Atypical antipsychotics for insomnia: a systematic review

Sleep Med. 2016 Jun;22:13-17. doi: 10.1016/j.sleep.2016.04.003. Epub 2016 May 11.


Background: Observational evidence suggests that atypical antipsychotics such as quetiapine are increasingly being used to manage insomnia. This is concerning given the uncertain efficacy and potential adverse effects associated with these medications.

Objectives: The objectives of this study are to evaluate the benefits and adverse effects of atypical antipsychotics used specifically for insomnia.

Methods: The methods used in this study are systematic review and narrative synthesis.

Data sources: The data were collected from PubMed; EMBASE; Cochrane Library; PsycINFO; grey literature; and the manufacturers of risperidone, quetiapine and olanzapine.

Participants and interventions: Adult patients ≥18 years of age using atypical antipsychotics specifically for primary or co-morbid insomnia for ≥ 1 week were compared to those receiving active intervention or placebo.

Appraisal and synthesis methods: Two independent reviewers screened titles, abstracts and full-text articles; extracted data; and conducted risk-of-bias analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was completed.

Results: One double-blind randomized controlled trial (n = 13) met the eligibility criteria. Statistically significant differences were not observed from baseline between quetiapine and placebo after 2 weeks for primary insomnia in terms of total sleep time (mean difference (MD) 52.68 min, 95% CI -27.27 to 132.6), reduction in sleep latency (MD 72.44 min, 95% CI -2.65 to 147.5) or improved sleep satisfaction measured with a visual analogue scale out of 100 (MD 6.16, 95% CI -12.32 to 24.64), despite a trend towards improved sleep parameters. The study was rated as very low quality.

Conclusions and implications: Very low quality evidence suggests that quetiapine does not significantly improve sleep parameters compared with placebo in primary insomnia, despite a trend towards clinical improvements. Atypical antipsychotics should be avoided in the first-line treatment of primary insomnia until further evidence is available.

Keywords: Antipsychotic agents; Insomnia; Off-label use; Sleep initiation and maintenance disorders.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Humans
  • Quetiapine Fumarate / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sleep Initiation and Maintenance Disorders / drug therapy*


  • Antipsychotic Agents
  • Quetiapine Fumarate