Pharmacotherapeutic Strategies and New Targets in OCD

Effective pharmacological and psychotherapeutic treatments are well established for obsessive-compulsive disorder (OCD). Serotonin reuptake inhibitors (SRIs) are first-line treatment and are of benefit to about half of patients. Augmentation of SRI treatment with low-dose neuroleptics is an evidence-based second-line strategy. Specialty psychotherapy is also used as both first-line and second-line treatment and can benefit many. However, a substantial number of patients do not respond to these treatments. New alternatives are urgently needed. This review summarizes evidence for these established pharmacotherapeutic strategies, and for others that have been investigated in refractory disease but are not supported by the same level of evidence. We focus on three neurotransmitter systems in the brain: serotonin, dopamine, and glutamate. We summarize evidence from genetic, neuroimaging, animal model, and other lines of investigation that probe these three systems in patients with OCD. We also review recent work on predictors of response to current treatments. While many studies suggest abnormalities that may provide insight into the pathophysiology of the disorder, most studies have been small, and non-replication of reported findings has been common. Nevertheless, the gradual accrual of evidence for neurotransmitter dysregulation may in time lead the way to new pharmacological strategies.