What medication should be started for a patient with bipolar 2 disorder who is currently taking Wellbutrin (bupropion) for depression and fluoxetine (Prozac) for anxiety?

Immediate Medication Management for Bipolar 2 Disorder

You must immediately discontinue or taper both bupropion (Wellbutrin) and fluoxetine, then initiate a mood stabilizer such as lithium or valproate as first-line monotherapy, as antidepressants without mood stabilizers carry significant risk of mood destabilization and manic switching in bipolar disorder. 1, 2

Critical First Steps: Address the Antidepressant Problem

Discontinue Current Regimen

• Both bupropion and fluoxetine pose substantial risk for precipitating hypomania or mania in bipolar 2 disorder when used without mood stabilizers 3, 4
• Bupropion specifically has demonstrated a 55% rate (6 of 11 patients) of inducing manic/hypomanic episodes in bipolar patients, even when combined with lithium and carbamazepine or valproate 3
• Antidepressant monotherapy is explicitly not recommended for bipolar disorder treatment 1
• Taper both medications over 1-2 weeks while simultaneously initiating mood stabilizer therapy 2

The Manic Switch Risk

• Fluoxetine monotherapy in bipolar 2 patients shows a 3.8% manic switch rate during short-term treatment, though this is relatively low compared to other antidepressants 5
• However, any antidepressant use without mood stabilizer coverage is contraindicated in established bipolar disorder 1, 4

First-Line Mood Stabilizer Selection

Lithium (Preferred Option)

• Lithium is the only FDA-approved medication for bipolar disorder in patients age 12 and older, approved for both acute mania and maintenance therapy 2
• Lithium demonstrates the best long-term evidence for maintenance treatment and suicide prevention in bipolar disorder 2, 1
• Initiate lithium 300 mg twice daily, titrating to therapeutic blood levels of 0.6-1.2 mEq/L 2
• Requires baseline and ongoing monitoring: serum lithium levels, thyroid function (TSH), renal function (creatinine, BUN), and ECG if indicated 2
• Lithium should only be initiated where personnel and facilities for close clinical and laboratory monitoring are available 2

Valproate (Alternative First-Line)

• Valproate is FDA-approved for acute mania in adults and recommended for maintenance treatment 2
• Initiate valproate 250-500 mg twice daily, titrating to therapeutic levels of 50-125 mcg/mL 2
• May be preferred over lithium if monitoring resources are limited or patient has renal concerns 2
• Both lithium and valproate should be continued for at least 2 years after the last bipolar episode 2

Lamotrigine (For Depressive Phase Emphasis)

• Lamotrigine is FDA-approved for maintenance therapy in adults and particularly effective for preventing depressive episodes 2, 1
• Requires slow titration (25 mg daily for 2 weeks, then 50 mg daily for 2 weeks, then 100-200 mg daily) to minimize risk of Stevens-Johnson syndrome 1
• Consider lamotrigine as first-line if the patient's bipolar 2 presentation is predominantly depressive with infrequent hypomanic episodes 1

Atypical Antipsychotics as Alternative First-Line

When to Consider Antipsychotics

• Quetiapine, aripiprazole, lurasidone, and cariprazine are all recommended first-line agents for bipolar disorder 1
• Quetiapine is FDA-approved for bipolar depression and may be particularly useful if rapid symptom control is needed 1, 4
• Aripiprazole, asenapine, lurasidone, and cariprazine are FDA-approved for various phases of bipolar disorder 1

Practical Considerations

• Atypical antipsychotics carry significant metabolic risks: 37% prevalence of metabolic syndrome, 21% obesity, and 14% type 2 diabetes in bipolar patients 1
• Monitor weight, fasting glucose, and lipid panel at baseline and regularly during treatment 1
• Consider quetiapine 50-300 mg at bedtime if insomnia is prominent, or aripiprazole 2-15 mg daily if metabolic concerns are paramount 6

If Antidepressants Are Eventually Needed

Only After Mood Stabilizer Established

• Antidepressants should never be used as monotherapy but may be considered for breakthrough depression only after establishing therapeutic mood stabilizer levels 2, 4
• SSRIs (particularly fluoxetine) are preferred over tricyclic antidepressants when antidepressants are necessary 2
• The combination of olanzapine plus fluoxetine is the only FDA-approved treatment specifically for bipolar depression 2, 4
• Bupropion may be used as an adjunct but carries the same manic switch risk as other antidepressants 4, 3

Treatment Algorithm Summary

1. Week 1-2: Taper fluoxetine and bupropion while simultaneously starting lithium 300 mg BID or valproate 250-500 mg BID 2
2. Week 2-4: Titrate mood stabilizer to therapeutic levels based on blood monitoring 2
3. Week 4-8: Assess response; if inadequate, consider adding atypical antipsychotic (quetiapine 50-300 mg or aripiprazole 2-15 mg) 1
4. After 8+ weeks: Only if significant depressive symptoms persist despite therapeutic mood stabilizer levels, consider cautiously reintroducing an SSRI (fluoxetine preferred) while maintaining mood stabilizer 2, 5

Critical Monitoring Points

• Suicide risk is 64 times higher in bipolar disorder (0.9% annual rate vs 0.014% in general population), with 15-20% lifetime suicide completion rate 1
• Assess suicide risk at every visit, particularly during medication transitions 1
• Life expectancy is reduced by 12-14 years in bipolar disorder, primarily due to cardiovascular disease occurring 17 years earlier than general population 1
• More than 50% of bipolar patients are non-adherent to treatment, requiring ongoing psychoeducation and family involvement 1, 2