- Email: [email protected]
Benzodiazepine sensitivity in panic disorder: effects of alprazolam treatment
Anxiety and Eating Disorders
BIOL PSYCmATRY
55A
1991;29:43A- 185A
ANXIETY AND EATING DISORDERS Thursday, May 9, 1:00-4:00 PM St. Charles A 27
BENZODIAZEPINE SENSITIVITY IN PANIC DISORDER: EFFECTS OF ALPRAZOLAM TREATMENT Peter P. Roy-Byme, M.D., Deborah S. Cowley, M.D., James Ritchie, M.S., Charles Nemeroff, M.D., Ph.D., Daniel W. Hommer, M.D. University of Washington; Psychiatry Department, RP-IO; Seattle, WA 98195. Chron': treatment with benzodiazepines (Bzs) produces tolerance to many of their effects. Most studies of Bz tolerance in humans have examined either normals or diagnostically mixed groups of anxious patients. In order to study this phenomenon in panic disorder, we compared pharmacodynamic responses to four logarithmically increasing doses of diazepam git~en at 15-rain intervals on one day in 20 Bz-naive panic disorder patients and a separate group of 15 panic disorder patients maintained on chronic alprazolam treatment (1-5 mg daily) for 4-24 months. Pharmacodynamic measures were selected that had ~,dready been shown to produce significant drug effects compared with placebo in this panic disorder group. Using druginduced change from baseline as the dependent measure, patients on chronic alprazolam treatment had less dose-dependent changes in two eye movement measures, reductions in saccadic velocity(F = 5. I, p = 0.002) and increases in saccadic latency (F = 10.8, p = 0.0001), and less overall change (dose-dependent) in self-rated sedation (F = 8.96, p = 0.005) and memory function {F = 8.6, p = 0.006). A log-line~ pharmacodynamic model was used to calculate the effective dose (ED30) and concentration (EC30) required to reduce SEV by 30% (the upper limit of SEV reduction in controls). Treated patients needed significantly higher doses and concentrations to reduce SEV by 30% (T = 3.2, p < 0.006). More importantly, treated patients had significantly greater variability in ED30s than untreated patients (F = 6.43, p < 0.001), suggesting differential development of tolerance among patients. Correiation of ED30s and EC30s with dose, duration of treatment, and current symptom severity in treated patients will be presented.
28
TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE (TPQ) AND SEROTONIN IN BULIMIA NERVOSA David A. Waller, M.D., Frederick Petty, M.D., Ph.D., Bettie W. Hardy, Ph.D., Christina M. Gullion, Ph.D., Mary V. Murdock, B.S.N., A. John Rush, M.D. UT Southwestern Medical Center, Dallas, TX 75235. To determine the relationship between TPQ scales and bulimia nervosa, TPQ scores of 27 bulimic women, age range 21-59, were compared to values for an age-matched sample of 128 no~-mal control women drawn from the national norming sample by Przybeck. Novelty Seeking (NS) and Harm Avoidance (HA) were significantly higher (p < 0.006 and < 0.0008 respectively) and Reward Dependence (RD) significantly lower (p < 0.002) for bulimics. A stepwise regression model of severity of p~ging on TPQ selected NS and a composite depression score (p < 0.04), with NS the stronger of the two predictors. Wh.ole blood serotonin levels (5-HT) did not relate to TPQ scores or to purging frequency. Analysis of interaction between response to fluoxetine (for 17 bulimics) and change in TPQ score from baseline to end of treatment in a 16-week study found a significant increase for the eight fluoxetine responders in NS subscale NSI (Exploratory Excitability) (p < 0.02). Serotonin decreased significantly for all subjects receiving fluoxetine (p < 0.05). These preliminary findings suggest that TPQ NS may be particularly relevant to bulimia. Assays for central 5-HT function may be more informative than whole blood 5-HT.
BIOL PSYCmATRY
55A
1991;29:43A- 185A
ANXIETY AND EATING DISORDERS Thursday, May 9, 1:00-4:00 PM St. Charles A 27
BENZODIAZEPINE SENSITIVITY IN PANIC DISORDER: EFFECTS OF ALPRAZOLAM TREATMENT Peter P. Roy-Byme, M.D., Deborah S. Cowley, M.D., James Ritchie, M.S., Charles Nemeroff, M.D., Ph.D., Daniel W. Hommer, M.D. University of Washington; Psychiatry Department, RP-IO; Seattle, WA 98195. Chron': treatment with benzodiazepines (Bzs) produces tolerance to many of their effects. Most studies of Bz tolerance in humans have examined either normals or diagnostically mixed groups of anxious patients. In order to study this phenomenon in panic disorder, we compared pharmacodynamic responses to four logarithmically increasing doses of diazepam git~en at 15-rain intervals on one day in 20 Bz-naive panic disorder patients and a separate group of 15 panic disorder patients maintained on chronic alprazolam treatment (1-5 mg daily) for 4-24 months. Pharmacodynamic measures were selected that had ~,dready been shown to produce significant drug effects compared with placebo in this panic disorder group. Using druginduced change from baseline as the dependent measure, patients on chronic alprazolam treatment had less dose-dependent changes in two eye movement measures, reductions in saccadic velocity(F = 5. I, p = 0.002) and increases in saccadic latency (F = 10.8, p = 0.0001), and less overall change (dose-dependent) in self-rated sedation (F = 8.96, p = 0.005) and memory function {F = 8.6, p = 0.006). A log-line~ pharmacodynamic model was used to calculate the effective dose (ED30) and concentration (EC30) required to reduce SEV by 30% (the upper limit of SEV reduction in controls). Treated patients needed significantly higher doses and concentrations to reduce SEV by 30% (T = 3.2, p < 0.006). More importantly, treated patients had significantly greater variability in ED30s than untreated patients (F = 6.43, p < 0.001), suggesting differential development of tolerance among patients. Correiation of ED30s and EC30s with dose, duration of treatment, and current symptom severity in treated patients will be presented.
28
TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE (TPQ) AND SEROTONIN IN BULIMIA NERVOSA David A. Waller, M.D., Frederick Petty, M.D., Ph.D., Bettie W. Hardy, Ph.D., Christina M. Gullion, Ph.D., Mary V. Murdock, B.S.N., A. John Rush, M.D. UT Southwestern Medical Center, Dallas, TX 75235. To determine the relationship between TPQ scales and bulimia nervosa, TPQ scores of 27 bulimic women, age range 21-59, were compared to values for an age-matched sample of 128 no~-mal control women drawn from the national norming sample by Przybeck. Novelty Seeking (NS) and Harm Avoidance (HA) were significantly higher (p < 0.006 and < 0.0008 respectively) and Reward Dependence (RD) significantly lower (p < 0.002) for bulimics. A stepwise regression model of severity of p~ging on TPQ selected NS and a composite depression score (p < 0.04), with NS the stronger of the two predictors. Wh.ole blood serotonin levels (5-HT) did not relate to TPQ scores or to purging frequency. Analysis of interaction between response to fluoxetine (for 17 bulimics) and change in TPQ score from baseline to end of treatment in a 16-week study found a significant increase for the eight fluoxetine responders in NS subscale NSI (Exploratory Excitability) (p < 0.02). Serotonin decreased significantly for all subjects receiving fluoxetine (p < 0.05). These preliminary findings suggest that TPQ NS may be particularly relevant to bulimia. Assays for central 5-HT function may be more informative than whole blood 5-HT.