Anxiolytics & Hypnotics by Sue Henderson

Therapeutic actions

1. Hypnotic

2. Anxiolytic

3. Anticonvulsant

4. Amnestic

5. Myorelaxant

• In what medical circumstances might the amnestic 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

• Benzodiazepine e.g. Diazepam

• Non Benzodiazepine e.g. Buspirone

Hypnotics: Sedatives

• Benzodiazepine e.g. Temazepam

• Non Benzodiazepine 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)

0

2

4

6

8

10

12

Temazepam Diazepam Otherbenzodiazepines

Oxazepam

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 EquivalentsDrug Daily range mg Equiv 5mg

diazepam.Duration (½ life)

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

Green, 1996, p. 88

Use of benzodiazepine

Reduced anxiety

Effect wears off

Even more

anxious

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

Increasing dose

of drug

ComaGeneral Anaesthesia

SleepSedation

DisinhibitionRelief 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

BenzodiazepineRapid onsetCan cause sedationMay impair performanceAdditive effects with alcoholMay cause dependence &

withdrawalPharmacokinetic change with

ageAssociated with falls in

elderly (Keltner & Folks, 2001)

Buspirone

Delayed onset (cannot be used PRN)

Does not cause sedationDoes not impair performanceNo additive effect with

alcoholNon addictiveNo pharmacokinetic change

with ageDoes not cause falls in

elderly

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.