Can bupropion be started as adjunct therapy with fluoxetine (selective serotonin reuptake inhibitor) for depression?

Bupropion Can Be Safely Used as Adjunct Therapy with Fluoxetine for Depression

Bupropion can be effectively and safely combined with fluoxetine as adjunct therapy for depression, with the added benefit of potentially reducing sexual dysfunction associated with fluoxetine. 1

Efficacy of Bupropion-Fluoxetine Combination

• Bupropion has a different mechanism of action than fluoxetine, inhibiting the reuptake of norepinephrine and dopamine rather than serotonin, making it a complementary adjunct therapy 2
• Combination therapy with bupropion and SSRIs like fluoxetine can boost antidepressant response in patients who have had an inadequate response to monotherapy 3
• Evidence from clinical trials shows that approximately 38% of patients do not achieve treatment response and 54% do not achieve remission with second-generation antidepressant monotherapy, supporting the rationale for combination approaches 1
• In a double-blind randomized study, combination therapy from treatment initiation with mirtazapine plus bupropion showed a 46% remission rate compared to 25% with fluoxetine monotherapy 4

Advantages of Adding Bupropion to Fluoxetine

• Bupropion has a significantly lower rate of sexual adverse events compared to fluoxetine and can actually help ameliorate sexual dysfunction caused by SSRIs 1, 3
• The combination targets different neurotransmitter systems - fluoxetine primarily affects serotonin reuptake, while bupropion affects dopamine and norepinephrine 2, 3
• Bupropion may be beneficial for patients with depression who also have symptoms of fatigue, low energy, or concentration difficulties due to its dopaminergic effects 5
• The American College of Physicians notes that bupropion can be considered for patients who experience sexual dysfunction with SSRIs like fluoxetine 1

Dosing and Administration

• Start with a low dose of bupropion and titrate gradually when adding to an existing SSRI like fluoxetine 3
• Bupropion is available in immediate-release (IR), sustained-release (SR), and extended-release (XR) formulations, with the latter two offering the advantage of less frequent daily dosing 5
• Bupropion should be administered earlier in the day to minimize the risk of insomnia 1
• If no improvement is observed after 6-8 weeks of combination therapy, the treatment approach should be reassessed 1

Safety Considerations and Monitoring

• Monitor patients regularly beginning within 1-2 weeks of initiation of combination therapy to assess therapeutic response and adverse effects 1
• The risk for suicide attempts is greater during the first 1-2 months of treatment, requiring close monitoring during this period 1
• Watch for potential drug interactions between bupropion and fluoxetine, as both medications are metabolized by the cytochrome P450 system 3
• Bupropion may lower the seizure threshold and should be used with caution in patients with a history of seizures 1

Potential Adverse Effects to Monitor

• The most commonly reported adverse events with second-generation antidepressants include constipation, diarrhea, dizziness, headache, insomnia, nausea, and somnolence 1
• There is a theoretical risk of serotonin syndrome when combining serotonergic medications like fluoxetine with other agents, although this risk appears to be low with bupropion 6
• Signs of serotonin syndrome include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 6
• Bupropion may be associated with an increased risk for seizures, while fluoxetine may be associated with an increased risk for nonfatal suicide attempts 1

Special Considerations

• The combination may be particularly beneficial for patients with depression who also smoke, as bupropion is FDA-approved for smoking cessation 2
• For patients with depression and comorbid obesity, bupropion-naltrexone ER is FDA-approved for weight management, suggesting bupropion may help mitigate weight gain associated with some antidepressants 1
• If the patient does not have an adequate response to the combination therapy within 6-8 weeks, treatment modification should be considered 1
• The American College of Physicians recommends that clinicians select antidepressants based on adverse effect profiles, cost, and patient preferences rather than presumed differences in efficacy 1