m-Chlorophenylpiperazine in patients with obsessive-compulsive disorder: absence of symptom exacerbation

Oral administration of the serotonin mixed agonist-antagonist meta-chlorophenylpiperazine (mCPP) at 0.5 mg/kg has been reported to exacerbate symptoms of obsessive-compulsive disorder (OCD). In an attempt to replicate these findings, double-blind behavioral and biochemical measures were obtained in 12 drug-free patients (9 men, 3 women) with OCD who received either oral mCPP (0.5 mg/kg), intravenous (IV) mCPP (0.1 mg/kg over 20 min), or placebo in random order on 3 separate test days. Neither oral nor IV mCPP had significant effects on the severity of OCD symptoms. The magnitude of the mCPP-induced plasma prolactin response and plasma mCPP levels were similar to those values obtained in other published studies in which mCPP exacerbated OCD symptoms. In contrast, both oral and IV mCPP were associated with significant increases in ratings of anxiety. These findings suggest that mCPP, whether administered by an oral or intravenous route (as a slow infusion), may not be a reliable probe for investigating obsessive-compulsive symptoms. It is possible, however, that more reproducible behavioral findings might be obtained by identifying susceptible subgroups of OCD or by including a behavioral exposure condition.