Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone

Arch Gen Psychiatry. 1999 Sep;56(9):812-20. doi: 10.1001/archpsyc.56.9.812.


Background: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence.

Methods: This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10.

Results: In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence.

Conclusions: Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analgesics, Opioid / therapeutic use*
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Buprenorphine / therapeutic use*
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / epidemiology
  • Comorbidity
  • Desipramine / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Heroin Dependence / epidemiology
  • Heroin Dependence / rehabilitation
  • Humans
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Narcotic Antagonists / therapeutic use*
  • Opioid-Related Disorders / epidemiology
  • Opioid-Related Disorders / rehabilitation*
  • Sex Factors
  • Treatment Outcome


  • Analgesics, Opioid
  • Antidepressive Agents, Tricyclic
  • Narcotic Antagonists
  • Buprenorphine
  • Desipramine
  • Methadone