Trazodone Improves Sleep Parameters in Alzheimer Disease Patients: A Randomized, Double-Blind, and Placebo-Controlled Study

doi:10.1016/j.jagp.2013.12.174

The American Journal of Geriatric Psychiatry

Volume 22, Issue 12, December 2014, Pages 1565-1574

https://doi.org/10.1016/j.jagp.2013.12.174 Get rights and content

Objectives

There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances (SD) in patients with Alzheimer disease (AD). We tested the efficacy and safety of trazodone to treat SD in patients with AD.

Design

We conducted a double-blind, randomized and controlled trial during periods of 7–9 days at baseline and 2 weeks of treatment.

Setting

Geriatric medical center of the university's general hospital.

Participants

Individuals with probable AD and SD. The complete analysis comprised 30 patients assigned to either the active treatment group (N = 15) or the placebo group (N = 15).

Intervention

Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks.

Measurements

Patients were evaluated using actigraphy and structured scales before and after intervention.

Results

Compared with the placebo group, trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment. Neither trazodone nor placebo induced significant daytime sleepiness or naps. The treatments with trazodone or placebo did not show any effects either on cognition (Mini-Mental State Examination, forward/backward digit span task, letter-number sequencing, arithmetic, digit symbol-coding, and symbol search) or functionality (Katz index). There were no differences in frequency or severity rating of adverse events between the groups.

Conclusions

This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD.

Section snippets

Trial Design

This trial incorporated two phases over a period of 7–9 days at baseline and for 2 weeks during treatment, when the patients were randomized to study drug. Patients received 50 mg of trazodone once daily at 10:00 P.M., contrasted with placebo in a 1:1 ratio. Based on a previous observational study, our primary hypothesis was that trazodone would improve sleep parameters in patients with AD who were diagnosed with sleep disturbance.⁹ Our secondary hypotheses were that trazodone would be safe and

Patients

Forty-seven subjects diagnosed with AD and sleep disorders were enrolled in the study. Thirty-six of these participants met the inclusion criteria and were randomized to either the active treatment group (N = 19) or the placebo counterpart (N = 17). Figure 1 shows the CONSORT flow chart. After allocation and randomization, one subject from the trazodone group was excluded because of failure in using antihypertensive and antiarrhythmic drugs and, thus, evolving into heart failure. One patient of

Discussion

This is the first double-blind, placebo-controlled study of trazodone in AD patients with sleep disorders. Our results suggest benefits for the use of trazodone 50 mg in these patients without any significant impact on daily sleepiness, cognitive performance, or AEs.

Trazodone is considered a multifunctional drug with dose-dependent pharmacologic actions.²⁵ It is a triazolopyridine derivative of a phenylpiperazine antidepressant that has a dual action on serotonin receptors, blocking

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Regular Research ArticleTrazodone Improves Sleep Parameters in Alzheimer Disease Patients: A Randomized, Double-Blind, and Placebo-Controlled Study

Objectives

Design

Setting

Participants

Intervention

Measurements

Results

Conclusions

Section snippets

Trial Design

Patients

Discussion

Sleep Med Rev

J Psychiatr Res

Biol Psychiatry

Pharmacol Biochem Behav

Sleep Med

Prog Neuropsychopharmacol Biol Psychiatry

Am J Geriatr Psychiatry

Sleep disturbances in patients with Alzheimer's disease: epidemiology, pathophysiology and treatment

CNS Drugs

Predictors of institutionalization for people with dementia living at home with a carer

Int J Geriatr Psychiatry

Sleep in non-institutionalized Alzheimer's disease patients

Aging (Milano)

Increasing walking and bright light exposure to improve sleep in community-dwelling persons with Alzheimer's disease: results of a randomized, controlled trial

J Am Geriatr Soc

Nighttime insomnia treatment and education for Alzheimer's disease: a randomized, controlled trial

J Am Geriatr Soc

Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits

BMJ

Mianserin for the treatment of sleep disorders in patients with dementia: a retrospective open-label study

J Clin Psychopharmacol

Trazodone for the treatment of sleep disorders in dementia: an open-label, observational and review study

Arq Neuropsiquiatr

Conference statement on manifestations and management of chronic insomnia in adults, June 13–15, 2005

Sleep

Regular Research Article
Trazodone Improves Sleep Parameters in Alzheimer Disease Patients: A Randomized, Double-Blind, and Placebo-Controlled Study