Benzodiazepines, Zolpidem and Zopiclone

Zolpidem and zopiclone bind the same GABA-A benzodiazepine site and share most of the same adverse effects. Key risks: overdose (especially combined with other sedatives) and dependence from long-term use.

• Use beyond a month — especially at high doses — risks dependence; there’s little justification for prescribing beyond a few days.
• As a general rule, avoid prescribing to patients not well known to the clinician.
• The highest rate of use is in older patients, despite this being the group most at risk from adverse effects (falls, cognitive impairment).
• Zolpidem/zopiclone safety is uncertain — some patients experience bizarre, sometimes dangerous sleep-related behaviours.

Overdose

Benzodiazepine overdose alone is not usually life-threatening; the greatest danger is combination with other sedatives (alcohol, opioids). Avoid flumazenil in mixed overdoses involving TCAs, amphetamines, or other proconvulsants — it can precipitate uncontrollable seizures and death — and in dependent patients, rapid reversal can precipitate severe withdrawal and seizures. Treatment is generally supportive; flumazenil is rarely indicated.

Withdrawal

Anxiety, insomnia, irritability, myoclonic jerks, palpitations, and sensory disturbance (hyperacusis, photophobia). Abrupt cessation at high doses (>50 mg/day diazepam-equivalent) can cause seizures.

• Short-term use can usually be stopped without a taper.
• Therapeutic-to-slightly-elevated dose, several months+ — reduce at ~15% of the starting dose per week, titrated to symptoms.
• Higher-dose use — stabilise on an equivalent diazepam dose first (usually not exceeding 80 mg/day), then reduce at a symptom-guided rate after a few days’ stabilisation. Inpatient reductions of 10%/day are achievable; outpatient tapers are usually much slower, often over ~2 months.

Approximate equivalent doses (to diazepam 5 mg):

Drug	Equivalent dose
Alprazolam	0.5 mg
Bromazepam	3 mg
Clobazam	10 mg
Clonazepam	0.25 mg
Diazepam	5 mg
Flunitrazepam	0.5 mg
Lorazepam	1 mg
Nitrazepam	5 mg
Oxazepam	15 mg
Temazepam	10 mg