In a patient with bipolar II disorder, comorbid depression and post‑traumatic stress disorder who is taking aripiprazole (Abilify) 5 mg and bupropion (Wellbutrin) 150 mg but remains very depressed, should the bupropion be discontinued and the aripiprazole dose increased?

Increase Aripiprazole and Continue Bupropion

In a patient with bipolar II disorder experiencing persistent depression despite aripiprazole 5 mg and bupropion 150 mg, the optimal strategy is to increase the aripiprazole dose while continuing bupropion, rather than stopping the bupropion. This approach addresses the inadequate antipsychotic dosing while maintaining the antidepressant effect without introducing unnecessary risk of mood destabilization.

Rationale for Increasing Aripiprazole

The current aripiprazole dose of 5 mg is at the lower end of the therapeutic range. Evidence specifically in bipolar II depression demonstrates that low-dose aripiprazole (1-5 mg) can be effective, but many patients require dose optimization 1. The study found that patients with bipolar II or bipolar NOS depression showed significant improvement with aripiprazole doses up to 5 mg, with the key being gradual titration and adequate time to respond 1.

Aripiprazole has demonstrated efficacy as augmentation therapy in treatment-resistant depression, including in patients with comorbid PTSD 2, 3. In the VAST-D trial, aripiprazole augmentation achieved a 68.4% response rate in patients with concurrent PTSD and depression, significantly better than switching strategies 2. Given your patient has both bipolar II depression and PTSD, aripiprazole augmentation is particularly well-suited.

Dosing Strategy for Aripiprazole

• Start by increasing to 7.5 mg daily for 1-2 weeks
• If tolerated but insufficient response, increase to 10 mg daily
• Maximum dose typically 15 mg daily for bipolar depression
• Monitor closely for akathisia, restlessness, and activation 1, 3

Why Continue Bupropion

Stopping bupropion is not indicated based on the current evidence. The FDA label explicitly warns that bupropion can precipitate manic episodes in patients with bipolar disorder 4, but this risk must be weighed against several factors:

1. The patient is already on a mood stabilizer (aripiprazole), which provides protection against mood switching
2. Bupropion at 150 mg is a relatively low dose (therapeutic range extends to 300-450 mg) 5
3. Abrupt discontinuation of antidepressants can precipitate depressive relapse 6
4. In bipolar depression with comorbid PTSD, combination therapy may be necessary for adequate symptom control 2

The evidence shows that bupropion augmentation can be effective in treatment-resistant depression 7, 8. One study specifically demonstrated rapid improvement when aripiprazole was added to bupropion-resistant depression 8, suggesting these medications can work synergistically.

Critical Safety Considerations

Monitor for Manic Switch

While bupropion carries a black box warning for activation of mania/hypomania in bipolar disorder 4, case reports of manic switch with bupropion in bipolar patients typically occurred when:

• Used without adequate mood stabilization 9
• Doses were increased too rapidly
• Patients had bipolar I (higher risk than bipolar II)

Your patient has bipolar II, which has lower risk of full manic episodes. Nonetheless, monitor weekly for:

• Decreased need for sleep
• Increased energy or goal-directed activity
• Racing thoughts or pressured speech
• Impulsivity or risk-taking behavior

Assess Response Timeline

• Evaluate response at 4-6 weeks after aripiprazole dose increase 6
• If no improvement by 6-8 weeks, consider further medication adjustment 6
• Do not make multiple changes simultaneously – this prevents identifying which intervention is effective or causing problems

Alternative Considerations Only If This Fails

If the patient shows no improvement after optimizing aripiprazole (up to 10-15 mg) while continuing bupropion 150 mg:

1. Increase bupropion to 300 mg (if no mood instability observed) 5, 10
2. Consider switching bupropion to an SSRI (though SSRIs also carry manic switch risk) 6
3. Add lamotrigine as a mood stabilizer with antidepressant properties (though this requires slow titration)

Common Pitfalls to Avoid

• Do not stop bupropion abruptly – taper over 10-14 days if discontinuation becomes necessary 6
• Do not increase both medications simultaneously – you won't know which caused benefit or harm
• Do not assume treatment failure at current doses – aripiprazole 5 mg may simply be subtherapeutic
• Do not overlook non-pharmacologic interventions – ensure the patient is engaged in evidence-based psychotherapy for both PTSD and bipolar depression

The evidence strongly supports optimizing your current regimen before abandoning it. The combination of aripiprazole and bupropion has demonstrated efficacy in treatment-resistant depression with comorbid PTSD 2, 8, and your patient is on suboptimal doses of both medications.