A sedative calms and reduces anxiety; a hypnotic induces sleep; an anxiolytic relieves anxiety. Many drugs do all three depending on the dose — rising doses move from calm → sleep → anesthesia → coma and respiratory arrest.

Antagonist: flumazenil competitively blocks the benzodiazepine site and reverses benzodiazepine and Z-drug effects — it does not reverse barbiturates, alcohol, or opioids.

Place in therapy

• Chronic insomnia: cognitive behavioral therapy for insomnia (CBT-I) is first-line; hypnotics are short-term adjuncts at the lowest dose.
• Anxiety disorders: SSRIs/SNRIs first-line; benzodiazepines for short-term or bridging use only.
• Alcohol withdrawal and status epilepticus: benzodiazepines are first-line.

US boxed warnings — benzodiazepines: (1) profound sedation, respiratory depression, coma, and death with opioids (2016); (2) abuse, misuse, addiction, physical dependence, and withdrawal reactions — abrupt stopping or rapid dose reduction can cause life-threatening withdrawal, including seizures (2020).

Z-drugs: boxed warning for complex sleep behaviors (2019); contraindicated in anyone who has had such an episode.

• Contraindicated: acute narrow-angle glaucoma (benzodiazepines, per labeling), severe respiratory insufficiency, history of complex sleep behaviors (Z-drugs), narcolepsy (orexin antagonists), porphyria (barbiturates).
• Avoid or use with caution: untreated sleep apnea, severe liver disease (lorazepam, oxazepam, temazepam preferred), myasthenia gravis.
• Older adults: avoid benzodiazepines and Z-drugs for insomnia or agitation (Beers Criteria) — falls, fractures, delirium, car crashes.
• Substance use: caution with a history of alcohol or drug misuse.
• Pregnancy and lactation: benzodiazepine use late in pregnancy can cause neonatal sedation and withdrawal (hypotonia, poor feeding, respiratory depression); weigh risk against untreated anxiety; do not stop abruptly without a plan. Observe breastfed infants for sedation.
• Interactions:
  • Opioids, alcohol, gabapentinoids, sedating antihistamines, antipsychotics, muscle relaxants → additive CNS and respiratory depression
  • CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, grapefruit) raise alprazolam, midazolam, triazolam, and orexin antagonist levels; inducers (rifampin, carbamazepine) lower them
  • Barbiturates induce liver enzymes → reduce warfarin, oral contraceptives, corticosteroids, and many antiseizure drugs
  • Buspirone + MAO inhibitors → hypertensive reaction; ramelteon + fluvoxamine → contraindicated (large level increase)
  • Clozapine with IV benzodiazepines → respiratory arrest reported

Listed in priority order.

1. Airway, breathing, level of consciousness
   • Check respiratory rate, SpO₂, and sedation before and after IV or high doses; continuous monitoring and bag-valve mask, suction, and flumazenil available during IV use.
   • Extra caution when opioids are also ordered — clarify combined orders.
2. Safety
   • Fall precautions: bed low, call light, assist with the first ambulation, orthostatic blood pressure checks.
   • Give hypnotics only when the client is in bed and ready to sleep, with 7–8 hours available.
   • Watch for complex sleep behaviors and confusion at night.
3. Administration
   • IV lorazepam and diazepam: give slowly (lorazepam no faster than about 2 mg/min; diazepam no faster than about 5 mg/min in adults) into a large vein; diazepam precipitates in many solutions — do not mix. IM diazepam is poorly absorbed; midazolam is the better IM choice.
   • Oral benzodiazepines can be given with food if GI upset occurs.
4. Withdrawal and dependence
   • Assess for withdrawal when a client on long-term benzodiazepines is admitted and doses are missed: anxiety, insomnia, tremor, tachycardia, sweating, perceptual changes, seizures, delirium. Onset is earlier (1–2 days) with short-acting drugs and later (up to about a week) with long-acting drugs.
   • Taper gradually over weeks to months; never stop abruptly after regular use.
   • Alcohol withdrawal: symptom-triggered dosing by CIWA-Ar (commonly treat at about 10 or more); monitor vital signs.
5. Mental health — assess mood and suicide risk; limit quantities dispensed to clients at risk; watch for misuse (early refill requests, multiple prescribers).
6. Evaluate effect — anxiety level, sleep quality, next-day function.

• Do not drink alcohol or take opioids, sleep aids, or other sedating drugs unless the prescriber knows.
• Do not drive or operate machinery until you know how the drug affects you; with hypnotics, next-morning driving may be impaired even when you feel awake.
• Take a hypnotic right before bed and only when you can stay in bed 7–8 hours. Stop zolpidem, eszopiclone, or zaleplon and call the provider if you do anything while not fully awake (walking, driving, eating).
• Never stop a benzodiazepine suddenly after regular use — withdrawal seizures can occur. Do not increase the dose on your own.
• Buspirone must be taken every day and needs 2–4 weeks to work; it will not stop a panic attack.
• Store medicines locked; do not share them.
• Sleep hygiene and CBT-I: fixed wake time, bed only for sleep, limit naps, caffeine, alcohol, and screens in the evening; get up if unable to sleep within about 20 minutes.
• Tell the provider about pregnancy plans, breastfeeding, snoring or sleep apnea, and low mood.

Flumazenil

• Dose: 0.2 mg IV over 15–30 seconds, then 0.2 mg every minute as needed (usual maximum 1 mg per series; 3 mg per hour).
• Best use: reversal of benzodiazepine procedural sedation in a client who is not dependent.
• Avoid in long-term benzodiazepine users, in mixed overdoses with tricyclic antidepressants or other seizure-provoking drugs, and in clients with seizure disorders — it can precipitate seizures that are then hard to treat.
• Re-sedation can occur because flumazenil (about 1 hour) is shorter-acting than many benzodiazepines — monitor for at least 2 hours.

• Benzodiazepines enhance GABA — sedation, anxiolysis, anticonvulsant, amnesia, muscle relaxation
• Boxed warnings: deadly with opioids; abuse, dependence, withdrawal seizures — taper, never stop abruptly
• Lorazepam, oxazepam, temazepam — preferred in liver disease and older adults when a benzodiazepine is necessary
• Benzodiazepine antidote: flumazenil — risk of seizures in dependent clients; watch for re-sedation
• Barbiturates: no ceiling, no antidote, enzyme inducers
• Z-drugs: complex sleep behaviors (boxed warning); take right before bed with 7–8 hours to sleep
• Orexin antagonists: contraindicated in narcolepsy
• Buspirone: no sedation or dependence; 2–4 weeks; not PRN
• CBT-I is first-line for chronic insomnia; SSRIs/SNRIs first-line for anxiety disorders
• Older adults: avoid benzodiazepines, Z-drugs, and sedating antihistamines — falls and delirium
• Alcohol withdrawal: benzodiazepines by CIWA-Ar