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Antidopaminergic and antiserotonergic actions of risperidone in schizophrenia
114A
BIOL PSYCHIATRY 1991;29:43A-185A
Serotonin Function in Psychiatric Disorders
151 ANTIDOPAMINERGIC AND A~ISEROTONERGIC ACTIONS
OF RISPERIDONE IN SCHIZOPHRENIA Richard L. Borison, M.D., Ph.D., Ananda P. Pathiraja, M.D. (by invitation), Bruce I. Diamond, Ph.D., Richard C. Meibach, Ph.D. (by invitation) Psychiatry Service, Augusta VA Medical Center and Medical College of Georgia, Augusta, GA, 30910 and Janssen R,,search Institute, Piscataway, NJ. Risperidone is a potent antagonist of dopamine-2 and serotonin-2 receptors. We report da~a on a study involving 36 schizophrenics, who after a l-week placebo washout were randomized into double-blind groups receiving risperidone (2-10 mg), haloperidol (4-20 mg), or placebo. Compared to baseline ratings on the Brief Psychiatric Rating Scale, both risperidone (p --< 0.001) and haloperidol (p <-- 0.006) produced a significant lowering of scores during the 6-week trial OVilcoxin signed rank test), whereas placebo did not. Using end-point analysis, risperidone (p <- 0.002) and haloperidol (p - 0.07) were significantly better than placebo treatment, with a trend (p - 0.105) for risperidone to be superior to haloperidol. Risperidone and placebo did not show increases from baseline in neurological side-effect scales, and risperidone produced a greater suppression of dyskinesias than did the haloperidol or placebo groups. In summary, risperidone appears to be a potent and effective antipsychotic drug with few EPS and strong dyskinesia suppressant properties.
152 AN OVERVIEW OF 5-HT STUDIES IN THE
EATING DISORDERS Timothy D. Brewerton, Dennis L. Murphy, David C. Jimerson Department of Psychiatry and Behavioral Sciences; Medical University of South Carolina, Charleston, SC 29425--0742. Studies of 5-HT function in normal controls (n = 16), normal weight patients with l~ulhnia nervosa (BN) (n = 26), and patients with anorexia nervosa (AN) before (n = 12) and after (n = 10) refeeding are reviewed. In double-blind, random fashion, subjects were challenged with L-TRP (100 mg/kg IV), mCPP (0.5 mg/kg orally) and placebo (IV and capsules) at least 48 hr apart. Neuroendocrine, temperature, cardiovascular, behavioral, and testmeal responses were obtained. Patients with BN, regardless of weight or mood, had blunted PRL responses to mCPP, but only those with concurrent AN or major depression (MD) showed blunting to L-TRP. Temperature elevation following mCPP was significantly higher in patients th~,a no~.,'m.a!s.After receiving an active drag, both patients and normals exhibited increases in ru-txiet-yand depression, especially following mCPP. mCPP, but not L-TRP or placebo, decreased meal size in both patients and normals; CHO intake was significantly decreased only in patients after mCPP. Differences in the various response measures following mCPP and L-TRP may relate to differential involvement of preand postsynaptic mechanisms, 5-HT receptor subtypes, and/or anatomic loci of action. These findings support the concept of altered postsynaptic 5-HT receptor sensitivity in BN, regardless of the presence of AN or MD, although these conditions may involve other 5-HT disturbances. These studies also produced other important findings, mCPP, but not L-TRP or placebo, induced late-onset migraine headaches in more than 50% of subjects. Significant differences in PRL responses following mCPP and L-TRP were found between summer and winter and parallel seasonal fluctuations in other measures of 5-HT function. These studies have also led to a better understanding of the interrelationships between multiple measures and probes of 5-HT function over time.
BIOL PSYCHIATRY 1991;29:43A-185A
Serotonin Function in Psychiatric Disorders
151 ANTIDOPAMINERGIC AND A~ISEROTONERGIC ACTIONS
OF RISPERIDONE IN SCHIZOPHRENIA Richard L. Borison, M.D., Ph.D., Ananda P. Pathiraja, M.D. (by invitation), Bruce I. Diamond, Ph.D., Richard C. Meibach, Ph.D. (by invitation) Psychiatry Service, Augusta VA Medical Center and Medical College of Georgia, Augusta, GA, 30910 and Janssen R,,search Institute, Piscataway, NJ. Risperidone is a potent antagonist of dopamine-2 and serotonin-2 receptors. We report da~a on a study involving 36 schizophrenics, who after a l-week placebo washout were randomized into double-blind groups receiving risperidone (2-10 mg), haloperidol (4-20 mg), or placebo. Compared to baseline ratings on the Brief Psychiatric Rating Scale, both risperidone (p --< 0.001) and haloperidol (p <-- 0.006) produced a significant lowering of scores during the 6-week trial OVilcoxin signed rank test), whereas placebo did not. Using end-point analysis, risperidone (p <- 0.002) and haloperidol (p - 0.07) were significantly better than placebo treatment, with a trend (p - 0.105) for risperidone to be superior to haloperidol. Risperidone and placebo did not show increases from baseline in neurological side-effect scales, and risperidone produced a greater suppression of dyskinesias than did the haloperidol or placebo groups. In summary, risperidone appears to be a potent and effective antipsychotic drug with few EPS and strong dyskinesia suppressant properties.
152 AN OVERVIEW OF 5-HT STUDIES IN THE
EATING DISORDERS Timothy D. Brewerton, Dennis L. Murphy, David C. Jimerson Department of Psychiatry and Behavioral Sciences; Medical University of South Carolina, Charleston, SC 29425--0742. Studies of 5-HT function in normal controls (n = 16), normal weight patients with l~ulhnia nervosa (BN) (n = 26), and patients with anorexia nervosa (AN) before (n = 12) and after (n = 10) refeeding are reviewed. In double-blind, random fashion, subjects were challenged with L-TRP (100 mg/kg IV), mCPP (0.5 mg/kg orally) and placebo (IV and capsules) at least 48 hr apart. Neuroendocrine, temperature, cardiovascular, behavioral, and testmeal responses were obtained. Patients with BN, regardless of weight or mood, had blunted PRL responses to mCPP, but only those with concurrent AN or major depression (MD) showed blunting to L-TRP. Temperature elevation following mCPP was significantly higher in patients th~,a no~.,'m.a!s.After receiving an active drag, both patients and normals exhibited increases in ru-txiet-yand depression, especially following mCPP. mCPP, but not L-TRP or placebo, decreased meal size in both patients and normals; CHO intake was significantly decreased only in patients after mCPP. Differences in the various response measures following mCPP and L-TRP may relate to differential involvement of preand postsynaptic mechanisms, 5-HT receptor subtypes, and/or anatomic loci of action. These findings support the concept of altered postsynaptic 5-HT receptor sensitivity in BN, regardless of the presence of AN or MD, although these conditions may involve other 5-HT disturbances. These studies also produced other important findings, mCPP, but not L-TRP or placebo, induced late-onset migraine headaches in more than 50% of subjects. Significant differences in PRL responses following mCPP and L-TRP were found between summer and winter and parallel seasonal fluctuations in other measures of 5-HT function. These studies have also led to a better understanding of the interrelationships between multiple measures and probes of 5-HT function over time.