New pharmacologic approaches to obsessive compulsive disorder.

Although obsessive compulsive disorder (OCD) traditionally has been considered a treatment-refractory syndrome, rigorous treatment studies over the past decade have demonstrated that most OCD patients respond to specific behavioral or pharmacologic therapies. In terms of the pharmacologic treatment of OCD, a relatively small group of antidepressant drugs (clomipramine, fluvoxamine, and fluoxetine) have been demonstrated to be antiobsessional. Several related antidepressants (desipramine, nortriptyline) appear to be ineffective for OCD. Clinical response requires prolonged treatment (greater than 6 weeks) with antiobsessional drugs and efficacy is not limited to depressed OCD patients. The few drugs that have been demonstrated to be antiobsessional share a high potency for the blockade of serotonin reuptake, suggesting a serotonergic mechanism for antiobsessional drug action. This suggestion has been further strengthened by studies demonstrating a high correlation between clinical response and changes in serotonergic markers with clomipramine treatment. Moreover, a serotonin antagonist, metergoline, appears to partly reverse the improvement observed following chronic clomipramine treatment. Overall, only about 50% of OCD patients appear to respond in any given pharmacologic treatment trial. Adjunctive treatments, such as lithium or L-tryptophan, have been reported to help in some cases. In addition, the use of neuroleptics either alone or in combination with antiobsessional drugs may be useful for OCD patients with psychotic features or tics. Pharmacologic treatments should be considered only one element of the therapeutic approach to be integrated with behavioral techniques as well as psychosocial interventions for the relief of this very intriguing syndrome.