DEPRESSION

PRESENTATION BY DR.MKOJI
• is a common, seriously disabling, disorder nonresponsive to
volitional efforts to feel better.
• Persistent low mood affecting all or almost all mental contents
and areas .
• Retarded form – sadness, decreased pleasure, decreased
appetite, decreased sleep
• Agitated form gives anxiety, sadness, psychomotor agitation,
difficulty concentrating, insomnia.
• Depression occurs on a continuum from mild to intense, from
acute to chronic, from one episode to many episodes
PATHOPHYSIOLOGY

• Clinical and preclinical trials suggest a disturbance in

central nervous system serotonin (5-HT) activity as an
important factor.
• Other neurotransmitters implicated include norepinephrine
(NE), dopamine (DA), glutamate, and brain-derived
neurotrophic factor (BDNF).
AETIOLOGY

• Genetic causes
• Environmental factors
• Certain pharmacological agents eg. Cortisol, b-blockers and
reserpine
• Poor parent child relations
• Endocrine factors – e.g elevated cortisol levels
diseases associated with depression
Drugs known to cause depression
EPIDEMIOLOGY

• Kenya was ranked at position four in Africa with 1.9 million

people who have the condition (WHO Report, 2014).
• According to the Kenya Mental Health Policy (2015-2030),
mental disorder cases in Kenya continue to rise rapidly.
• Worldwide depression is a major concern
• Women are twice as likely as men to experience MDD
CLINICAL PRESENTATION

• Depressed mood
• Markedly diminished interest / pleasure
• Significant weight loss
• Insomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Diminished ability to think or concentrate
• Recurrent thoughts of deaths or suicide
DIAGNOSIS

• The diagnosis of a major depressive episode requires the

presence of five depressive symptoms for a minimum of 2
weeks that cause clinically significant effects
TREATMENT

• Treatment of depression is most effective when a

combination of medication and psychotherapy is
prescribed. Psychotherapy alone is an initial treatment
option for mild to moderate depression
• it may be useful combined with pharmacotherapy for the
treatment of severe depression.
2. Electroconvulsive therapy
• is a highly efficacious treatment for depression
• The response rate is about 80-90% & even exceeds 50% for patients who
have failed pharmacotherapy
• may be beneficial for MDD that is complicated with psychotic features, severe
suicidality, refusal to eat, pregnancy, or contraindication or nonresponse to
pharmacotherapy.
• 6-12 treatments are typically necessary with response occurring in 10-14
days.
• When ECT is discontinued, antidepressants are initiated to help maintain
response
• Side effect: confusion & memory impairment
1. SSRIs

• Are considered first line in major depressive disorder

• they inhibit the reuptake of 5-HT into the pre-synaptic
neuron.
• Adverse effects:
a) sexual dysfunction (eg, delayed or absent orgasms)
b) CNS stimulation (eg, nervousness & insomnia
c) GI disturbances (eg, nausea and diarrhea)
Strategies to deal with antidepressant
induced sexual dysfunction
• Sexual dysfunction, common and challenging to manage, often leads to
noncompliance
a) Waiting for symptoms to subside- usually does not work, because sexual
dysfunction may very well persist throughout the duration of therapy.
b) Reducing the dosage and drug holidays - may weaken the
antidepressant effects.
c) Prescribing adjunctive therapy - dopaminergic drugs (eg, bupropion,
amantadine) ,5-HT2 antagonists (cyproheptadine, nefazodone),
phosphodiesterase inhibitors (eg, sildenafil)
d) Switching antidepressant - switch to antidepressants with less likelihood
of causing these effects, such as bupropion, mirtazapine, or nefazodone
Treatment algorithm for severe
depression
Time course of treatment

• antidepressants do not produce a clinical response

immediately.
• Improvement in physical symptoms, such as sleep,
appetite, and energy, can occur within the first week or so
of treatment.
• it takes ~2-4 weeks of treatment before improvement is
seen in emotional symptoms of depression, such as
sadness and anhedonia.
• it may take as long as 6-8 weeks of treatment to see the
full effects of antidepressant therapy
Duration of treatment

• Treatment of MDD can be conceptualized as a series of

three phases: acute, continuation & maintenance
• During a major depressive episode, a clinician will initiate
antidepressant therapy for the purpose of attaining
remission of symptoms.
• This acute phase of treatment typically lasts 6-12 weeks.
• When treating the first depressive episode, antidepressants
must be given for an additional 4-9 months in the
continuation phase for the purpose of preventing relapse
• Maintenance treatment takes place after the normal course
of a major depressive episode in order to prevent
recurrence
• This phase can last for years, if not for a lifetime
• all patients who suffer a major depressive episode should
receive both acute & continuation treatment, not all of
them will require maintenance treatment.
• The reason for this is because not all patients experience
multiple major depressive episodes
discontinuation of therapy
• When the decision is made to discontinue maintenance pharmacotherapy, it
is best to taper the medication over the course of at least several weeks to
few months.
• Such tapering may allow for the detection of emerging symptoms or
recurrences when patients are still partially treated and therefore can be
easily returned to full therapeutic intensity.
• In addition, such tapering can help minimize the risks of antidepressant
medication discontinuation syndromes. Discontinuation syndromes have been
found to be more frequent after discontinuation of medications with shorter
half-lives, and patients maintained on short-acting agents may be given even
longer, more gradual tapering. Paroxetine, venlafaxine, TCAs, and MAOIs tend
to have higher rates of discontinuation symptoms while bupropion-SR,
citalopram, fluoxetine, mirtazapine, and sertraline have lower rates
treatment of depression in special populations

1. Pregnant or Breastfeeding Patients

Sertraline, fluoxetine, citalopram & the TCAs have the
greatest reproductive safety data and should be considered
first-line treatments when pharmacotherapy is indicated
no rigorous study has confirmed in infants exposed to
antidepressants through breast milk
benefits of breastfeeding outweigh the risks to the infant
exposed by antidepressants
2. Geriatric Patients
Age-related pharmacokinetic & pharmacodynamics changes
cause geriatric patients to be more sensitive to
antidepressant medications
lower starting doses of antidepressants & slow upward
titrations as tolerated are recommended
The SSRIs are chosen frequently for geriatric depression
because of their overall favorable adverse effect profiles &
low toxicity
3. Pediatric Patients
Fluoxetine & escitalopram are the only antidepressants FDA
approved for depression in children younger than 18 years
The SSRIs generally are considered the initial
antidepressants of choice
The FDA warns that antidepressants increase the risk of
suicidality in children and young adults.
4. Resistant depression
• Adequate treatment for at least 4-6 weeks is necessary
before concluding that a patient is not responsive to a
particular medication.
• First step in care of a patient who has not responded to
medication is carrying out a thorough review and reappraisal
of the psychosocial and biological information base, aimed at
revarifying the diagnosis and identifying any neglected and
possibly contributing factors, including the general medical
problems, alcohol or substance abuse or dependence, other
psychiatric disorders, and general psychosocial issues
impeding recovery.
The end