• Clinical science



Benzodiazepines have a wide‑range of therapeutic effects and are employed as anxiolytics, sedatives, muscle relaxants, and anticonvulsants. They act by binding to the GABAA receptor and increasing inhibitory GABAergic transmission. Although they are predominantly used to treat stress and anxiety disorders, sleep disorders, and seizures, they may also be used for muscle relaxation in minor orthopedic procedures and perioperative sedation. Important adverse effects include confusion, impaired motor coordination, amnesia, drowsiness, and respiratory depression. In everyday clinical practice, benzodiazepines are administered cautiously because of the extremely high risk of benzodiazepine dependence.


  • Benzodiazepines are indirect GABAA agonists → bind to GABAA receptorsaffinity of GABA to bind to GABAA receptors GABA action↑ opening frequency of chloride channelshyperpolarization of the post-synaptic neuronal membrane → decreased neuronal excitability


Side effects

Adverse effects

  • Blunted affect
  • “Hangover” effect on the next day
  • Motor incoordination and muscle weakness
  • Amnesia
  • Drug tolerance
  • Paradoxical excitability
  • Increased appetite
  • CNS depression
    • Concurrent use of alcohol, opioids, 1st generation anti-histamines (e.g., diphenhydramine), and other CNS depressants (sedative-hypnotics) should be avoided
      • Potentiate the action of benzodiazepines; increased sedation, impaired motor coordination, slurred speech, disorientation, dizziness, confusion, and respiratory depression.

Benzodiazepine overdose

Benzodiazepine overdose is very rarely life-threatening unless associated with the co-ingestion of alcohol or other respiratory depressants!

Most cases of benzodiazepine overdose occur in patients who are on chronic benzodiazepine therapy. Flumazenil can precipitate withdrawal symptoms and seizures in patients with benzodiazepine dependence.

Benzodiazepine dependence

Benzodiazepine dependence can develop even after just a few weeks of use. Benzodiazepines should therefore only be prescribed when strongly indicated!


We list the most important adverse effects. The selection is not exhaustive.


  • Neuromuscular disease
  • Ataxia
  • Narrow-angle glaucoma
  • Pregnancy
  • Respiratory depression (COPD, respiratory failure)
  • Drug dependence (Alcohol, drug, or prescription medication abuse (including polydrug use))


We list the most important contraindications. The selection is not exhaustive.


Benzodiazepine-like substances

Although these drugs do not structurally resemble the benzodiazepine family, they also bind at the GABAA receptor and therefore their pharmacodynamic effect is similar. Since these drugs have a marked sedative effect and are not associated with drug dependence, they are preferred over benzodiazepines to treat sleep disorders.

  • Drugs
  • Effect
    • Good sedative and hypnotic action
    • Less effective as an anticonvulsant and an anxiolytic when compared to benzodiazepines
  • Indication: Sleep disorders (especially with difficulty falling asleep)
  • Side effects
    • Development of drug tolerance
      • After long-term use, the daily dose should be tapered gradually.
    • The hangover effect and the rebound phenomenon are seen very rarely.
    • In the case of overdose: symptoms are similar to those seen with benzodiazepine toxicity
  • Contraindications: similar to “contraindications for benzodiazepines



Duration of action Pharmacologic agent


Potential for dependence


  • Procedural sedation and anaesthesia induction
  • Sleep-onset insomnia
  • Very high
  • High to very high
  • High

In principle, there is no indication for long-term benzodiazepine therapy. Long-term therapy should only be considered in exceptional cases after carefully weighing the risks involved!