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Abnormal cerebro-vascular autoregulation in panic disorder
164A
BIOL PSYCHIATRY 1990;27:41A-179A
Panic, Anxiety, and Other Disorders
serotonin re-uptake inhibitors such as fluoxetine makes it possible to study the role of serotonin L,~ the etiology of affective and behavioral dyscontrol in BPD. In this preliminary medication trial, 5 patients with BPD were treated openly with 20-40 mg of fluoxetine for 8 weeks, with weekly ratings of symptoms. All patients had a history of multiple suicide attempts and exhibited prominent symptoms of depression, impulsivity, and suicidality. Large, statistically significant decreases in depression were note~ on the Beck Depression Inventory (A = 15.0 points, t = 2.60, p = 0.032), and the Hamilton Depression Scale. Suicidality, as measured on the Hamilton Depression Scale, dropped sharply from a baseline level of 2.2 (moderate to seven:) to a final level of 0.2 (minim~) (t = 3.!6, p < 0.05). Evaluation of impulsivity on the Ward Scale demonstrated a large, significantdecrease (A = 10.2, t = 4.51,p "- 0.002). These findings suggest promise for fluoxetine in the ~eatment of the depressive and impulsive symptoms of patients with BPD. Large, double-blind, placebo-controlled studies v.~th serotonergic agents are warranted in BPD patients.
278 ABNORMAL CEREBRO-VASCULAR AUTOREGULATION IN d
PANIC DISORDER Suzanne Fontaine, M.D. (by invitation), Alfonso Ontiveros, M.D. (by invitation), R6jean Fontaine, M.D., Robert Elie, M.D., Ph.D. (by invitation), Guy Breton, M.D. (by i:~vitation) Louis H. Lafontaine Hospital, University of Montreal, Montreal, Q~wbecHIN 3M5, Canada. Several recent studies have shown neurophysiological abnormah¢ies in panic disorders (PD). The aim of this study is to assess the neurovascular changes in PD patients by use of trans-cranial Doppler (TCD). 30 patients with PD (DSM-III-R) and 25 controls were included in this study, all between 20 and 40 years old and fight handed. TCD stl~dies ~vere performed with a Transpect TCD (Medasonic). The middle cerebral arterial (MCA) flow was recorded bilaterally by the, transtemporal window during sodium lactate infusion (at baseline, and every 3 rain). Patients who presented a panic attack (21 of 30, 70%) showed more rapid accelerations (p < 0.05) as compared to controls. Furthermore, blood flow differences were observed on the rig~t side in patients sensitive to lactate as compal~d with patients who did not panic and controls (p < 0.05), Our results suggest that local cerebrovasculat, autoregulation abnormalities occurred during panic attacks. This could explain the blood flow change..~ in PD previously reported and, possibly, neuroanatomical changes found with MRI.
279 DIVALPROEX SODIUM'S ANTIPANIC EFFECT IN PANIC
DISORDER: A PLACEBO-CONTROLLED STUDY Millie Lum, M.Sc. Pharm. (by invitation): R6jean Fontaine, M.D., Robert Elie, M.D., Ph.D. (by invitation), Alfonso Ontiveros, M.D. (by invitation) Louis H. Lafontaine Hospital, Un:iversity of Montreal, Montreal, Quebec HIN 3M5, Canada. s
Divalproex sodium (DS) and c)onazepam (CZ) arc both antiepileptic drugs which enhance GABAergic ~ransmission. CZ is an accepted antipanic drug and recent open trials showed that DS has antipanic properties in panic disorder (PD). In :his placebo-controlled study, the antipanic effect of DS was assessed in a doubleblind, placel~o-controlled stt),ly with a 2 × 2 crossover design. Twelve consecutive outpatients with PD (DSM-III-R) underwent a 7 day ~lacebo (P) washout and were then randomly assigned to 2 treatments of 6 weeks: to ~gi.n, DS versus P and then crossed to the alternative treatment of P vetsu..; DS. Baseline and weekly ratings of PD index HAM-A, CGI, and SCL-90 were performed. Variance analysis of the endpoint vaiues showed a significant (D < 0.05) imDrovement with DS as compared with P on CGI severity and improvement, length and intensity of panic attacks, psychic and somatic HAM-A scores. DS plasma
BIOL PSYCHIATRY 1990;27:41A-179A
Panic, Anxiety, and Other Disorders
serotonin re-uptake inhibitors such as fluoxetine makes it possible to study the role of serotonin L,~ the etiology of affective and behavioral dyscontrol in BPD. In this preliminary medication trial, 5 patients with BPD were treated openly with 20-40 mg of fluoxetine for 8 weeks, with weekly ratings of symptoms. All patients had a history of multiple suicide attempts and exhibited prominent symptoms of depression, impulsivity, and suicidality. Large, statistically significant decreases in depression were note~ on the Beck Depression Inventory (A = 15.0 points, t = 2.60, p = 0.032), and the Hamilton Depression Scale. Suicidality, as measured on the Hamilton Depression Scale, dropped sharply from a baseline level of 2.2 (moderate to seven:) to a final level of 0.2 (minim~) (t = 3.!6, p < 0.05). Evaluation of impulsivity on the Ward Scale demonstrated a large, significantdecrease (A = 10.2, t = 4.51,p "- 0.002). These findings suggest promise for fluoxetine in the ~eatment of the depressive and impulsive symptoms of patients with BPD. Large, double-blind, placebo-controlled studies v.~th serotonergic agents are warranted in BPD patients.
278 ABNORMAL CEREBRO-VASCULAR AUTOREGULATION IN d
PANIC DISORDER Suzanne Fontaine, M.D. (by invitation), Alfonso Ontiveros, M.D. (by invitation), R6jean Fontaine, M.D., Robert Elie, M.D., Ph.D. (by invitation), Guy Breton, M.D. (by i:~vitation) Louis H. Lafontaine Hospital, University of Montreal, Montreal, Q~wbecHIN 3M5, Canada. Several recent studies have shown neurophysiological abnormah¢ies in panic disorders (PD). The aim of this study is to assess the neurovascular changes in PD patients by use of trans-cranial Doppler (TCD). 30 patients with PD (DSM-III-R) and 25 controls were included in this study, all between 20 and 40 years old and fight handed. TCD stl~dies ~vere performed with a Transpect TCD (Medasonic). The middle cerebral arterial (MCA) flow was recorded bilaterally by the, transtemporal window during sodium lactate infusion (at baseline, and every 3 rain). Patients who presented a panic attack (21 of 30, 70%) showed more rapid accelerations (p < 0.05) as compared to controls. Furthermore, blood flow differences were observed on the rig~t side in patients sensitive to lactate as compal~d with patients who did not panic and controls (p < 0.05), Our results suggest that local cerebrovasculat, autoregulation abnormalities occurred during panic attacks. This could explain the blood flow change..~ in PD previously reported and, possibly, neuroanatomical changes found with MRI.
279 DIVALPROEX SODIUM'S ANTIPANIC EFFECT IN PANIC
DISORDER: A PLACEBO-CONTROLLED STUDY Millie Lum, M.Sc. Pharm. (by invitation): R6jean Fontaine, M.D., Robert Elie, M.D., Ph.D. (by invitation), Alfonso Ontiveros, M.D. (by invitation) Louis H. Lafontaine Hospital, Un:iversity of Montreal, Montreal, Quebec HIN 3M5, Canada. s
Divalproex sodium (DS) and c)onazepam (CZ) arc both antiepileptic drugs which enhance GABAergic ~ransmission. CZ is an accepted antipanic drug and recent open trials showed that DS has antipanic properties in panic disorder (PD). In :his placebo-controlled study, the antipanic effect of DS was assessed in a doubleblind, placel~o-controlled stt),ly with a 2 × 2 crossover design. Twelve consecutive outpatients with PD (DSM-III-R) underwent a 7 day ~lacebo (P) washout and were then randomly assigned to 2 treatments of 6 weeks: to ~gi.n, DS versus P and then crossed to the alternative treatment of P vetsu..; DS. Baseline and weekly ratings of PD index HAM-A, CGI, and SCL-90 were performed. Variance analysis of the endpoint vaiues showed a significant (D < 0.05) imDrovement with DS as compared with P on CGI severity and improvement, length and intensity of panic attacks, psychic and somatic HAM-A scores. DS plasma