Acute Psychosis after Administration of Bupropion Hydrochloride (Zyban™)

Cigarette smoking is associated with leading preventable illnesses, including lung cancer and respiratory and cardiovascular disease. Bupropion hydrochloride acts as an aid in smoking cessation. The clear mechanism still is not known, although bupropion has been demonstrated to inhibit dopamine transport, whereas its mode of interaction with the adrenergic system seems to be less well understood [1] [6].

Sustained-release bupropion, 300 mg/day for 7 or 9 weeks, significantly increases smoking cessation rates [3] [5]. A treatment effect on withdrawal symptoms was demonstrated for bupropion in a dose-ranging study [3]. Short-term bupropion was well tolerated in smoking cessation trials, and the only adverse events that were more common with the drug than with placebo were insomnia and dry mouth [3] [5]. Immediate-release bupropion is associated with seizures [4]. A number of adverse events with immediate-release bupropion were asthenia, fever, sweats, agitation, dyspepsia, flatulence, irritability, amblyopia, and urinary frequency. Three patients were reported to have taken an overdose (3000 or 3600 mg) provoking a seizure, blurred vision, light-headedness, lethargy, nausea, and visual hallucinations [1]. A case of fatal intoxication with alcohol and bupropion has been reported [7].

A 29-year-old Caucasian and otherwise healthy engine fitter had been admitted to our institution with acute onset of schizophreniform psychosis after 5-day administration of bupropion hydrochloride (Zyban™), which had been prescribed for nicotine withdrawal in a daily dosage of 300 mg (sustained release). The patient described visions of the Revelation of St. John, Hitler, and the Antichrist and feared that extraterrestrians may be installing certain devices on Earth. He reported a female voice saying ”Steiner, Steiner!” (a German name, not the patient’s). Television news was experienced to have a relation to the patient’s thoughts. Suicidal ideas had occurred to him. The patient complained of blurred vision, difficulty sleeping, and deterioration of concentration. Psychiatric history showed a long-term consumption of alcohol (40-80 g per week), nicotine (20 cigarettes per day), and cannabis (daily consumption of 1-2 marijuana cigarettes for several years). According to the patient, his daily cannabis consumption in the time period preceding the onset of the psychosis, when he apparently tried to stop smoking cigarettes, remained the same as before. Physical and neurological examination, CAT scan, EEG, and blood routine were found to be completely normal, apart from a positive drug screen for cannabis. There was no clinical and biochemical evidence for current alcohol consumption. Lumbar puncture had been refused by the patient.

After treatment with amisulpride (max. dosage 800 mg qd), symptoms receded within two weeks. A follow-up examination six months later showed complete remission of psychotic symptoms, although alcohol, nicotine, and cannabis abuse had been continued.

A contact with the AMSP drug safety program revealed no other case of bupropion-related psychosis [2]. We hypothesize that bupropion had induced psychotic symptoms in this patient. In all probability, psychotic symptoms could not be attributed to the patient’s alcohol or cannabis abuse, because no biochemical evidence for current alcohol consumption could be found and cannabis had been used on a long-term basis with no change in daily dosage. The daily cannabis consumption in the time preceding the onset of the psychosis, when the patient tried to stop smoking cigarettes, remained the same; therefore, it seemed very unlikely that the psychotic symptoms had been induced by cannabis.

The patient’s symptoms resembled those described with an overdose (blurred vision, hallucinations) [1]. However, other symptoms of a bupropion overdose - such as lethargy, seizure, or nausea - were missing.

References

• 1 Ascher J A, Cole J O, Colin J N, Feighner J P, Ferris R M, Fibiger H C, Golden R N, Martin P, Potter W Z, Richelson E. et al . Bupropion: a review of its mechanism of antidepressant activity.  J Clin Psychiatry. 1995;  2 (9) 395-401
• 2 Grohmann R, Rüther E, Engel R R, Hippius H. Assessment of adverse drug reactions in psychiatric inpatients with the AMSP drug safety program: methods and first results for tricyclic antidepressants and SSRI.  Pharmacopsychiatry. 1999;  32 21-28
• 3 Hurt R D, Sachs D PL, Glover E D. et al . A comparison of sustained-release bupropion and placebo for smoking cessation.  N Engl J Med. 1997;  337 1195-1202
• 4 Johnston J A, Lineberry C G, Ascher J A,. et al . A 102-center prospective study of seizure in association with bupropion.  J Clin Psychiatry. 1991;  52 450-456
• 5 Jorenby D E, Leischow S J, Nides M A. et al . A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.  N Engl J Med. 1999;  340 685-691
• 6 Nomikos G G, Damsma G, Wenkstern D, Fibiger H C. Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis.  Neuropsychopharmacology. 1989;  2 (4) 273-279
• 7 Ramcharitar V, Levine B S, Goldberger B A, Caplan Y H. Bupropion and alcohol fatal intoxication: case report.  Forensic Sci Int. 1992;  56 (2) 151-156