Does adding mirtazapine or buspirone help with irritability in patients taking bupropion?

Managing Irritability in Patients Taking Bupropion

Adding mirtazapine may help with irritability in patients taking bupropion, while buspirone lacks sufficient evidence to support its use for this specific indication.

Mechanism and Rationale

Bupropion works primarily by inhibiting the reuptake of norepinephrine and dopamine, with minimal effect on serotonin. This unique mechanism can sometimes lead to side effects such as irritability, agitation, and insomnia in some patients 1.

Mirtazapine as an Adjunct Option

Mirtazapine has a complementary mechanism of action that makes it potentially beneficial for managing bupropion-induced irritability:

• Acts by enhancing norepinephrine and serotonin neurotransmission through blocking alpha-2 presynaptic adrenoceptors
• Has antagonistic effects at 5-HT2, 5-HT3, and H1 receptors 2
• The sedating properties can counterbalance bupropion's activating effects
• May help with sleep disturbances that can contribute to irritability

Mirtazapine's sedating effects are most pronounced at lower doses (15mg) and may decrease at higher doses, making dose selection important based on the patient's specific symptoms 2.

Buspirone Considerations

Buspirone has less evidence supporting its use specifically for bupropion-induced irritability:

• Acts as a 5-HT1A receptor partial agonist
• While it can be helpful for anxiety, there is insufficient evidence to recommend it specifically for managing irritability in patients taking bupropion
• The American Journal of Psychiatry study showed that when used as an augmentation strategy after citalopram failure, buspirone had low remission rates 3

Clinical Approach

1. First-line approach: Add mirtazapine at a low dose (15mg) at bedtime

   • Start with 15mg and titrate based on response
   • Maximum dose typically 45mg daily 2
   • Monitor for common side effects: sedation, increased appetite, weight gain

2. Monitoring parameters:

   • Improvement in irritability symptoms
   • Sleep quality
   • Potential side effects: sedation, weight gain, dry mouth
   • Blood pressure and heart rate, especially in the first few weeks

3. Alternative approaches if mirtazapine is not tolerated or ineffective:

   • Consider switching from bupropion to an SNRI like duloxetine 1
   • Evaluate for other causes of irritability (sleep disorders, substance use)
   • Consider behavioral interventions like CBT 1

Important Precautions

1. Avoid serotonin syndrome risk:

   • While the combination of bupropion and mirtazapine has a low risk of serotonin syndrome compared to other combinations, monitor for symptoms 4
   • Symptoms include confusion, agitation, muscle rigidity, hyperthermia

2. Special populations:

   • In older adults, start with lower doses of mirtazapine (7.5mg) due to increased sensitivity to side effects 1
   • In patients with seizure disorders, use caution with bupropion and consider alternatives 1, 5

3. Discontinuation considerations:

   • If discontinuing either medication, taper gradually to avoid withdrawal symptoms
   • Bupropion should be tapered by reducing to 150mg once daily for 1-2 weeks before complete discontinuation 5

Clinical Pearls

• Mirtazapine's most sedating effects occur at lower doses (15mg), which can be advantageous for patients with bupropion-induced irritability and insomnia
• Morning dosing of bupropion and evening dosing of mirtazapine can help optimize the complementary effects
• Weight gain is a potential side effect of mirtazapine that should be monitored
• Regular follow-up within 2 weeks of starting combination therapy is recommended to assess efficacy and side effects

By adding mirtazapine to a bupropion regimen, you may effectively address irritability while maintaining the positive effects of bupropion on depression and energy levels.