What is the recommended dose of bupropion (Wellbutrin) for a patient with a history of psychosis?

Bupropion Should Generally Be Avoided in Patients with a History of Psychosis

Bupropion is contraindicated or should be used with extreme caution in patients with a history of psychosis due to its dopaminergic effects that can precipitate or exacerbate psychotic symptoms. If clinical circumstances absolutely require its use despite this history, start at the lowest possible dose with intensive monitoring and concurrent antipsychotic coverage.

Primary Recommendation: Avoid Bupropion in This Population

• Bupropion enhances dopamine neurotransmission through inhibition of neuronal dopamine reuptake, which can unmask or worsen psychotic symptoms 1, 2
• Multiple case reports document bupropion-induced psychosis occurring at standard therapeutic doses (300 mg/day), with symptoms appearing after an average of 10 days of treatment 3, 2
• Approximately 85% of reported cases involve hallucinations (auditory, visual, or cenesthetic), often accompanied by paranoid or mystical delusions 2
• The mechanism resembles amphetamine-induced psychosis, suggesting dopaminergic hyperreactivity as the underlying cause 2

If Bupropion Must Be Used Despite History of Psychosis

Absolute Prerequisites

• Concurrent antipsychotic medication is mandatory - patients with depression and psychosis require concomitant antipsychotic treatment 4
• The patient must be on a stable, adequate dose of an antipsychotic (e.g., risperidone 2-4 mg/day or olanzapine 7.5-20 mg/day) before initiating bupropion 4

Conservative Dosing Protocol

• Start with 37.5 mg once daily in the morning, increasing by 37.5 mg every 3 days only if tolerated 4, 5
• Maximum dose should not exceed 150 mg twice daily (300 mg total daily), and many experts would recommend staying at 150 mg daily or lower in this population 4, 5
• Administer the second dose (if titrating to twice daily) before 3 PM to minimize insomnia risk 4, 5

Intensive Monitoring Requirements

• Monitor for emergence of psychotic symptoms within the first 24-48 hours after each dose increase and throughout the first several weeks 6
• Watch specifically for: paranoid delusions, auditory/visual hallucinations, restlessness, confusion, increased agitation, or worsening of pre-existing psychotic symptoms 1, 3, 2
• If any psychotic symptoms emerge, immediately discontinue bupropion - complete remission typically occurs within 3-10 days of discontinuation 1, 3, 2

Additional Risk Factors That Further Increase Psychosis Risk

The following conditions amplify the risk of bupropion-induced psychosis and represent relative contraindications even with antipsychotic coverage:

• History of traumatic brain injury or structural brain lesions 7
• Active or recent cocaine/stimulant abuse - cocaine sensitization can precipitate psychosis at lower bupropion doses 7
• Seizure disorders - bupropion lowers seizure threshold and is absolutely contraindicated 4, 5, 6
• History of bulimia or anorexia nervosa - increased seizure risk makes this an absolute contraindication 5, 6

Clinical Pitfalls to Avoid

• Do not assume the sustained-release (SR) or extended-release (XL) formulations are safer - psychosis has been documented with all formulations, including SR at therapeutic doses 1, 8
• Do not discontinue the antipsychotic once depression improves - the antipsychotic must be maintained throughout bupropion treatment to prevent psychotic breakthrough 4
• Do not use benzodiazepines alone to manage emerging psychotic symptoms - while benzodiazepines may help with agitation, antipsychotics are required for psychotic symptoms, and bupropion must be stopped 2
• Do not increase the dose if there is no response after 6-8 weeks at 150 mg daily - consider alternative antidepressants rather than pushing to higher doses in this vulnerable population 5

Safer Alternative Antidepressants

For patients with a history of psychosis requiring antidepressant treatment:

• SSRIs (e.g., sertraline 50-200 mg/day, paroxetine 10-40 mg/day) are generally safer first-line options when combined with antipsychotics 4
• Mirtazapine 7.5-30 mg at bedtime may be particularly useful if sedation and appetite stimulation are desired 4
• Nortriptyline 10-40 mg/day can be considered with therapeutic drug monitoring (target level 50-150 ng/mL) 4