CNS Depressants · Medicine Class
Positive allosteric modulation of GABA-A receptors
Benzodiazepines bind to the GABA-A receptor at the benzodiazepine site (distinct from the GABA binding site) and allosterically increase the frequency of chloride channel opening in response to GABA. This enhances inhibitory GABAergic neurotransmission throughout the CNS, producing anxiolytic, sedative, hypnotic, anticonvulsant, and muscle relaxant effects. Unlike barbiturates, benzodiazepines only modulate — not directly activate — the GABA-A receptor, giving them a much higher safety margin.
Alprazolam (Xanax)
Short-to-intermediate acting; most prescribed BZD in the US; high misuse potential; significant discontinuation syndrome.
Lorazepam (Ativan)
Intermediate acting; no active metabolites (preferred in hepatic impairment, elderly); IV use for status epilepticus.
Diazepam (Valium)
Long-acting; multiple active metabolites; rectal gel for seizure clusters; useful in alcohol withdrawal.
Clonazepam (Klonopin)
Long-acting; preferred for panic disorder; also used for seizure maintenance and restless legs.
Temazepam (Restoril)
Intermediate-acting; specifically indicated for insomnia. No active metabolites.
Midazolam (Versed)
Ultra-short acting; IV/IM procedural sedation; buccal formulation for acute seizures in children.
Opioids — CNS/respiratory depression; combination is leading cause of overdose death; FDA black box warning
Alcohol — synergistic CNS depression
Other CNS depressants (muscle relaxants, antihistamines, antipsychotics) — additive sedation
CYP3A4 inhibitors (azole antifungals, macrolides) — increase levels of CYP3A4-metabolized BZDs
Flumazenil — competitive BZD antagonist; reverses sedation and respiratory depression
Yes — physical dependence (physiological adaptation requiring continued use to avoid withdrawal) develops with regular use as quickly as 2-4 weeks. Psychological dependence (believing one cannot function without the medicine) also commonly develops. True 'addiction' (loss of control, continued use despite harm) occurs less commonly in prescribed patients than in recreational users but is a real risk.
Benzodiazepine withdrawal is potentially life-threatening and more dangerous than opioid withdrawal. Symptoms include anxiety, insomnia, tremor, sweating, and in severe cases — seizures and psychosis. Withdrawal intensity is proportional to dose, duration, and half-life of the medicine. Long-acting BZDs (diazepam, clonazepam) produce milder withdrawal than short-acting ones (alprazolam). Supervised tapering over weeks to months is essential.