Can Wellbutrin (bupropion) and Strattera (atomoxetine) be taken together?

Can Wellbutrin and Strattera Be Taken Together?

Yes, Wellbutrin (bupropion) and Strattera (atomoxetine) can be safely taken together—there are no absolute contraindications to this combination, and no significant pharmacokinetic interactions preclude their concurrent use. However, this combination requires careful monitoring for cardiovascular effects, seizure risk, and neuropsychiatric symptoms 1.

Key Safety Considerations Before Starting

Absolute Contraindications to Verify

Before combining these medications, confirm the patient does not have:

• Active seizure disorder or history of seizures—bupropion lowers the seizure threshold with a documented 0.1% seizure risk at therapeutic doses 1, 2
• Brain metastases or structural brain lesions 1
• Eating disorders (bulimia or anorexia nervosa)—these conditions significantly increase seizure risk with bupropion 1, 2
• Alcohol withdrawal or abrupt benzodiazepine discontinuation—both dramatically lower seizure threshold 1, 2
• Uncontrolled hypertension—both medications can elevate blood pressure and heart rate 1, 3
• Current or recent MAOI use (within 14 days) 2

Cardiovascular Screening Required

• Measure baseline blood pressure and heart rate before initiating the combination 1, 3
• Both bupropion and atomoxetine can independently raise blood pressure and heart rate 1, 4
• Atomoxetine was associated with statistically (but not clinically) significant increases in heart rate and blood pressure in pediatric patients 5

Dosing Strategy for the Combination

Bupropion Dosing

• Start at 150 mg once daily (SR formulation) 2, 1
• Increase to 150 mg twice daily (300 mg total) after 3–7 days if tolerated 2, 1
• Maximum dose is 300 mg/day when combined with other CNS-active medications to minimize seizure risk 1, 3
• Do not exceed 450 mg/day under any circumstances 2

Atomoxetine Dosing

• Start at 40 mg once daily 4
• Titrate every 7–14 days to 60 mg, then 80 mg as tolerated 4
• Maximum dose is 1.4 mg/kg/day or 100 mg/day, whichever is less 4
• Atomoxetine dosing does not require specific adjustment when combined with bupropion 1

Special Population Dose Adjustments

• Moderate to severe hepatic impairment: Maximum bupropion dose is 150 mg daily 2, 1
• Moderate to severe renal impairment (GFR <90 mL/min): Reduce bupropion dose by 50% 2, 1
• Poor CYP2D6 metabolizers: Atomoxetine exposure is significantly higher; monitor closely for adverse effects 5

Monitoring Protocol

First Month (Weekly Monitoring)

• Blood pressure and heart rate at each visit 1, 3
• Mental status assessment focusing on suicidal ideation, agitation, irritability, or unusual behavioral changes—the risk of suicide attempts is highest during the first 1–2 months 2, 1
• Mood symptoms, sleep quality, and appetite 1

After First Month (Monthly Monitoring)

• Continue blood pressure and heart rate checks monthly 1, 3
• Assess for neuropsychiatric symptoms including agitation, restlessness, anxiety, panic attacks, insomnia, irritability, hostility, or worsening depression 3

Timeline for Efficacy Assessment

• Allow 6–8 weeks at therapeutic doses before determining treatment response 2, 1
• Early improvement in energy may occur with bupropion within the first few weeks, but definitive response assessment should wait until 6–8 weeks 2
• If no adequate response by 6–8 weeks, modify the treatment approach (dose adjustment, switch, or augmentation) 2, 1

Clinical Rationale for This Combination

Complementary Mechanisms

• Bupropion works via noradrenergic/dopaminergic pathways, providing activating properties that improve energy, motivation, and apathy 2, 1
• Atomoxetine selectively inhibits norepinephrine reuptake in the prefrontal cortex, improving attention and executive function 5, 6
• The combination addresses different neurotransmitter systems and may be particularly beneficial for patients with ADHD plus comorbid depression, low energy, or apathy 1

Specific Patient Populations Who May Benefit

• Patients with ADHD and comorbid depression who have not responded adequately to monotherapy 1
• Patients at risk for substance abuse—atomoxetine has negligible abuse potential and is not a controlled substance 5, 6
• Patients with comorbid anxiety or tics—atomoxetine is particularly useful in these populations 5
• Patients concerned about sexual dysfunction—bupropion has significantly lower rates of sexual dysfunction compared to SSRIs 2

Critical Safety Warnings

Black Box Warning

• Bupropion carries an FDA black box warning for increased risk of suicidal thoughts and behavior in patients younger than 24 years with depression 2, 3
• Weekly monitoring is mandatory during the first month, especially in patients under 24 years 2, 3

Seizure Risk Management

• The seizure risk with bupropion at 300 mg/day is approximately 0.1% (1 in 1,000) 2
• Never exceed 300 mg/day when combining with other CNS-active medications 1, 3
• Avoid rapid dose escalation—titrate gradually over 3–7 days 2, 1

Hepatotoxicity Monitoring (Atomoxetine)

• Atomoxetine has been associated with rare cases of serious liver injury 5
• Monitor for signs of hepatic dysfunction (jaundice, dark urine, right upper quadrant tenderness, unexplained flu-like symptoms) 5

Common Pitfalls to Avoid

• Do not skip the intensive monitoring window during weeks 1–2, as this period carries the highest risk for emergent suicidal ideation 2, 1
• Do not exceed maximum bupropion doses—seizure risk rises markedly above 450 mg/day, and should be capped at 300 mg/day when combined with other medications 1, 3
• Do not discontinue abruptly—both medications should be tapered gradually to minimize withdrawal symptoms 2
• Do not combine with MAOIs or initiate within 14 days of MAOI discontinuation 2
• Both medications are activating—this can be advantageous for patients with significant fatigue but may worsen anxiety or insomnia 1, 3