What medication should be added to sertraline (Selective Serotonin Reuptake Inhibitor) 300mg daily for a patient with Obsessive-Compulsive Disorder (OCD) experiencing mild ongoing intrusive thoughts?

Augmentation Strategy for Treatment-Resistant OCD on Sertraline 300mg

Add cognitive-behavioral therapy with exposure and response prevention (EX/RP) as the first-line augmentation strategy, as it demonstrates superior efficacy compared to antipsychotic augmentation and has a more favorable adverse effect profile. 1

Primary Recommendation: CBT with Exposure and Response Prevention

• CBT with EX/RP added to ongoing SSRI therapy achieved an 80% response rate compared to only 23% with risperidone augmentation and 15% with placebo in a head-to-head randomized controlled trial 1
• EX/RP augmentation resulted in significantly greater Y-BOCS score reduction (mean reduction of 9.72 points more than risperidone) and 43% of patients achieved minimal symptoms versus only 13% with risperidone 1
• Meta-analyses confirm that adding CBT to pharmacotherapy produces larger effect sizes compared to antipsychotic augmentation alone 2
• The treatment protocol consists of 17 sessions delivered twice weekly over 8 weeks while continuing the current SSRI dose 1

If CBT is Not Accessible: Antipsychotic Augmentation

First-Choice Antipsychotics

• Risperidone or aripiprazole have the strongest evidence for efficacy in SSRI-resistant OCD according to systematic reviews 2, 3
• Risperidone at low doses (mean 2.2 mg/day, range up to 4 mg/day) achieved 50% response rates in placebo-controlled trials, compared to 0% with placebo 4
• Approximately one-third of patients with SSRI-resistant OCD show clinically meaningful response to antipsychotic augmentation 2

Dosing and Monitoring for Antipsychotics

• Start risperidone at 0.5-1 mg daily and titrate slowly to 2-4 mg/day over several weeks based on tolerability 4
• Monitor metabolic parameters including weight, fasting glucose, and lipid profiles due to metabolic side effect risks 2
• Common side effects include mild sedation (usually transient), extrapyramidal symptoms, and increased appetite 5

Alternative Glutamatergic Augmentation Strategies

N-Acetylcysteine (NAC)

• NAC has the strongest evidence among glutamatergic agents, with three out of five randomized controlled trials showing superiority to placebo 2
• NAC can be considered as an augmentation option, particularly if patients decline antipsychotics or have contraindications 2
• The safety profile is favorable with minimal drug interactions 2

Memantine

• Memantine has demonstrated efficacy in several trials and represents a third-line augmentation option after optimizing SSRI therapy and considering antipsychotics or NAC 6
• Consider memantine as an alternative glutamatergic agent with an established safety profile, though evidence is more mixed than for NAC 6

Important Clinical Considerations

Confirm Adequate SSRI Trial First

• Ensure the patient has been on sertraline 300mg for at least 8-12 weeks with confirmed adherence before adding augmentation 2
• Sertraline 300mg represents an adequate high-dose trial for OCD, as higher SSRI doses are typically required for OCD than for depression or other anxiety disorders 2

Treatment Duration

• Maintain treatment for at least 12-24 months after achieving remission due to high relapse rates after discontinuation 2
• Full therapeutic effects may not be apparent until 12 weeks or longer of combined treatment 7

Safety Monitoring

• Monitor for serotonin syndrome when combining serotonergic agents, particularly if considering multiple augmentation strategies simultaneously 7, 2
• Watch for symptoms including agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity, or hyperthermia 2
• Be aware that sertraline has been associated with discontinuation syndrome, so any future medication changes should involve gradual tapering 7

Treatment Algorithm Summary

1. First-line augmentation: Add CBT with EX/RP (17 sessions over 8 weeks) 1
2. If CBT unavailable or declined: Add risperidone 2-4 mg/day or aripiprazole 2, 4
3. Alternative augmentation: Consider NAC if antipsychotics are declined or contraindicated 2
4. Third-line options: Memantine or switching to clomipramine if multiple augmentation strategies fail 6, 2

Common Pitfall to Avoid

• Do not add antipsychotics before ensuring adequate SSRI trial duration and dose - many clinicians prematurely augment before allowing sufficient time (8-12 weeks minimum) at maximum tolerated SSRI doses 2
• Do not overlook CBT as first-line augmentation - the evidence clearly demonstrates superior efficacy over medication augmentation with fewer adverse effects 1