What can be used to augment Wellbutrin (bupropion) for anxiety?

Augmenting Wellbutrin (Bupropion) for Anxiety

For patients experiencing anxiety while taking Wellbutrin (bupropion), adding buspirone is the most effective augmentation strategy based on the available evidence.

Understanding the Challenge

Wellbutrin (bupropion) is an effective antidepressant that works primarily on dopamine and norepinephrine systems, but it lacks significant serotonergic activity which can be beneficial for anxiety symptoms. This creates a clinical challenge when patients experience anxiety while taking bupropion.

Evidence-Based Augmentation Options

First-Line Option: Buspirone

• Buspirone acts as a 5-HT1A partial agonist, providing complementary serotonergic activity to bupropion's dopaminergic/noradrenergic effects 1
• Low-quality evidence showed that augmentation of antidepressant treatment with buspirone led to 59% of patients showing complete or partial remission of depressive symptoms 2
• Buspirone has minimal drug interactions with bupropion and doesn't significantly increase side effect burden 1
• Dosing typically starts at 5-7.5mg twice daily, gradually increasing to 15-30mg daily divided into multiple doses

Second-Line Options:

1. SSRI Augmentation

   • Consider for patients with high anxiety levels, as SSRIs showed modest advantages over bupropion in anxious depression (65.4% vs. 59.4% response rates) 3
   • However, adding an SSRI requires careful monitoring for serotonin syndrome and increased side effects 1
   • This combination provides comprehensive neurotransmitter coverage (serotonin, norepinephrine, and dopamine)

2. Mirtazapine

   • Provides complementary effects through its action on multiple receptors including alpha-2 adrenergic and serotonin receptors 1
   • Particularly useful when insomnia is a component of anxiety
   • Start at 7.5mg at bedtime, with a maximum dose of 30mg 1

3. SNRIs (e.g., Duloxetine)

   • SNRIs could be offered to patients with anxiety disorders 4
   • Start at 30mg daily, increasing to 60mg daily after 1 week 1
   • Provides both serotonergic and noradrenergic effects

Monitoring and Management

1. Initial Phase (First 2-4 Weeks)

   • Monitor weekly for signs of serotonin syndrome (hyperthermia, agitation, hyperreflexia) 1
   • Assess for increased anxiety, insomnia, or other adverse effects
   • Evaluate treatment response using standardized symptom rating scales

2. Maintenance Phase

   • Monitor for metabolic effects, particularly with certain combinations 1
   • Assess ongoing efficacy and side effect burden
   • Consider dose adjustments based on clinical response

Special Considerations

• Contraindications: Avoid these combinations in patients with seizure disorders due to bupropion's seizure risk 1
• Pregnancy: Carefully weigh risks and benefits for pregnant patients or those planning pregnancy 1
• Hepatic Impairment: Use caution in patients with severe hepatic impairment 1

Non-Pharmacological Approaches

Consider adding cognitive-behavioral therapy (CBT) with exposure components, which has shown effectiveness rates of 60-95% for anxiety disorders 1. Recent evidence suggests no difference in response, remission, or depression severity when augmenting antidepressant treatment with cognitive therapy versus another medication 4.

Recent Research Insights

Contrary to common clinical belief, a recent 2023 naturalistic study found no significant difference in anxiety outcomes between patients prescribed SSRIs versus bupropion across 12 weeks of treatment when using propensity matching 5. This challenges the traditional view that bupropion exacerbates anxiety and suggests that for many patients, bupropion alone may be sufficient for managing both depression and anxiety.

Additionally, a small pilot study found that bupropion XL demonstrated comparable anxiolytic efficacy to escitalopram in outpatients with generalized anxiety disorder 6, further suggesting that bupropion may have more anxiolytic properties than previously believed.