How to safely taper bupropion (Wellbutrin) and fluoxetine (Prozac) in a patient with bipolar 2 disorder?

Tapering Bupropion and Fluoxetine in Bipolar 2 Disorder

In a patient with bipolar 2 disorder, both bupropion and fluoxetine should be tapered gradually over at least 1 week, with bupropion discontinued first due to its risk of precipitating mania in bipolar patients, followed by fluoxetine taper. 1, 2

Critical Safety Considerations for Bipolar 2 Patients

Why These Medications Are Problematic in Bipolar Disorder

• Bupropion is not approved for bipolar depression and carries significant risk of precipitating manic, mixed, or hypomanic episodes, with the risk appearing increased in patients with bipolar disorder. 1
• The FDA label explicitly warns that antidepressant treatment can precipitate manic episodes in bipolar patients, and bupropion should be discontinued if psychosis, delusions, hallucinations, or manic symptoms occur. 1
• Research shows that 55% (6 of 11) of bipolar patients experienced manic or hypomanic episodes requiring bupropion discontinuation, even when stabilized on lithium and mood stabilizers. 3
• Fluoxetine monotherapy in bipolar 2 disorder carries a 3.8% manic switch rate during short-term therapy, though this is relatively low compared to other antidepressants. 4

Specific Tapering Protocol

Step 1: Discontinue Bupropion First

Bupropion Taper Schedule:

• If on 300 mg/day: Reduce to 150 mg once daily for 3-7 days, then discontinue. 5
• If on 150 mg twice daily: Reduce to 150 mg once daily for 3-7 days, then discontinue. 5
• The 15 mg/92 mg dose (in combination products) should not be discontinued abruptly and requires tapering over at least 1 week. 5
• Monitor closely for worsening depression, suicidal ideation, anxiety, agitation, panic attacks, insomnia, irritability, hostility, or akathisia during the taper. 2, 1

Step 2: Taper Fluoxetine After Bupropion Discontinuation

Fluoxetine Taper Approach:

• Fluoxetine has a long half-life (4-6 days for fluoxetine, 4-16 days for its active metabolite norfluoxetine), which provides a built-in taper effect.
• If the patient has been on fluoxetine long-term, taper by reducing the dose by 25-50% every 1-2 weeks. 6
• For example, if on 40 mg daily: reduce to 20 mg daily for 1-2 weeks, then to 10 mg daily for 1-2 weeks, then discontinue.
• Abrupt discontinuation can be associated with withdrawal symptoms, so medication should be tapered as rapidly as feasible while monitoring for discontinuation symptoms. 2

Monitoring During Taper

Critical Symptoms to Monitor

• Watch for emergence of manic or hypomanic symptoms: decreased need for sleep, racing thoughts, increased energy, impulsivity, grandiosity, pressured speech. 1, 5
• Monitor for worsening depression or suicidal ideation, especially during the first few weeks of dose changes. 2, 1
• Screen for anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, and akathisia, as these may represent precursors to emerging suicidality or mood destabilization. 2
• Follow up at least weekly during the initial taper period, then every 2 weeks until both medications are fully discontinued. 6

Common Pitfalls to Avoid

• Never discontinue both medications simultaneously - this increases the risk of severe withdrawal symptoms and mood destabilization. 6
• Do not taper too rapidly - rushing the taper increases the risk of withdrawal symptoms and mood episodes. 6
• Do not abandon the patient if tapering is difficult - maintain the therapeutic relationship and consider pausing the taper if severe symptoms emerge. 6
• Ensure the patient is on adequate mood stabilizer therapy before and during the taper - lithium, valproate, or other mood stabilizers should be optimized to prevent mood destabilization. 5

Alternative Considerations

• If the patient requires ongoing antidepressant therapy for bipolar 2 depression, consider switching to a mood stabilizer alone or the FDA-approved combination of olanzapine and fluoxetine for bipolar depression rather than continuing antidepressant monotherapy. 5
• Antidepressants should only be used as adjuncts to mood stabilizers in bipolar disorder, never as monotherapy. 5
• The American Academy of Child and Adolescent Psychiatry guidelines note that antidepressants may destabilize mood or incite manic episodes in bipolar patients, and caution must be taken. 5