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| Neuropsychopharmacology (1995) 12 147-157. Benzodiazepine Sensitivity in Panic Disorder: Effects of Chronic Alprazolam Treatment Deborah S Cowley MD 1, Peter P Roy-Byrne MD 1, Allen Radant MD 2, James C Ritchie MPH 4, David J Greenblatt MD 6, Charles B Nemeroff MD, Ph.D 5 and Daniel W Hommer MD 3 | |
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| 1From the Departments of Psychiarty and Behaviorial Sciences, University of Washington and Harborview Medical Center 2The Department of Psychiatry and Behaviorial Sciences, Veterans Affairs Medical Center, Seattle, WA 3The National Institute of Alcohoal Abuse and Alcoholism, Duke University Medical Center, Durham NC 4The Departments of Psychiatry and Pharmacology, Duke Medical Center, Durham, NC 5The Departments of Psychiatry and Behaviorial Sciences, Emory University School of Medicine, Tuffs-New England Medical Center, Boston, MA 6The Division of Clinical Pharmacology, Tuffs-New England Meddical Center, Boston, MA Correspondence: Deborah S. Cowley, MD, Department of Psychiarty and Behaviorial Sciences ZA-99, Harborview Medical Center, Seattle, WA 98104 This work was supported by NIH grants MH43449, MH49413, and AA08161. | |
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| ABSTRACT | |
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| The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment. Keywords: Panic disorder; Benzodiapines; Alprazolam; Eye movements; Saccades | |
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