Rationales for Combined Medication of Heroin Addiction with Naltrexone and Selective Serotonin Reuptake Inhibitors (SSRIs)

E. Krupitsky

E. Krupitsky, Y. Bespalov, A. Burakov, T. Didenko, V. Egorova, A. Grinenko, E. Ivanova, D. Masalov, N. Neznanov, T. Romanova, M. Tsoi, E. Verbitskaya, G. Woody, and E. Zvartau St. Petersburg Scientific-Research Center of Addictions and Psychopharmacology affiliated with St. Petersburg State Pavlov Medical University, Russia/ University of Pennsylvania, Department of Psychiatry, Philadelphia, United States of America

Background: Clinical trials previously done with naltrexone demonstrated that its efficacy is limited by poor compliance with the medication. Most heroin addicts soon after termination of acute withdrawal are suffering from protracted withdrawal (syndrome of anhedonia) which includes affective disorders (depression and anxiety), sleep disorders, and craving for heroin. The syndrome of anhedonia is one of the reasons for poor compliance with naltrexone in heroin addicts.

Methods: There were two studies. In Study 1, 73 recently detoxified heroin addicts were randomly assigned to 1 of 3 groups: 26 subjects of the first group were treated for 3 weeks with SSRI citalopram (20mg/day), 20 subjects of the second group were treated with placebo, and 24 subjects of the third group with amitryptiline (75 mg/day). The study design was single blind placebo controlled and randomized. In Study 2, 52 recently detoxified heroin addicts were randomly assigned to one of two groups. Subjects in the first group (N=27, age 22.8?0.8) were administered naltrexone (50 mg/day) with twice-a-month drug counseling for 6 months. Subjects of the second group (N=25, age 20.7?0.8) took placebo with twice-a-month drug counseling. Riboflavin was added to the naltrexone and placebo capsules. All subjects had twice-monthly urine testing for heroin; detecting for the presence/absence of riboflavin in the urine assessed compliance with medication. The study design was double blind, placebo controlled, and randomized.

Results: In Study 1, citalopram and amitryptiline were more effective than placebo in the treatment of all symptoms of protracted withdrawal, including depression, anxiety, anhedonia, and craving for heroin. The rate of relapse did not differ significantly between groups. The severity of side effects was much higher in the amitryptiline group than with citalopram or placebo. In Study 2, the rate of abstinence in the naltrexone group was significantly higher than in the placebo group beginning at the end of the first month and continuing throughout the 6 months of the study, while the corresponding rate of relapse was much lower. Psychiatric symptoms (anxiety, depression, and anhedonia) were equally reduced in naltrexone and abstinent heroin addicts alike and there were few side effects in both groups.

Conclusions: From Study 1, we conclude that citalopram is a well-tolerated antidepressant that improves the syndrome of anhedonia (protracted withdrawal) in recently detoxified heroin addicts. However, it does not prevent relapse. From Study 2, we conclude that naltrexone is an effective and safe medication for relapse prevention in heroin addicts in Russia. However it does not influence symptoms of the syndrome of anhedonia.

Hypothesis: Combined medication with an SSRI and naltrexone might be more effective than either of these drugs alone, since the SSRI might reduce the severity of anhedonia and thus improve compliance with naltrexone. We are currently testing this hypothesis in a double blind, placebo controlled, randomized clinical trial.

Abstract Year: 
2003
Abstract Region: 
East Asia
Abstract Country: 
Russian Federation