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Other drugs for the management of insomnia in adults

Other drugs for the management of insomnia in adults
Other drugs Mechanism of action Clinical use* Adult dose
(usual)
Dose in older adults
(≥65 years)
Half-life
(hours)
Potential for drug interactions
Doxepin Histamine H1 receptor antagonismΔ Sleep maintenance insomnia 3 to 10 mg 3 to 6 mg Long (15 drug; 31 active metabolite)

Moderate

Doxepin clearance is largely dependent on CYP2D6

Avoid use within two weeks of MAOI administration
Ramelteon Melatonin receptor agonist Sleep onset insomnia 8 mg 8 mg Short (1 to 2.6 drug; 2 to 5 active metabolite)

Moderate

Ramelteon clearance is largely dependent on CYP1A2 and CYP2C9
Lemborexant Orexin receptor antagonist Sleep onset or sleep maintenance insomnia 5 to 10 mg 5 mg Long (17 to 19)

Significant drug interactions

Lemborexant clearance is dependent on CYP3A4

If used in combination with mild inhibitors of CYP3A4, recommended dose is 5 mg

Avoid use of lemborexant with moderate and strong inhibitors and inducers of CYP3A4
Suvorexant Orexin receptor antagonist Sleep onset or sleep maintenance insomnia 10 to 20 mg 10 to 15 mg Intermediate (12)

Significant drug interactions

Suvorexant clearance is largely dependent on CYP3A

If used in combination with moderate inhibitors of CYP3A, recommended dose is 5 mg; may increase to 10 mg

Avoid use of suvorexant with strong inhibitors or inducers of CYP3A
Daridorexant Orexin receptor antagonist Sleep onset or sleep maintenance insomnia 25 to 50 mg 25 to 50 mg Intermediate (8)

Significant drug interactions

Daridorexant clearance is largely dependent on CYP3A

If used in combination with moderate inhibitors of CYP3A, recommended dose is 25 mg

Avoid use of daridorexant with strong inhibitors or moderate/strong inducers of CYP3A
Trazodone§ Serotonin 5-HT2A, alpha-1 adrenergic, and histamine H1 receptor antagonismΔ Sleep onset or sleep maintenance insomnia 50 to 100 mg 25 to 100 mg Intermediate (5 to 9)

Moderate

Trazodone is metabolized by CYP3A4 to an active metabolite; use with caution in combination with other serotonergic drugs
Dosing in this table is for adult patients with normal organ (eg, kidney, liver) function. For dosage adjustments, refer to Lexicomp drug information included with UpToDate.
CYP: cytochrome P450; MAOI: monoamine oxidase inhibitor; FDA: US Food and Drug Administration.
* Appropriate clinical uses may differ from the FDA-approved indication(s) for a given drug.
¶ For specific drug interactions, including management recommendations and combinations that should be avoided, use Lexi-Interact drug interactions program included with UpToDate.
Δ Although classified as antidepressants, these drugs are not therapeutic for treating depression at the doses used for insomnia.
FDA-approved for insomnia at doses of 3 and 6 mg daily using tablet formulation.
§ Not approved by the FDA for insomnia indication.
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