Le bupropion, ou amphébutamone, est antidépresseur atypique désormais indiqué dans l’aide au sevrage tabagique, situation à haut risque de manifestations psychiques aiguës. Structurellement proche de l’amphétamine et des monoamines endogènes, dopamine et noradrénaline, dont il inhibe la recapture, le bupropion serait également un antagoniste non-compétitif des récepteurs nicotiniques. Nous avons récemment rapporté le cas d’une patiente schizoaffective ayant développé deux épisodes psychotiques aigus consécutifs dans les suites d’une mise sous bupropion. Nous avons donc conduit une recherche bibliographique visant à recenser les autres publications établissant un lien entre ce traitement et la survenue d’épisodes psychotiques (et/ou thymiques avec caractéristiques psychotiques) aigus. Outre les données de la pharmacovigilance et des études randomisées, 22 cas circonstanciés du même type ont été publiés entre décembre 1985 et novembre 2008. Les troubles surviennent généralement après une exposition brève à une posologie de 300mg/j environ. Dans la majorité des cas, les patients sont indemnes d’antécédent psychotique. Au plan étiopathogénique, l’action dopaminergique du bupropion, parfois potentialisée par interaction médicamenteuse, pourrait être incriminée. L’expression clinique et le profil évolutif des troubles les rapprochent des psychoses « organiques » et « toxiques » traditionnellement décrites. La stratégie thérapeutique consiste habituellement en un arrêt du bupropion et l’introduction d’un neuroleptique. L’utilisation des benzodiazépines pourrait constituer une alternative valable, par référence au modèle des psychoses aiguës amphétaminiques.

Bupropion, or amfebutamone, is an atypical antidepressant also used during tobacco cessation. From a structural standpoint, it resembles amphetamine drugs with psychostimulant effects, and endogenous monoamines. From a pharmacological standpoint, bupropion, and two of its most important active metabolites, inhibit dopamine and norepinephrine reuptake. It has recently been discovered that bupropion may act as a non-competitive cholinergic nicotinic receptor antagonist, and that it may inhibit the activation of reward systems triggered by nicotine. Buproprion’s efficacy as a smoking cessation aid has been demonstrated by numerous clinical trials that have compared its effects with those of placebo and other nicotinic substitutes. In 2001, buproprion SR received marketing authorization in France as a smoking cessation aid, under the name ZYBAN^®. Tobacco addiction indeed remains a major public health issue. Among patients with psychiatric conditions, chronic tobacco consumption is frequent. The development of non-nicotinic drugs may therefore enhance therapeutic possibilities. However, the psychotropic effects of these molecules should be taken into account. We have recently reported the case of a patient with schizoaffective disorder, who presented two acute bupropion-induced psychotic episodes. We have also undertaken an exhaustive bibliographical research on this subject. The aim of the present study is to present the information available to us, in order to suggest aetiopathogenic hypotheses and therapeutic proposals.

The following databases were consulted on a regular basis, with no date restriction: Medline, Cochrane and Elsevier. The present study identified 22 cases of psychotic conditions associated with buproprion, as well as randomized and pharmacovigilance studies published in English, from December 1985 to November 2008. Since 2002, there have been three published case-reports on patients who underwent a tobacco cessation program.

Psychotic disorders associated with buproprion appear after an average of 10days of 300mg/d bupropion intake. In about two third of cases, the patients have no history of psychiatric conditions. In one third of cases, they have a history of thymic disorders. In our review, auditory, visual or cenaesthetic hallucinations frequently occur (85% of the reported cases), and are sometimes characterized by single episodes and/or are rationalized. Some of them occur along with delusional episodes (mystical, paranoid, etc.). The patients are restless, confused, but seldom exhibit dissociative and thymic symptoms.

From an aetiopathogenic, clinical and evolutive standpoint, buproprion-induced psychotic episodes share many similarities with acute organic or toxic psychosis (notably induced by amphetamines). The hypothesis of a dopaminergic hyper-reactivity should be analyzed. Moreover, most of these patients were taking other medication, and the possibility of a dopaminergic potentialization prior to buproprion intake could be suggested. In such cases, bupropion should be discontinued and complete remission is expected within an average of 10 days. Even though neuroleptic drugs are still frequently used in these cases, benzodiazepines could become a valid alternative, according to the model of amphetamine-induced acute psychosis.