CHANGES IN CEREBROSPINAL-FLUID NEUROCHEMISTRY DURING TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER WITH CLOMIPRAMINE

Background: This study examined the effect of longterm (mean, 19 month s) treatment with clomipramine hydrochloride on cerebrospinal fluid (C SF) levels of several neuropeptides and monoamine metabolites in child ren and adolescents with obsessive-compulsive disorder. Methods: The C SF levels of corticotropin-releasing hormone, vasopressin, somatostati n, and oxytocin and of the monoamine metabolites 5-hydroxyindolacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were meas ured in 17 children and adolescents with obsessive-compulsive disorder before and after longterm treatment with clomipramine. Results: Treat ment resulted in significant decreases in CSF levels of corticotropin- releasing hormone (mean+/-SD, 175+/-32 vs 152+/-25 pmol/L, P<.03) and vasopressin (mean+/-SD, 1.30+/-0.57 vs 0.86+/-0.54 pmol/L, P<.02) and a trend toward a decrease in somatostatin levels (mean+/-SD, 21.3+/-8. 5 vs 15.3+/-9.8 pmol/L, P<.06). Treatment also significantly increased CSF oxytocin levels (mean+/-SD, 6.05+/-1.60 vs 6.70+/-1.44 pmol/L, P< .01). Significant changes in CSF monoamine metabolite levels with trea tment included significant decreases in CSF levels of 5-hydroxyindolac etic acid (mean+/-SD, 109+/-31 vs 77+/-23 pmol/mL, P<.001), CSF homova nillic acid (mean+/-SD, 273+/-111 vs 237+/-101 pmol/mL, P<.04), and 3- methoxy-4-hydroxyphenylglycol (mean+/-SD, 42.4+/-10.2 vs 36.1+/-4.8 pm ol/L, P<.02) and a significant increase in the homovanillic acid-5-hyd roxyindolacetic acid ratio (mean+/-SD, 2.44+/-0.46 vs 3.42+/-0.84, P<. 0001). Conclusions: These neuropeptide results coupled with evidence t hat central administration of corticotropin-releasing hormone, vasopre ssin, and somatostatin to laboratory animals increases arousal and acq uisition of conditioned behaviors whereas central administration of ox ytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologi c treatment of obsessive-compulsive disorder.