What SSRI (Selective Serotonin Reuptake Inhibitor) can be used as an adjunct to Wellbutrin XL (bupropion) 300mg to help with motivation?

SSRI Selection to Adjunct Wellbutrin XL for Motivation Enhancement

Escitalopram is the recommended SSRI to adjunct Wellbutrin XL 300mg for improving motivation, due to its favorable efficacy and side effect profile. 1

Rationale for SSRI Addition to Bupropion

Bupropion (Wellbutrin XL) primarily works as a dopamine-norepinephrine reuptake inhibitor 2, which helps with energy and motivation but may not adequately address other aspects of mood regulation. Adding an SSRI can provide complementary serotonergic effects to enhance overall treatment outcomes.

The combination of an SSRI with bupropion is a well-established approach that offers several advantages:

• Targets multiple neurotransmitter systems (serotonin, dopamine, norepinephrine)
• May provide better symptom relief than monotherapy
• Can specifically address motivation issues through complementary mechanisms

Specific SSRI Recommendations

First Choice: Escitalopram

• Starting dose: 10mg daily
• Maximum dose: 20mg daily 1
• Benefits:
  • Associated with less sexual dysfunction than other SSRIs when combined with bupropion 3
  • Well-tolerated with minimal drug interactions
  • Demonstrated efficacy when combined with bupropion-SR with 50% remission rates 3

Alternative Options:

1. Sertraline

   • Starting dose: 25-50mg daily
   • Maximum dose: 200mg daily
   • Benefits: Good safety profile, particularly for cardiovascular concerns 1

2. Fluoxetine

   • Starting dose: 10-20mg daily
   • Maximum dose: 80mg daily
   • Benefits: Longer half-life may provide more stable blood levels

Implementation Strategy

1. Initial Dosing:

   • Begin with a low dose of escitalopram (10mg daily)
   • Continue current Wellbutrin XL 300mg dose
   • Consider starting with a "test dose" if concerned about initial anxiety/agitation 4

2. Titration:

   • Increase escitalopram gradually over 1-2 weeks as tolerated
   • Target dose of 20mg daily if needed and tolerated 1

3. Monitoring:

   • Assess for treatment response every 2-4 weeks 1
   • Watch for serotonin syndrome (confusion, agitation, muscle twitching, hyperthermia)
   • Monitor for sexual side effects, which may be mitigated by the bupropion 5

Important Precautions

Serotonin Syndrome Risk

There is a potential risk of serotonin syndrome when combining bupropion with SSRIs, although this is relatively rare. One case report documented serotonin syndrome with the combination of bupropion and sertraline 6. Monitor for:

• Confusion or agitation
• Muscle twitching or rigidity
• Hyperthermia
• Autonomic instability

Special Considerations

• If there is a history of bipolar disorder, avoid antidepressant monotherapy and consider mood stabilizers 1
• For patients with cardiovascular concerns, start with lower doses of sertraline (25mg) 1
• If chronic pain is present, consider duloxetine (an SNRI) instead of an SSRI 1

Evidence for Combination Therapy

In an open pilot study, the combination of escitalopram and bupropion-SR showed promising results:

• 62% response rate
• 50% remission rate
• Low discontinuation rate due to side effects (only 6%) 3

For patients who have previously tried fluoxetine without success, switching to or adding bupropion has shown approximately 60% full or partial response rates 7.

Bupropion has also demonstrated effectiveness in treating SSRI-induced sexual side effects 5, making this combination particularly advantageous for maintaining treatment adherence and quality of life.