Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study.
As part of the cross-national collaborative panic study, a double-blind comparison of alprazolam, imipramine and placebo was performed in Scandinavian outpatients with panic disorder according to DSM-III; 41 patients were randomly allocated to each drug. Doses were increased for 3 weeks to an average of about 6 mg alprazolam, 150 mg imipramine and a corresponding number of placebo capsules, which were then given for 5 weeks. No more than supportive psychotherapy was given. Key symptoms were rated weekly. The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months. Compliance at 3 weeks was 95% for alprazolam, 83% for imipramine and 88% for placebo; at 8 weeks 95% for alprazolam, 73% for imipramine and 46% for placebo. At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0% for alprazolam, 19% for imipramine and 31% for placebo; at 8 weeks the corresponding proportions were 3%, 11% and 16%. Intention-to-treat analysis showed that freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms. Globally rated by physicians and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. At least partial remission was obtained in about 85% with alprazolam, 70% with imipramine and 40% with placebo. Alprazolam had a more rapid onset of action than imipramine on all symptoms. Side effects were generally mild, with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine. Tapering was uneventful without significant discontinuation phenomena. During taper and follow-up, several patients in remission relapsed, leaving approximately 30% patients in complete remission in all groups. To obtain more stable improvement, either long-term drug treatment or combinations of drug treatment and psychotherapy should be evaluated.
Andersch
S
S
Department of Psychiatry, Sahlgrenska Sjukhuset, Gothenburg, Sweden.
Rosenberg
N K
NK
Kullingsjö
H
H
Ottosson
J O
JO
Bech
P
P
Bruun-Hansen
J
J
Hanson
L
L
Lorentzen
K
K
Mellergård
M
M
Rasmussen
S
S
D000293:Adolescent; D000328:Adult; D000525:Alprazolam / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology; D001143:Arousal / Q000187:drug effects; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007099:Imipramine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010200:Panic / Q000187:drug effects*; D010556:Personality Tests / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D012537:Scandinavian and Nordic Countries
D007099:Imipramine; D000525:Alprazolam