Can a Patient Start Remeron and Buspar at Once?
Yes, a patient can safely start Remeron (mirtazapine) and Buspar (buspirone) simultaneously, as these medications work through different mechanisms and are explicitly recognized as safe to combine. 1
Mechanism and Safety Profile
The combination is pharmacologically sound because:
Mirtazapine works as a noradrenergic and specific serotonergic antidepressant (NaSSA) that blocks central α2-adrenergic receptors and enhances both noradrenergic and 5-HT1 receptor-mediated neurotransmission while directly blocking 5-HT2 and 5-HT3 receptors 2
Buspirone acts primarily through 5-HT1A receptors with some affinity for DA2 autoreceptors and 5-HT2 receptors, leading to inhibition of serotonin synthesis and release through combined neuroreceptor interactions 3
The American Academy of Family Physicians explicitly states that buspirone and mirtazapine can be safely administered together as they work through different mechanisms and have complementary effects for treating anxiety and depression 1
Recommended Starting Doses
When initiating both medications simultaneously:
Mirtazapine: Start at 7.5 mg at bedtime, which can be gradually increased to an effective dose of 15-30 mg at bedtime 1
Buspirone: Start at 5 mg twice daily, which can be gradually titrated up to a maximum of 20 mg three times daily as needed 1
Begin with lower doses of each medication and titrate gradually while monitoring for side effects 1
Clinical Benefits of This Combination
This dual-agent approach offers several therapeutic advantages:
Mirtazapine addresses sleep disturbances and appetite issues often present in anxiety and depression, as it promotes sleep, appetite, and weight gain 1, 2
Buspirone provides anxiolytic effects without risk of dependence, tolerance, or withdrawal associated with benzodiazepines 1, 3
The combination may be particularly helpful for patients with comorbid anxiety and depression who haven't responded adequately to monotherapy 1
This represents a rational polypharmacy approach with a clear rationale for each medication in the combination 4
Drug Interaction Considerations
The FDA labels and clinical evidence provide reassurance:
The mirtazapine FDA label specifically lists buspirone among medications to inform your healthcare provider about, but does not contraindicate their combination 5
While there are theoretical concerns about serotonergic effects when combining multiple serotonergic agents, this specific combination has not been associated with significant adverse interactions 1
The risk of serotonin syndrome with this specific combination is low compared to combinations with SSRIs 1
Buspirone displays minimal affinity for muscarinic cholinergic receptors, reducing anticholinergic burden when combined with other agents 2
Expected Side Effects to Monitor
Mirtazapine-related effects:
- Sedation (particularly at lower doses), increased appetite, and weight gain are common 1, 6
- Drowsiness occurs in 23% of patients versus 14% with placebo 2
- Dry mouth occurs in 25% versus 16% with placebo 2
Buspirone-related effects:
- Headaches, dizziness, nervousness, and lightheadedness are most common 3
- The frequency of adverse effects is low overall 3
- Drowsiness is significantly less frequent than with benzodiazepines 7
Combined therapy monitoring:
- Monitor for potential serotonergic effects, though risk is low 1
- Neither medication carries significant risk for dependence or withdrawal symptoms 1
Important Clinical Considerations
Timing of therapeutic effects:
- Buspirone requires several weeks for full therapeutic effect, unlike benzodiazepines which work immediately 1
- Mirtazapine may show early onset of antidepressant action, with significant improvements noted as early as 1 week after starting treatment 6
- Patients should be counseled not to expect immediate anxiolytic effects from buspirone 1
Contraindications to verify before starting:
- Do not combine with MAOIs - both medications are contraindicated with MAOIs 5, 8
- Allow 14 days after stopping an MAOI before starting either medication 5, 8
- Buspirone should not be used with reversible MAOIs such as linezolid or intravenous methylene blue 8
Common Pitfalls to Avoid
Discontinuing either medication abruptly - although withdrawal syndromes are less common than with other psychotropics, gradual tapering is still recommended 1
Expecting immediate anxiolytic effects from buspirone - unlike benzodiazepines, buspirone requires several weeks for full therapeutic effect 1
Using subtherapeutic doses of mirtazapine - increased sedation is related to subtherapeutic dosages, and substantially fewer patients report sedation when the drug is used in appropriate dosages (≥15 mg as a single evening dose) from the beginning of treatment 6
Failing to counsel patients about weight gain - mirtazapine commonly causes increased appetite (11% vs 2% placebo) and bodyweight gain (10% vs 1% placebo) 2