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Imipramine Treatment of Opiate-Dependent Patients With Depressive Disorders
A Placebo-Controlled Trial
Edward V. Nunes, MD;
Frederic M. Quitkin, MD;
Stephen J. Donovan, MD;
Deborah Deliyannides, MD;
Katja Ocepek-Welikson, MPhil;
Teresa Koenig, RN;
Ronald Brady, MD;
Patrick J. McGrath, MD;
George Woody, MD
Arch Gen Psychiatry. 1998;55:153-160.
Background The literature is inconclusive on the role of antidepressant medications in treating drug dependence. Studies have either not focused on depressed patients or have selected patients with depressive disorders based on cross-sectional symptoms rather than a syndromal diagnosis. A clinical trial of an antidepressant was, therefore, conducted on drug-dependent patients with syndromal depression.
Methods Patients receiving methadone hydrochloride maintenance treatment were selected if they met the criteria for a DSM-III-R depressive disorder that was chronologically primary, had persisted during a past abstinent period or was long-standing, and persisted during at least 1 month of stable methadone treatment. Subjects were randomized to a 12-week, double-blind, placebo-controlled trial of imipramine hydrochloride. A favorable response was defined as a Clinical Global Impression scale score for depression of 2 ("much improved") or 1 ("very much improved") and at least a 75% reduction in self-reported drug or alcohol use or abstinence.
Results One hundred thirty-seven patients were randomized, and 84 completed a minimum adequate trial of at least 6 weeks. Among the 84 adequately treated patients, 57% (24/42) receiving imipramine were rated as responders compared with 7% (3/42) receiving placebo (P<.001). On measures of mood, there was a robust effect of imipramine. Imipramine was superior to placebo on some self-reported measures of substance use and craving, and mood improvement was associated with improvement in self-reported substance use. However, few patients achieved urine-confirmed abstinence.
Conclusions Imipramine was an effective antidepressant in patients receiving methadone who were selected via syndromal criteria for depressive illness. Imipramine may reduce substance abuse among patients whose mood improves; however, this effect was less robust.
From the Depression Evaluation Service, New York State Psychiatric Institute, and the Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York (Drs Nunes, Quitkin, Donovan, Deliyannides, and McGrath and Mss Ocepek-Welikson and Koenig), the Bridge Plaza Treatment and Rehabilitation Services, New York (Dr Brady), and the Department of Psychiatry, the Long Island Jewish/Hillside Hospital, Glen Oaks (Drs Nunes, Quitkin, and Donovan), NY; and the Department of Psychiatry, Philadelphia Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia (Dr Woody).
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