Quetiapine for Sleep: Not Recommended
Quetiapine should not be prescribed off-label for insomnia due to insufficient evidence of efficacy and significant safety concerns, including increased mortality, dementia, and falls in older adults, with no established therapeutic role outside of psychiatric comorbidities. 1, 2
Guideline-Based Recommendations Against Use
The strongest clinical practice guidelines explicitly advise against quetiapine for insomnia:
The 2020 VA/DoD guidelines strongly recommend against antipsychotics, including quetiapine, for chronic insomnia disorder. The evidence supporting quetiapine use is sparse with small sample sizes and short treatment durations, making efficacy determinations inconclusive. 1
All antipsychotics, including low-dose quetiapine, carry known harms including increased risk for death in elderly populations with dementia-related psychosis and increased suicidal tendencies in younger populations. 1
The 2008 American Academy of Sleep Medicine guidelines categorize quetiapine under "Other prescription drugs" with insufficient evidence for chronic primary insomnia, warranting avoidance of off-label administration given weak efficacy evidence and potential for significant side effects (neurological effects, weight gain, dysmetabolism). 1
Safety Concerns Outweigh Any Potential Benefits
Recent high-quality research demonstrates serious safety risks even at low doses:
A 2025 retrospective cohort study of older adults (≥65 years) found low-dose quetiapine significantly increased mortality risk (HR 3.1) compared to trazodone, along with increased dementia risk (HR 8.1 vs trazodone, HR 7.1 vs mirtazapine) and falls (HR 2.8 vs trazodone). 2
A 2012 safety review concluded that use of low-dose quetiapine for insomnia is not recommended based on limited data showing weight gain, fatal hepatotoxicity, restless legs syndrome, akathisia, and metabolic adverse events. 3
A 2013 systematic review found insufficient scientific evidence to justify off-label prescribing of low-dose quetiapine for sleeping disorders, with potentially severe adverse effects even at low doses. 4
Limited Efficacy Data
While a 2023 meta-analysis showed some improvement in sleep quality (SMD: -0.57), critical limitations undermine clinical applicability:
Effects were demonstrated primarily in patients with generalized anxiety disorder or major depressive disorder, not primary insomnia. 5
Adverse events and discontinuation due to adverse events were common among quetiapine users. 5
The 2009 review concluded that current data do not support quetiapine as first-line treatment for sleep complications, noting uncertain clinical significance of improvements and concerning adverse effects including periodic leg movements, akathisia, and metabolic complications. 6
Preferred Alternatives for Insomnia
First-line treatment should be cognitive behavioral therapy for insomnia (CBT-I), with proven effectiveness in improving sleep outcomes. 7
When pharmacotherapy is necessary after behavioral interventions:
Preferred options include trazodone 25-100 mg at bedtime, zolpidem 5 mg at bedtime, or mirtazapine 7.5-30 mg at bedtime. 7
For older adults specifically, doxepin is recommended with moderate-quality evidence, or low-dose eszopiclone/zolpidem with caution. 7
Benzodiazepine receptor agonists (eszopiclone, zolpidem, zaleplon) should be used at the lowest effective dose for the shortest duration. 1
Critical Clinical Pitfalls
Never prescribe quetiapine as first-line therapy for primary insomnia given the lack of FDA approval, insufficient efficacy evidence, and documented safety risks. 1
Avoid quetiapine in older adults for insomnia due to significantly elevated risks of mortality, dementia, and falls compared to safer alternatives like trazodone or mirtazapine. 2
Do not assume low doses are safe—metabolic complications, weight gain, and serious adverse events occur even at subtherapeutic doses (25-200 mg/day). 3, 4
The Only Potential Exception
Quetiapine may have a limited role in patients with established psychiatric disorders (bipolar disorder, schizophrenia) who have insomnia that has not responded to primary or secondary treatments, where the drug is being used at therapeutic doses for the underlying psychiatric condition and sleep improvement is a secondary benefit. 6 However, this represents treatment of the psychiatric disorder, not off-label use for primary insomnia.