Can reducing Bupropion (buproion) cause psychosis in patients?

From the Guidelines

Reducing bupropion dosage too quickly can potentially trigger psychosis in some patients, particularly those with underlying psychiatric conditions. If a patient needs to discontinue bupropion, it should be done gradually under medical supervision, typically by reducing the dose by 50-100mg every 3-7 days depending on the starting dose and individual response. Abrupt discontinuation can cause withdrawal symptoms including irritability, anxiety, agitation, and in rare cases, psychotic symptoms. This occurs because bupropion affects dopamine and norepinephrine levels in the brain, and sudden changes to these neurotransmitter systems can disrupt brain chemistry. Some key points to consider when reducing bupropion dosage include:

• Patients with a history of bipolar disorder, schizophrenia, or previous psychotic episodes are at higher risk for this reaction 1.
• The risk of serious neuropsychiatric adverse events, including psychosis, is relatively low, but it is still a concern, particularly in patients with a history of mental illness 1.
• A gradual tapering schedule can help minimize the risk of withdrawal symptoms and psychotic episodes 1. If psychotic symptoms develop during bupropion reduction (such as hallucinations, delusions, or severe paranoia), immediate medical attention is necessary, and temporary antipsychotic medication might be required while adjusting the tapering schedule. Always consult with the prescribing physician before making any changes to bupropion dosage. Some important considerations for clinicians include:
• Monitoring patients closely for signs of withdrawal or psychotic symptoms during the tapering process 1.
• Adjusting the tapering schedule as needed to minimize the risk of adverse events 1.
• Providing patients with clear instructions and support during the tapering process to ensure their safety and well-being 1.

From the FDA Drug Label

1. 6 Psychosis and Other Neuropsychiatric Reactions Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. Discontinue bupropion hydrochloride extended-release tablets (XL) if these reactions occur.

Reducing bupropion in patients may help alleviate psychosis, as some cases of psychosis abated upon dose reduction. However, discontinuation of treatment may be necessary if these reactions occur. 2

From the Research

Reducing Bupropion in Patients and Psychosis

• There is no direct evidence in the provided studies that reducing bupropion in patients causes psychosis.
• However, study 3 found that participants randomized to bupropion were more likely to report psychiatric adverse events compared with those randomized to placebo.
• Study 4 suggests that the co-prescription of bupropion and antipsychotic medication may be affected by historical misconceptions regarding bupropion's purportedly pro-dopamine properties.
• Study 5 states that bupropion is relatively safe in overdose with seizures being the predominant concern, but does not mention psychosis as a side effect.
• Study 6 found that bupropion improved quit rates significantly in the medium and long term in patients with severe mental ill health, but does not mention psychosis as a side effect of reducing bupropion.

Bupropion and Psychiatric Adverse Events

• Study 3 found that bupropion resulted in more trial dropouts due to adverse events of the drug than placebo, and participants randomized to bupropion were more likely to report psychiatric adverse events.
• Study 5 mentions that common side effects of bupropion are nervousness and insomnia, but does not mention psychosis.
• Study 6 found that trials suggest few adverse events, although safety data were not always reported, and does not mention psychosis as a side effect of bupropion.

Antipsychotic Medication and Bupropion

• Study 4 found that clozapine and the microsphere formulation of risperidone were prescribed with bupropion significantly less often than chance, suggesting that prescribers may be cautious when combining bupropion with antipsychotic medication.
• Study 4 suggests that further study on the safety and efficacy of the combination of bupropion and antipsychotic medication is needed.