Is Wellbutrin (bupropion) a suitable alternative to mirtazapine?

Bupropion (Wellbutrin) vs. Mirtazapine: Clinical Decision-Making

Bupropion is the superior choice over mirtazapine for most patients with depression, particularly when weight management, sexual function, and energy levels are clinical priorities. 1

Weight Impact: The Primary Differentiator

Bupropion is the only antidepressant consistently shown to promote weight loss, while mirtazapine is closely associated with significant weight gain. 1

• Bupropion decreases body weight by suppressing appetite and reducing food cravings, making it FDA-approved for chronic weight management (in combination with naltrexone as Contrave). 1
• Mirtazapine causes weight gain through antagonism of histamine H1 receptors in the hypothalamus, with increased appetite being a prominent adverse effect. 1, 2
• For patients with obesity or metabolic concerns, bupropion is clearly preferable. 1

Efficacy Comparison

Both medications demonstrate comparable antidepressant efficacy for major depressive disorder:

• Bupropion (all formulations) shows equivalent efficacy to tricyclic antidepressants and SSRIs like fluoxetine and escitalopram. 3
• Mirtazapine demonstrates efficacy comparable to amitriptyline, clomipramine, and doxepin, with responder rates of 61-70% at 6 weeks. 4
• Both medications show onset of clinical effect in 2-4 weeks, though mirtazapine may improve sleep disturbances and anxiety symptoms within the first week. 2, 3

Side Effect Profiles: Critical Clinical Distinctions

Bupropion Advantages:

• No sexual dysfunction (major advantage over SSRIs and SNRIs). 3
• Activating properties beneficial for patients with low energy, apathy, or psychomotor retardation. 1, 5
• Weight loss rather than weight gain. 1, 6
• Minimal anticholinergic, cardiac, and sedating effects. 3

Bupropion Cautions:

• Contraindicated in seizure disorders (lowers seizure threshold). 5, 7
• Activating effects can exacerbate anxiety or be inappropriate for bipolar disorder. 1
• Contraindicated with MAOIs or within 14 days of discontinuation. 5, 7
• Should be avoided in patients with uncontrolled hypertension. 5

Mirtazapine Characteristics:

• Significant sedation (23% vs. 14% with placebo), particularly at lower doses. 8, 4
• Weight gain (10% vs. 1% with placebo) and increased appetite (11% vs. 2% with placebo). 4
• Beneficial for insomnia and anxiety associated with depression. 2, 8
• Minimal anticholinergic, cardiovascular, and sexual dysfunction compared to TCAs and SSRIs. 2, 8

Specific Clinical Scenarios

Choose Bupropion When:

• Patient has weight concerns or obesity. 1
• Sexual dysfunction is a concern or has occurred with prior antidepressants. 3
• Patient has low energy, apathy, or psychomotor retardation. 5
• Patient wants to quit smoking (dual indication). 5, 3
• Depression without significant anxiety or insomnia. 1

Choose Mirtazapine When:

• Patient has severe insomnia requiring sedation. 1
• Patient has poor appetite or unintended weight loss. 1, 2
• Patient has severe anxiety accompanying depression. 2, 8
• Patient has cardiovascular disease (safer profile than TCAs). 1
• Patient cannot tolerate activating antidepressants. 1

Dosing Considerations

Bupropion:

• Start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (SR formulation). 5
• Maximum dose: 400 mg/day (SR) or 450 mg/day (XL). 5
• Second dose must be before 3 PM to minimize insomnia risk. 5
• Reduce dose by 50% in moderate-to-severe renal impairment. 5
• Maximum 150 mg daily in moderate-to-severe hepatic impairment. 5

Mirtazapine:

• Start with 15 mg once daily at bedtime. 2
• Effective range: 15-45 mg daily. 2
• Sedation paradoxically decreases at higher therapeutic doses. 8

Critical Safety Monitoring

For bupropion: Monitor for seizures (especially doses >450 mg/day), blood pressure elevation, and neuropsychiatric effects in patients <24 years old. 5, 7

For mirtazapine: Rare cases of reversible severe neutropenia and agranulocytosis have been reported, though uncommon since 1994 market introduction. 8, 4

Bottom Line Algorithm

Start with bupropion unless:

1. Patient has seizure disorder or eating disorder → absolute contraindication to bupropion 5
2. Patient has severe anxiety or bipolar disorder → mirtazapine preferred 1
3. Patient has severe insomnia requiring sedation → mirtazapine preferred 1
4. Patient needs appetite stimulation/weight gain → mirtazapine preferred 1, 2

Otherwise, bupropion offers superior metabolic profile, no sexual dysfunction, and activating properties that benefit most patients with depression. 1, 3