What are the considerations for using Contrave (bupropion/naltrexone) in patients with bipolar disorder?

Contrave (Bupropion/Naltrexone) in Patients with Bipolar Disorder

Contrave (bupropion/naltrexone) should be avoided in patients with bipolar disorder due to significant risk of triggering manic episodes, even when patients are on mood stabilizers. 1, 2

Risk of Mania/Hypomania

• The FDA label for bupropion (a component of Contrave) explicitly states that antidepressant treatment can precipitate manic, mixed, or hypomanic episodes, with increased risk in patients with bipolar disorder 1
• Clinical evidence shows that bupropion can trigger manic episodes in bipolar patients:
  • In a study of 11 bipolar patients, 6 (55%) experienced manic or hypomanic episodes necessitating discontinuation of bupropion, even when stabilized on mood stabilizers like lithium, carbamazepine, or valproate 2
  • Case reports document manic shifts in bipolar patients when bupropion was added as an adjunct to mood stabilizer treatment 3

Dosing Considerations

• There may be a dose-related threshold for triggering mania with bupropion:
  • Evidence suggests that exceeding the maximum recommended daily dose of 450 mg may increase risk of manic switch 4
  • Contrave contains a substantial dose of bupropion (up to 360 mg daily at maintenance dose) 5, approaching this threshold

Contraindications and Precautions

• Bupropion can cause neuropsychiatric reactions including:

  • Delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion 1
  • These symptoms may be particularly problematic in patients with bipolar disorder

• Additional precautions with Contrave:

  • May lower seizure threshold 5
  • Can cause increases in blood pressure, particularly in the first 8 weeks 5, 6
  • Should not be used with opioids due to naltrexone component 5
  • Should be discontinued before procedures requiring opioid analgesia 5

Alternative Weight Management Options

• For bipolar patients needing weight management:
  • Consider weight-neutral antipsychotics like lurasidone and ziprasidone 5
  • Aripiprazole generally demonstrates lower risk for weight gain compared to other antipsychotics 5
  • Topiramate (alone or in combination with phentermine as Qsymia) has been associated with weight loss and may be a safer alternative for some bipolar patients 5

Recent Evidence on Bupropion in Bipolar Disorder

• A meta-analysis found that while bupropion can improve depressive symptoms in bipolar disorder, the rate of phase shifting (switching to mania) was similar to other antidepressants, contradicting previous beliefs about bupropion's lower switch risk 7

Monitoring If Use Is Unavoidable

If Contrave must be used in a bipolar patient (which is generally not recommended):

• Ensure patient is on adequate mood stabilizer therapy
• Start with lowest possible dose and titrate slowly
• Monitor closely for signs of mania/hypomania
• Discontinue immediately if signs of mood elevation occur
• Monitor blood pressure and heart rate regularly, especially during the first 12 weeks 5
• Discontinue if less than 5% weight loss after 12 weeks at maintenance dose 5

In conclusion, the risks of using Contrave in bipolar disorder generally outweigh the benefits, and alternative weight management strategies should be strongly considered.