Harrison's Manual of Medicine
ANXIOLYTICS
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Benzodiazepines bind to sites on the γ-aminobutyric acid receptor and are cross-tolerant with alcohol and with barbiturates. Four clinical properties: (1) sedative, (2) anxiolytic, (3) skeletal muscle relaxant, and (4) antiepileptic. Individual drugs differ in terms of potency, onset of action, duration of action (related to half-life and presence of active metabolites), and metabolism (Table 200-2). Benzodiazepines have additive effects with alcohol; like alcohol, they can produce tolerance and physiologic dependence, with serious withdrawal syndromes (tremors, seizures, delirium, and autonomic hyperactivity) if discontinued too quickly, especially for those with short half-lives.
| NAME | EQUIVALENT PO DOSE, mg | ONSET OF ACTION | HALF-LIFE, h | COMMENTS |
|---|---|---|---|---|
| Benzodiazepines | ||||
| Diazepam (Valium) | 5 | Fast | 20–70 | Active metabolites; quite sedating |
| Flurazepam (Dalmane) | 15 | Fast | 30–100 | Flurazepam is a prodrug; metabolites are active; quite sedating |
| Triazolam (Halcion) | 0.25 | Intermediate | 1.5–5 | No active metabolites; can induce confusion and delirium, especially in elderly |
| Lorazepam (Ativan) | 1 | Intermediate | 10–20 | No active metabolites; direct hepatic glucuronide conjugation; quite sedating; FDA approved for anxiety with depression |
| Alprazolam (Xanax) | 0.5 | Intermediate | 12–15 | Active metabolites; not too sedating; FDA approved for panic disorder and anxiety with depression; tolerance and dependence develop easily; difficult to withdraw |
| Chlordiazepoxide (Librium) | 10 | Intermediate | 5–30 | Active metabolites; moderately sedating |
| Oxazepam (Serax) | 15 | Slow | 5–15 | No active metabolites; direct glucuronide conjugation; not too sedating |
| Temazepam (Restoril) | 15 | Slow | 9–12 | No active metabolites; moderately sedating |
| Clonazepam (Klonopin) | 0.5 | Slow | 18–50 | No active metabolites; moderately sedating; FDA approved for panic disorder |
| Clorazepate (Tranxene) | 15 | Fast | 40–200 | Low sedation; unreliable absorption |
| Nonbenzodiazepines | ||||
| Buspirone (BuSpar) | 7.5 | 2 weeks | 2–3 | Active metabolites; tid dosing—usual daily dose 10–20 mg tid; nonsedating; no additive effects with alcohol; useful for controlling agitation in demented or brain-injured pts |
Buspirone is a nonbenzodiazepine anxiolytic that is nonsedating, is not cross-tolerant with alcohol, and does not induce tolerance or dependence. It requires at least 2 weeks at therapeutic doses to achieve full effects.
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Benzodiazepines bind to sites on the γ-aminobutyric acid receptor and are cross-tolerant with alcohol and with barbiturates. Four clinical properties: (1) sedative, (2) anxiolytic, (3) skeletal muscle relaxant, and (4) antiepileptic. Individual drugs differ in terms of potency, onset of action, duration of action (related to half-life and presence of active metabolites), and metabolism (Table 200-2). Benzodiazepines have additive effects with alcohol; like alcohol, they can produce tolerance and physiologic dependence, with serious withdrawal syndromes (tremors, seizures, delirium, and autonomic hyperactivity) if discontinued too quickly, especially for those with short half-lives.
| NAME | EQUIVALENT PO DOSE, mg | ONSET OF ACTION | HALF-LIFE, h | COMMENTS |
|---|---|---|---|---|
| Benzodiazepines | ||||
| Diazepam (Valium) | 5 | Fast | 20–70 | Active metabolites; quite sedating |
| Flurazepam (Dalmane) | 15 | Fast | 30–100 | Flurazepam is a prodrug; metabolites are active; quite sedating |
| Triazolam (Halcion) | 0.25 | Intermediate | 1.5–5 | No active metabolites; can induce confusion and delirium, especially in elderly |
| Lorazepam (Ativan) | 1 | Intermediate | 10–20 | No active metabolites; direct hepatic glucuronide conjugation; quite sedating; FDA approved for anxiety with depression |
| Alprazolam (Xanax) | 0.5 | Intermediate | 12–15 | Active metabolites; not too sedating; FDA approved for panic disorder and anxiety with depression; tolerance and dependence develop easily; difficult to withdraw |
| Chlordiazepoxide (Librium) | 10 | Intermediate | 5–30 | Active metabolites; moderately sedating |
| Oxazepam (Serax) | 15 | Slow | 5–15 | No active metabolites; direct glucuronide conjugation; not too sedating |
| Temazepam (Restoril) | 15 | Slow | 9–12 | No active metabolites; moderately sedating |
| Clonazepam (Klonopin) | 0.5 | Slow | 18–50 | No active metabolites; moderately sedating; FDA approved for panic disorder |
| Clorazepate (Tranxene) | 15 | Fast | 40–200 | Low sedation; unreliable absorption |
| Nonbenzodiazepines | ||||
| Buspirone (BuSpar) | 7.5 | 2 weeks | 2–3 | Active metabolites; tid dosing—usual daily dose 10–20 mg tid; nonsedating; no additive effects with alcohol; useful for controlling agitation in demented or brain-injured pts |
Buspirone is a nonbenzodiazepine anxiolytic that is nonsedating, is not cross-tolerant with alcohol, and does not induce tolerance or dependence. It requires at least 2 weeks at therapeutic doses to achieve full effects.
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