By H.R. Christopher O’Brien, PharmD, BCPP, APP
Program Director, In-Home Psychiatric Services
Seroquel (quetiapine) is one of the most frequently prescribed antipsychotics in psychiatric care. Originally approved for schizophrenia, its indications have expanded over time to include bipolar disorder and adjunctive treatment for major depression. It is also used off-label for sleep disturbances, agitation, and behavioral symptoms in dementia. While it has a favorable tolerability profile and unique antidepressant properties, concerns persist about overuse, sedation, and metabolic risks, particularly in vulnerable populations.
Schizophrenia
Seroquel is FDA-approved for treating schizophrenia in adults and adolescents aged 13–17. It has a lower risk of extrapyramidal symptoms (EPS) than typical antipsychotics, making it appealing for patients who are sensitive to motor side effects. However, it requires higher doses for antipsychotic efficacy (typically 400–800 mg/day), and is less potent than agents like risperidone or olanzapine. Sedation and orthostatic hypotension are common during initiation (Citrome, 2007).
Bipolar Disorder
Quetiapine is approved for both manic and depressive episodes in bipolar I disorder and for maintenance therapy when combined with a mood stabilizer. Its ability to treat bipolar depression is a key advantage, setting it apart from many antipsychotics. Still, it carries a high burden of metabolic side effects and sedation compared to alternatives like aripiprazole (Suppes et al., 2010).
Major Depressive Disorder (Adjunctive)
As an adjunct to antidepressants, quetiapine has shown benefit in treatment-resistant major depressive disorder (MDD), especially for patients with insomnia or anxiety. Effective at low doses (50–300 mg), it offers anxiolytic and sleep-promoting effects. However, these benefits must be weighed against side effects like weight gain, sedation, and lipid/glucose disturbances (Bauer et al., 2009).
Autism Spectrum Disorder (ASD)
Though not FDA-approved for ASD, Seroquel is used off-label to address irritability and aggression. It tends to be more sedating than risperidone or aripiprazole (both FDA-approved for ASD-related irritability), and may be preferred in patients who also have sleep difficulties. However, data supporting its use is limited, and weight gain and sedation are common (Aman et al., 2005).
Intermittent Explosive Disorder (IED)
Seroquel has been prescribed off-label for IED, particularly in patients who do not respond to SSRIs or who present with comorbid mood symptoms. Its calming effects may reduce impulsive aggression, though evidence is anecdotal and SSRIs remain first-line. Long-term use requires monitoring due to sedation and cardiometabolic concerns (Coccaro et al., 2015).
Sleep Disorders
One of the most common off-label uses of Seroquel is for insomnia, often at low doses (25–100 mg). Patients report faster sleep onset and reduced nighttime awakenings. However, using antipsychotics for primary insomnia is not guideline-supported and poses risks, especially long-term. Alternatives like melatonin, trazodone, or doxepin are preferred unless comorbid mood or psychotic disorders are present (Wiegand, 2008).
Dementia-Related Agitation
Despite an FDA black box warning for increased mortality in elderly patients with dementia-related psychosis, quetiapine remains a commonly used off-label option in long-term care settings. It may be preferred over risperidone or olanzapine in patients with Parkinsonism due to its lower EPS risk. Still, risks of sedation, falls, stroke, and cardiovascular events remain significant (Schneider et al., 2006).
Use Across Age Groups
- Pediatrics: Approved for adolescent schizophrenia and bipolar disorder, but carries risks of weight gain, sedation, and dyslipidemia. Off-label use in ASD or aggression should be closely monitored.
- Adults: Broadly used in mood and psychotic disorders. Monitoring is necessary due to cumulative metabolic risks and potential for misuse as a sedative.
- Elderly: Particularly vulnerable to orthostasis, cognitive dulling, and cardiovascular risks. Seroquel should be used cautiously and only when non-pharmacologic interventions fail.
Black Box Warnings
Seroquel carries multiple black box warnings:
- Increased mortality in elderly patients with dementia-related psychosis.
- Suicidality in children, adolescents, and young adults during antidepressant treatment.
- Risk of severe sedation and orthostatic hypotension, particularly during dose escalation or polypharmacy (FDA, 2023).
Laboratory Monitoring
Patients taking Seroquel should undergo routine monitoring to detect adverse effects:
- Baseline and periodic metabolic labs (glucose, lipids)
- Weight and BMI checks
- Blood pressure and heart rate assessments
- Annual eye exams (due to rare reports of cataracts) Monitoring should be more frequent in patients with cardiovascular risk factors, diabetes, or on long-term therapy (American Diabetes Association, 2004).
Pros and Cons Compared to Other Antipsychotics
| Feature | Seroquel | Risperidone | Aripiprazole | Olanzapine |
|---|---|---|---|---|
| EPS Risk | Low | Moderate-High | Low | Moderate |
| Sedation | High | Low-Moderate | Low | Moderate |
| Weight Gain | High | Moderate | Low | Very High |
| Prolactin Elevation | Low | High | Low | Low |
| Antidepressant Benefit | Yes | No | Partial | Partial |
| Approved for Bipolar Depression | Yes | No | No | Yes |
Conclusion
Seroquel remains a versatile antipsychotic with proven benefits in mood and psychotic disorders, and some practical off-label uses. However, its side effect profile—notably sedation, metabolic disruption, and fall risk—requires careful consideration. Clinicians should avoid defaulting to Seroquel for sleep or agitation when safer options exist and must apply individualized, evidence-informed prescribing.
References
Aman, M. G., et al. (2005). Risperidone treatment of children with autistic disorder: Long-term safety and effectiveness. Journal of the American Academy of Child & Adolescent Psychiatry, 44(11), 1137–1146.
American Diabetes Association. (2004). Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care, 27(2), 596–601.
Bauer, M., et al. (2009). Quetiapine monotherapy in bipolar depression: Combined analysis of two phase III trials. International Journal of Neuropsychopharmacology, 12(5), 647–662.
Citrome, L. (2007). Quetiapine for schizophrenia and bipolar disorder: A review of the literature. Expert Review of Neurotherapeutics, 7(7), 817–831.
Coccaro, E. F., et al. (2015). Intermittent explosive disorder: Clinical characteristics and pharmacologic treatment. Current Psychiatry Reports, 17(3), 7.
FDA. (2023). Seroquel (quetiapine fumarate) prescribing information. https://www.accessdata.fda.gov
Schneider, L. S., et al. (2006). Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. New England Journal of Medicine, 355(15), 1525–1538.
Suppes, T., et al. (2010). Quetiapine monotherapy for bipolar depression: A systematic review and meta-analysis. Bipolar Disorders, 12(4), 451–461.
Wiegand, M. H. (2008). Antipsychotics for primary insomnia? A review of the literature. Journal of Clinical Psychiatry, 69(9), 1448–1452.
