PharmacologyBiochemistry &Behavior, Vol. 29, pp. 815--817. © PergamonPress plc, 1988. Printed in the U.S.A. 0091-3057/88$3.00 + .00 The Relative Efficacy of Buspirone, Imipramine and Placebo in Panic Disorder: A Preliminary Report DAVID V. SHEEHAN, ASHOK B. RAJ, K. HARNETT SHEEHAN AND SONIA SOTO Department of Psychiatry and Behavioral Medicine University of South Florida College of Medicine, Tampa, FL 33613 SHEEHAN, D. V., A. B. RAJ, K. H. SHEEHAN AND S. SOTO. The relative efficacy ofbuspirone, imipramine and placebo in panic disorder: A preliminary report. PHARMACOL BIOCHEM BEHAV 29(4) 815-817, 1988.--There is a need for safe effective alternatives to benzodiazepines in the treatment of panic disorder. Buspirone, a new nonbenzodiazepine anxiolytic, is compared to imipramine and placebo in the treatment of panic disorder in an 8 week double-blind controlled study of 52 randomly assigned patients. Weekly assessments were made using the Hamilton Anxiety Scale, the Sheehan Clinician Rated Anxiety Scale, the Sheehan Patient Rated Anxiety Scale, the Phobia Scale, the Disability Scale, the Hamilton Depression Scale, the Montgomery Asberg Depression Scale, the Investigator Rated Global Improvement Scale and the Patient Rated Global Improvement Scale~ Preliminary results of repeated measures Anovas are reported. Imipramine was superior to placebo on many of the outcome measures. Imipramine was superior to buspirone on the Patient Rated Global Improvement Scale and on the Investigator Rated Global Improvement Scale, but not on other measures. Although buspirone appeared to be more effective than placebo, differences were not statistically significant. Some buspirone patients did very well compared to others, suggesting a possible bimodal distribution of response. Patients on buspirone had fewer and less disruptive side effects than those on imipramine. Panic disorder Anxiety Buspirone Imipramine Placebo Benzodiazepine RECENT observations that alprazolam and clonazepam are effective in the treatment of panic disorder has stimulated considerable research interest in the use of benzodiazepines and other mild anxiolytic drugs for the treatment on this disorder. Although it is possible that other benzodiazepines are effective in panic disorder if given in adequate doses, the disadvantages of these drugs in producing sedation, ataxia, significant withdrawal effects and potentiation with alcohol are well known. There is a need for new antipanic drugs that will deliver the same antipanic effect without these disadvan- tages. This prompted us to study buspirone, a new non- benzodiazepine anxiolytic in the treatment of panic disorder. Buspirone belongs to a new class of psychotropic drugs--the azaspirodecanediones [25]. Its pharmacologic profile differs in several ways from that of the ben- zodiazepines [19]. It does not interact with benzodiazepine or gamma-aminobutyric acid receptors, like benzodiazepines [19]. It shows little activity at alpha adrenergic, cholinergic, histaminergic, picrotoxic, calcium channel, amine uptake, or opiate receptor sites [7,22]. Unlike the benzodiazepines, buspirone is active primarily at the serotonergic and presynaptic dopaminergic receptor sites [7,22]. Like the ben- zodiazepines, it reduces serotonergic activity in the dorsal raphe [22]. Buspirone enhances nonadrenergic activity on the locus coeruleus and dopaminergic activity in the sub- stantia nigra-c, whereas benzodiazepines depress both [22]. Its mechanism of anxiolytic activity remains uncertain [6,22]. Like the benzodiazepines, buspirone has anticonflict [7, 12, 19, 24] antiaggressive [7, 19, 23] and anti-conditioned avoidance response activity in animals [7]. Unlike ben- zodiazepines, it has no significant anticonvulsant properties [7,19], does not produce muscle relaxation [19], sedative hypnotic effects [18], nor does it show potential for physical dependence, or abuse in animals [1,19] or humans [5,11]. It does not interact significantly with CNS depressants such as alcohol [14,15]. In contrast to benzodiazepines, it shows no significant impairment of psychomotor or cognitive skills [2, 14, 15, 21] in normal subjects. Abrupt discontinuation of buspirone is not associated with typical anxiolytic with- drawal effects in animals [19] or humans [13]. It shows no euphoriant or stimulating properties compared to placebo in humans [5]. In outpatients with generalized anxiety disorder (GAD), double blind studies have found buspirone to be as effective as diazepam [8, 9, 20] and chlorazepate [3,10], lorazepam and alprazolam [4], while being better tolerated and produc- ing significantly less sedation [3, 4, 8--10, 16, 17]. The DSMIII considers panic disorder to be different from and more severe than generalized anxiety disorder. There have been no studies investigating the efficacy of a nonben- zodiazepine anxiolytic in the treatment of panic disorder. We conducted a double blind placebo controlled study of 55 pa- tients comparing buspirone, imipramine and placebo over eight weeks of active drug treatment. The impact of these drugs on the various dimensions of this disorder were studied in detail. 815