What are the risks and considerations for using bupropion (Wellbutrin) in patients with stimulant use disorder?

Bupropion in Stimulant Use Disorder: Risks and Considerations

Direct Answer

Bupropion shows promise as adjunctive therapy in patients with stimulant use disorder, particularly when comorbid with opioid use disorder, as it is associated with a 23% reduction in stimulant-related emergency department and hospital admissions. 1 However, bupropion itself carries significant misuse potential in this population, with documented cases of abuse via chewing, insufflation, and intravenous injection to achieve a "cocaine-like" high. 2, 3

Key Safety Considerations and Contraindications

Absolute Contraindications

• Seizure disorder is an absolute contraindication to bupropion use. 4
• Current or prior diagnosis of bulimia or anorexia nervosa is contraindicated due to increased seizure risk. 4, 5
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is an absolute contraindication due to dramatically increased seizure risk. 4

Seizure Risk Management

• The maximum daily dose must not exceed 450 mg to minimize seizure risk, with dose-dependent seizure incidence. 4
• Gradual dose titration is mandatory to reduce seizure risk. 4
• Seizures are the most common serious adverse effect in bupropion misuse cases, typically responsive to IV benzodiazepines. 3

Misuse Potential in Stimulant Use Disorder Populations

At-Risk Patient Profile

Bupropion insufflation and intravenous injection occur almost exclusively in patients with a substance use disorder history, with a preponderance of patients having stimulant use disorder or multiple substance use disorders. 3 Many are dual-diagnosis patients with both ADHD and stimulant use disorder who were prescribed bupropion therapeutically. 3

Routes and Patterns of Misuse

• Patients describe bupropion insufflation/IV injection effects as a milder "cocaine-like" high that is brief, with less severe withdrawal effects of anxiety and agitation compared to cocaine. 3
• Bupropion can be misused by chewing even at extremely high doses (up to 2,250 mg) in attempts to get "high." 2
• IV injection causes particularly severe vascular complications including cellulitis, tissue necrosis, and digital ischemia. 3

Clinical Presentation of Misuse

• Tachycardia is the most common presenting sign, followed by seizures. 3
• Other presentations include headaches, anxiety, insomnia, and grand mal seizures at high doses. 5

Potential Therapeutic Benefits

Evidence for Harm Reduction

Compared to days without active prescriptions, days with bupropion treatment were associated with 23% decreased odds of stimulant-related ED or hospital admissions (OR = 0.77; 95% CI, 0.72-0.82) in patients with opioid use disorder. 1 This protective effect was sustained across both cocaine and amphetamine subtypes. 1

Comorbid Conditions

• In patients with comorbid PTSD and methamphetamine use disorder, bupropion showed greater reduction in PTSD symptom severity (PTSD checklist scores decreased from 77 to 29) compared to serotonergic agents alone (51 to 53). 6
• Bupropion-treated patients showed lower methamphetamine relapse rates (25.0% vs 48.8%) and reduced hospital utilization (0% vs 29.3%). 6

Drug Interactions Critical for This Population

Contraindicated Combinations

• MAOIs are absolutely contraindicated with bupropion or within 14 days of discontinuation due to increased risk of hypertensive reactions. 4
• Bupropion should not be used concomitantly with opiate medications when prescribed as naltrexone-bupropion combination. 7

Combination with Stimulants

There are no studies of the combination of bupropion and stimulants in the treatment of ADHD or other psychiatric conditions. 7 The PDR does not warn against interactions between bupropion and stimulants, and no case reports of side effects when these agents were combined could be located, but clinicians should proceed with caution in combining these agents until further studies are available. 7

Monitoring Requirements

Essential Monitoring Parameters

• Blood pressure and heart rate should be monitored periodically, especially in the first 12 weeks of treatment, as bupropion can increase blood pressure. 7, 4
• Screen for bipolar disorder before initiating treatment and monitor for activation of mania/hypomania. 4
• Observe for neuropsychiatric adverse events including changes in mood, psychosis, hallucinations, paranoia, aggression, hostility, agitation, anxiety, and suicidal ideation. 4

Screening Before Prescribing

• Clinicians must screen for anorexia nervosa and bulimia nervosa histories prior to prescribing bupropion. 5
• Obtain comprehensive substance use history, particularly stimulant use patterns. 3
• Assess for seizure disorder history in patient and first-degree family members. 7

Clinical Decision Algorithm

When to Consider Bupropion

1. Patient has comorbid opioid use disorder and stimulant use with goal of reducing stimulant-related harms. 1
2. Patient has comorbid PTSD and methamphetamine use disorder where traditional serotonergic agents have failed. 6
3. Patient has comorbid depression requiring treatment in the context of stimulant use disorder. 8

When to Avoid Bupropion

1. Any history of seizure disorder, bulimia, or anorexia nervosa. 4, 5
2. Active polysubstance use disorder with multiple routes of administration (high diversion risk). 3
3. History of medication misuse via non-oral routes (insufflation, injection). 3
4. Uncontrolled hypertension. 7

Common Pitfalls

Prescribing Errors

• Failing to recognize that patients with dual ADHD and stimulant use disorder are at particularly high risk for bupropion misuse. 3
• Prescribing bupropion without adequate screening for eating disorder history, which dramatically increases seizure risk. 5
• Exceeding the 450 mg maximum daily dose, which exponentially increases seizure risk. 4

Monitoring Failures

• Not providing adequate patient education about the serious risks of crushing, chewing, or insufflating tablets, which can lead to rapid absorption and seizures. 2, 3
• Failing to implement additional screening and follow-up in at-risk populations with substance use disorder history. 3
• Not recognizing that bupropion's over-the-counter accessibility in some settings and lower stigmatization could increase misuse prevalence. 2

Special Populations

Dose Adjustments

• Moderate to severe hepatic impairment: 150 mg every other day maximum. 8
• Moderate to severe renal impairment: reduce total daily dose by half. 8
• Mild hepatic or renal impairment: consider reducing dose and/or frequency. 4