Am J Psychiatry 1995; 152:673-682
Copyright © 1995 by American Psychiatric Association
Imipramine treatment of panic disorder with agoraphobia: dose ranging and plasma level-response relationships
MR Mavissakalian and JM Perel
Department of Psychiatry, Ohio State University College of Medicine, Columbus, USA.
OBJECTIVE: The aim of this study was to characterize the specific effects
of imipramine in the treatment of panic disorder with agoraphobia and to
delineate dose-response and possibly plasma level- response relationships.
METHOD: Eighty patients with panic disorder with agoraphobia were randomly
assigned, for an 8-week, double-blind dose-ranging trial, to placebo or to
a weight-adjusted dose of imipramine: (low) 0.5 mg/kg per day, (medium) 1.5
mg/kg per day, or (high) 3.0 mg/kg per day. Plasma levels of imipramine and
N- methylimipramine, patients' and clinicians' ratings of panic and phobic
symptoms, and response to treatment according to operationalized criteria
were ascertained after 4 and 8 weeks. RESULTS: Rates of dropouts due to
drug side effects were 6%, 15%, and 36% in the low-, medium-, and high-dose
groups, respectively; 63 patients completed the study. Compliance with the
drug regimen was high. There was a positive dose-response relationship,
with significant group differences involving primarily the high- and
medium-dose groups versus the placebo group. There were no significant
differences between the placebo and low-dose groups or the medium- and
high-dose groups. For phobias, the best total drug plasma level was in the
range of 110-140 ng/ml; higher levels had a detrimental effect. For panic,
the probability of response increased quickly with greater plasma levels
and then tapered off, with no improvement at levels beyond 140 ng/ml.
CONCLUSIONS: The results provide strong evidence that imipramine has
specific, clinically significant effects in this disorder, with practical
implications for target doses and optimal plasma concentrations, and
suggest that different mechanisms underlie the drug's antipanic and
antiphobic effects.
