There is no single antidepressant or class of antidepressants that is most effective for the treatment of insomnia in patients with depression. The use of antidepressant medications can have a positive impact on sleep physiology, but does not seem to improve subjective ratings of sleep quality. (Strength of Recommendation: B, based on one qualitative study and one meta-analysis.

Clark, Molly S.

Jamieson, Barbara

Smith, Patrick O.

English

University of Missouri: MOspace

November 1, 2011 ◆ Volume 84, Number 9 www.aafp.org/afp American Family Physician  1Clinical QuestionWhich antidepressant medications are most effective for treating insomnia in patients with depression?Evidence-Based AnswerThere is no single antidepressant or class of antidepressants that is most effective for the treatment of insomnia in patients with depression. The use of antidepressant medi-cations can have a positive impact on sleep physiology, but does not seem to improve subjective ratings of sleep quality. (Strength of Recommendation: B, based on one quali-tative study and one meta-analysis.) Evidence SummaryThe relationship between depression, insom-nia, and treatment is complex. A meta-analysis of sleep and psychiatric disorders found that patients with comorbid sleep disturbances and depression typically have increased sleep latency, increased rapid eye movement (REM) sleep, increased midcycle awakening, decreased slow wave sleep, and shortened REM latency.1 Therefore, select-ing antidepressant agents that increase sleep continuity (i.e., uninterrupted sleep), pro-long REM latency, and decrease REM sleep is one strategy for treating insomnia in patients with depression.2-5 Research on the impact of antidepressants on objective sleep measures is summarized in Table 1.2 Studies have consistently demonstrated differences between objective and subjective sleep measures in patients taking antidepres-sants.6 In a study comparing objective and subjective sleep measures in patients with depression, 18 patients (78 percent) showed at least a 30-minute over- or underestimation of total sleep time. Twelve patients (52 percent) over- or underestimated total sleep time by at least 60 minutes when comparing their sub-jective sleep ratings with polysomnography.7 Research measuring the effect of anti-depressants on subjective sleep ratings is sparse. There are no systematic reviews or meta-analyses. Subjective measures of sleep quality are often included as secondary out-comes in clinical trials of antidepressants. Existing studies are further limited by small sample size, short duration, incomplete data reporting, lack of a placebo arm, concur-rent hypnotic use, or heterogeneity in rating instruments of perceived sleep quality.Studies that measured subjective sleep ratings used the three sleep items on the Hamilton Rating Scale for Depression or the Leeds Sleep Evaluation Questionnaire.2 These studies found that selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) improved subjective sleep measures in patients with depression. In addition, studies have shown that nefazo-done, trazodone, or mirtazapine (Remeron) also can improve subjective sleep ratings compared with placebo, SSRIs, or TCAs in patients with depression.2Recommendations from OthersFor patients with depression and comorbid insomnia, the American Academy of Sleep Medicine recommends the addition of a low-dose, sedating antidepressant if not contra-indicated. Low-dose trazodone, mirtazapine, doxepin, amitriptyline, or trimipramine (Sur-montil) may be given in addition to another full-dose antidepressant.8 Guidelines from the American College of Physicians report con-flicting evidence, with some studies indicating Antidepressants for the Treatment of Insomnia  in Patients with DepressionMOLLY S. CLARK, PhD, and PATRICK O. SMITH, PhD, University of Mississippi Medical Center, Jackson, MississippiBARBARA JAMIESON, MLS, Medical College of Wisconsin, Milwaukee, WisconsinClinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medi-cine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recom-mendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).The complete database of evidence-based ques-tions and answers is copyrighted by FPIN. If interested in submit-ting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.A collection of FPIN’s Clinical Inquiries pub-lished in AFP is available at http://www.aafp.org/afp/fpin.FPIN’s Clinical InquiriesDownloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2011 American Academy of Family Physicians. For the private, noncom-mercial use of one individual user of the Web site. All other rights reserved. Contact copyrights@aafp.org for copyright questions and/or permission requests.Clinical Inquiries2  American Family Physician www.aafp.org/afp Volume 84, Number 9 ◆ November 1, 2011improved sleep ratings with escitalopram (Lexapro) over citalopram (Celexa), nefazodone over fluoxetine (Prozac), and trazodone over fluoxetine. However, the authors caution that in randomized controlled trials and mul-tiple head-to-head trials, there is limited evidence for the comparative effectiveness of antidepressants in treating insomnia in patients with depression.9Copyright Family Physicians Inquiries Network. Used with permission.Address correspondence to Molly S. Clark, PhD, at MClark@umc.edu. Reprints are not available from the authors.Author disclosure: No relevant financial affiliations to disclose.REFERENCES	 1.	Benca	RM,	Obermeyer	WH,	Thisted	RA,	Gillin	JC.	Sleep	and	psychiatric	disorders.	A	meta-analysis.	Arch Gen Psychiatry.	1992;49(8):651-668.	 2.	Wilson	 S,	 Argyropoulos	 S.	 Antidepressants	 and	 sleep:	 a	 qualitative	review	of	the	literature.	Drugs. 2005;65(7):927-947.	 3.	Winokur	A,	Gary	KA,	Rodner	S,	Rae-Red	C,	Fernando	AT,	Szuba	MP.	Depression,	sleep	physiology,	and	antidepressant	drugs.	Depress Anxi-ety.	2001;14(1):19-28.	 4.	Gursky	JT,	Krahn	LE.	The	effects	of	antidepressants	on	sleep:	a	review.	Harv Rev Psychiatry.	2000;8(6):298-306.	 5.	Mayers	 AG,	 Baldwin	 DS.	 Antidepressants	 and	 their	 effect	 on	 sleep.	Hum Psychopharmacol.	2005;20(8):533-559.	 6.	Ware	JC.	Tricyclic	antidepressants	in	the	treatment	of	insomnia.	J Clin Psychiatry.	1983;44(9	pt	2):25-28.	 7.	Tsuchiyama	K,	Nagayama	H,	Kudo	K,	Kojima	K,	Yamada	K.	Discrepancy	between	 subjective	 and	 objective	 sleep	 in	 patients	 with	 depression.	Psychiatry Clin Neurosci. 2003;57(3):259-264.	 8.	Schutte-Rodin	S,	Broch	L,	Buysse	D,	Dorsey	C,	Sateia	M.	Clinical	guide-line	for	the	evaluation	and	management	of	chronic	insomnia	in	adults.	J Clin Sleep Med. 2008;4(5):487-504.	 9.	Qaseem	 A,	 Snow	 V,	 Denberg	 TD,	 Forciea	 MA,	 Owens	 DK;	 Clinical	Efficacy	Assessment	Subcommittee	of	American	College	of	Physicians.	Using	second-generation	antidepressants	to	treat	depressive	disorders:	a	 clinical	 practice	 guideline	 from	 the	 American	 College	 of	 Physicians	[published	 correction	 appears	 in	 Ann Intern Med.	 2009;150(2):148].	Ann Intern Med. 2008;149(10):725-733.	■Table 1. Impact of Antidepressants on Objective Sleep Measures Short term (five to 10 days) Long term (more than 21 days)   Drug Continuity REM sleepREM sleep latency Continuity REM sleepREM sleep latencyWithdrawal REM reboundMAOI 	 	 	 	 	 	 	Phenelzine	(Nardil) ∞ *** ††† ∞ *** ††† †SSRI 	 	 	 	 	 	 	Citalopram	(Celexa),	fluvoxamine,	paroxetine	(Paxil),	and	sertraline	(Zoloft)↔ ** ††† ↔ ** †† †Fluoxetine	(Prozac) ↓ ** † ↓ * † ∞TCA 	 	 	 	 	 	 	Amitriptyline ↔ ** †† ↑ * †† †Imipramine	(Tofranil) ↔ ** ††† ↔ * †† ∞Other 	 	 	 	 	 	 	Bupropion	(Wellbutrin) ∞ ∞ ∞ ↔ ↔/↓ †/↔ ∞Mirtazapine	(Remeron) ↑ ↔ ↔ ↑ ↔ †/↔ ∞Nefazodone ↑ ↔ ↔ ↑ ↔ ↔/↓ ∞Trazodone ↔/↑ * † ↑ ↔ † ∞MAOI = monoamine oxidase inhibitor; REM = rapid eye movement; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.↔ = no change; ∞ = no data; ↑ = increase; ↓ = decrease; * = 10 to 30 percent decrease; ** = 30 to 60 percent decrease; *** = greater than 60 percent decrease; † = 30 to 100 percent increase; †† = 100 to 200 percent increase; ††† = greater than 200 percent increase. Adapted with permission from Wilson S, Argyropoulos S. Antidepressants and sleep: a qualitative review of the literature. Drugs. 2005;65(7):932. 

Antidepressants for the Treatment of Insomnia in Patients with Depression

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Antidepressants for the Treatment of Insomnia in Patients with Depression

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