What is the recommended dosage and monitoring protocol when prescribing Prozac (fluoxetine) and Wellbutrin (bupropion) together?

Dosage and Monitoring Protocol for Prozac and Wellbutrin Combination Therapy

When prescribing fluoxetine (Prozac) and bupropion (Wellbutrin) together, start with fluoxetine 10 mg every other morning and bupropion 37.5 mg every morning, then gradually increase bupropion by 37.5 mg every 3 days to a maximum of 150 mg twice daily, while fluoxetine can be increased to 20 mg every morning as tolerated. 1

Dosing Recommendations

Fluoxetine (Prozac)

• Initial dose: 10 mg every other morning 1
• Maximum dose: 20 mg every morning 1
• Characteristics: Activating with very long half-life; side effects may not manifest for a few weeks 1

Bupropion (Wellbutrin)

• Initial dose: 37.5 mg every morning 1
• Titration: Increase by 37.5 mg every 3 days 1
• Maximum dose: 150 mg twice daily 1
• Characteristics: Activating with possible rapid improvement of energy level 1
• To minimize insomnia risk: Give second dose before 3 p.m. 1

Monitoring Protocol

Initial Assessment (Before Starting)

• Screen for seizure disorders (contraindication for bupropion) 1
• Assess for agitation (bupropion should not be used in agitated patients) 1
• Evaluate baseline mood, energy, sleep patterns, and anxiety levels 1

Follow-up Schedule

• Weekly for the first month to assess response and side effects 1
• Monthly visits once stabilized on medication 1
• Assess need for continued medication after 9 months with potential dosage reduction over 10-14 days to limit withdrawal symptoms 1

Parameters to Monitor

• Neuropsychiatric symptoms: Monitor for development or worsening of depression, hostility, or suicidal ideation 1
• Sleep patterns: Both medications can be activating and may cause insomnia 1
• Weight and appetite changes 1
• Sexual function: Bupropion may help counteract SSRI-induced sexual dysfunction 2
• Treatment response: A full therapeutic trial requires 4-8 weeks 1

Evidence for Combination Therapy

• The combination of fluoxetine (SSRI) and bupropion (NDRI) targets multiple neurotransmitter systems (serotonin, norepinephrine, and dopamine) 3, 2
• Open-label studies suggest combination therapy is effective for patients with inadequate response to monotherapy 4, 2
• In one study, combination therapy of an SSRI with bupropion-SR showed 62% response and 50% remission rates 4

Special Considerations

Drug Interactions

• Fluoxetine may prolong half-life of other drugs by inhibiting cytochrome P450 isoenzymes 1
• Monitor for serotonin syndrome, especially when combining with other serotonergic medications 1
• Avoid MAOIs when using either medication 1

Side Effect Management

• Common side effects of fluoxetine: Sweating, tremors, nervousness, insomnia or somnolence, dizziness, gastrointestinal and sexual disturbances 1
• Common side effects of bupropion: Agitation, dry mouth, insomnia, headaches, nausea, constipation, and tremor 3
• Most serious side effect of bupropion is seizures, which is why gradual dose titration is essential 3

Potential Pitfalls and Caveats

• Bupropion is contraindicated in patients with seizure disorders 1
• Do not use bupropion in agitated patients 1
• Start with lower doses in patients with panic disorder who may be sensitive to activating effects 5
• The combination may increase the risk of side effects, particularly activation, insomnia, and anxiety 1, 2
• If insomnia occurs, ensure the second dose of bupropion is given before 3 p.m. 1
• Although rare, monitor for serotonin syndrome symptoms including mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 1

Efficacy Assessment

• Evaluate response after 4-8 weeks of treatment 1
• Consider standardized symptom rating scales to objectively measure improvement 1
• If inadequate response after 8 weeks of optimal dosing, reassess diagnosis or consider alternative treatment 1