Pharm World Sci (2009) 31:238–240 DOI 10.1007/s11096-008-9272-x
CASE REPORT
Two acute psychotic episodes after administration of bupropion: a case of involuntary rechallenge Herve´ Javelot Æ Alexandre Baratta Æ Luisa Weiner Æ Thierry Javelot Æ Cathy Nonnenmacher Æ Jean-Fre´de´ric Westphal Æ Michae¨l Messaoudi
Received: 12 August 2008 / Accepted: 16 November 2008 / Published online: 28 November 2008 Springer Science+Business Media B.V. 2008
Abstract Bupropion is an antidepressant drug also used as a smoking cessation aid, which inhibits norepinephrine and dopamine re-uptake. Given its pharmacological properties, it has been associated with reports on psychosis and acute delirious episodes. Case We report the case of a patient with schizoaffective disorder who developed two psychotic episodes respectively after a four and a two-day administration of sustained-release (SR) bupropion at a dose of 150 mg/day. To our knowledge, this is the first reported case of involuntary rechallenge with bupropion SR during a smoking cessation program. Conclusion There is a serious risk of incorrectly identifying bupropion as only a therapy for nicotine withdrawal without taking the precaution of exploring possible psychiatric co-morbidity with addiction. Our case illustrates the problem.
Keywords Acute psychosis Adverse drug reaction Bupropion Rechallenge Side effects
Impact of findings on practice •
•
There is a risk of acute psychosis or delirium associated with the use of bupropion, especially in patients with a history of psychotic symptoms. Bupropion should not be identified as being solely a smoking cessation drug without taking into account its potential adverse effects. This is particularly important in countries like France where the treatment is not marketed as an antidepressant.
Introduction H. Javelot (&) C. Nonnenmacher Secteur Pharmacie, Etablissement Public Sante´ Alsace Nord (EPSAN), 67170 Brumath, France e-mail:
[email protected];
[email protected] T. Javelot Secteur 38G11, Centre Psychothe´rapique du Vion, 38110 Saint Clair de La Tour, France A. Baratta Secteur G06, Etablissement Public Sante´ Alsace Nord (EPSAN), 67170, Brumath, France L. Weiner J.-F. Westphal Secteur G03, Etablissement Public Sante´ Alsace Nord (EPSAN), 67170 Brumath, France M. Messaoudi Neuropsychopharmacology Department, ETAP Research Centre, 54500 Vandoeuvre-les-Nancy, France
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There are a number of reports of psychosis in association with bupropion, probably because of its dopamine uptake blocking nature [1–8]. Ames et al. [4] and Golden et al. [1] report cases of patients with bipolar disorder who developed such symptoms during treatment with bupropion. Past research has also often shown cases of patients who had no history of psychotic symptoms or mania [1, 5, 7]. Acute psychosis or delirium in association with bupropion has been more frequently reported during treatment of depressive disorders [1, 4, 5, 7–12] than during nicotine withdrawal [6, 13]. In the present study, we report the case of a young woman who developed two psychotic episodes respectively after a four and a two-day administration of sustainedrelease (SR) bupropion (bupropion SR) at a dose of 150 mg/day.
Pharm World Sci (2009) 31:238–240
To our knowledge, this is the first case of two acute delirious episodes after administration of bupropion SR in the same patient, during a smoking cessation program.
Case report Presentation Miss S. is a 31-year-old Caucasian woman. She is 52 kg and 50 300 , her BMI is 20.56. She lives with her parents, and works in part-time jobs. Her medical history is characterized by a positive smoking history of at least 10 package-years. She had a 4-year-long history of schizoaffective disorder, having been initially hospitalized during 3 months for acute delirium and mania. After she was discharged, she consulted our outpatient psychiatry unit twice a month and her psychiatric state remained stable. She was treated with olanzapine in a daily dosage of 10 mg and alprazolam at a dose of 0.25 mg, twice a day. No delusional or mood disorders were observed. The patient did not suffer from any other medical conditions. First episode of acute delirium For the first time in 4 years, Miss S.’s mental state required hospitalization in our unit, as she suddenly presented with a psychomotor agitation. During an interview with family members, it was revealed that she had undertaken a smoking cessation program. The patient’s outpatient physician had recently prescribed bupropion SR (ZYBAN LP: 150 mg/day) and Miss S. had begun her treatment with bupropion 2 days before her acute delirious episode. She was not taking any other medications. Upon admission, the patient presented with delusions of persecution, a dissociative syndrome and manifested hetero-aggressiveness. Results of admission biological analyses were inconclusive. Bupropion was discontinued, and olanzapine 20 mg q.d. (quaque die), cyamemazine 30 mg t.i.d. (ter in die) and alprazolam 0.5 mg t.i.d. were prescribed. Shortly afterwards, the patient developed delusions of poisoning and refused treatment. Injections of loxapine 50 mg i.m., administered PRN (Pro Re Nata) were prescribed. Her mental state gradually improved, aggressiveness decreased, delusions were rationalized and she agreed to follow the treatment. Miss S. returned home after being hospitalized for 12 days. She consulted a psychiatrist once a week and her mental state was stable. Her outpatient medication was olanzapine 5 mg/day and alprazolam 0.25 mg b.i.d.
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Second episode of acute delirium One month after her first acute delirious episode, Miss S. developed another severe agitation state with delusions of persecution and theft. On admission, she showed symptoms of a severe manic episode. Her speech was pressured and she displayed clear evidence of flight of ideas. She also exhibited a strong aggressiveness and suffered from total insomnia. A subsequent family interview revealed that Miss S. had taken bupropion SR (150 mg/day) again, 4 days before her second acute delirious episode. Moreover, on the eve of her hospitalization, the patient was very irritable and slept badly. Miss S. was so eager to stop smoking that she had not taken into account her psychiatrist’s recommendations on bupropion during the first hospitalization. Miss S. was treated with olanzapine 20 mg/day, clonazepam 2 mg t.i.d. and divalproate 2,5 g/day. She responded well to treatment: Her mental state gradually stabilized and Miss S. was normothymic 15 days after treatment initiation. One month later, Miss S. left the hospital and agreed to outpatient follow-up. Bupropion was permanently discontinued. The patient did not experience a recurrence of either psychotic manifestation during the 7 months that followed her second acute delirious episode.
Discussion To our knowledge, the present case is the first occurrence of a patient suffering from two psychotic episodes in association with the treatment with slow release bupropion for nicotine addiction. Golden et al. [1] reported the only other case of positive rechallenge during treatment with bupropion SR in a patient with rapid cycling manic-depressive illness. However, that example illustrates a case of voluntary rechallenge unlike the case presented here. Our patient’s case reveals a lack of communication between the physicians and the patient, as she failed to take into account the potential danger of bupropion in relation to her psychiatric condition. According to the Food and Drug Administration, the SR formulation of bupropion presents a lower risk of side effects, including agitation, compared to the IR formulation (bupropion IR) [12, 14]. The clinical case presented here provides evidence of the potential risks of acute psychosis during therapy with the SR formulation of bupropion. As mentioned earlier, acute psychosis or delirium are reported more often in association with the use of bupropion for treatment of depressive disorders [1, 4, 5, 7–9, 11, 12] than for treatment of nicotine addiction [6, 13]. Our
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clinical case differs from these two cases of bupropioninduced psychosis in two ways: first, our patient had previously showed acute psychotic episodes with visual hallucinations, and, secondly, her bupropion-induced psychosis was not accompanied by hallucinations. The patient reported by Neumann et al. [6] was a chronic alcohol, nicotine and cannabis consumer and the case presented by Baylet and Waters [13] involved a patient with no chronic psychiatric illness. None of these patients had previously presented with acute delirium or psychosis, but their bupropion-induced psychotic episodes were marked by auditory hallucinations (and visual hallucinations in the case reported by Neumann et al. [6]) and suicidal ideation. The symptoms presented by our patient are similar to those described in the depressive patient reported by Wang et al. [7], who exhibited psychomotor agitation, irritability, heteroaggressiveness and delusions of persecution, after a suicide attempt by ingestion of 28 tablets of 150 mg bupropion SR. Our clinical case involves a remarkably fast development of a delusional episode compared to the others: after 6 weeks and 1 month of exposure to bupropion in two cases presented by Ames et al. [4], and after 5 weeks in a case published by Golden et al. [1]. These cases involved patients who had never presented with a psychotic episode before. In contrast, our patient and other reported cases, who had a history of psychotic episodes, presented with acute psychosis or delirium after a short-term exposure to bupropion, regardless of the dose administered (several cases described by Golden et al. [1]). Therefore, a history of psychotic episodes could help predict the rapid development of such adverse reactions to this treatment. Our patient, suffering from a schizoaffective disorder, developed two delusional episodes in association with bupropion very quickly, respectively, 2 and 4 days after exposure to bupropion at a dose of 150 mg/day. The treatment administered during bupropion-induced psychosis is often haloperidol, to stop the hallucinations or simply to sedate the patient [4, 7, 9, 12]. However, a rapid decline of the delirious state can be observed by discontinuing bupropion without prescribing any other antipsychotic and/or anxiolytic treatment [1, 4, 13]. In our patient’s case, the first episode was treated with higher doses of her preceding treatment (olanzapine and alprazolam) plus cyamemazine, and the second one with a further increase in the olanzapine dosage with the addition of clonazepam and divalproate. The patient’s positive response to the second treatment suggests that the repeated use of bupropion had probably led to a severe manic state. Indeed, the Naranjo adverse drug reaction probability scale [15] was used to assess the probability of adverse drug reactions (ADR). In our patient’s case the score was 7, which suggests a probable ADR.
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Pharm World Sci (2009) 31:238–240
Conclusion This case is a reminder that a great amount of caution is needed when starting treatment with bupropion, especially in patients with a history of psychotic episodes. To our knowledge, this is the first reported case of involuntary rechallenge during treatment with bupropion that has induced two acute psychotic episodes. Acknowledgements The authors want to express their gratitude to the translators, Mr Jean-Yves Bart and Mr Jesse David Tatum, for revising the text. Conflicts of interest All the authors of this article attest that there was no potential conflict of interest that could have influenced this work.
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