Table 3.
Medications Recommended for Treatment of Insomnia by the American Academy of Sleep Medicine (16)
| Drug Class | Agent(s) | FDA-approved for sleep onset (80) |
FDA-approved for sleep maintenance (80) |
Controlled substance |
Generic Available |
Relevant contraindications include (80) |
RCT-demonstrated efficacy for insomnia up to |
Relevant drug interactions |
|---|---|---|---|---|---|---|---|---|
| Short/Intermedi ate Acting Benzodiazepine Receptor Agonists |
Eszopiclone (Lunesta) | Yes | Yes | Yes | Yes | Impaired motor/cognitive performance with higher dosage in elderly |
6 months | CNS depressants, rifampicin, ketoconazole |
| Temazepam (Restoril) | Yes | Yes | Yes | Yes | Oversedation, confusion, ataxia with higher dosage in elderly |
8 weeks | CNS depressants, hypnotics, diphenhydramine |
|
| Triazolam (Halcion) | Yes | No | Yes | Yes | Compromised respiratory function, renal or hepatic impairment, pulmonary insufficiency |
5 weeks | Ketoconazole, itraconazole, nefazodone, HIV protease inhibitors, medications that impair the oxidative metabolism mediated by CYP3A |
|
| Zaleplon (Sonata) | Yes | No | Yes | Yes | Conditions affecting metabolism or hemodynamic responses or compromised respiratory function |
4 weeks | Promethazine; rifampin; CYP3A4 inducers; CYP3A4 inhibitors; cimetidine; additive CNS depression with other psychotropic medications, anticonvulsants, antihistamines, narcotic analgesics, anesthetics, ethanol, and other CNS depressants |
|
| Zolpidem (Ambien) | Yes | No | Yes | Yes | Compromised respiratory function, conditions affecting metabolism or hemodynamic responses, renal or hepatic impairment, risk of impaired motor/cognitive performance in elderly |
8 months | CNS depressants; other sedative- hypnotics; imipramine; chlorpromazine; alcohol; sertraline; CYP3A4 inhibitors; rifampin; fluoxetine; ketoconazole |
|
| Zolpidem (Ambien CR) | Yes | Yes | Yes | Yes | Compromised respiratory function, conditions affecting metabolism or hemodynamic responses, renal or hepatic impairment, risk of impaired motor/cognitive performance in elderly |
6 months | CNS depressants; other sedative- hypnotics; imipramine; chlorpromazine; alcohol; sertraline; CYP3A4 inhibitors; rifampin; fluoxetine; ketoconazole |
|
| Zolpidem (Intermezzo) | No | Yes | Yes | No | Compromised respiratory function, risk of impaired motor/cognitive performance in elderly |
4 weeks | CNS depressants; imipramine; chlorpromazine; rifampin; ketoconazole |
|
| Melatonin Receptor Agonist |
Ramelteon (Rozerem) | Yes | No | No | Yes | Hepatic impairment, may affect reproductive hormones |
6 months | CYP inducers, CYP1A2 inhibitors, CYP3A4 inhibitors, CYP2C9 inhibitors; donepezil; doxepin; zolpidem; CNS depressants; alcohol |
| Intermediate/Lo ng Acting Benzodiazepine Receptor Agonist |
Clonazepam (Klonopin) | No | No | Yes | Yes | Renal or hepatic impairment, respiratory diseases, elderly patients, glaucoma |
None | CYP450 inducers; propantheline; CYP3A inhibitors; alcohol; narcotics; barbiturates; hypnotics; antianxiety agents; phenothiazines; thioxanthene; butyrophenone antipsychotics; MAOIs; TCAs; anticonvulsant drugs; CNS depressants; valproic acid |
| Estazolam (ProSom, Eurodin) |
Yes | No | Yes | Yes | Renal or hepatic impairment, compromised respiratory function, depression |
1 week | CNS-acting drugs; anticonvulsants; antihistamines; alcohol; barbiturates; MAOIs; narcotics; phenothiazines; psychotropic medications; CNS depressants; smoking; CYP3A inhibitors; CYP3A inducers |
|
| Flurazepam (Dalmane) | Yes | Yes | Yes | Yes | Depression, hepatic or renal impairment, pulmonary insufficiency |
3 weeks | CNS depressants; alcohol |
|
| Lorazepam (Ativan) | No | No | Yes | Yes | Compromised respiratory function, impaired renal or hepatic function, elderly |
None | CNS depressants; clozapine; valproate; probenecid; theophylline; aminophylline |
|
| Sedating low- dose antidepressant |
Amitriptyline | No | No | No | Yes | Liver dysfunction | None | Guanethidine; CNS depressants; CYP2D6 inhibitors; TCAs; SSRIs; “caution with thyroid drugs”; disulfiram; ethchlorvynol; anticholinergics; sympathomimetics; neuroleptics; cimetidine |
| Doxepin (Silenor) 3- 6mg |
No | Yes | No | Yes | Compromised respiratory function |
12 weeks | Alcohol; CNS depressants; sedating antihistamines; CYP2C19 inhibitors; CYP2D6 inhibitors; CYP1A2 inhibitors; CYP2C9 inhibitors; cimetidine; tolazamide; sertraline |
|
| Mirtazapine (Remeron) | No | No | No | Yes | Neutropenia and hyponatremia reported, renal or hepatic impairment, conditions affecting metabolism or hemodynamic responses, elderly, may cause orthostatic hypotension |
None | MAOIs; serotonergic drugs; drugs affecting hepatic metabolism; CYP enzyme inducers; drugs metabolized by or inducers of cytochrome P450; antihypertensives known to cause hyponatremia; phenytoin; carbamazepine; hepatic metabolism inducers; cimetidine; ketoconazole; cimetidine; alcohol; diazepam; CYP3A4 inhibitors; HIV protease inhibitors; azole antifungals; erythromycin; nefazodone; warfarin |
|
| Trazodone (Oleptro) | No | No | No | Yes | Hypotension and syncope reported, elderly, renal or hepatic impairment, hyponatremia may occur |
1 week | Serotonergic drugs; drugs which impair serotonin metabolism; antipsychotics; dopamine agonists; serotonin precursors; CYP3A4 inhibitors; Carbamazepine; MAOIs; alcohol; barbiturates; CNS depressants; warfarin; antihypertensives; NSAIDs; aspirin; drugs that affect coagulation or bleeding; diuretics; drugs that prolong QT interval |
|
| Trimipramine (Surmontil) |
No | No | No | Yes | Liver dysfunction, elderly |
None | Serotonergic drugs; drugs which impair serotonin metabolism; caution on patients on thyroid medication; guanethidine; cimetidine; alcohol; catecholamines; anticholinergics; sympathomimetic amines; local decongestants; local anesthetics containing epinephrine; atropine; CYP2D6 inhibitors; SSRIs; TCAs |
|
| Other prescription drugs |
Gabapentin (Neurontin) | No | No | No | Yes | Liver dysfunction, hepatic impairment |
None | Maalox; naproxen sodium; hydrocodone |
| Olanzapine (Zyprexa) | No | No | No | Yes | Hepatic impairment; prostatic hypertrophy; may cause orthostatic hypotension; leukopenia, neutropenia, and agranulocytosis reported; may cause cognitive and motor impairment |
None | Diazepam; alcohol; carbamazepine; omeprazole; rifampin; CYP1A2 inducers; fluoxetine; fluvoxamine; other centrally-acting drugs; potentially hepatotoxic drugs; antihypertensives; levodopa; dopamine agonists; anticholinergic drugs; parenteral benzodiazepines |
|
| Tiagabine (Gabitril) | No | No | No | Yes | Tiagabine (Gabitril) No No No Yes Incapacitating weakness reported |
1 night | valproate; carbamazepine; phenytoin; phenobarbital; ethanol; triazolam; drugs that lower seizure threshold (antidepressants, antipsychotics, stimulants, narcotics); drugs that induce or inhibit hepatic metabolizing enzymes; highly protein-bound drugs |
|
| Quetiapine (Seroquel) | No | No | No | Yes | May induce orthostatic hypotension; leukopenia, neutropenia, and agranulocytosis reported; may impair physical/mental abilities |
None | Centrally-acting drugs; alcohol; CYP3A4 inhibitors; CYP3A4 inducers; antihypertensives; levodopa; dopamine agonists; drugs known to cause electrolye imbalance; drugs known to prolong QTc interval (e.g., antiarrhythmics, antipsychotics, antibiotics); anticholinergic medications |