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Abuse of bupropion.

The Problem

You work in one of America's contemporary long-term psychiatric treatment centers, also known as a state prison. Inmates who come to outpatient appointments and complain of depressive symptoms frequently request bupropion (Wellbutrin). The history they provide is speciously similar: "It's the only antidepressant that's ever worked." You start to inquire about how this medication is used in the prison yard, and some of your more frank patients say it is snorted to provide a methamphetaminelike high.

The Question

What is known about the abuse potential of bupropion outside of the prison environment?

The Analysis

We looked at popular culture first by doing Google searches for "Wellbutrin snort" and "snorting Wellbutrin." Some Web sites describe the effects of snorting bupropion (www.erowid.org/experiences/exp.php?ID=9266) and some give advice on extracting bupropion from Wellbutrin SR tablets for the purpose of insufflation (http://bupropion.home.comcast.net). Wondering what has been published on this topic in the medical literature, we first searched the Cochrane Database of Systematic Reviews (www.cochrane.org/reviews) without result. We then searched Medline, combining "bupropion" and "abuse or misuse."

The Evidence

Bupropion's amphetaminelike abuse potential was suggested in preclinical trials in which animals substituted bupropion for amphetamine in a drug-discrimination task, and in another study in which it was self-administered intravenously by monkeys.

We were able to find two case reports (N. Engl. J. Med. 2002;347:951;J. Child Adol. Psychopharm. 2004;14:157-8) that described adolescents who insufflated bupropion in an attempt to obtain an amphetaminelike effect. One 16-year-old boy insufflated 600 mg of sustained-release bupropion and experienced a seizure. A 15-year-old girl snorted an unspecified amount of sustained-release bupropion and reported a marijuanalike buzz that only lasted a few seconds.

In a double-blind crossover study conducted to determine the amphetaminelike abuse potential of bupropion, 13 male subjects (aged 22-31 years) with "substantial" histories of psychostimulant abuse were randomized to receive, at intervals of at least 3 days, bupropion (100 mg, 200 mg, and 400 mg); d-amphetamine (15 mg and 30 mg); and placebo (J. Clin. Psychiatry 1983;44:206-8).

Drugs were administered at 8:00 a.m., with physiologic measures taken a half hour before administration and then hourly post dose. Bupropion had no measurable effect (relative to placebo) on blood pressure, pulse rate, respiratory rate, temperature, pupil size, appetite, caloric intake, or sleep. On self-rating scales, bupropion was perceived as an active drug only as often as placebo. The investigators concluded, "It is unlikely that bupropion will give rise to [amphetaminelike] patterns of abuse among normals or among those predisposed to psychostimulant abuse." (The study came from the Baylor College of Medicine, the Houston Veterans Administration Medical Center, and the Burroughs Wellcome Research Laboratories.)

A double-blind, placebo-controlled, crossover study conducted at the Medical University of Innsbruck (Austria) examined the abuse liability of bupropion using caffeine as a positive control (Pharmacology 2004;70:206-15).

In all, 60 male smokers, aged 18-65 years, were enrolled; 50 completed the trial. The subjects were given two doses, 6 hours apart, of placebo, caffeine (178 mg), or bupropion slow-release (Zyban, 150 mg). They completed standardized telephone questionnaires at hourly intervals. Of the 50 subjects, 50% were able to report "any effect" to caffeine or bupropion. In those who reported "any effect" to caffeine, bupropion was reported as having essentially no effect. Subjects who reported effects from bupropion reported "much more intense effects" after bupropion than caffeine. The authors concluded that bupropion might be of some abuse liability.

The authors of this study cited another study, not picked up by our search, which was in part sponsored by a pharmaceutical company. That study compared bupropion with dexamphetamine and showed essentially no abuse liability of bupropion (Br. J. Clin. Pharmacol. 1979;7:469-78).

Investigators at the University of Chicago conducted a double-blind, placebo-controlled crossover study examining the effects of d-amphetamine and bupropion on cigarette smoking (Psychopharmacology 2001;157:243-53). In this study, 17 subjects, aged 19-54 years, received d-amphetamine (10 mg and 20 mg); bupropion (150 mg and 300 mg); and placebo. Subjective, physiologic, and behavioral effects were monitored, and amphetamine and bupropion increased self-reports of arousal, mood, and euphoria.

The Conclusion

The two university sponsored studies found an abuse liability of bupropion, and the two studies that were partly sponsored by pharmaceutical companies found no abuse liability. Our experience suggests that ingenious and determined patients have found ways, overlooked by published studies, to bypass bupropion's first-pass metabolism and achieve highs similar to amphetamine.

DR. LEARD-HANSSON is a forensic psychiatrist who practices in San Diego. DR. GUTTMACHER is chief of psychiatry at the Rochester (N.Y.) Psychiatric Center.

BY JAN LEARD-HANSSON, M.D.

BY LAURENCE GUTTMACHER, M.D.
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Title Annotation:EVIDENCE-BASED PSYCHIATRIC MEDICINE
Author:Leard-Hansson, Jan; Guttmacher, Laurence
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Sep 1, 2007
Words:783
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