What is the recommended medication for Obsessive-Compulsive Disorder (OCD)?

Recommended Medication for OCD

Start with fluoxetine 40-80 mg daily or sertraline 150-200 mg daily as first-line treatment for OCD, as these SSRIs have superior safety profiles, FDA approval for OCD, and equivalent efficacy to other agents. 1

First-Line Treatment: SSRIs

Preferred Agents and Dosing

• Fluoxetine 40-80 mg daily or sertraline 150-200 mg daily are the recommended first-line options based on their safety profiles, FDA approval status, and proven efficacy 1
• All SSRIs demonstrate similar effect sizes for OCD treatment, so selection should prioritize safety profile and drug interactions 1
• Higher doses than depression treatment are mandatory: fluoxetine requires 60-80 mg daily and paroxetine requires 60 mg daily for optimal OCD efficacy 1
• The FDA label confirms paroxetine dosing at 40 mg daily as the target dose, with a range of 20-60 mg daily 2
• Sertraline is FDA-approved for OCD treatment in both adults and children 3

Treatment Duration and Response Assessment

• Allow 8-12 weeks at maximum tolerated dose before declaring treatment failure, though early response by 2-4 weeks predicts eventual success 1
• Maintain treatment for a minimum of 12-24 months after achieving remission due to high relapse risk after discontinuation 1
• Do not use depression-level SSRI doses for OCD, as this is inadequate and leads to treatment failure 1

Critical Safety Considerations

• Screen for CYP2D6 poor metabolizer status before high-dose fluoxetine or paroxetine, especially in patients with cardiac risk factors 1
• CYP2D6 poor metabolizers have 7-fold higher paroxetine exposure and 3.9-11.5-fold higher fluoxetine exposure, with FDA warnings for QT prolongation risk 4
• Fluoxetine causes more drug-drug interactions due to potent CYP2D6 inhibition, converting approximately 43% of extensive metabolizers to poor metabolizer phenotype during chronic use 4
• Paroxetine carries increased suicidality risk compared to other SSRIs and causes more severe discontinuation syndrome characterized by dizziness, sensory disturbances, and paresthesias 4

Second-Line Treatment: Clomipramine

• Reserve clomipramine 150-250 mg daily for patients who fail at least one adequate SSRI trial (defined as 8-12 weeks at maximum tolerated dose) 1
• SSRIs are preferred over clomipramine as first-line agents due to superior safety and tolerability profiles, which is critical for long-term treatment adherence 1
• The FDA label confirms clomipramine is indicated for OCD with demonstrated efficacy in 8-10 week trials, with maximum doses of 250 mg/day for adults and 3 mg/kg/day (up to 200 mg) for children 5

Treatment-Resistant OCD (After SSRI Failure)

Augmentation Strategies

• Approximately 50% of patients fail to fully respond to first-line SSRI monotherapy, with even higher rates in real-world settings 1
• CBT augmentation of SSRIs shows larger effect sizes than antipsychotic augmentation and should be the preferred first augmentation strategy when available 1
• Risperidone or aripiprazole have the strongest evidence for SSRI-resistant OCD, with approximately one-third of patients showing clinically meaningful response 1, 6
• N-acetylcysteine has the strongest evidence among glutamatergic agents, with three out of five randomized controlled trials showing superiority to placebo 1, 6
• Memantine can be considered in clinical practice based on several positive trials 6

Neuromodulation for Highly Resistant Cases

• Deep repetitive transcranial magnetic stimulation (rTMS) has FDA approval for treatment-resistant OCD, with moderate therapeutic effect (effect size = 0.65) and 3-fold increased likelihood of response compared to sham 6
• Other neuromodulation options include transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) for severe, highly treatment-resistant cases 6

Common Pitfalls to Avoid

• Do not declare SSRI failure before 8-12 weeks at maximum tolerated dose, as premature switching is a common error 1
• Do not use depression-level SSRI doses for OCD, as this is inadequate and will lead to treatment failure 1
• Do not discontinue effective treatment prematurely—maintain for a minimum of 12-24 months after remission to prevent relapse 1
• When using antipsychotics for augmentation, monitor for metabolic side effects including weight gain, blood glucose, and lipid profiles 6