What is a suitable medication to add to Wellbutrin (bupropion) for a male patient with depression and anxiety?

Adding Medication to Wellbutrin for Depression and Anxiety in Males

For a male patient with depression and anxiety already on Wellbutrin (bupropion), add an SSRI—specifically sertraline or escitalopram—as these agents effectively treat both depression and comorbid anxiety symptoms. 1

Rationale for SSRI Addition

The evidence strongly supports combining bupropion with an SSRI for treatment-resistant depression and anxiety:

• Combination therapy with bupropion plus an SSRI is effective for patients who have not achieved remission on monotherapy. Multiple studies demonstrate that this combination is well-tolerated and can boost antidepressant response through synergistic effects on serotonergic, dopaminergic, and noradrenergic systems. 2, 3

• SSRIs show superior efficacy to bupropion alone for anxious depression. In a pooled analysis of 10 studies (N=1,275 patients with anxious depression), SSRIs demonstrated significantly higher response rates compared to bupropion (65.4% vs 59.4%, p=0.03) for patients with high anxiety levels. 4

• Sertraline, escitalopram, or venlafaxine are preferred choices. Head-to-head trials show similar antidepressive efficacy for patients with major depressive disorder and anxiety symptoms when comparing sertraline with bupropion, though one trial showed venlafaxine had statistically better response rates than fluoxetine for anxiety. 1

Specific Medication Recommendations

First-Line Options:

Sertraline (Zoloft):

• Start 50 mg daily, can increase to 200 mg daily as needed 5
• Effective for both depression and anxiety symptoms 1
• Generally well-tolerated with manageable side effect profile 1

Escitalopram (Lexapro):

• Start 10 mg daily, can increase to 20 mg daily 1
• Showed modest benefits over citalopram in meta-analyses 1

Alternative Option:

Venlafaxine (SNRI):

• May be superior to some SSRIs specifically for treating anxiety in depression 1
• One trial showed statistically better response and remission rates versus fluoxetine 1

Important Considerations for Males

Sexual dysfunction is a critical concern:

• SSRIs commonly cause ejaculatory delay (14% with sertraline vs 1% placebo) and decreased libido (6% vs 1% placebo) in males 5
• The existing bupropion may partially mitigate SSRI-induced sexual side effects, as bupropion is specifically used to reverse antidepressant-associated sexual dysfunction 3
• This combination strategy addresses both efficacy and tolerability concerns 3

Dosing Strategy

Start low and titrate gradually:

• Begin with subtherapeutic "test" doses to assess tolerability, as SSRIs can initially cause anxiety or agitation 1
• For shorter half-life SSRIs (sertraline, citalopram), increase dose at 1-2 week intervals 1
• Monitor for response at 4-6 weeks before making further adjustments 1

Safety Monitoring

Watch for drug interactions:

• Bupropion inhibits CYP2D6, which can increase concentrations of SSRIs metabolized by this pathway (paroxetine, fluoxetine, sertraline) 6
• Consider dose reduction of the SSRI if combining with bupropion to avoid excessive drug levels 6
• Monitor for serotonin syndrome symptoms (tremor, agitation, diaphoresis, fever) when combining serotonergic agents 1

Avoid abrupt discontinuation:

• SSRIs, particularly paroxetine but also sertraline, can cause withdrawal syndrome with missed doses or sudden cessation 1
• Taper gradually when discontinuing 1

What NOT to Use

Avoid paroxetine in this population:

• Higher discontinuation rates and more problematic withdrawal syndrome compared to other SSRIs 1
• Not preferred for older patients due to adverse effect profile 1

Exercise caution with MAOIs:

• Increased risk of hypertensive reactions when combined with bupropion 6
• Generally not recommended as add-on therapy