The effect of m-CPP on tics and obsessive-compulsive phenomena in Gilles de la Tourette syndrome

Rationale: Family genetic and phenomenological studies support an interrelationship between Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD). Some authors consider GTS as part of a serotonergically mediated cluster of OCD spectrum disorders. Objective: To study serotonergic mechanisms in GTS, the effect of the relatively selective 5-HT2c agonist meta-chlorophenylpiperazine (m-CPP) was assessed. Methods: We studied the behavioural effects of m-CPP on ties, obsessions, compulsions and impulsions of GTS. Twelve medication-free GTS patients (ten men, two women) were included in a single dose 0.5 mg/kg oral m-CPP challenge study with a double-blinded placebo-controlled cross-over design. Global symptom scores, target symptom scores as well as biochemical measures were followed up to 24 h after baseline. Results: While m-CPP caused a significant rise in plasma cortisol and prolactin levels, no significant effects were found on the ties, obsessions and compulsions. Impulsions showed a trend to ameliorate. Conclusions: This study does not support a predominant role for 5-HT on the ties in GTS. The trend of impulsions to ameliorate after m-CPP can be interpreted as circumstantial support for impulsivity-related 5-HT hypofunctionality in GTS. However, the large variability of m-CPP plasma concentrations found in this study casts doubts upon the reliability of m-CPP as a probe for challenge studies.