This chart on A4Medicine is an overview of the commonly used pharmacological agents in the management of insomnia in the UK. Z-drugs particularly the commonly used Zopiclone and Zolpidem are discussed in greater details. Temazepam is another commonly used medication and reader will find the information practical and clinically useful in prescribing this medication. The onset of action and duration of the drugs are mentioned which can help clinicians give appropriate advice. Melatonin ( circadian ) licensed for use up to 13 weeks- that is the time it should take to restore the sleep pattern is discussed. Mechanism of action of all the agents is described briefly.
Z-hypnotics Zopiclone Zolpidem Zaleplon Non benzodiazepine short-acting hypnotics Act on benzodiazepine receptors Have less overall risk of adverse effects Boost the effect of GABA All are rapidly absorbed and have short 1/2 lives Mainly eliminated by hepatic mechanism Use lower dose- hepatic , renal, respiratory insufficiency Zopiclone-Onset of action about an hour Longest duration of action 4-8 hrs ( amongst Z drugs ) ○ used when patients c/o waking throughout the night ○ negligible residual effects are seen the following morning Rapidly initiates and sustains sleep with ↓ of total REM sleep and with preservation of slow sleep wave Warn- may adversely affect the ability to drive or to use machines ( if taken within 12 hrs ) Licenced duration 4 weeks Dependence is minimal when used not more than 4 weeks
Zolpidem-Imidazopyridine -binds the omega-1 receptor subtype which corresponds to GABA-A receptors containing the alpha1 subunit Rapid absorption ( works in 15-20 mins ) and short duration of action ( up to 6 hrs ) Shown to preserve sleep stages and no influence on paradoxical sleep duration ( REM ) Atleast 8 hrs is recommended betwen taking zolpidem and driving , using machinery and working at heights Lowest effective dose , in a single intake just before bedtime- should not be retaken in the same night Licenced duration 4 weeks Modified versions available in US and have seperate dose warning for ♀ from FDA Zaleplon-Fast onset of action ( 15-20 mins ) and ultra short acting ( 2-4 hrs ) Decreases sleep-onset latency Produces less memory and psychomotor impairment Can be used up to 5 hrs before driving Useful if sleep disturbance is intermittent Licenced duration 2 weeks
Temazepam-Rapidyl absorbed – peak plasma levels within 50 mins 1/2 life between 8-15 hrs Mainly metabolised in liver and excreted in urine Duration of use should be as short as possible but should not exceed 4 weeks for insomnia ( including tapering off process ) Start of treatment pts may suffer from drowsiness and light headedness the next day ○ confusion and ataxia ( particularly elderly ) ○ amnesia may occur ○ reduced alertnes , dizziness ○ fatigue , muscle weakness ○ numbed emotions ○ double vision ○ respiratory depression ○ slurred speech Can impair cognitive function and affect ability to drive safely Dependence →can lead too physical dependence : discontinuation may result in withdrawal or rebound phenomena Risk of dependence ( physical or psychological ) ↑es with dose and duration of Rx and is greater in patients with a h/o alcohol or drug abuse or pts with marked personality disorder Withdrawal-Headache Muscle pain Extreme anxiety Tension Restlessness Confusion and irritability Sleep disturbance Diarrhoe and mood changes Severe cases-Feeling of unreality Feeling of being seperated from body Depersonalization Hyperacusis Confusional states Numbness and tingling of the extremities Hypersensitivity to light noise and physical contact Psychotic manifestations Epileptic seizures
Melatonin ( circadin®) Psycholeptic melatoninn receptor agonist Monotherapy for short term treatment of primary insomnia in pts > 55 yrs ( up to 13 weeks ) Can restore sleep pattern 2 mg od 1-2 hrs before bedtime after food May cause drowsiness Avoid alcohol use with Circadin ( ↓ effectiveness ) Activity of melatonin at the MT1 , MT2 and MT3 receptors is believed to contribute to its sleep promoting properties Endogenous melatonin production is ↓ in elderly- hence rationale for use in over 55s with primary insomnia No data exists for use in people with autoimmune disease- hence not used Contains lactose – avoid if known to suffer with galactose intolerance , the LAPP lactase deficiency or glucose- galactose-galactose malabsorption
Sedating anti-depressants Mirtazepine -usually when other medications have not worked and as an add on ○ begins to exert effect after 1-2 weeks and a +ve response within 2-4 weeks Trazodone- is a potent antidepressant ○ not related to known tricyclic , tetracycylic and other antidepressants ○ precise mech of action not known but may concern noradrenergic potentiation by mechanisms other than uptake blockade Amitriptyline-low dose at 10-25 mg ( not licenced but widely used )