What is the best antipsychotic for augmentation in Obsessive-Compulsive Disorder (OCD)?

Best Antipsychotic for Augmentation in OCD

Risperidone and aripiprazole have the strongest evidence for efficacy in SSRI-resistant OCD, with risperidone being the most extensively studied and recommended as first-line antipsychotic augmentation. 1

Primary Recommendation: Risperidone or Aripiprazole

• The American College of Psychiatry identifies risperidone and aripiprazole as having the strongest evidence base for SSRI-resistant OCD. 1
• Meta-analyses confirm efficacy for both risperidone and aripiprazole augmentation, though other antipsychotics require additional study. 2
• Approximately one-third of patients with SSRI-resistant OCD show clinically meaningful response to antipsychotic augmentation. 2, 1

When to Consider Antipsychotic Augmentation

Antipsychotic augmentation should only be initiated after:

• Adequate SSRI trial at maximum tolerated doses for at least 8-12 weeks has failed. 1
• Cognitive Behavioral Therapy (CBT) with Exposure and Response Prevention (ERP) has been attempted or is unavailable. 2
• Treatment resistance is defined as inadequate response to both CBT with ERP and adequate SSRI trials. 1

Dosing and Duration

• Use low-to-medium dosages for a duration not exceeding 3 months initially. 3
• Risperidone is typically dosed at a mean of 3 mg/day. 4
• Mandatory discontinuation if there is no response within the trial period. 3
• If effective, maintain treatment for 12-24 months after achieving remission due to high relapse rates. 1

Choosing Between Risperidone and Aripiprazole

Since head-to-head trials are limited, the choice should be based on:

• Side effect profile considerations: Risperidone carries higher risk of metabolic effects and prolactin elevation, while aripiprazole may cause akathisia. 5
• Patient's medication history and tolerability. 5
• Comorbidity patterns: Patients with comorbid tics or Tourette Syndrome may benefit from risperidone or haloperidol. 6, 3
• Patients with comorbid bipolar disorder may particularly benefit from aripiprazole augmentation. 7

Special Considerations for Predictors of Response

• Presence of comorbid tics and/or schizotypal disorder predicts better response to antipsychotic augmentation. 3
• Patients with lifetime comorbidity with bipolar disorder showed particularly strong reduction in obsessive-compulsive symptoms with risperidone. 4

Critical Monitoring Requirements

When using antipsychotics, mandatory monitoring includes: 1

• Weight and metabolic parameters (blood glucose and lipid profiles)
• Extrapyramidal symptoms (tremors, akathisia)
• Sedation and postural hypotension
• Signs of serotonin syndrome when combining serotonergic medications

Important Caveats and Pitfalls

• Antipsychotic augmentation has a smaller effect size than the initial SSRI trial, with only one-third of patients responding. 2
• Ongoing monitoring of the risk-benefit ratio is essential, with particular attention to weight gain and metabolic dysregulation. 2
• The effect of time spent on SSRI monotherapy (6 months) may be more important than augmentation strategy itself. 2
• Do not use antipsychotics as first-line treatment; they are strictly for augmentation after SSRI failure. 5, 3

Alternative Augmentation Strategies if Antipsychotics Fail

If antipsychotic augmentation is ineffective or poorly tolerated:

• N-acetylcysteine has the strongest evidence among glutamatergic agents, with three out of five RCTs showing superiority to placebo. 2, 1
• Memantine can be considered as several trials demonstrate efficacy. 2, 1, 8
• Deep repetitive transcranial magnetic stimulation (FDA-approved for treatment-resistant OCD). 1
• Clomipramine augmentation or switching, though this carries risk of drug interactions and serious adverse events. 2, 1