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 antagonism^Δ	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 antagonism^Δ	Sleep onset or sleep maintenance insomnia	50 to 100 mg	25 to 100 mg	Intermediate (10 to 12)	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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