Background

Bupropion is a dopamine/norepinephrine reuptake inhibitor that is FDA approved for the treatment of smoking cessation. Although the exact mechanism is not fully understood, the therapeutic effects of bupropion are thought to be due to inhibition of presynaptic dopamine and serotonin reuptake transporters and possible antagonism of nicotinic acetylcholine receptors.¹ Although antidepressant therapy is not generally recommended in bipolar disorder, bupropion is thought to have a reduced risk of inducing mood shifts compared to other antidepressants when used for the treatment of depression in bipolar patients.² Minimal information is available on the induction of mood shifts when bupropion is used for smoking cessation in patients without a history of bipolar disorder. Additionally, electroconvulsive therapy (ECT) has been shown to achieve remission in 60%–80% of acutely manic patients, but the evidence of ECT in mania refractory to medication therapy is limited.³ In this case report, a female patient who experienced mania following initiation of bupropion for nicotine dependence is described, and a literature review is provided.

Case

A 38-year-old African American female presented to the emergency department for chest pain. The patient's past medical history was significant for hypertension, for which she had not taken her lisinopril for about 2 years, and diabetes, controlled with diet. Additionally, the patient had a history of smoking for 20 years and had quit about 3 months prior to admission; however, 1 week prior to the onset of chest pain, the patient was started on oral bupropion 150 mg every morning for smoking cessation for tobacco cravings. In the emergency department, the patient received aspirin chewable 162 mg by mouth and 3 sublingual nitroglycerin tablets, which relieved the chest pain, and was admitted to the general medicine floor in order to rule out an acute coronary syndrome. The next day, prior to her stress test, the patient went to the cardiology clinic, where she became confused and began talking about demons and auras. The patient's husband noted that this behavior was strange, and the patient was escorted back to the medical unit. On the medical floor, the patient was requesting to be examined by a female because having a male examine her would be “inappropriate” because “together (they) are the body of Christ.”

The patient was evaluated by psychiatry, and the patient's husband provided further insight into the patient's bizarre behavior. According to the patient's husband, the patient started acting strange when she woke up the morning before coming to the emergency department. She was hyperverbal, religiously preoccupied, and distracted with flight of ideas. The husband also reported that the patient had similar manic symptoms about 5 years prior after using cannabis and was hospitalized for a brief period at a private hospital. Per the husband, the symptoms resolved, and the patient was discharged with a diagnosis of schizophrenia. The patient was treated with oxcarbazepine 300 mg per day, risperidone 1 mg twice daily, and fluoxetine 20 mg daily, and it appears that the patient took these medications for approximately 6 months following this previous hospitalization. Because of the current sudden changes in mood, the patient was admitted to the inpatient mental health floor for mood stabilization. While in the inpatient psychiatry unit, the patient continued to exhibit behaviors consistent with manic delirium, such as agitation, hypersexuality, and combativeness, requiring multiple doses of intramuscular haloperidol 5 mg and lorazepam 4 mg, given as needed. The patient was started on lithium 600 mg twice daily, and appropriately drawn lithium trough levels increased up to 1.74 mEq/L due to acute worsening of renal function. However, the patient was without side effects or any resolution of symptoms. The patient's mania and psychosis continued to worsen despite trials of haloperidol 10 mg twice daily and risperidone 1 mg at bedtime, and ultimately the patient required restraints as she was no longer responding to intramuscular haloperidol 10 mg, lorazepam 2 mg, or olanzapine 10 mg. After 10 days of admission on the mental health unit, lack of response, and dangerous behaviors, the psychiatry team resolved to perform emergency ECT. After the first ECT treatment, the patient remained agitated and delusional and continued to require restraints and as needed haloperidol and lorazepam. She received her second treatment of ECT the following day, which she tolerated.

The psychiatry team resolved to admit the patient to the intensive care unit (ICU) for sedation to avoid injury with a goal of 24 hours without restraints and intravenous medications before being transferred back to inpatient psychiatry. The patient was admitted and placed on a dexmedetomidine infusion with haloperidol and lorazepam as needed for agitation, which the patient continued to need during the initial ICU course. The patient's third ECT resulted in some improvement in her behaviors. The patient remained in the ICU for a total of 6 days, and during the last 2 days of the ICU stay, the patient was not sedated and did not require any medication or restraints. The patient was stable and not psychotic or manic, so she was discharged home after her fourth ECT with instructions to follow up with outpatient psychiatry. Postdischarge, the patient received 4 more ECT treatments. Three months postdischarge and 2 months post-ECT, the patient remained stable without any pharmacologic treatment and only psychotherapy.

Literature Search

A literature search was conducted through PubMed using the following MeSH terms: “bupropion,” “bipolar disorder,” and “smoking cessation.” Results written in English were included. The initial search used “bupropion” and “bipolar disorder,” which yielded 76 articles that were reviewed for case reports discussing bupropion-induced mania and hypomania. An additional literature search was conducted adding “smoking cessation” to determine if previous literature was available regarding bupropion-induced mania when used for smoking cessation rather than treatment of bipolar depression. This search produced 10 reviewable articles. For review of ECT treatment in mania, a PubMed search using MeSH terms “electroconvulsive therapy,” “bipolar disorder,” and “delirium” was conducted, and it yielded 21 results. Results written in English were included.

Discussion

Conclusions

Patients with significant psychiatric history not maintained with mood-stabilizing agents may be at risk for mood shifts from bupropion when used for the treatment of nicotine dependence. This case report suggests the importance of carefully monitoring patients for mood shifts when using bupropion for smoking cessation regardless of whether or not the patient is taking other mood-stabilizing agents at the time of bupropion initiation. This case highlights the possibilities of missing psychiatric history and the resulting adverse reaction to bupropion. Thorough patient counseling should be performed at the time of bupropion initiation, instructing patients to report changes in their mood or behaviors.