Can You Take Lithium or Lurasidone for Bipolar with Wellbutrin?
Yes, both lithium and lurasidone can be safely combined with bupropion (Wellbutrin) in patients with bipolar disorder, as there are no documented pharmacokinetic interactions or contraindications between these medications. 1
Evidence for Lithium + Bupropion Combination
- The American Academy of Child and Adolescent Psychiatry explicitly states there are no studies of the combination of bupropion and stimulants (or other medications) showing adverse interactions, and the PDR does not warn against interactions between bupropion and mood stabilizers like lithium 1
- Lithium is recommended as a first-line treatment for bipolar disorder in patients age 12 and older, with strong evidence for both acute mania and maintenance therapy 2, 3
- When adding antidepressants like bupropion to mood stabilizers for bipolar depression, the National Institute for Health and Care Excellence recommends preferring bupropion over tricyclic antidepressants due to lower risk of mood destabilization 2
- Bupropion must always be combined with a mood stabilizer (such as lithium) in bipolar disorder—never use it as monotherapy, as antidepressant monotherapy can trigger manic episodes or rapid cycling 2
Evidence for Lurasidone + Bupropion Combination
- Lurasidone is FDA-approved both as monotherapy and as adjunctive therapy with lithium or valproate for acute bipolar I depression 4, 5, 6
- Lurasidone combined with mood stabilizers has demonstrated efficacy in treating bipolar depression with effect sizes of 0.34 for adjunctive therapy and minimal metabolic side effects 5, 6
- There are no documented drug-drug interactions between lurasidone and bupropion, as lurasidone's pharmacological profile (high-affinity antagonism at D2, 5-HT2A, and 5-HT7 receptors) does not interfere with bupropion's norepinephrine-dopamine reuptake inhibition mechanism 6
- When lurasidone is combined with lithium specifically, notably larger antidepressant effect sizes are observed (d = 0.45 on MADRS) compared to combination with valproate (d = 0.22) 7
Clinical Algorithm for Combination Therapy
- For bipolar depression: Start with lithium or lurasidone as the primary mood stabilizer, then add bupropion (150-300mg/day) if depressive symptoms persist after 6-8 weeks at therapeutic doses 2
- For maintenance therapy: Continue the combination that successfully treated the acute episode for at least 12-24 months 2, 8
- Triple combination (lithium + lurasidone + bupropion): This is rational for treatment-resistant bipolar depression, as lurasidone can be safely combined with lithium (FDA-approved combination), and bupropion can be added to this regimen without pharmacokinetic concerns 8, 4, 7
Monitoring Requirements
- For lithium: Check serum levels (target 0.8-1.2 mEq/L for acute treatment, 0.6-1.0 mEq/L for maintenance), renal function, and thyroid function every 3-6 months 2, 3
- For lurasidone: Monitor BMI monthly for 3 months then quarterly, blood pressure, fasting glucose, and lipids at 3 months then yearly 2
- Assess for mood destabilization, suicidal ideation, or worsening symptoms within 1-2 weeks of adding bupropion 2
Critical Pitfalls to Avoid
- Never use bupropion as monotherapy in bipolar disorder—it must always be combined with a mood stabilizer to prevent mood destabilization 2
- Do not combine bupropion with stimulants without extreme caution, as there are no controlled studies of this combination 1
- Avoid rapid titration of bupropion; start at 150mg daily and increase gradually to minimize risk of behavioral activation 2
- If adding bupropion to an existing lithium or lurasidone regimen, schedule close follow-up within 1-2 weeks to assess for mood destabilization 2