A 30-year-old woman has moderate OCD (Y-BOCS = 22) unresponsive to adequate trials of two different SSRIs at maximum doses. What is the next evidence-based pharmacological step?

• A Add clomipramine to the current SSRI or switch to clomipramine monotherapy; if adding, monitor for serotonin syndrome and QTc prolongation ✓
• B Augment with lithium
• C Switch to an SNRI (venlafaxine)
• D Add buspirone augmentation

Explanation

After failure of two adequate SSRI trials, clomipramine (a tricyclic with potent serotonin reuptake inhibition) is the next pharmacological step per international guidelines. It can be used as monotherapy or as augmentation. The combination carries risk of pharmacodynamic (serotonin syndrome) and pharmacokinetic interactions — SSRIs (especially fluvoxamine, fluoxetine) inhibit CYP2D6/1A2, increasing clomipramine levels and the risk of QTc prolongation and seizures; ECG monitoring is mandatory. Low-dose clomipramine (25–75 mg) added to an SSRI is safer than full-dose monotherapy. Atypical antipsychotic augmentation (aripiprazole, risperidone) is also evidence-based for SSRI-refractory OCD.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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