Frequently asked questions — Benzodiazepines and hypnotics
1) What are the main indications for benzodiazepines?
Benzodiazepines are mainly used as anxiolytics, hypnotics, anticonvulsants and muscle relaxants. Their use should preferably be acute or short term, for example in anxiety attacks, acute insomnia, seizures or alcohol withdrawal. For chronic disorders such as generalised anxiety disorder, panic disorder or chronic insomnia, maintenance treatment should be based on SSRIs/SNRIs, psychotherapy and sleep-hygiene measures, reserving benzodiazepines for temporary bridging treatment or as-needed use.
2) How should short-, intermediate- and long-acting benzodiazepines be selected?
Selection depends on the clinical indication, age, comorbidities and risk of accumulation.
Short-acting benzodiazepines, such as triazolam, midazolam and brotizolam, may be useful for sleep-onset insomnia or procedures, but carry a greater risk of withdrawal symptoms and complex sleep behaviours.
Intermediate-acting benzodiazepines, including lorazepam, oxazepam and alprazolam, may be used for acute anxiety attacks and short-term insomnia.
Long-acting benzodiazepines, such as diazepam, clonazepam, prazepam, mexazolam and ketazolam, have a greater risk of accumulation and daytime sedation and should be avoided in older adults and patients with liver disease, although they may be useful in alcohol or benzodiazepine withdrawal and some forms of epilepsy.
3) Which benzodiazepines are preferable in older adults or patients with liver disease?
In older adults and patients with liver disease, benzodiazepines undergoing Phase II metabolism and without active metabolites should be preferred: the “LOT” group — lorazepam, oxazepam and temazepam. These have a lower risk of accumulation, although they are not free from adverse effects. They should be used at the lowest effective dose and for a very limited period. Long half-life benzodiazepines with active metabolites, including diazepam, flurazepam, prazepam, mexazolam, ketazolam, clorazepate and chlordiazepoxide, should be avoided in these patients because of the risk of falls, delirium and prolonged sedation.
4) What is the role of benzodiazepines in insomnia?
In insomnia, benzodiazepines and Z-drugs, such as zolpidem, should be regarded as short-term treatments, generally for no more than 2–4 weeks, while sleep-hygiene measures are implemented and underlying causes such as depression, anxiety, pain, obstructive sleep apnoea or medication effects are assessed. Short- or intermediate-acting benzodiazepines may be used for acute insomnia, with the profile selected according to whether the main problem is sleep initiation or sleep maintenance. Prolonged use is associated with tolerance, dependence, rebound insomnia and cognitive impairment, particularly in older adults.
5) What are the main risks of long-term benzodiazepine use?
Long-term benzodiazepine use is associated with physical and psychological dependence, tolerance, requiring progressively higher doses, withdrawal syndrome on discontinuation, cognitive impairment involving attention and memory, an increased risk of falls and fractures, particularly in older adults, road traffic accidents and possible long-term sleep dysregulation. In some studies, prolonged use has also been associated with a poorer functional prognosis in anxiety and depressive disorders, delaying response to first-line treatments.
6) How should a benzodiazepine be tapered?
Tapering should be slow, structured and individualised, particularly after prolonged use or at high doses. As a general approach, the total dose may be reduced by 10–25% every 2–4 weeks, adjusted according to withdrawal symptoms. For short-acting benzodiazepines, conversion to an intermediate- or long-acting benzodiazepine may be useful before tapering. It is essential to combine tapering with psychoeducation, psychological intervention and optimisation of maintenance treatment, such as an SSRI for anxiety, while avoiding the introduction of another hypnotic merely to “replace” the benzodiazepine.
7) What precautions are required when combining benzodiazepines with alcohol, opioids or other central nervous system depressants?
Combining benzodiazepines with alcohol, opioids, sedating antipsychotics, first-generation antihistamines or other central nervous system depressants significantly increases the risk of respiratory depression, profound sedation, falls and death. Combination with opioids should be particularly avoided or, when unavoidable, closely monitored using the lowest possible doses and frequent reassessment. Patients should be advised not to drive or operate machinery while using these combinations.
8) Are non-benzodiazepine hypnotics such as zolpidem safer?
Z-drugs, such as zolpidem, also act on the GABA-A receptor and, despite some selectivity for sleep-related receptor subunits, share several risks with benzodiazepines, including tolerance, dependence, rebound insomnia, falls and accidents. Complex sleep behaviours, such as walking, eating or driving while asleep, and anterograde amnesia have also been reported. They should be subject to the same restrictions: the lowest effective dose, for a very limited period, always as part of a broader insomnia-management strategy.
