Advances in pharmacotherapy in the past decade have provided clinicians with many safe and effective medications for the treatment of patients with obsessive-compulsive disorder (OCD). Serotonin reuptake inhibitors (SRIs), including the selective serotonin reuptake inhibitors (SSRIs) and clomipramine, are the first-line pharmacologic therapies for patients with OCD. The treatment of patients with OCD with SRIs is unique in that a selective efficacy exists (other antidepressants are ineffective), a longer therapeutic lag occurs, and higher doses often are required than in treating patients with other disorders. SRIs provide clinically significant relief to most patients, but they are not effective in all patients, and although they alleviate the symptoms of OCD, they do not “cure” the illness. No one SRI has been demonstrated to be superior to the others in head-to-head trials.

Because 40% to 60% of patients with OCD do not respond to adequate treatment trials of SRIs, augmentation strategies are for SRI partial and nonresponders, including serotonergic and other neurotransmitter mechanisms.