Can I start Contrave (bupropion/naltrexone) for weight loss while taking Adderall XR 30 mg in the morning plus an evening Adderall dose, propranolol 10 mg daily, cariprazine 4.5 mg daily, lamotrigine 200 mg twice daily, and eszopiclone 3 mg at bedtime?

Can Contrave Be Started with This Medication Regimen?

No, Contrave (naltrexone/bupropion) should not be started with this medication regimen due to multiple high-risk drug interactions and absolute contraindications, most critically the combination of bupropion in Contrave with existing Adderall doses creating dangerous seizure risk and potential serotonin syndrome. 1

Critical Safety Concerns

Seizure Risk from Bupropion Overload

• Contrave contains 360 mg of bupropion daily at maintenance dose (32 mg naltrexone/360 mg bupropion), which when added to any existing stimulant regimen dramatically increases seizure threshold lowering. 2, 1
• The maximum safe bupropion dose is 450 mg/day to maintain seizure risk at 0.1%, and Contrave alone approaches this limit at 360 mg daily. 1
• Combining bupropion with amphetamine stimulants (Adderall) creates additive seizure risk that is not quantified in safety studies but is pharmacologically predictable. 1
• Lamotrigine 200 mg twice daily (400 mg total) is an antiepileptic drug; abrupt changes in this regimen while adding bupropion would further elevate seizure risk. 1

Serotonin Syndrome and Sympathomimetic Toxicity

• The combination of bupropion with lisdexamfetamine or amphetamine salts can potentially precipitate serotonin syndrome, despite bupropion having minimal direct serotonergic activity. 1
• Monitor for altered mental status (confusion, agitation), neuromuscular hyperactivity (tremor, clonus), and autonomic hyperactivity (elevated blood pressure, tachycardia, sweating) within the first 24–48 hours of any dose change. 1
• Both bupropion and amphetamines increase norepinephrine and dopamine, creating additive sympathomimetic effects including dangerous blood pressure elevation and tachycardia. 1, 3

Cardiovascular Contraindications

• Contrave causes statistically significant increases in systolic and diastolic blood pressure, most prominently in the first 8 weeks of treatment. 2
• Propranolol 10 mg daily is a very low dose and will not adequately control the blood pressure elevations from Contrave plus dual Adderall dosing. 2
• Uncontrolled hypertension is an absolute contraindication to Contrave use; blood pressure must be controlled before initiating treatment. 2, 3
• The combination of stimulants plus bupropion can cause cardiac arrhythmias, with excess arrhythmias reported in clinical trials. 4

Psychiatric Medication Interactions

• Cariprazine (Vraylar) 4.5 mg is an atypical antipsychotic; while not an absolute contraindication, the addition of activating bupropion to this regimen requires extreme caution for worsening agitation or psychosis. 1
• Bupropion carries a black box warning for increased suicidal thoughts in patients under 24 years, requiring intensive monitoring during weeks 1–2 of treatment. 1, 3
• In clinical trials, 25% of patients discontinued Contrave due to adverse effects (versus 10% placebo), with neuropsychiatric disorders including anxiety, depression, seizures, cognitive impairment, and psychotic symptoms reported. 2, 4

Specific Drug-by-Drug Analysis

Adderall XR 30 mg AM + Evening Adderall Dose

• This dual stimulant regimen already carries cardiovascular and seizure risks that are magnified by adding 360 mg bupropion. 1
• No safety data exist for combining therapeutic-dose amphetamines with Contrave's bupropion component. 1
• The activating properties of both drugs taken together create insomnia risk even with eszopiclone 3 mg at bedtime. 1

Propranolol 10 mg Daily

• This dose is inadequate to counteract the blood pressure elevations from Contrave (average increases of several mmHg systolic/diastolic) plus dual Adderall dosing. 2
• Bupropion can undermine the action of antihypertensive drugs through pharmacodynamic interactions. 4

Cariprazine 4.5 mg Daily

• While psychiatric disorders showed no significant difference between Contrave and placebo groups in obesity trials (anxiety 0.6–5.4% vs 0.2–4.3%, depression 0.1–1.3% vs 0.2–1.6%), these trials excluded patients on complex psychiatric regimens. 2
• The combination of an atypical antipsychotic with bupropion's dopaminergic effects requires monitoring for akathisia, agitation, or psychotic breakthrough. 1

Lamotrigine 200 mg Twice Daily

• Abrupt discontinuation of antiepileptic drugs is an absolute contraindication for bupropion use due to increased seizure risk. 1
• This patient is maintained on a stable antiepileptic regimen, but adding bupropion still lowers seizure threshold independently. 1, 3

Eszopiclone (Lunesta) 3 mg at Bedtime

• Contrave's second dose must not be taken late in the day to minimize insomnia risk, but even with proper timing, the activating effects of bupropion plus dual Adderall may overwhelm eszopiclone's sedative effects. 2, 1

Alternative Weight-Loss Strategies

Safer Pharmacologic Options

• GLP-1 receptor agonists (semaglutide, liraglutide) do not have the seizure, cardiovascular, or drug interaction profile of Contrave and are preferred first-line agents for weight loss in patients on complex psychiatric regimens. 2
• These agents achieve superior weight loss (10–15% vs 4.5% placebo-subtracted for Contrave) with better safety profiles. 2, 5

If Bupropion Is Considered for Depression or Smoking Cessation

• Bupropion monotherapy for depression or smoking cessation (without naltrexone) at 300 mg/day maximum could theoretically be considered, but only after discontinuing or significantly reducing Adderall doses. 1
• Start with 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated, with maximum 150 mg twice daily (300 mg total). 1
• The second dose must be given before 3 PM to minimize insomnia. 1
• Monitor blood pressure, heart rate, and neuropsychiatric symptoms weekly for the first month. 1, 3

Clinical Decision Algorithm

Step 1: Confirm blood pressure is controlled (<130/80 mmHg) on current propranolol dose. If not, uptitrate propranolol or add additional antihypertensive before considering any weight-loss medication. 2, 3

Step 2: Assess whether stimulant doses can be reduced or consolidated to once-daily dosing. Dual Adderall dosing plus Contrave is not safe. 1

Step 3: If weight loss is the primary goal, initiate GLP-1 receptor agonist (semaglutide 2.4 mg weekly or liraglutide 3 mg daily) instead of Contrave. 2

Step 4: If bupropion is needed for depression or smoking cessation (not weight loss), discontinue or reduce Adderall to lowest effective dose, then start bupropion monotherapy at 37.5 mg with slow titration. 1

Step 5: Monitor weekly for 4 weeks after any medication change for blood pressure elevation, seizure activity, serotonin syndrome signs, or psychiatric decompensation. 1, 3

Common Pitfalls to Avoid

• Do not assume low-dose propranolol provides adequate cardiovascular protection against Contrave plus stimulants. 2
• Do not start Contrave without first establishing controlled blood pressure (<130/80 mmHg). 2, 3
• Do not combine full-dose stimulants with Contrave's 360 mg bupropion component. 1
• Do not overlook the 25% discontinuation rate due to adverse effects with Contrave, primarily nausea (4.6–9.6%), vomiting, headache, and dizziness. 2
• Do not prescribe Contrave if the patient requires opioid medications now or in the future, as naltrexone blocks opioid receptors and precipitates withdrawal. 2, 3