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Buspirone challenge in patients with OCD and controls
174A
BIOL PSYCHIATRY
1992;31:61A-252A
Obsessive-Compulsive Disorder
260 ACUTE ADMINISTRATION OF ONDANSETRON AND m-CPP IN
PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER (OCD) AND CONTROLS: BEHAVIORAL AND BIOLOGICAL RESULTS A. Broocks, T.A. Pigott, S. Canter, T.A. Grady, F. L'Heureux, J.L. Hill, D.L. Murphy National Institute of Mental Health, Bethesda, MD 20892. Acute administration of the 5-HT agonist, m-chlorophenylpiperazine (m-CPP), has been associated with an exacerbation of OCD and behavioral symptoms in patients with OCD in comparison with controls. In order to (!) investigate 5 HT3 function in OCD and (2) potentially localize the 5-HT receptor site(s) affected by m-CPP, we intravenously administered m-CPP (0.08 mg/kg), and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg), to OCD patients and controls. All of the subjects received four separate challenges (m-CPP after pretreatment with ondansetron or placebo; ondansetron with placebo, and placebo alone). This was performed under double-blind conditions utilizing standardized rating scales; serial blood samples and vital signs were obtained throughout the 3-h procedure. Physical symptoms were recorded ,)r a total of l0 h. In controls, ondansetron or placebo administration did not produce any behavioral effects or sedation. In contrast, m-CPP administration was associated with significant behavioral effects, p~:ticularly anxiety, activation, and functional impairment. Interestingly, m-CPP's acute bchasioral eftects (0-15 min) after pretreatment with ondansetron were not significantly different from m-CPPadminiswation alone, but later behavioral ratings (~>45 min after m-CPP administration) revealed significant reductions in some of the behavioral responses after pretreatment with ondansetron. Comparative behavioral effects between the OCD patients and the controls, as well as the neuroendocrine data will be presented. Our preliminary results in controls suggest that some of m-CPP's effects may be mediated by 5-HTa pathways.
261 BUSPIRONE CHALLENGE IN PATIENTS WITH
OCD AND CONTROLS Teresa A. Pigott, Tana A. Grady, Suzanne E. Bernstein, James L. Hill, Francine L'Heureux, Biliinda Dubbert, Dennis L. Murphy National Institute of Mental Health, Bethesda, MD 20892. In order to further investigate serotonin (5..HT) functzon in OCD, we administered the 5-HTla agonist, buspirone, which has been previously reported to possess some antiobsessonal effects in obsessive-compulsive disorder (OCD) to a group of OCD patients (n = I1) and age-matched controls (n = 10), Each subject received two separate challenges (buspirone 30 mg or placebo) administered under double-blind, placebo-controlled conditions and at least 48 h apart. The OCD patients (mean age 32.8 __ 2.3 years; mean YBOC~: 20.2 ~ !.9, mean Ham-D 13.3 ± 2.9) and the controls (mean age 29.0 __ 2.8 years) had been medication t'~e for at least 3 weeks prior to the challenge procedure. Standardized rating scales (CPRSOC-5, NIMH-OCR, NIMH Global Ratings of OCD, Anxiety, and Depression, and the NIMH Self-Rating Scales), vital signs, and blood samples were obtained throughout the procedure. Repeated measures ANOVA failed to demonstrate significant buspirone versus placebo differences on any of the OCD scales; in addition, self-rating increases on behavioral ratings after buspirone versus placebo were similar in patients versus controls. There were significant and similar elevations from baseline in plasma prolactin after buspi~one, in comparison with placebo, administration in both groups. There were no significant group or drug differences in plasma concentrations of ACTH, cortisol, or norepinephrine associated with buspirone versus placebo administration. Unlike previous studies with the 5-HTIc agonist, m-CPP, which has noted significant behavior~':l and neuroendocrine differences between OCD patients and controls, these results suggest that OCD is not characterized by evidence of 5-HTla receptor dysfunction.
BIOL PSYCHIATRY
1992;31:61A-252A
Obsessive-Compulsive Disorder
260 ACUTE ADMINISTRATION OF ONDANSETRON AND m-CPP IN
PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER (OCD) AND CONTROLS: BEHAVIORAL AND BIOLOGICAL RESULTS A. Broocks, T.A. Pigott, S. Canter, T.A. Grady, F. L'Heureux, J.L. Hill, D.L. Murphy National Institute of Mental Health, Bethesda, MD 20892. Acute administration of the 5-HT agonist, m-chlorophenylpiperazine (m-CPP), has been associated with an exacerbation of OCD and behavioral symptoms in patients with OCD in comparison with controls. In order to (!) investigate 5 HT3 function in OCD and (2) potentially localize the 5-HT receptor site(s) affected by m-CPP, we intravenously administered m-CPP (0.08 mg/kg), and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg), to OCD patients and controls. All of the subjects received four separate challenges (m-CPP after pretreatment with ondansetron or placebo; ondansetron with placebo, and placebo alone). This was performed under double-blind conditions utilizing standardized rating scales; serial blood samples and vital signs were obtained throughout the 3-h procedure. Physical symptoms were recorded ,)r a total of l0 h. In controls, ondansetron or placebo administration did not produce any behavioral effects or sedation. In contrast, m-CPP administration was associated with significant behavioral effects, p~:ticularly anxiety, activation, and functional impairment. Interestingly, m-CPP's acute bchasioral eftects (0-15 min) after pretreatment with ondansetron were not significantly different from m-CPPadminiswation alone, but later behavioral ratings (~>45 min after m-CPP administration) revealed significant reductions in some of the behavioral responses after pretreatment with ondansetron. Comparative behavioral effects between the OCD patients and the controls, as well as the neuroendocrine data will be presented. Our preliminary results in controls suggest that some of m-CPP's effects may be mediated by 5-HTa pathways.
261 BUSPIRONE CHALLENGE IN PATIENTS WITH
OCD AND CONTROLS Teresa A. Pigott, Tana A. Grady, Suzanne E. Bernstein, James L. Hill, Francine L'Heureux, Biliinda Dubbert, Dennis L. Murphy National Institute of Mental Health, Bethesda, MD 20892. In order to further investigate serotonin (5..HT) functzon in OCD, we administered the 5-HTla agonist, buspirone, which has been previously reported to possess some antiobsessonal effects in obsessive-compulsive disorder (OCD) to a group of OCD patients (n = I1) and age-matched controls (n = 10), Each subject received two separate challenges (buspirone 30 mg or placebo) administered under double-blind, placebo-controlled conditions and at least 48 h apart. The OCD patients (mean age 32.8 __ 2.3 years; mean YBOC~: 20.2 ~ !.9, mean Ham-D 13.3 ± 2.9) and the controls (mean age 29.0 __ 2.8 years) had been medication t'~e for at least 3 weeks prior to the challenge procedure. Standardized rating scales (CPRSOC-5, NIMH-OCR, NIMH Global Ratings of OCD, Anxiety, and Depression, and the NIMH Self-Rating Scales), vital signs, and blood samples were obtained throughout the procedure. Repeated measures ANOVA failed to demonstrate significant buspirone versus placebo differences on any of the OCD scales; in addition, self-rating increases on behavioral ratings after buspirone versus placebo were similar in patients versus controls. There were significant and similar elevations from baseline in plasma prolactin after buspi~one, in comparison with placebo, administration in both groups. There were no significant group or drug differences in plasma concentrations of ACTH, cortisol, or norepinephrine associated with buspirone versus placebo administration. Unlike previous studies with the 5-HTIc agonist, m-CPP, which has noted significant behavior~':l and neuroendocrine differences between OCD patients and controls, these results suggest that OCD is not characterized by evidence of 5-HTla receptor dysfunction.