Is augmenting a Selective Serotonin Reuptake Inhibitor (SSRI) with a Second-Generation Antipsychotic (SGA) recommended for a patient with Obsessive-Compulsive Disorder (OCD) and a history of psychiatric illness who has shown a partial response to SSRI treatment?

Augmenting SSRI with SGA for Partial Response in OCD

Yes, augmenting an SSRI with a second-generation antipsychotic (SGA) is recommended for OCD patients with partial response, with risperidone and aripiprazole having the strongest evidence base. 1, 2

First Confirm Adequate SSRI Trial

Before adding an SGA, verify the patient has received:

• Maximum tolerated SSRI dose for 8-12 weeks minimum 1, 2, 3
• Higher doses are typically required for OCD than for depression or other anxiety disorders 1
• Some patients may benefit from trials extending beyond 12 weeks, as time on SSRI monotherapy (up to 6 months) is associated with better response 3

Prioritize CBT-ERP Before or Alongside SGA Augmentation

Adding Cognitive Behavioral Therapy with Exposure and Response Prevention (CBT-ERP) produces larger effect sizes than antipsychotic augmentation alone. 1, 2, 3 This can be delivered in-person, remotely via internet protocols, or in group format over 10-20 sessions. 3

Recommended SGA Augmentation Strategy

First-Line SGAs:

• Risperidone: Gold standard based on highest quality controlled trial data, demonstrating 50% response rates in SSRI-refractory OCD 2
• Aripiprazole: Equivalent first-line option with the advantage of lower metabolic side effects compared to risperidone 2

Dosing:

• Risperidone: median effective dose 1 mg/day 4
• Aripiprazole: median effective dose 3 mg/day 4

Set Realistic Expectations:

Only approximately one-third of SSRI-resistant OCD patients achieve clinically meaningful response to antipsychotic augmentation. 1, 2 This is lower than the response rate to initial SSRI therapy, so patients must understand the modest benefit. 2

Mandatory Monitoring Requirements

When using SGA augmentation, monitor at baseline and regularly throughout treatment: 1, 2

• Weight
• Blood glucose
• Lipid profiles
• Signs of extrapyramidal symptoms 5
• Sedation 5

Treatment Duration

Continue successful augmentation for 12-24 months after achieving remission due to high relapse rates upon discontinuation. 1, 2, 3

Alternative Augmentation Options if SGAs Declined or Ineffective

Glutamatergic Agents:

• N-acetylcysteine: Strongest evidence among glutamatergic agents, with three out of five RCTs showing superiority to placebo 1, 2
• Memantine: Demonstrated efficacy in several trials 1, 2

Switching Strategies:

• Consider switching to a different SSRI or clomipramine (more efficacious but more side effects) if augmentation fails 1, 3
• Never combine clomipramine with fluoxetine due to dangerous drug-drug interactions risking seizures, cardiac arrhythmias, and serotonin syndrome 2

Triple Combination for Severe Treatment-Resistant Cases

For patients who fail both SRI-SGA and SRI-CBT/ERP augmentation, combining SSRI + SGA + CBT/ERP shows promise, with 61% improvement, 46% partial response, 32% response, and 29% remission rates at 12 months. 4 This approach is easier to implement than advanced neuromodulation options. 4

Advanced Options for Highly Refractory Cases

If multiple medication trials and adequate CBT fail: 1, 3

• Deep repetitive transcranial magnetic stimulation (rTMS) - FDA approved for treatment-resistant OCD with moderate effect size (0.65) and 3-fold increased likelihood of response versus sham 1
• Intensive outpatient or residential treatment 3
• Deep brain stimulation only after failure of three serotonin reuptake inhibitors (including clomipramine), adequate CBT trial, and disease incapacitation 3

Critical Pitfall to Avoid

Monitor for serotonin syndrome when combining serotonergic medications, watching for agitation, confusion, rapid heart rate, dilated pupils, muscle rigidity, or hyperthermia. 1, 3 The risk is particularly elevated when switching or combining multiple serotonergic agents. 1