What can be added to Wellbutrin (bupropion) for a patient with persistent low energy and fatigue, who is also taking Lexapro (escitalopram) for Major Depressive Disorder (MDD) and Risperdal (risperidone) for anger outbursts?

Managing Low Energy and Fatigue in a Patient on Wellbutrin, Lexapro, and Risperdal

For a patient taking Wellbutrin who still experiences low energy and fatigue while also on Lexapro for MDD and Risperdal for anger outbursts, mirtazapine (Remeron) is the most appropriate medication to add to the regimen.

Understanding the Current Medication Profile

The patient is currently taking:

• Bupropion (Wellbutrin) - a norepinephrine-dopamine reuptake inhibitor
• Escitalopram (Lexapro) - an SSRI for major depressive disorder
• Risperidone (Risperdal) - an antipsychotic for anger outbursts

This combination presents several considerations:

• Bupropion is typically activating and should improve energy levels 1
• The continued fatigue suggests the need for an augmentation strategy
• The patient already has both dopaminergic (bupropion) and serotonergic (escitalopram) agents
• Risperidone may contribute to fatigue as a side effect

Recommended Augmentation Strategy

First-Line Option: Mirtazapine (Remeron)

Mirtazapine is the optimal choice for several reasons:

• Well-tolerated and potent antidepressant 1
• Promotes sleep quality while paradoxically improving daytime energy
• Enhances appetite and weight gain, which may be beneficial if the patient has poor appetite 1, 2
• Complementary mechanism to both bupropion and escitalopram
• Starting dose: 7.5mg at bedtime
• Maximum dose: 30mg at bedtime 1

Medication Interaction Considerations

When adding mirtazapine:

• Monitor for potential serotonin syndrome with escitalopram, though this risk is low at therapeutic doses
• Bupropion inhibits CYP2D6 and can increase concentrations of other medications, but this is not a significant concern with mirtazapine 3
• The combination of mirtazapine with bupropion provides both noradrenergic and dopaminergic effects (from bupropion) and serotonergic effects (from both mirtazapine and escitalopram)

Alternative Options

If mirtazapine is not suitable:

1. Optimize Current Medications

• Ensure bupropion is at an optimal dose (maximum 150mg twice daily) 1
• Consider timing of bupropion administration (second dose before 3 p.m. to minimize insomnia) 1
• Evaluate if risperidone dose can be minimized while maintaining anger control, as it may contribute to fatigue

2. Consider Switching Strategies

• If fatigue persists despite optimization, consider switching escitalopram to sertraline, which may have better efficacy for melancholia and psychomotor symptoms 1
• Sertraline starting dose: 25-50mg daily, maximum 200mg daily 2

3. Other Augmentation Options

• Aripiprazole (2.5-5mg) may be considered for persistent anger with less sedation than risperidone 2
• L-thyroxine or triiodothyronine augmentation may help with energy levels, though evidence is limited 2

Monitoring and Follow-up

• Assess response within 2-4 weeks of initiating mirtazapine
• Monitor for:
  • Improvement in energy levels and fatigue
  • Changes in sleep quality
  • Weight changes (mirtazapine often increases appetite)
  • Potential sedation (typically improves after initial adaptation)

Important Cautions

• Avoid adding another activating agent like a stimulant, which could worsen the patient's anger issues
• Be cautious about drug interactions, particularly with the existing three-medication regimen
• Ensure adequate trial periods (6-8 weeks) before determining efficacy of the augmentation strategy 2

The combination of bupropion, escitalopram, and mirtazapine provides coverage across multiple neurotransmitter systems (dopamine, norepinephrine, and serotonin) and addresses both the depression and energy components while maintaining control of anger outbursts with risperidone.