Is it safe for an adult with a history of opioid dependence and depression to take Wellbutrin (bupropion) with Suboxone (buprenorphine and naloxone)?

Safety of Combining Wellbutrin (Bupropion) with Suboxone (Buprenorphine/Naloxone)

Combining Wellbutrin with Suboxone is generally safe and can be clinically beneficial for patients with both opioid dependence and depression, though close monitoring for serotonin syndrome is essential, particularly during treatment initiation. 1, 2

Key Safety Considerations

Primary Contraindication to Avoid

• Naltrexone-bupropion combination products (used for weight management) are absolutely contraindicated with any opioid therapy, including Suboxone, because naltrexone is an opioid antagonist that will precipitate severe withdrawal in opioid-dependent patients. 3, 1

• This contraindication does NOT apply to bupropion monotherapy (Wellbutrin) for depression or smoking cessation, which operates through different mechanisms. 3, 1

Serotonin Syndrome Risk

• One case report documented serotonin syndrome when buprenorphine/naloxone was combined with a tricyclic antidepressant, presenting with clonus, agitation, and altered mental status requiring intubation and treatment with cyproheptadine. 2

• While bupropion is not a serotonergic agent, buprenorphine has weak serotonergic properties that can theoretically contribute to serotonin syndrome when combined with other medications. 2

• Monitor closely for signs of serotonin syndrome during the first 1-2 weeks of combination therapy, including agitation, confusion, tremor, muscle rigidity, hyperthermia, and autonomic instability. 1, 2

Clinical Benefits of This Combination

Addressing Comorbid Conditions

• Bupropion may be particularly beneficial for patients with opioid dependence and comorbid depression, as it addresses both conditions through complementary mechanisms. 1, 4

• Buprenorphine itself may have antidepressant properties, though this has not been extensively studied, making the addition of bupropion a rational augmentation strategy. 4

• For patients who smoke, this combination addresses three conditions simultaneously: opioid dependence, depression, and nicotine dependence. 1

Dosing Strategy for Safe Initiation

Starting Bupropion in Patients on Suboxone

• Start with bupropion SR 37.5 mg every morning, increasing by 37.5 mg every 3 days as tolerated, targeting 150 mg twice daily (maximum 300 mg/day). 1

• Administer the second dose before 3 PM to minimize insomnia risk, as bupropion has activating properties. 1

• This gradual titration minimizes seizure risk while allowing assessment of tolerability in patients on multiple medications. 1

Monitoring Parameters

• Monitor blood pressure and heart rate at baseline and periodically during the first 12 weeks, as bupropion can cause elevations in both parameters. 1

• Assess for neuropsychiatric adverse effects including increased agitation, restlessness, and behavioral changes, particularly in patients under 24 years old. 1

• Watch for signs of serotonin syndrome during the first 1-2 weeks: agitation, confusion, tremor, muscle rigidity, diaphoresis, and hyperthermia. 1, 2

• Evaluate treatment response after 6-8 weeks at therapeutic doses before considering modification. 1

Critical Contraindications for Bupropion

Absolute Contraindications

• Seizure disorders or any condition that lowers seizure threshold (seizure risk approximately 1 in 1,000). 1

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs. 1

• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. 1

• Uncontrolled hypertension. 1

• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk. 1

Dose Adjustments Required

• For moderate to severe hepatic impairment, maximum dose is 150 mg daily. 1

• For moderate to severe renal impairment (GFR <90 mL/min), reduce total daily dose by 50%. 1

Common Pitfalls to Avoid

• Do not confuse bupropion monotherapy (Wellbutrin) with naltrexone-bupropion combination products (Contrave) - only the latter is contraindicated with opioids. 3, 1

• Do not exceed 300 mg/day total dose for depression to maintain seizure risk at 0.1%. 1

• Do not administer the second dose late in the day, as this significantly increases insomnia risk. 1

• Do not discontinue treatment prematurely before 6-8 weeks unless significant adverse effects occur, as full therapeutic effect requires adequate time. 1