Combining Mirtazapine and Buspirone: Safety and Clinical Considerations
Combining mirtazapine and buspirone is generally safe and can be used together without dose adjustment, though patients must be monitored for serotonin syndrome risk. 1
Serotonin Syndrome Risk
The primary concern when combining these medications is the potential for serotonin syndrome, as both drugs affect serotonergic pathways:
The FDA label for mirtazapine explicitly warns that concomitant use with buspirone increases the risk of serotonin syndrome, particularly during treatment initiation and dose increases 1
Serotonin syndrome symptoms include mental status changes (agitation, hallucinations, delirium, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus), and gastrointestinal symptoms (nausea, vomiting, diarrhea) 1
If serotonin syndrome is suspected, both medications should be discontinued immediately and supportive symptomatic treatment initiated 1
Clinical Rationale for Combination
Despite the theoretical risk, there is evidence supporting this combination:
The STAR*D trial demonstrated that buspirone augmentation of antidepressants showed similar efficacy to other augmentation strategies for patients who did not achieve remission with initial antidepressant treatment 2
However, buspirone augmentation had a 20.6% discontinuation rate due to adverse events, which was higher than bupropion augmentation (12.5%) 2
Pharmacokinetic Considerations
No dose adjustment is required when combining these medications, as buspirone does not significantly interact with mirtazapine's metabolism through cytochrome P450 enzymes 1
Mirtazapine is primarily metabolized by CYP2D6, CYP1A2, and CYP3A4, and buspirone does not inhibit these pathways to a clinically significant degree 1
Common Adverse Effects to Monitor
When using this combination, monitor for additive side effects:
Mirtazapine commonly causes somnolence (23%), dry mouth (25%), increased appetite (11%), weight gain (10%), and dizziness 3, 4
Buspirone commonly causes headaches, dizziness, nervousness, and lightheadedness 5
The combination may result in additive sedation and dizziness, requiring caution with activities requiring alertness 1
Practical Monitoring Strategy
Monitor closely during the first 1-2 weeks of combined therapy for early signs of serotonin syndrome (restlessness, confusion, rapid heart rate, dilated pupils, muscle twitching) 1
Assess for excessive sedation or dizziness that could impair driving or operating machinery 1
Watch for weight gain and increased appetite, which are common with mirtazapine and may affect long-term adherence 3, 4
Important Caveats
Mirtazapine has minimal anticholinergic effects and does not cause typical SSRI side effects (nausea, sexual dysfunction, insomnia), making it better tolerated than many alternatives 4
All long-term safety data for mirtazapine is limited to 12 weeks maximum in clinical trials, so extended monitoring is prudent 3
If the patient develops fever, sore throat, or signs of infection while on mirtazapine, check complete blood count immediately due to rare risk of agranulocytosis 1