Can Lithium and Wellbutrin Be Taken Together?
Yes, lithium and Wellbutrin (bupropion) can be taken together, and this combination has been used successfully in clinical practice for bipolar depression, though it requires careful monitoring due to potential risks of manic switching and, in rare contexts like ECT, seizure complications.
Evidence Supporting Combined Use
The combination of lithium and bupropion has demonstrated clinical utility in specific populations:
Rapid cycling bipolar disorder patients showed dramatic improvement when bupropion was added to lithium, with sustained response averaging 2 years and notably without the hypomania or rapid cycling typically seen with conventional antidepressants 1
In bipolar II patients with established rapid cycling patterns unresponsive to other interventions, adding bupropion to lithium (and/or levothyroxine) produced significant improvement in four of six patients, with responses sustained over an average of 2 years 1
Long-term maintenance studies showed patients with cyclic mood disorders could be maintained on bupropion alone or combined with other medications for 1 year or more with minimal relapse 2
Critical Safety Concerns
Risk of Manic Switching
The most significant concern with this combination is precipitation of manic or hypomanic episodes:
In one case series, 6 of 11 bipolar patients (55%) experienced manic or hypomanic episodes requiring bupropion discontinuation, even when stabilized on lithium plus carbamazepine or valproate 3
This suggests bupropion may carry similar risks to other antidepressants in triggering mood elevation in bipolar patients, despite some earlier optimistic reports 3
Seizure Risk in Specific Contexts
Bupropion lowers seizure threshold and should be used with extreme caution in patients with seizure disorders 4
One case report documented prolonged seizure activity during ECT in a patient receiving the combination of bupropion, lithium, and venlafaxine together 5
The American Academy of Child and Adolescent Psychiatry notes conflicting reports about lithium safety with ECT, including reports of acute brain syndrome, and recommends avoiding lithium during ECT when clinically possible 6
Monitoring Requirements
When using this combination, close clinical vigilance is essential:
Monitor for early signs of hypomania or mania (increased energy, decreased need for sleep, racing thoughts, impulsivity) particularly in the first weeks after adding bupropion 1, 3
Blood pressure and heart rate monitoring may be needed, as bupropion combinations can potentially increase these parameters 4
Standard lithium monitoring (serum levels, renal function, thyroid function) should continue as usual 7
Clinical Decision Algorithm
When to consider this combination:
- Bipolar depression inadequately responsive to lithium monotherapy 1
- Rapid cycling bipolar II patients who have failed other interventions 1
- Patients who have not tolerated or responded to conventional antidepressants 2
When to avoid or use extreme caution:
- History of antidepressant-induced mania or rapid cycling 3
- Seizure disorders or eating disorders (bupropion contraindications) 4
- During ECT treatment (discontinue both medications if possible) 6, 5
- Severe hepatic impairment 4
Dosing approach:
- Start bupropion at lower doses (150 mg/day) and titrate gradually up to 150-400 mg/day as tolerated 4
- Maintain therapeutic lithium levels (typically 0.6-1.2 mEq/L for maintenance)
- Ensure adequate mood stabilization before adding the antidepressant 1
Common Pitfalls to Avoid
Do not assume bupropion is "safer" than other antidepressants for bipolar depression - the evidence shows similar manic switching rates despite earlier optimistic reports 3
Avoid combining with MAOIs due to potential dangerous interactions 4
Do not discontinue mood stabilizers prematurely when adding bupropion - maintain lithium throughout treatment 1