difficulty in treating manic or hypomanic states at the outset is usually in
enlisting cooperation and compliance w ith treatment. A good rapport or rela¬
tionship with the patient is critical; working with and through the family is
often critical as well.
• Do not be misled by the ability of patients to hold it together for a doctor s
visit. Those patients who are clearly manic and who exhibit the classic signs
on mental status exams should be referred immediately to a psychiatrist.
 except for those rare patients with insight and who present themselves for
treatment (and these usually have a history of prior episodes).
• Lithium carbonate is the drug of choice. Failure of the patient to respond to
lithium should trigger a referral to, or consultation with*, a psychiatrist.

In this case, you are fortunate in that the patient has seen you in the past for
physical exams and minor medical problems, and you have had good rapport.
With professional concern and authoritative directness, hut without condescen¬
sion, you tell the patient that while he may not agree, it is your medical opinion
that he has a medical condition that is well known and produces the kind of symp¬
toms he has been having. You may want to review the reported behavior and your
own observations if they have included hypomanic or manic behavior. Do not do
this in an exhortatory way but in an analytical manner which arrives at your rec¬
ommendation for treatment. You then educate the patient about the major side ef¬
fects of lithium and get an informed consent. If the patient attempts to minimize
or escape by declaring “he’ll think about it,” recognize with him that you cannot
make him take the medication, of course, but that you really think it is important
for him to take the lithium and proffer the prescription.
Assuming compliance, you begin lithium 300 mgs. b.i.d., with meals and mea¬
sure the serum lithium level in two days on a stat basis. If the lithium level is be¬
low 1.0 meq/L increase to 300 mg. t.i.d., and again measure the serum lithium
level in two days. At each visit inquire about side effects and reassure him, if they
are in a tolerable range, that they are not dangerous and will lessen in the near fu¬
ture. The maintenance goal is 1.0 meq/L but side effects may necessitate a com¬
promise. Levels below 0.5 meq/L are generally considered subtherapeutic.
Continue to raise the dose by 300 mg. q.d., and measure the lithium level every
two days until it is 1.0 meq/L. If the patient fails to respond within two weeks,
consult a psychiatrist.

If the patient responds beautifully, he should remain on maintenance therapy

indefinitely. A patient will rarely comply with this but monthly checks over the
next several months encourage the patient to share with you his feelings about
having a chronic mental disorder and the need to have chronic treatment; answer
those questions which you can. As long as the patient remains in treatment, he w ill
need periodic blood tests for lithium, TSH (lithium occasionally produces hy¬
pothyroidism, a serious problem when untreated but easily treated) and creatinine
(lithium is excreted by the kidney and decreased renal clearance could lead to
lithium toxicity). This should be done usually about every three months. In gen¬
eral, proceed as in case C.

CASE C: Another Case of Bipolar Disorder

A 45 year-old married housewife w ith a history of three episodes of mania and

two mild depressions during her twenties presents with a request to continue her
lithium and to get “blood checks.” She has been quite stable on lithium since be¬
ginning treatment around the age of 28, experiencing only two mild elated peri¬
ods. She is in good health except for diabetes mellitus, controlled with diet alone.
The patient has been quite compliant with treatment and states that her husband
is fully informed of her condition and is able to identify her mood swings, often
before she does. A review of her prior medical records indicates the presence
of clear criteria for bipolar disorder including one brief hospitalization for the
second episode of elation during which she was engaged in some sexually promis¬
cuous behavior which was embarrassing and quite out of character. Her depres¬
sions were significant but not associated with suicidal behavior. She had been
responsive to lithium but stopped it after leaving the hospital. She quickly re¬
sponded to lithium again on the third episode of elation, obviating the need for
hospitalization. The records also revealed that a lithium level of 0.8meq/L con¬
trolled her symptoms adequately, but that higher levels produced some shakiness
in her hands, which she found annoying. She was quite satisfied with her care, but
had recently moved to the area because of her husband’s transfer secondary to a
promotion. The only psychiatrist in the area was not taking new patients.
Increasingly, the family practitioner will be sought out for medication mainte¬
nance by already diagnosed and regulated patients who have moved, changed
insurance coverage, or whose psychiatrist has retired or moved. Once again, the
history should be reviewed and only those cases which are uncomplicated (see
above points to keep in mind) should be accepted.
The follow-up interval is arbitrary, but every three months is adequate in un¬
complicated situations. An elevated TSH should be treated by thyroid replace¬
ment. An elevation in lithium or creatinine levels should trigger an evaluation of
kidney function. Symptoms of lithium toxicity should be reviewed with the pa¬
tient and her husband, with instructions to report in if these toxic symptoms arc
noted at any time. These brief routine visits not only establish the rapport so vital
to treatment of episodes, but they also allow the practitioner to establish a base¬
line mental status to compare with changes produced by a mood shift. Blood lor
lab studies is best drawn in the morning before eating (fluids arc permitted, but
milk or cream should be avoided) and before the morning lithium dose. Finally,
any increase in frequency of episodes, even mild ones, should trigger psychiatric
consultation.

CASE D: A Case of Acute Situational Anxiety

Background and Presenting Problems: Mrs. M. is a 47 year-old bank execu¬

tive. She is married and has three teenage children. Her history is one ot reason¬
ably good adjustment and no episodes of prior psychiatric symptoms. I wo weeks
ago her husband was diagnosed with malignant melanoma He is undergoing
treatment and the prognosis is fairly positive. However, since the diagnosis Mrs
M. has experienced a considerable amount ot anxiety and worry. She can hardly
put her husband's illness out of her mind, and throughout the day she ruminates

61
Her ability to concentrate at work has become noticeably impaired. She has fre¬
quent waves of nervousness in which she trembles and experiences a mild degree
of shortness of breath and tachycardia. She also reports difficulties falling asleep
(requires I Vi-2 hours to go to sleep, although when asleep she is able to sleep
through the night). She is in good health and currently is taking no prescription
medications.
Diagnostic Issues: Given this presentation several important questions come
to mind:

• Is there any evidence that she is clinically depressed? Many patients that ini¬
tially appear to have anxiety symptoms are, in fact, depressed. This differen¬
tial diagnosis is important. So you question her about important symptoms
such as: self-esteem, anhedonia, decreased libido, fatigue, early morning
awakening, etc.
• Is she using/abusing drugs (being especially concerned with determining the
amount of caffeine use)?
• Are there any undiagnosed medical problems (remember, fleas and ticks)
e.g„ hyperthyroidism?

She is sad. especially when imagining that her husband could die. However, she
does not exhibit severe or entrenched symptoms of major depression. She is not
abusing drugs and, in fact, is in good health. You diagnosis is an adjustment dis¬
order with anxiety symptoms (i.e., stress-related anxiety).
Initial Medication Treatment Issues and Decisions: Brief counseling or psy¬
chotherapy is the treatment of choice for this type of disorder. Medications can also
be a helpful adjunct. You tell Mrs. M. that her symptoms are understandable given
her life circumstances, but you also acknowledge that the impaired concentration
at work and her insomnia certainly are problematic, and short term medication
treatment may be helpful. One very important question must be addressed prior to
initiating treatment: Is there any personal or family history of alcoholism or drug
abuse? If so, she should be considered at risk for misuse or abuse of benzodi¬
azepines. Assuming she denies any reported history of substance abuse, she is pre¬
scribed one of the following: a) a low dose benzodiazepine for occasional daytime
use (e.g., lorazepam 0.5 mg. b.i.d, prn), if the target symptoms are daytime anxi¬
ety and impaired concentration or, b) a low to moderate dose of a hypnotic (e.g.,
temazepam, 15 mg. q.h.s., prn) if you choose to treat the insomnia.
Mrs. M. is told that this medication is for short-term use only (probably 1-4
weeks). Should her stressors and symptoms continue beyond this point, it will
probably be necessary for her to be in counseling and to be reevaluated. If she is
using these medications appropriately and circumstances warrant it. continued
treatment beyond 4 weeks may be indicated and helpful. You are especially alert
to monitor tw'o issues as treatment progresses:

• Many patients may not fully benefit from very low doses of benzodiazepines,
and a dosage increase may be appropriate. However, overuse of medications

62
 or ongoing requests/demands for higher doses, should alert the clinician to
the possibility of benzodiazepine abuse.
• Should Mrs. M. require daily use of a benzodiazepine for more than 3 or 4
weeks, the clinician must consider that dependence can develop. Tolerance
generally does not develop for the antianxiety effects of benzodiazepines;
however, habituation that can occur neurophysiologically and can (and often
does) result in withdrawal symptoms if the medication is abruptly discontin¬
ued. Thus, when you determine that it is time to discontinue, this should be
done gradually. A wise approach is to take at least one month to progressively
wean Mrs. M. from her antianxicty medication (if she has been on it for more
than one month).

Once again, especially in cases of reactive distress, keep in mind that counsel¬
ing or psychotherapy are very important, in addition to psychotropic medications,
patient education, and general reassurance.

CASE E: A Case of Panic Disorder

Background and Presenting Problems: Ms. B. is a 32 year-old, single vocational

counselor. Although she has not had a history of major psychiatric symptoms, she
did have several bouts of “nervousness,” each time in response to significant life
transitions. The first of these was in high school w hen her family moved to a new
state. It was a difficult adjustment for her. She missed her old friends a lot. and for
2-3 months felt extremely anxious. She was often afraid to leave the house, al¬
though she did manage to go to school despite her distress. She also felt afraid when
her parents left her at home alone for an evening. After several months, her anxiety
subsided. The second episode w as w hen she went to college. She attended a school
some 2(X) miles aw ay from her home town. She again felt very anxious, developed
some type of undiagnosablc stomach pain, and eventually dropped out. Ms. B.
moved home and enrolled in a local community college, and her anxiety subsided.
After graduation from college, she secured a job w ith a company in her home
tow n and has maintained fairly close contact with her parents over the years.
Six weeks ago her father suffered a heart attack. He was in critical condition
for two days, but progressively recovered and currently is doing well. However,
the day after his heart attack Ms. B. experienced a lull blow n panic attack. This
frightened her tremendously, in part because she believed that she too w as has mg
a heart attack. Her family doctor saw her later that day. diagnosed the symptoms
as anxiety, reassured her and gave her a limited prescription of dia/epam. 5 mg.
However, the initial attack was not an isolated episode; in the ensiling weeks
she experienced approximately four attacks jx*r week. Phis continued to ixcur
even after she was reassured that her father was making a sale recovery. Most at
tacks were spontaneous (not associated with acute stressful precipitant*) I hey
came on rapidly (about 2 minutes from the first sign of symptoms to the height ol
the attack) and subsided, usually within 5-10 minutes.
 Ms. B. was again seen by her physician who ran a battery of tests and concluded
that aside from the panic attacks, she was in good health.
Diagnostic Issues: As noted in the previous case, anytime anxiety is seen as a
dominant symptom, it is important to rule out medical causes including substance
use/abuse. Ms. B. denied alcohol and illicit drug use, but did admit to drinking
3-4 cups of coffee and at least one diet cola per day. Caffeine rarely causes full
blown panic attacks, although it often contributes significantly to generalized anx¬
iety and can lower the threshold for panic attacks. Thus, she was advised to grad¬
ually (over a period of 3 weeks) replace coffee and sodas with decaffeinated
beverages. The gradual reduction in caffeine was done to reduce the likelihood of
caffeine withdrawal (a problem frequently seen with abrupt discontinuation). In
Ms. B.’s case the reduction in caffeine did reduce some generalized anxiety and
improved her ability to fall asleep at night. However, the frequency of panic at¬
tacks was relatively unchanged. It is also worth noting that the prn use of 5 mg.
diazepam did little to ward off her periodic attacks.
As in the last case, the clinician asked detailed questions to assess for the pres¬
ence of depression. In Ms. B's case, she was beginning to feel quite discouraged
and sad. She also experienced a good deal of pessimistic thinking, low self-esteem
and fatigue. But other signs of a major depression were absent.
The diagnostic impression is one of panic disorder with associated mild de¬
pressive symptoms.
Initial Medication Treatment Issues and Decisions: The clinician decided to use
a two-pronged approach: a) she was started on the antidepressant paroxetine, and
b) referral to a psychotherapist who specialized in behavioral treatment. She had
developed some phobias about leaving her house and this would be the target for
behavioral treatment once panic symptoms were eliminated or reduced.
Course of Treatment: The initial dose of paroxetine was 20 mg. q.h.s., which she
tolerated well. On day 3 the dose was increased to 30 mg. q.h.s., however, the next
day she experienced two panic attacks. An increase in anxiety and panic symptoms
often occurs during the first 2-3 weeks of treatment with antidepressants. Thus,
although this was a complication, it was not completely unexpected. The clinician
then decided to add alprazolam 1.0 mg. t.i.d. to the 30 mg. of paroxetine (common
and often successful strategy). The panic attacks subsided; Ms. B. only experienced
two attacks during the next week and these were less intense than prior attacks.
The clinician continued to increase the paroxetine dose to a level of 40 mg.
q.h.s. and after three weeks reduced the dose of alprazolam to 0.5 mg. t.i.d. (for
one week) followed by a further reduction (0.25 mg. t.i.d.). Since the increase in
paroxetine, Ms. B. has only experienced two additional minor attacks (sometimes
referred to as limited symptom attacks).
By week four the alprazolam was discontinued altogether. However, the next
day Ms. B. experienced her first full blown attack in several weeks. Several ques¬
tions must be asked at this point:

• Were there any new or increased psychosocial stressors?

• Did she consume alcohol or caffeine w ithin the past day?

M
 In Ms. B.’s case, there were no new or increased stressors, no alcohol or caffeine
use. and she did take her medications as prescribed. The most likely hypothesis was
the low dose of alprazolam was, in fact, instrumental in warding off panic attacks.
The clinician reinstated the alprazolam at 0.25 mg. t.i.d. and continued the
paroxetine dose at 40 mg. q.h.s. No further attacks occurred during the next week.
Then the alprazolam was again discontinued. Ms. B. remained stable over the next
two weeks, with only one limited symptom attack. She was also told she could
take one 0.25 mg. alprazolam as needed for situational anxiety (which she did 2-3
times per week over the next two months).
With panic symptoms well controlled, the behavior therapist began using
graded exposure techniques with Ms. B. to help her overcome her phobia. In ad¬
dition she began to explore her feelings related to her father's illness and what she
identified as “my problems growing up and separating from my parents.” She con¬
tinued to deal with these psychological issues in psychotherapy, long after all
panic and phobic symptoms disappeared.
Nine months after starting treatment, her physician initiated a gradual reduc¬
tion of the paroxetine. However, five days after taking a dose of 30 mg. q.h.s.. Ms.
B. had another panic attack. It was necessary to resume the 40 mg. q.h.s. dose.
Four months later a gradual discontinuation trial was successful.
Psychotropic medication treatment is very effective with panic disorders, but
almost always requires concurrent psychotherapy and/or behavior therapy.

CASE F: A Case of Acute Schizophrenia

Background and Presenting Problems: Mr. P. is a 22 year-old. unmarried jani¬

tor who comes to the clinic complaining of “insomnia.” He has been experienc¬
ing initial insomnia, restless sleep, and "bad dreams” during the past month. He
is quite thin and has marginal personal hygiene, but otherwise is in good health.
He reports some alcohol use but denies abuse of illicit drugs. He smokes three
packs of cigarettes per day and drinks “a lot of coffee."
In addition to his reported problems, upon clinical evaluation you discover that
he has been hearing voices over the past few weeks. The voices generally mum¬
ble unintelligible things to him. and on occasion he will hear them say. "you are
a loser.” He is not especially concerned about the voices, but docs worry a lot
about buses that pass his apartment. "The way they slow down right by my apart¬
ment is weird ... I think they arc sent there to watch me." Beyond this vague de¬
scription of the activity of buses, he can offer little additional elaboration. Mr. P.
also appears to be quite anxious and somewhat agitated.
Mr. P. graduated from high school with a C+ average. He has always been a
loner, and his only real human connections are with Ins immediate family, who
live nearby. There is no prior history of psychiatric treatment. He strikes you as a
rather shallow and empty man.
Diagnostic Issues: The history and evolution of his symptoms suggest the pic¬
ture of acute psychosis (likely schizophrenia, although because ol the absence o!
 %

prior florid psychotic symptoms, initially this is best seen as schizophreniform

disorder). He is evaluated medically to rule out disorders that may cause psychosis
(none are found) and you learn that he takes no prescription medications. There
have been no acute psychosocial stressors precipitating his slip into psychosis.
Initial Medication Treatment Issues and Decisions: The treatment of choice for
schizophrenia are antipsychotics; Mr. P. is prescribed haloperidol 2 mg. b.i.d.
Scenario One: Mr. P. tolerates the haloperidol. and on day 4 you increase the
dose to 3 mg. b.i.d. Within a week he reports to you that he is sleeping better, and
he appears somewhat less anxious. However, unrealistic thinking, auditory hallu¬
cinations and inadequate personal hygiene continue.
After 5 weeks of treatment, Mr. P. reports that the voices have stopped. Two
weeks later, when again questioned about the buses, he states, “Oh, they aren’t
bothering me ... I haven't paid much attention to them lately.” Hygiene has im¬
proved a bit. He appears to be significantly less anxious, although he remains so¬
cially isolated and emotionally empty.
Treatment is continued for an additional ten months and then the haloperidol is
gradually reduced over a period of six weeks. Mr. P. is stable and not psychotic.
Followup appointments are scheduled on a once-a-month basis, and he is moni¬
tored closely, especially because his disorder is notoriously recurring.
Scenario Two: As in scenario one. Mr. P. is treated with haloperidol, 3 mg. b.i.d.
However, within the first week of treatment he develops side effects: a mild
tremor and feelings of increased restlessness (probably akathisia). He is pre¬
scribed the anticholinergic benzotropine, 5 mg. q.d., and within a few days the
side effects disappear. He continues on the benzotropine until the haloperidol is
phased out ten months later.
Scenario Three: Mr. P. does not respond to the 6 mg. q.d. of haloperidol and de¬
velops considerable side effect problems: marked restlessness, dystonias and flat
affect. The coadministration of benzotropine reduces side effects somewhat, but
after three weeks of treatment, there are no noticeable changes in his psychotic
symptoms. The haloperidol is increased, first to 8 mg. q.d., and a week later to 10
mg. q.d. He is now sleeping somewhat better, but extrapyramidal symptoms have
increased and are only partially responding to benzotropine. You are concerned
both by the lack of response to haloperidol and the concern that he will (due to
unpleasant side effects) either drop out of treatment or fail to comply with the
medication treatment.
The decision is made to discontinue the haloperidol and benzotropine, and be¬
gin treating Mr. P. with olanzepine. 3 mg. b.i.d. He tolerates this medication well
and within a week appears to be more calm. At day 14. hallucinations and delu¬
sional thinking continue, so the dose of olanzepine is increased to 5 mg. b.i.d. By
day 22, Mr. P. reports, “the voices have stopped.” and during the following two
weeks his thinking gradually becomes more rational and realistic. By the seventh
week of treatment. Mr. P. appears to be somewhat more spontaneous and there is
a noticeable change in personal hygiene. He is showing a good response to the
new medication, and continues to take it at the 5 mg. b.i.d. dose for ten months.
At that time you gradually reduce the dose.

66
 In each scenario the clinician had the patient sign an informed consent for treat¬
ment and remained alert to the emergence of any abnormal movements that might
signal the onset of tardive dyskinesia. Under the best of circumstances, Mr. P. will
continue to be at risk for relapse, although since it was his first psychotic episode,
it was reasonable to conduct a trial without medications about one year follow ing
his initial treatment. It is wise to also talk with the patient and (if appropriate) with
his family about warning signs of possible relapse, so that should this occur, an¬
tipsychotic medications can be started immediately.

67
 Appendix A
History and Personal Data Questionnaire

Name: Date of birth:

Main reason for seeking help at this time:

Current Problems or Symptoms

Please read each item below and determine which statement is true for you. Then,
place an “X*’ in the appropriate box to indicate how often you feel the statement
applies to you during the past month or since your last visit.

None or Some Most or

EXAMPLE a little of of the all of
Be sure to rate every item. the time time the time
feel sad

DURING THE PAST None or Most or

MONTH OR SINCE a little of all of
LAST VISIT the time the time
Wake up at night in the early morn¬
ing and unable to return to sleep
Very restless sleep
Fatigue or loss of ener
Decreased sex drive
Unable to enjoy life; have lost a
zest for life
Have withdrawn from others
Strong thoughts about suicide
Loss of appetite
Memory problem, forgetfulness,
poor concentration
Feel irritable or easily frustrated
Feelings of sadness or hopelessness
Sleeping a lot
Decreased need for slee
Increased sex drive
Increased energy
So happy or energetic that people
describe me as “manic”
Can't gel to sleep
 Appendix A
History and Personal Data Questionnaire, Cont’d.
DURING THE PAST None or
MONTH OR SINCE a little of
.LAST VISIT the time
18. Sudden episodes of nervousness
or panic
19. Fear of losing self-control
20. Palpitations or rapid heart beat
21. Shortness of breath
22. Feel tense or anxious all day
23. Feel very anxious in social
situations
24. Have recurring, troubling ,
thoughts, images or impulses that
I can’t get out of my mind
25. Repetitive behaviors such as
excessive hand washing, etc.
26. Feel very confused about my
thoughts
27. Strange or bizarre thoughts
28. Hallucinations, hear voices, or
see things that aren't there
29. Very peculiar experiences that
others do not understand
30. Feel ready to explode
31. Thoughts about harming someone
32. Excessive use of alcohol/drugs
33. Unusual eating habits
34. Weight loss—How much in past month? lbs
Weight gain—How much in past month? _lbs.
Have you been trying to diet? Yes No
35. In the past 1 have tried to cut down
*

on my use of alcohol or other drugs

o
1

Previous Treatment for Psychological or Emotional Problems

Hospitalization or
Year Problem Therapist/Location Medical Treatment

l)o You Take Any of the Following Medications?

Antihypertensives (for high blood pressure or migraine headaches)
□ Steroids 71 Hormones “1 Tranquili/ers

Thanh You
 Appendix B

SPECIAL CAUTIONS WHEN TAKING MAO

INHIBITORS

A Patient Hand-Out

MAO Inhibitors can be very safe and effective antidepressant medications. How¬
ever. certain foods and drugs must be avoided while taking MAO Inhibitors. Mix¬
ing MAO Inhibitors with the following drugs/foods can cause a serious rise in
blood pressure.

FOODS TO AVOID

■ Cheese (Philadelphia cream cheese and cottage cheese are OK.)

■ Chicken liver and beef liver
■ Yeast preparations (avoid Brewer's yeast, powdered and caked yeast as sold in
health food stores. Bakery yeast is OK.)
■ Fava or broad beans
■ Herring (pickled or kippered)
■ Beer, sherry, ale, red wine, liqueurs
■ Canned figs
■ Protein extracts (found in some dried soups, soup cubes, and commercial gravies)
■ Certain meat products; bologna, salami, pepperoni. Spam

AVOID EXCESSIVE AMOUNTS OF THESE FOODS

■ Yogurt and/or sour cream

■ Ripe avacados and guacamole
■ Chocolate and/or caffeine
■ White wine and liquors

MEDICATIONS TO AVOID

■ Stimulant drugs (amphetamines, dexadrine, benzedine, methedrine. methyl-

phenidate)
■ Diet pills
■ Cocaine, “crack”
■ Cold preparations, including over-the-counter products which contain decon¬
gestants (e.g.. Sudafed. Contac, etc.). Antihistamines and aspirin are OK.
■ Nasal sprays
■ Adrenalin (Make sure that your dentist knows you are taking MAO Inhibitors
because many local anesthetics contain adrenalin.)
■ Please talk with your physician before taking any new medications (prescrip¬
tion or over-the-counter.)

SYMPTOMS OF DRUG FOOD INTERACTION

While taking MAO Inhibitors, if you ever experience the following symptoms,
please contact your physician or an emergency room immediately.

■ Severe headache
■ Excessive perspiration
■ Lightheadedness
■ Vomiting
■ Increased heart rate

/ have read and understand the above precautions.

Patient’s Name_Date
Signature
 References

American Psychiatric Association (1987) Diagnostic und Statistical Manual of

Mental Disorde rs-111-Revised (DSM-111R). APA, Washington, DC.

Baldessarini, R. J. and Cole J. O. (1988) “Chemotherapy” in The New Harvard

Guide to Psychiatry, edited by A. M. Nicholi, Harvard University Press, Cam¬
bridge, Mass.

Depression in Primary Care: Treatment of Major Depression. (1993) Rockville,

MD, U.S. Department of Health and Human Services. AHCPR Pub. No. 93-0551.

Goldberg, Stephen (1999) The Four-Minute Neurologic Exam, MedMaster, Inc.,

Miami.

Green W. H. (1991) Child and Adolescent Clinical Psychopharmacology.

Williams & Wilkins, Baltimore.

Katon, W. Panic Disorder in the Medical Setting (1994) Rockville, MD, U.S. De¬
partment of Health and Human Services, NIH Pub. No. 94-3482.

Klein, D. Dysthymia and Atypical Depression (1995) U.S. Psychiatric and Men¬
tal Health Congress.

Maxmen, J. and Ward, N. Psychotropic Drugs: Fast Facts (Second edition-1995)

W. W. Norton and Company, New York.

Nicholi, A. M. (ed.) (1988) The New Harvard Guide to Psychiatry. Harvard Uni¬
versity Press, Cambridge Mass.

Pearlman, C. A. (1986) “Neuroleptic malignant syndrome: A review of the litera¬

ture.” Journal of Clinical Psychopharmacology, 6:257-273.

Practice Guideline for Major Depressive Disorder in Adults (1993) American

Psychiatric Association, Washington, D.C.

Preston, J., Lucas, J., and O’Neal. J. (1995) Understanding Psychiatric Medica¬
tions in the Treatment of Chemical Dependency and Dual Diagnosis. Charles C.
Thomas, Springfield, 111.

Preston, J. D., O’Neal, J. H. and Talaga, M. C. (2000) Handbook of Clinical Psy¬

chopharmacology for Therapists. New Harbinger Publications, Oakland, CA.

Unlenhuth E. H. DeWit, H., Balter. M. B., Johanson, C. E. and Mellinger, G. D.

(1988) "Risks and benefits of long term benzodiazepine use." Journal of Clinical
Psychopharmacology, 8:161 -167.
Index

A D D . 48 Desyrel. 7. II. 14
Adapin. 7. 14 Dexedrine. 49
Adderall, 49 dextroamphetamine. 48
aggression. 49 dextroamphetamine. 49
akathisia, 39. 44 diazepam. 4. 30. 63
alprazolam. 30. 64 divalproex, 23
Alzheimer’s disease. 37 Doral. 30
Ambien. 30 doxepin. 7. 10. 14
amitriptyline. 7. 10. 14 dysphoric mania. 19
amoxapine, 7. 14 dysthymia. 8. 15
amphetamine. 42. 48. 49 dystonia. 40
Anafranil. 46 eating disorders. 50
anorexia nervosa. 51 Effexor. 7. II. 14
anticholinergic side effects. 7. 41 Elavil. 7. 14
anxiety disorders, 25. 61 estazolam. 30
Asendin. 7. 14 extrapyramidal side effects. 39. 41
Ativan. 30 fluoxetine. 7. 10. II. 14. 46. 56
Attention Deficit Disorder. 48 fluphenazine. 40
Aventyl. 7. 14 flurazepam. 30
benzodiazepines. 28. 62 fluvoxamine. 7. 14. 46
benzotropine. 66 G.A.D.. 25
bipolar illness. 18. 59. 60 gabapenlin. 24
Borderline Personality Disorder. 47 generalized anxiety disorder. 25. 33
bulimia, 51 grief. 2
bupropion. 7. 10. II. 14. 49. 58 Halcion. 30
BuSpar. 30 Haldol. 40
buspirone. 28. 30. 50 haloperidol. 40. 66
caffeine, and anxiety. 64 hypomania. 18
carbamazepine. 23. 50 imipramine. 7. 10. 14. 49
Celexa. 7. II. 14.46 Inderal. 30
Centrax. 30 isocarboxazid. 7. 14
chlordiazepoxide, 30 Klonopin. 24. 30
chlorpromazine, 40 Lamictal. 24
citalopram. 7. 10. II. 14. 46 lamotnginc. 24
clomipramine. 46 L-Dopa. 42
clonazepam. 24. 30 l.ihhum. 30
clonidinc. 50 lithium. 20. 22. 40. 58. 60
clorazepate. 30 lora/cpam. 29. 30. 62
clozapine. 40. 44 loxapine. 40
Clozaril. 40. 44 Loxitanc. 40
cocaine. 42 l.udiomil. 7. 14
Cylert. 49 Luvox. 7.14.46
Dal mane. 30 munia. IK
Depakote. 23 MAO inhibitors. 6. 23. 30. 58. 70
depression. 2 muprotilinc. 7. 14
depression. 56 Marplan, 7. 14
desipramine. 49 Mellaril. 40
dcsipraminc. 7. 14 mesorida/ine. 40

73
melhylphenidate. 4K, 49 Ritalin. 49
mirtazapine. 7. II. 14 S.A.D.. 15
Mohan. 40 schizophrenia. 36. 65
molindone. 40 Seasonal Affective Disorder. 15
Nardil. 7, 14 Selective Serotonin Reuptake Inhibitors. 6.
Nuvane, 40 12. 16
nefazodone. 7. 10. II. 14 Serax. 30
Neuronlin. 24 Serentil. 40
Norpramin. 7. 14. 49 Seroquel. 40
nortriptyline, 7. 10. 14 sertraline. 7. 10. II. 14. 46
Obsessive-Compulsive Disorder. 46 Serzonc, 7. II. 14
olanzapine. 40. 44.66 Sinequan, 7. 14
Orap. 40 Sonata. 30
oxazepam. 30 SSRIs.6. 12. 16. 29. 50
P.D.D.. 15 St. John's Wort. 16
P.T.S.D.. 51 Stclazine. 40
Pamelor. 7. 14 Surmontil. 7. 14
panic disorder. 25. 33. 63 tardive dyskinesia. 40. 44
Parkinson-like effects. 39. 44 Tegretol. 23
Parnate, 7. 14 temazepam. 30. 62
paroxetine. 7. 10. II. 14. 46, 64 thioridazine. 40
Paxil. 7. II. 14.46 thiothixene. 40
pemoline. 49 Thorazine. 40
perphenazine. 40 Tofranil. 7. 14.49
phenelzine. 7. 10. 14 Tranxene. 30
phobias. 25. 32 tranylcypromine. 7. 10. 14
pimozide. 40 trazodone, 7, 10. II, 14
Post-traumatic Stress Disorder. 51 trazolam. 30
prazepam, 30 tricyclics. 11,16
Prementrual Dysphoric Disorder. 15 trifluoperazone. 40
Prolixin. 40 Trilafon. 40
propranolol, 30. 50 trimipramine. 7, 14
Prosom. 30 Valium. 4. 30
protriptyline. 7. 14 venlafaxine. 7. 10. II. 14
Prozac. 7. II. 14. 46 verapamil. 24
psychotic depression. 16 Vestra. 7, II. 14
psychotic disorders. 36 Vivactil. 7. 14
quazepam. 30 Wcllbutrin. 7. II. 14.49
quetiapine, 40. 44 Xanax, 30
reactive sadness. 2 zalcplon. 30
reboxetine. 7. 10, II. 14 Zeldox, 40
Remeron. 7. II. 14 ziprasidone. 40. 44
Restoril, 30 Zoloft. 7, II. 14.46
Risperdal. 40 zolpidem. 30
risperidone. 40. 44 Zyprexa. 40

74
RAPID LEARNING AND RETENTION THROUGH THE M EDM ASTER SERIES:

CLINICAL NEUROANATOMY MADE RIDICULOUSLY SIMPLE, by S Goldberg

CLINICAL BIOCHEMISTRY MADE RIDICULOUSLY SIMPLE, by S Goldberg
CLINICAL ANATOMY MADE RIDICULOUSLY SIMPLE, by S. Goldberg
CLINICAL PHYSIOLOGY MADE RIDICULOUSLY SIMPLE, by S. Goldberg
CLINICAL MICROBIOLOGY MADE RIDICULOUSLY SIMPLE, by M. Gladwin and B
T rattler
CLINICAL PHARMACOLOGY MADE RIDICULOUSLY SIMPLE, by J M Olson
OPHTHALMOLOGY MADE RIDICULOUSLY SIMPLE, by S. Goldberg
PSYCHIATRY MADE RIDICULOUSLY SIMPLE, by W V. Good and J Nelson
CLINICAL PSYCHOPHARMACOLOGY MADE RIDICULOUSLY SIMPLE, by J Preston
and J. Johnson
ACUTE RENAL INSUFFICIENCY MADE RIDICULOUSLY SIMPLE, by C Rotellar
MEDICAL BOARDS STEP 1 MADE RIDICULOUSLY SIMPLE, by A Carl
MEDICAL BOARDS STEP 2 MADE RIDICULOUSLY SIMPLE, by A Carl
MEDICAL BOARDS STEP 3 MADE RIDICULOUSLY SIMPLE, by A Car!
BEHAVIORAL MEDICINE MADE RIDICULOUSLY SIMPLE, by F. Seitz and J Carr
USMLE BEHAVIORAL SCIENCE MADE RIDICULOUSLY SIMPLE, by F.S Sicrlcs
ACID-BASE, FLUIDS, AND ELECTROLYTES MADE RIDICULOUSLY SIMPLE, by
R. Preston
THE FOUR MINUTE NEUROLOGIC EXAM, by S. Goldberg
MEDICAL SPANISH MADE RIDICULOUSLY SIMPLE, by T. Espinoza Abrams
THE DIFFICULT PATIENT, by E. Sohr
CLINICAL ANATOMY AND PATHOPHYSIOLOGY FOR THE HEALTH
PROFESSIONAL, by J.V. Stewart
CONSCIOUSNESS, INFORMATION, AND MEANING: THE ORIGIN OF THE MIND,
by S. Goldberg
PREPARING FOR MEDICAL PRACTICE MADE RIDICULOUSLY SIMPLE, by DM
Lichtstein
MED'TOONS (260 humorous medical cartoons by the author) by S Goldberg
CLINICAL RADIOLOGY MADE RIDICULOUSLY SIMPLE, by II Ouellette
NCLEX-RN MADE RIDICULOUSLY SIMPLE, by A Carl
THE PRACTITIONER S POCKET PAL: ULTRA RAPID MEDICAL REFERENCE by
J. Hancock
NEUROLOGIC LOCALIZATION (Macintosh computer program), by S Goldberg

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 A concise guide to file pharmacologic treatment of psychologic disorders.

"Clinical Psychopharmacology Math- Ridiculously Simple is that rare b(x>k

that has successfully simplified a complicated topic so that practitioners can
provide the benefits of psychopharmacology to patients with confidence that
they will do more good than harm. An excellent, succinct guide to psychophar¬
macology in primary care settings.”

John H. Greist, M.D.,

Distinguished Senior Scientist
Dean Foundation, Department of Psychiatry
University of Wisconsin Medical Schtxil

"This is an excellent little text. Not only does it have appeal for physicians,
but mental health practitioners and patients on psychotropics will also find it
most useful. Highly condensed, authoritative, well-written and comprehensive.
Also provides up-to-date important information on diagnostics, differential diag¬
nosis and medication strategies. Highly recommended.”

Patrick T. Donlon. M.D.

Coauthor of A Manual of Psychotropic Drugs

"There is an ever increasing need for a concise, practical, clinically relevant guide for
the many health care professionals that care for patients receiving psychotropic medi¬
cation. The complexity and number of medications for psychiatric disorders require
psychologists, social workers, clinical pharmacists, as well as physicians to participate
in maximizing benefits and minimizing adverse events. Clinical Psychopharmacology
Made Ridiculously Simple fills that need exceptionally well.”

Glen L. Stimmel, Pharm.D.. F.C.C.P.

Professor of Clinical Pharmacy and Psychiatry
University of Southern California
Schools of Pharmacy and Medicine
Los Angeles. California

ISBN 0 - cm07fiQ - 4 4-5