What medication can be added to Remeron (mirtazapine) and Buspar (buspirone) to help with depression?

Adding an Antidepressant to Mirtazapine and Buspirone for Depression

For a patient already taking mirtazapine (Remeron) and buspirone (Buspar) who needs additional medication for depression, bupropion (Wellbutrin) is the most appropriate choice due to its complementary mechanism of action and favorable side effect profile.

Rationale for Adding Bupropion

Bupropion offers several advantages when added to the current regimen:

• Complementary mechanism of action: Bupropion primarily affects dopamine and norepinephrine systems, while mirtazapine affects serotonin and norepinephrine through different mechanisms 1
• Activating properties: Bupropion tends to be activating and can reduce apathy, with possible rapid improvement in energy levels 2
• Avoids serotonin syndrome risk: Unlike adding an SSRI or SNRI to this regimen, bupropion doesn't significantly increase serotonergic activity, reducing the risk of serotonin syndrome 1
• Favorable side effect profile: Bupropion can counteract some common side effects of mirtazapine, such as weight gain and sexual dysfunction 2, 1

Dosing and Administration

• Starting dose: Begin with 37.5 mg every morning, then increase by 37.5 mg every 3 days 2
• Maximum dose: Titrate up to 150 mg twice daily as needed 2
• Timing considerations: To minimize risk of insomnia, administer the second dose before 3 p.m. 2

Monitoring and Precautions

• Initial assessment: Evaluate baseline vital signs, particularly blood pressure and heart rate 1
• Follow-up: Schedule follow-up within 1-2 weeks of initiation to assess for adverse effects 1
• Ongoing monitoring: Regular monitoring of vital signs at each follow-up visit 1
• Symptom tracking: Monitor for signs of excessive stimulation, including insomnia, anxiety, agitation, tremor, tachycardia, and hypertension 1

Important Contraindications

Bupropion should not be used in:

• Patients with seizure disorders 2, 1
• Agitated patients 2
• Patients with a history of recent MAO inhibitor use 1
• Patients with uncontrolled hypertension 1

Alternative Options

If bupropion is contraindicated or not tolerated, consider:

1. Venlafaxine: Has shown efficacy when combined with bupropion for treatment-resistant depression 3, though caution is needed due to potential serotonergic effects when combined with mirtazapine
2. SSRI (such as sertraline): Effective for depression but carries higher risk of serotonin syndrome when combined with mirtazapine 2
3. Tricyclic antidepressant (such as nortriptyline): May be useful in patients with agitated depression and insomnia 2, but has higher risk of anticholinergic and cardiac side effects

Evidence for Combination Therapy

Combination therapy with medications having different mechanisms of action is effective for treatment-resistant depression 1. The combination of bupropion with mirtazapine provides complementary neurotransmitter effects:

• Mirtazapine: Enhances serotonin and norepinephrine through alpha-2 antagonism and 5-HT2/5-HT3 blockade 4
• Buspirone: Partial 5-HT1A agonist with anxiolytic properties 5
• Bupropion: Dopamine and norepinephrine reuptake inhibitor 2

This triple combination targets multiple neurotransmitter systems involved in depression, potentially offering more complete symptom relief than dual therapy alone.