Is it safe to take Contrave (bupropion and naltrexone) with sertraline (Zoloft) and Adderall (amphetamine and dextroamphetamine)?

Safety of Contrave with Sertraline and Adderall

The combination of Contrave (bupropion/naltrexone), sertraline, and Adderall carries significant risks and is not recommended due to the potential for serotonin syndrome, additive neuropsychiatric effects, and cardiovascular complications.

Medication Interactions and Risks

Serotonin Syndrome Risk

• The combination of bupropion (in Contrave) with sertraline significantly increases the risk of serotonin syndrome, a potentially life-threatening condition 1
• Symptoms of serotonin syndrome include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity that can progress to fever, seizures, and even death 2
• Adding Adderall (amphetamine) further increases this risk as stimulants are listed among medications that can contribute to serotonin syndrome when combined with serotonergic drugs 2

Cardiovascular Concerns

• Both Contrave and Adderall can increase blood pressure and heart rate:
  • Contrave causes modest increases in blood pressure, particularly in the first 8 weeks 3
  • Adderall has stimulant effects on the cardiovascular system
  • The combination may lead to additive effects on blood pressure and heart rate 3

Neuropsychiatric Effects

• The combination may increase risk of:
  • Insomnia
  • Anxiety
  • Mood changes
  • Seizures (bupropion lowers seizure threshold) 2, 3
• Approximately 25% of patients discontinue Contrave due to adverse effects even without these additional medications 3, 4

Specific Contraindications

• Bupropion is chemically related to amphetamines, making the combination with Adderall particularly concerning 4
• The American Academy of Child and Adolescent Psychiatry recommends caution when combining medications that affect serotonin levels 2
• Contrave has many pharmacokinetic and pharmacodynamic interactions that can lead to additive convulsive or hypertensive effects 4

Alternative Approaches

If weight management is the goal:

• Consider alternative weight management approaches for patients already on Adderall and sertraline 3
• If medication is necessary, consider medications with fewer interaction potentials
• Focus on dietary measures and regular physical activity as the foundation of weight management 4

Monitoring If Combination Is Deemed Necessary

If, despite these risks, the combination is deemed absolutely necessary:

1. Start with lower doses of all medications
2. Implement more frequent monitoring of:
   • Vital signs (especially blood pressure and heart rate)
   • Neuropsychiatric symptoms
   • Signs of serotonin syndrome
3. Educate the patient about warning signs requiring immediate medical attention:
   • Confusion, agitation, or anxiety
   • Muscle rigidity, tremors, or twitching
   • Fever, sweating, or shivering
   • Rapid heart rate or blood pressure changes

Warning Signs Requiring Immediate Discontinuation

• Any symptoms suggesting serotonin syndrome
• Significant increases in blood pressure or heart rate
• New or worsening neuropsychiatric symptoms
• Any signs of seizure activity

The evidence strongly suggests avoiding this three-drug combination due to the overlapping and potentially dangerous side effect profiles, with particular concern for serotonin syndrome, cardiovascular effects, and neuropsychiatric complications.