The pathogenesis and treatment of obsessive-compulsive disorder

The outlook for patients with obsessive-compulsive disorder (OCD) began to change in the early 1980s with the introduction of clomipramine (CMI), a serotonergic antidepressant. The observation that only drugs with a serotonergic profile are effective in OCD has been the basis for the serotonergic hypothesis of OCD. The serotonin-selective reuptake inhibitors are effective alternatives for CMI and can be used when the patient cannot use or tolerate CMI. In this review, we examine the pathophysiology of OCD, based on drug response profile, peripheral markers of serotonergic function, pharmacologic challenge studies, and neuroimaging. We also consider the medications found to be effective in OCD, the length of treatment, with special regard for maintenance therapy, and such issues as the approach for the treatment-resistant patient, augmentation strategies, and nonpharmacological treatments.