How Quetiapine (Seroquel) Affects Sleep: A Review of Latest Research

Quick Summary

• Quetiapine (brand name Seroquel), an atypical antipsychotic, significantly improves sleep quality in patients with generalized anxiety disorder (GAD), major depressive disorder (MDD), and even in healthy adults.

• Effective doses for sleep improvement range from 50 mg to 300 mg per day, with no clear dose-response relationship.

• Quetiapine increases total sleep time compared to placebo but shows no advantage over other psychiatric medications.

• Adverse effects are common with quetiapine use, warranting cautious prescribing, especially in elderly patients.

• Older age and male sex are associated with better sleep quality responses to quetiapine.

Quetiapine (Seroquel) And Sleep

If you're struggling with sleep, you might have heard about quetiapine (also known by brand name Seroquel) being prescribed as a sleep aid. 

Despite becoming an increasingly common choice among medical practitioners, you might be surprised to find that Quetiapine isn’t “officially approved” for sleep problems like insomnia, so it’s prescribed “off label” (meaning it’s being used for a condition it wasn’t originally approved to treat, an “unofficial” use). 

The problem with this usage is that there hasn’t been a lot of research about whether quetiapine actually works for sleep and insomnia, who might it work best for, and what are the risks? 

Noting this situation, a recent systematic review and meta-analysis published in the European Neuropsychopharmacology journal by Lin and colleagues (2023) examined the effects of quetiapine on sleep across different conditions and dosages.

So let's break down what the researchers found and what it might mean for people with sleep problems.

First, a bit of background.

What Exactly Is Quetiapine (Seroquel)? 

Quetiapine is an atypical antipsychotic with approved use by the FDA for schizophrenia, acute manic episodes, and as adjunct therapy for major depressive disorder (Maan et al., 2022).

It is prescribed at different dose ranges depending on the indication: typically 400–800 mg/day for schizophrenia and 150–300 mg/day for depression.

So why is an anti-psychotic being used for sleep then?

Why Is Quetiapine (Seroquel) Used for Sleep?

At lower doses, quetiapine (Seroquel) strongly blocks histamine H1 and serotonin 5-HT2C receptors, producing sedative effects that can make people feel drowsy which can help with sleep (Stahl, 2021).

This sedative property has made quetiapine a popular off-label choice for insomnia, especially in patients with co-occurring mental health conditions (psychiatric comorbidities) such as anxiety or depression. 

So how “popular” is prescribing quetiapine like this?

Is Quetiapine (Seroquel) Commonly Prescribed For Sleep?

Despite not being officially approved for insomnia, quetiapine (Seroquel) has become one of the most commonly prescribed off-label medications for sleep problems. This off-label use has increased notably over the past two decades (Kelly et al., 2018).

Okay, so what does the actual evidence say about whether this drug helps or not?

How Did The Researchers Investigate Quetiapine’s Effect on Sleep?

Lin et al., 2023 conducted a systematic review and meta-analysis. This is a powerful type of study where scientists gather all the high-quality individual studies on a topic and then statistically pool the data together. This process gives a more reliable and comprehensive result than any single study could.

The team identified 21 relevant clinical trials to include in their analysis. Nineteen of these were randomized controlled trials, which are the gold standard in medical research.

The studies covered adults with various health conditions, including:
- Generalized Anxiety Disorder (GAD),
- Major Depressive Disorder (MDD or “depression”)
- Fibromyalgia, and
- healthy volunteers. 

To focus specifically on its sleep-helping effects rather than antipsychotic effects, the researchers only included trials that used low-dose quetiapine (a dose of 300 mg or less). The primary outcome they measured was the change in sleep quality.

Sleep quality was the primary outcome, assessed mainly by the Pittsburgh Sleep Quality Index (PSQI) and other validated tools. Secondary outcomes included total sleep time, anxiety, depression, and adverse effects.

What did the researchers find?

Does Quetiapine (Seroquel) Help Sleep Across Different Mental Health and Physical Health Conditions?

Subgroup analyses by Lin et al’s (2023) revealed that quetiapine improved sleep quality in:

• Generalized Anxiety Disorder (GAD);

• Major Depressive Disorder (MDD);

• Healthy adults

The findings suggest that quetiapine is particularly effective when poor sleep is a co-occurring condition in addition to an anxiety or depressive disorder. In fact, the most consistent positive responses were seen in patients with GAD and MDD. 

The results were less clear for other conditions. 

• A single trial on patients with fibromyalgia showed an improvement in sleep quality, but 

• A single trial looking at primary insomnia (insomnia with no known underlying cause) found no significant benefit.

Does Quetiapine (Seroquel) Improve Sleep Quality?

Yes. The pooled results from Lin et al’s (2023) analysis of 21 studies showed that quetiapine significantly improved sleep quality compared with placebo, a "dummy" pill with no active ingredient. 

The effect size was “moderate” which means that if a person experiences a change from taking quetiapine, it will probably make a meaningful difference.

Does Quetiapine (Seroquel) Help You Sleep for Longer?

Yes, quetiapine (Seroquel) increased total sleep time by an average of about 48 minutes compared with placebo (mean difference 47.91 minutes; 95% CI: 28.06 to 67.76). These measurements were taken using objective methods like polysomnography (a clinical sleep study) and actigraphy (a wrist-worn device), as well as sleep logs (Lin et al., 2023).

However, when compared to other psychiatric drugs such as haloperidol or mirtazapine, quetiapine did not show a significant advantage (MD: -4.19 minutes; 95% CI: -19.43 to 11.05) (Lin et al., 2023).

Okay, so that’s the impact on sleep. What doses are required to get these effects?

What Dose of Quetiapine (Seroquel) Is Effective for Sleep?

Quetiapine improved sleep quality significantly at doses of

• 50 mg/day, 150 mg/day, and 300 mg/day, 

• A 25 mg dose, however, did not show a statistically significant improvement.

Interestingly, no clear dose-response relationship was observed, meaning a higher dose didn’t necessarily lead to a greater improvement in sleep.

Based on the evidence, the study authors concluded that moderate doses (50–150 mg/day) may be sufficient to achieve sleep benefits while potentially minimizing side effects (Lin et al., 2023).

Who Seems to Respond Best to Quetiapine (Seroquel) for Sleep?

To look for factors that might influence how well the drug works, the researchers performed a meta-regression. This statistical technique looks for relationships between study characteristics and the outcomes. They found that two factors that had a bigger improvement in sleep quality scores: Age and Sex

How Does Age Affect Quetiapine’s (Seroquel) Sleep Benefits?

Lin et al (2023) found that studies with older participants tended to show a greater improvement in sleep quality

The researchers noted that excluding the two trials that focused on elderly patients dramatically reduced the variation between studies, suggesting the elderly might respond better than younger adults.

Does Sex Influence Quetiapine’s (Seroquel) Effect on Sleep?

Male sex was also linked to better sleep quality responses to quetiapine (Lin et al., 2023).

The underlying reasons why males responded better are unclear and the study authors note it may involve age-related hormonal changes affecting drug metabolism (Castberg et al., 2017; Dziurkowska & Wesołowski, 2020). 

What Are the Effects of Quetiapine (Seroquel) on Anxiety and Depression?

Quetiapine treatment was associated with significant reductions in anxiety and depression scores compared to placebo. 

In patients with MDD, improvements were noted in anxiety and clinical severity scales, although depression rating scales showed mixed results.

This suggests quetiapine’s anxiolytic and antidepressant properties may contribute to its sleep-enhancing effects (Lin et al., 2023).

So that’s the good stuff. What about the bad stuff?

What Are the Risks and Side Effects of Quetiapine (Seroquel) For Sleep?

Lin et al (2023) found that adverse effects (AEs) were common among quetiapine (Seroquel) users in the studies they investigated and led to higher discontinuation rates compared with placebo. 

This is the most significant caution raised by the study. The benefits of quetiapine for sleep do not come without risks. 

Reported side effects included:

- Weight gain

- Increased triglyceride levels

- Daytime drowsiness

- Dizziness

- Dry mouth

- Headache

In one long-term study of quetiapine in GAD patients, 86.9% of participants experienced side effects, and 19.4% stopped treatment because of them (Katzman et al., 2011).

This risk of metabolic side effects is so well-known that some researchers and official guidelines warn against prescribing quetiapine for insomnia unless the patient also has a specific comorbid psychiatric disorder (Anderson & Vande Griend, 2014; Modesto-Lowe et al., 2021).

What Practical Advice Can Be Drawn for Clinicians and Patients?

The research suggests that quetiapine (Seroquel) might be helpful for sleep, but it's not an approved first-line treatment for insomnia and shouldn’t be prescribed for those without other psychiatric conditions. This study found no benefit for primary insomnia patients without a co-occurring mental health condition.

What is the first line recommended treatment for chronic insomnia? The first line treatment is CBT for insomnia, also known as CBT-i.

The FDA has approved several other medications specifically for sleep, and these are second-line recommendations for insomnia, after CBT-i. These include:

• Benzodiazepine receptor agonists

• Orexin receptor antagonists

• Melatonin receptor agonists

• Histamine receptor antagonists

These approved sleep medications come with their own potential issues, including daytime drowsiness, fatigue, tolerance, rebound insomnia after stopping, and cognitive effects. Some also carry risks of misuse and dependence.

So the decision to use quetiapine for sleep should be made carefully, weighing potential benefits against risks, and considering whether you have other conditions (like anxiety or depression) that might also respond to the medication.

If you are considering quetiapine (seroquel) then, breaking it down, according to Lin et al (2023): 

• Quetiapine at doses between 50 and 150 mg/day can improve sleep quality in patients with anxiety, depression, and even healthy individuals experiencing sleep difficulties.

• Older adults and males may experience more pronounced benefits.

• Total sleep time may increase by up to 48 minutes compared to placebo.

• Side effects are common and can affect treatment adherence; metabolic monitoring is essential.

• Start with the lowest effective dose and carefully weigh the benefits against potential risks.

• Quetiapine should not be considered a first-line treatment for primary insomnia without psychiatric comorbidity due to safety concerns.

• Continuous evaluation and patient education about side effects and risks of misuse are critical.

Clinical Comment

This study by Lin and colleagues (2023) suggests that quetiapine, at doses below those used for schizophrenia or manic episodes, can offer a potential option for improving sleep quality in insomnia patients, especially those co-occurring mental health conditions such as generalized anxiety disorder, major depressive disorder. Given how common it is to see GAD, in particular, with insomnia this is worth noting.

Lin et al’s (2023) findings suggest the sedative effects of quetiapine could result in better subjective sleep and increased total sleep time compared to placebo. This is generally what we hear from patients that we work with that have been prescribed quetiapine (however, we do note that while “increased total sleep” can be perceived by patients as “good”, extending sleep beyond typical sleep lengths can create issues with discontinuation or “coming off” quetiapine (but see our comment on tapering below).

People should pay careful attention to the risk of adverse effects, particularly metabolic change, prescribers and patients should be cautious and there should be vigilant monitoring when it is used. 

The evidence supports starting quetiapine at 50 to 150 mg/day, especially in elderly patients with anxiety or depression and potentially males.
In the clinic, we tend to see quetiapine prescribed to females, including pregnant and breast-feeding mums (evidence suggests quetiapine may be safer than traditional sleeping medications for these populations). Unlike this research, we see doses starting at around 25mg being effective, and rarely see doses more than 50mg. 

The good news is, we have had good success combining CBT for insomnia with a taper plan for patients on quetiapine. This has included long term users (up to 20yrs of nightly use) and with minimal rebound insomnia. A key issue with quetiapine is that, as noted in the study, it can result in sleep extension beyond typical sleep, which can give patients unrealistic expectations of what normal sleep is really like.

Frequently Asked Questions - Quetiapine (Seroquel) and Sleep

Q1: What is quetiapine (seroquel) and why is it sometimes used for sleep?

A1: Quetiapine is an antipsychotic medication that is FDA-approved for conditions like schizophrenia and major depressive disorder at higher doses. However, at lower doses, it significantly occupies receptors in the brain (H1 and 5-HT2C) that induce sedative effects (Lin et al., 2023).

Because of these sedating properties, quetiapine has become a common "off-label" choice for treating insomnia, especially when insomnia occurs alongside other conditions like anxiety or depression.

Q2: Does quetiapine (seroquel) actually help improve sleep quality?

A2: Yes, based on a systematic review and meta-analysis of clinical trials by Lin et al (2023), quetiapine treatment showed a significant improvement in sleep quality when compared to a placebo. This effect was observed across different groups, including those with generalized anxiety disorder (GAD), major depressive disorder (MDD), and even healthy subjects. However, the only study of those with

Q3: Can quetiapine (seroquel) help you sleep longer?

A3: A systematic review and meta-analysis by Lin et al (2023) indicated that quetiapine treatment significantly increased total sleep time compared to a placebo (approximately 47mins). However, when compared to other psychiatric medications, no significant difference in total sleep time was found.

Q4: What dosage of quetiapine (seroquel) is effective for sleep?

A4: The systematic review and meta-analysis by Lin et al (2023) suggests that quetiapine treatment showed significant improvement in sleep quality at dosages of 50 mg/day, 150 mg/day, and 300 mg/day. The 25 mg/day dose did not show a statistically significant improvement in sleep quality in this analysis. Interestingly, the study found no clear dose-response pattern within the effective range (50-300 mg/day).

Q5: Does quetiapine (seroquel) work the same way for sleep in everyone?

A5: The effectiveness of quetiapine for sleep can vary. A systematic review and meta-analysis by Lin et al (2023) found significant improvements in sleep quality in subgroups with generalized anxiety disorder (GAD), major depressive disorder (MDD), and healthy subjects. Patients with GAD and MDD seemed to respond more consistently than those with other primary health problems or healthy subjects, possibly because insomnia is often linked to these conditions. A single study of those with insomnia only found no improvement in sleep.

Q6: Are there side effects when using quetiapine (seroquel) for sleep?

A6: Yes, a systematic review and meta-analysis by Lin et al (2023) found adverse events (AEs) and discontinuing treatment due to AEs were found to be common among quetiapine users compared to placebo. The pooled results showed an increased risk of most reported AEs.

Q7: Is quetiapine (seroquel) safe for long-term use for insomnia?

A7: A systematic review and meta-analysis by Lin et al (2023) found that trials and studies observing the long-term efficacy, safety, and adverse effects of quetiapine treatment for insomnia in the general population are limited. Therefore, quetiapine should be used cautiously for primary insomnia, with appropriate monitoring for potential adverse effects and the risk of abuse. More studies with longer follow-up periods are needed to fully understand the long-term effects.

Q8: Does age or sex influence how well quetiapine (seroquel) works for sleep?

A8: A systematic review and meta-analysis by Lin et al (2023) found that older age and male sex were correlated with better responses to quetiapine for sleep quality. However, the mechanisms behind this are likely complex and involve interacting biochemical pathways related to sex and aging. More research is needed to fully clarify these observations.

Q9: What is a recommended starting dose for quetiapine (seroquel) when used for sleep?

A9: A systematic review and meta-analysis by Lin et al (2023) suggested a starting dosage range of 50-150 mg/day may be considered for sleep, particularly for patients with generalized anxiety disorder (GAD) or major depressive disorder (MDD). It is crucial to monitor for potential adverse events when initiating treatment.

References

Anderson, S. L., & Vande Griend, J. P. (2014). Quetiapine for insomnia: a review of the literature. American Journal of Health-System Pharmacy, 71(5), 394–402.

Castberg, I., Westin, A. A., Skogvoll, E., & Spigset, O. (2017). Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine. Acta Psychiatrica Scandinavica, 136(5), 455–464.

Dubath, C., et al. (2021). Effect of quetiapine, from low to high dose, on weight and metabolic traits: results from a prospective cohort study. Pharmacopsychiatry, 54(6), 279–286.

Dziurkowska, E., & Wesołowski, M. (2020). Effects of age, drug dose, and sampling time on salivary levels of olanzapine, quetiapine, and their metabolites. Journal of Clinical Medicine, 9(10), 3288.

Kelly, M., Dornan, T., & Pringsheim, T. (2018). The lesser of two evils: a qualitative study of quetiapine prescribing by family physicians. CMAJ Open, 6(2), E191–E196.

Lin, C.-Y., Chiang, C.-H., Tseng, M.-C. M., Tam, K.-W., Loh, E.-W., et al. (2023). Effects of quetiapine on sleep: A systematic review and meta-analysis of clinical trials. European Neuropsychopharmacology, 67, 22–36.

Maan, J. S., Ershadi, M., Khan, I., & Saadabadi, A. (2022). Quetiapine. In StatPearls. StatPearls Publishing.

Modesto-Lowe, V., Harabasz, A. K., & Walker, S. A. (2021). Quetiapine for primary insomnia: consider the risks. Cleveland Clinic Journal of Medicine, 88(5), 286–294.

Stahl, S. M. (2021). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (5th ed.). Cambridge University Press.

Vázquez-Bourgon, J., et al. (2018). Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis. Psychopharmacology, 235(1), 245–255.

Wine, J. N., Sanda, C., & Caballero, J. (2009). Effects of quetiapine on sleep in nonpsychiatric and psychiatric conditions. Annals of Pharmacotherapy, 43(5), 707–713.

Written By The Better Sleep Clinic

Reviewed By Dan Ford, Sleep Psychologist