What is the role of Seroquel (quetiapine) augmentation in treating patients with depression and obsessive-compulsive disorder (OCD) who have not responded to sertraline alone?

Quetiapine Augmentation for Sertraline-Resistant Depression and OCD

Quetiapine is NOT a first-line augmentation strategy for treatment-resistant OCD, as risperidone and aripiprazole have the strongest evidence for efficacy in SSRI-resistant OCD, with approximately one-third of patients showing clinically meaningful response to antipsychotic augmentation. 1

Primary Recommendation: Use Evidence-Based Antipsychotics First

• Risperidone and aripiprazole should be prioritized over quetiapine for augmentation of sertraline in treatment-resistant OCD, as these agents have the strongest evidence base according to current guidelines 1
• Approximately 50% of OCD patients fail to fully respond to first-line SSRI treatments, making augmentation strategies necessary 1, 2
• Before considering any antipsychotic augmentation, ensure sertraline has been trialed at maximum tolerated doses for at least 8-12 weeks 1, 2

When Quetiapine May Be Considered

If risperidone or aripiprazole are contraindicated or not tolerated, quetiapine can be considered as an alternative augmentation strategy, though the evidence is less robust:

• Open-label studies show approximately 50% response rates when quetiapine (25-200 mg/day) is added to SSRIs in treatment-resistant OCD patients 3, 4
• One small open-label study (n=10) demonstrated 70% response rate with mean YBOCS score reduction of 35.4% after 8 weeks of quetiapine augmentation 4
• A 6-month follow-up case series showed sustained improvement in patients who initially responded to quetiapine augmentation 5

Dosing Strategy for Quetiapine Augmentation

• Start at 25 mg/day and titrate up to 200-600 mg/day based on response and tolerability 5, 4, 6
• Most studies used doses in the 200-600 mg range for optimal effect 6, 7
• Allow at least 4-8 weeks to assess response, though some patients may show improvement within 4 weeks 3, 4

Critical Monitoring Requirements

• Monitor for metabolic side effects including weight gain, blood glucose, and lipid profiles when using any antipsychotic augmentation 1
• Assess for extrapyramidal symptoms, though quetiapine has relatively low risk 6
• Watch for sedation, orthostatic hypotension, and constipation, which are the most common side effects 7
• Screen for signs of serotonin syndrome when combining serotonergic medications 1

Alternative Strategies to Consider First

Before resorting to quetiapine augmentation, consider these evidence-based alternatives:

• Adding CBT with Exposure and Response Prevention (ERP) to pharmacotherapy has shown larger effect sizes compared to antipsychotic augmentation 1
• N-acetylcysteine has the strongest evidence among glutamatergic agents, with three out of five RCTs showing superiority to placebo 1
• Switching to clomipramine for severe, treatment-resistant OCD after SSRI failure 1
• Switching to a different SSRI or SNRI if augmentation strategies fail 2

Treatment Duration

• Maintain treatment for a minimum of 12-24 months after achieving remission due to high relapse rates after discontinuation 1, 2
• Patients who respond to quetiapine augmentation in the acute phase tend to maintain improvement over 6 months 5

Important Caveats

• The evidence for quetiapine specifically in OCD consists primarily of small open-label studies and case series, not large controlled trials 5, 3, 4
• Published controlled trials of quetiapine augmentation in OCD have shown mixed results 5
• For depression alone, quetiapine augmentation shows more robust evidence with remission rates of 67% at week 1 and 94% at week 6 6
• The combination of bipolar depression with comorbid OCD may respond better to quetiapine than unipolar depression with OCD 7