Anxiolytics & Hypnotics
by Sue Henderson
Therapeutic actions
1. Hypnotic • In what medical
2. Anxiolytic circumstances
3. Anticonvulsant might the
4. Amnestic amnestic
5. Myorelaxant properties of
benzodiazepines
be useful?
Indications
• Why are
benzodiazepines
useful in the
treatment of alcohol
detoxification?
• Can they be used in
the long term to
prevent further
alcohol abuse?
Anti-Anxiety & Hypnotics
Anti-Anxiety Hypnotics: Sedatives
• Benzodiazepine e.g. • Benzodiazepine e.g.
Diazepam Temazepam
• Non Benzodiazepine • Non Benzodiazepine
e.g. Buspirone e.g. Zopiclone
Differentiate
• What is the
difference between
an anti-anxiety
medication and a
hypnotic?
Antidepressants for anxiety
Clomipramine (TCA) OCD
Fluvoxamine (SSRI) OCD
Paroxetine (SSRI) OCD, panic disorder,
social phobia
Sertraline (SSRI) OCD, panic dis, PTSD
Venlafaxine (SNRI) GAD
Fluoxetine (SSRI) OCD
Benzodiazepines
• Used mostly in primary care rather than
psychiatry.
• Often prescribed for problems that are
more effectively managed with non-drug
therapies.
• Temazepam in 10 most frequently
prescribed up until 2001.
Benzodiazepines
• Should not be 1st line therapy in mental
health & sleep management.
• Limit use to less than 2 weeks.
• Only benefit of continued use is
avoiding withdrawal effects (NPS, 1999).
• All equally effective but differ in
metabolism, speed of onset & half life
2004-05 National Health Survey
• 5% of Australians had used a benzodiazepine
for anxiety management in the 2 weeks prior
to the survey.
• Benzodiazepine use was higher in women
and in older age groups (mostly due to
sleeping tablets).
• Overall use has fallen since 80’s but total use
remains high (ABS, 2006).
Anxiolytic/hypnotic (% of pop all age groups)
12
10
8
6
4
2
0
Temazepam Diazepam Other Oxazepam
benzodiazepines
MCQ
Benzodiazepines can safely be
prescribed during pregnancy.
• A. True
• B. False
Indications Drug
Anxiolytic Diazepam, Alprazolam,
Bromazepam, Lorazepam,
Oxazepam, Buspirone*
Muscle relaxant Diazepam
Pre-med Diazepam, Lorazepam
Alcohol withdrawal Diazepam, Oxazepam,
Panic disorder Alprazolam, Clonazepam.
Anti-convulsant Clobazam, Clonazepam,
Diazepam, Lorazepam
Hypnotic Flunitrazepam, Nitrazepam
Temazepam, Zolpidem,
Zopiclone*
Dose Equivalents
Drug Daily range mg Equiv 5mg Duration (½ life)
diazepam.
alprazolam 1–4 0.5 - 1 Short/Intermediate
bromazepam 6–9 3–6 Short/Intermediate
clobazam 30 – 80 10 Intermediate
clonazepam 4–8 0.5 Intermediate
diazepam 5 – 20 5 Long
flunitrazepam 0.5 – 2 1–2 Intermediate
lorazepam 2–4 1 Short/Intermediate
nitrazepam 5 – 20 5 – 10 Intermediate
oxazepam 45 – 90 15 – 30 Short
temazepam 10 – 30 10 - 20 Short
triazolam 0.125 - 0.25 0.25 Short
buspirone* 15 – 30 - Short
zopiclone* 3.75 - 7.5 - Short
Short Acting: 3 - 8 hrs
• Oxazepam
• Temazepam
• Triazolam
• Buspirone*
• Zopiclone*
Intermediate Acting: 10 - 20
hours
• Alprazolam
• Bromazepam
• Clobazam
• Clonazepam
• Flunitrazepam
• Lorazepam
• Nitrazepam
Hypnotics
• Explain the benefit
of using Temazepam
over Nitrazepam for
assisting with sleep.
• Why should
hypnotics be used
for a limited time to
assist with sleep?
Long Acting 1- 3 days:
Diazepam
X X X
Addiction
• Why are short acting
benzodiazepines
more of a problem
with addiction than
the long acting
ones?
Dependency cycle of
benzodiazepines
Use of
benzodiazepine
Even
Reduced
more
anxiety
anxious
Effect
wears off
Green, 1996, p. 88
Benzodiazepines: Action
• CNS depressant
• Enhance the effect of
GABA.
• GABA is a
neurotransmitter that
inhibits neuronal activity
i.e. reduces the firing
rate of neurones.
Agonist = Facilitate
• Benzodiazepines bind to a site near the GABA
binding site thus facilitating the action of GABA
Death
Coma
General Anaesthesia Increasing
Sleep dose
Sedation of
Disinhibition drug
Relief from anxiety
No effect
•(Julien, 2001)
Combination CNS depressants
Contra-indications
• Myasthenia gravis.
• Severe respiratory
impairment e.g
sleep apnoea,
COAD.
Avoid (if possible)
• Pregnancy
• Lactation
Adverse Effects
• Physical dependence occurs in about 1
in 3 patients.
• History substance abuse > risk
dependence
• Increased accident risk.
• Tolerance & rebound insomnia.
• Alcohol & CNS depressants potentiate
adverse effects.
Adverse effects
• 60y+ > vulnerability to confusion,
memory impairment, over sedation
(most common S/E) & falls.
• Adverse mood effects: depression,
emotional anaesthesia, aggression,
increased suicide risk in elderly.
Withdrawal from
Benzodiazepines
• Abrupt cessation: > seizures
• Withdrawal symptoms may occur between
doses during continuous use (inter-dose
withdrawal). Patients may think these
symptoms are due to the original problem.
• Withdrawal symptoms: increased anxiety,
sleep disorder, aching limbs, nervousness &
nausea.
Withdrawal from
Benzodiazepines
• Withdrawal experienced by 45% of patients
discontinuing low dose benzodiazepines &
100% patients on high doses.
• Short half life benzodiazepines are
associated with more acute & intense
withdrawal symptoms.
• Long half life benzodiazepines - milder, more
delayed withdrawal (NPS, 1999).
Withdrawal from
benzodiazepines
• Benzodiazepines should not be ceased
abruptly.
• Dose reduced by 10-20% per week.
• Patient allowed to stabilise between
each reduction.
• Admission for high dose users, history
of seizures or psychosis, or for more
rapid withdrawal.
Withdrawal from
benzodiazepines
• Implement relaxation/cognitive
techniques.
• If necessary referral:
• Drug & Alcohol Services
• Self Help group TRANX
www.tranx.org.au
• Psychologist (for CBT)
Overdose Benzodiazepines
• Generally safe in overdose unless
mixed with alcohol/CNS depressants.
• Symptoms overdose: hypotension,
respiratory depression & coma.
• Treatment: Supportive
• Flumazenil rarely indicated
IV Flumazenil
• Dangerous to use if mixed overdose (e.g
benzodiazepine + tricyclics, amphetamines,
other pro-convulsants) - Result in uncontrolled
seizure
• In dependent individuals severe withdrawal
• Flumazenil has a shorter half life ( one hour)
than all benzodiazepines Therefore, repeat
doses of flumazenil may be required to prevent
recurrent symptoms of overdosage once the
initial dose of flumazenil wears off.
Flumazenil is a
benzodiazepine Antagonist
= Blocker
Flumazenil binds to GABA receptor displacing
benzodizepine
Non benzodiazepines
Anxiolytic: Buspirone (Buspar)
• Different action to bzd.
• Not a CNS depressant.
• Partial agonist (stimulant) of dopaminergic &
serotoninergic receptors.
• No sedation, anti-convulsant or muscle
relaxant properties - just anxiolytic.
• Delayed action (1-2 weeks)
• Effect reduced if benzodiazepine used in last
3/12
Comparison of benzodiazepine &
buspirone
Buspirone
Benzodiazepine Delayed onset
Rapid onset (cannot be used PRN)
Can cause sedation Does not cause sedation
May impair performance Does not impair performance
Additive effects with alcohol No additive effect with
alcohol
May cause dependence &
withdrawal Non addictive
No pharmacokinetic change
Pharmacokinetic change with with age
age Does not cause falls in
Associated with falls in elderly
elderly (Keltner & Folks, 2001) Expensive (Not on PBS)
Presentation: Buspar
• White scored
• 5 mg & 10 mg tabs
Buspirone: Agonist = Mimic
• Buspirone attaches to serotonin receptor
mimicking serotonin.
Non benzo Hypnotic:
Zopiclone (Imovane)
• Similar action, side effects &
contraindications to benzo’s.
Benzodiazepines key points
• Should not be used in patients with liver
disease, history of substance abuse, severe
respiratory distress, performing hazardous
tasks
• Avoid during pregnancy/lactation if possible
• Assess for over sedation
• Cease slowly
• Monitor elderly (cognition, falls)
• Be aware they raise seizure threshold, and
• Potentiate CNS depressants (alcohol)
Hypnotic key points
• Advise re rebound insomnia when
medications ceased
• Should not be used in sleep apnoea
• Avoid alcohol
• Hangover effect (impairing performance)
• Monitor in elderly (falls, double dosing)
References
• Australian Bureau of Statistics. (2006). National
health survey 2004-05: Summary of results.
Canberra: Australian Bureau of Statistics.
• Fortinash, K. M., & Holoday-Worret, P. A. (2000).
Psychiatric mental health nursing ( 2nd ed.). St.
Louis: Mosby.
• Galbraith, A., Bullock, S. & Manias, E. (2001).
Fundamentals of pharmacology (3rd ed.).
Melbourne: Prentice Hall.
References
• Julien, R. M. (2001). A primer of drug action: A concise, non-
technical guide to the actions, uses, and side effects of
psychoactive drugs. New York: W. H. Freeman and Co.
• Keltner, N. L., & Folks, D. G. (2001). Psychotropic drugs (3rd
ed.). St. Louis: Mosby.
• National Prescribing Service. (1999). Helping patients
withdraw. National Prescribing Service Newsletter, No. 4
June.
• National Prescribing Service. (1999). Benzodiazepines
reviewing long term use: A suggested approach.
Prescribing Practice Review, No. 4 July.
