Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression.
BACKGROUND
Although various strategies have been proposed to treat antidepressant nonresponders, little controlled research has been published that examines prospectively the use of switching to an alternate antidepressant.


METHODS
This was a multisite study in which outpatients with chronic major depression (with or without concurrent dysthymia), who failed to respond to 12 weeks of double-blind treatment with either sertraline hydrochloride (n = 117) or imipramine hydrochloride (n = 51), were crossed over or switched to 12 additional weeks of double-blind treatment with the alternate medication. Outcome measures included the 24-item Hamilton Rating Scale for Depression and the Clinical Global Impressions--Severity and Improvement scales.


RESULTS
The switch from sertraline to imipramine (mean dosage, 221 mg/d) and from imipramine to sertraline (mean dosage, 163 mg/d) resulted in clinically and statistically significant improvements. The switch to sertraline treatment was associated with fewer adverse effect complaints and significantly less attrition owing to adverse effects. Although sertraline treatment also resulted in significantly higher response rates in the intent-to-treat samples (60% in the sertraline group and 44% in the imipramine group), neither the intent-to-treat remission rates nor the response and remission rates among study completers differed significantly. Moreover, after considering the effect of attrition, there were no significant treatment effects on the more comprehensive generalized estimating equation analyses of the continuous dependent measures.


CONCLUSIONS
More than 50% of chronically depressed antidepressant nonresponders benefited from a switch from imipramine to sertraline, or vice versa, despite a high degree of chronicity. As in the initial trial, sertraline was generally better tolerated than imipramine. Switching to a standard antidepressant of a different class is a useful treatment strategy for antidepressant nonresponders and could be considered a standard of comparison for future studies of novel alternate strategies.
Thase
Michael E
ME
Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213, USA. thaseme@msx.upmc.edu
Rush
A John
AJ
Howland
Robert H
RH
Kornstein
Susan G
SG
Kocsis
James H
JH
Gelenberg
Alan J
AJ
Schatzberg
Alan F
AF
Koran
Lorrin M
LM
Keller
Martin B
MB
Russell
James M
JM
Hirschfeld
Robert M A
RM
LaVange
Lisa M
LM
Klein
Daniel N
DN
Fawcett
Jan
J
Harrison
Wilma
W
D000328:Adult; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D019263:Dysthymic Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D007099:Imipramine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D011446:Prospective Studies; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007099:Imipramine; D020280:Sertraline