Escitalopram and Mirtazapine Combination Therapy
Yes, escitalopram can be prescribed with mirtazapine, but this combination requires careful monitoring for serotonin syndrome and other potential adverse effects. 1
Pharmacological Rationale
Escitalopram (SSRI) and mirtazapine (tetracyclic antidepressant) work through different mechanisms:
- Escitalopram selectively inhibits serotonin reuptake
- Mirtazapine acts as an α2-adrenergic antagonist and blocks 5-HT2 and 5-HT3 receptors 2
This combination may provide complementary effects:
- Enhanced antidepressant efficacy through dual-action on serotonergic and noradrenergic systems
- Mirtazapine may help counteract some SSRI side effects like sexual dysfunction and insomnia 3
Safety Considerations
Serotonin Syndrome Risk
While the combination increases the theoretical risk of serotonin syndrome, the AACAP guideline notes that caution should be exercised when combining two or more non-MAOI serotonergic drugs, but doesn't contraindicate such combinations 1. The risk is significantly lower than when combining either drug with MAOIs, which is absolutely contraindicated.
Monitoring Requirements
When prescribing this combination:
- Start the second medication at a low dose
- Increase doses slowly
- Monitor closely for symptoms of serotonin syndrome, especially during the first 24-48 hours after dosage changes 1
- Watch for signs of:
- Mental status changes (confusion, agitation)
- Neuromuscular hyperactivity (tremors, hyperreflexia)
- Autonomic hyperactivity (hypertension, tachycardia)
QT Interval Considerations
Citalopram/escitalopram may have the least effect on CYP450 isoenzymes compared to other SSRIs, giving them a lower propensity for drug interactions 1. However, both medications have some potential for QT prolongation, so ECG monitoring may be warranted, especially in patients with cardiovascular risk factors 1, 4.
Dosing Strategy
When combining these medications:
- Start with one medication at a therapeutic dose before adding the second
- Begin mirtazapine at a low dose (7.5-15mg) and titrate gradually
- Lower doses of mirtazapine (7.5-15mg) tend to be more sedating due to predominant H1 antagonism
- Higher doses (30-45mg) are typically needed for optimal antidepressant effect
Potential Adverse Effects to Monitor
- Increased sedation (mirtazapine is highly sedating, especially at lower doses)
- Weight gain (both medications can contribute)
- Dry mouth and other anticholinergic effects
- Rare but serious: agranulocytosis with mirtazapine 4
- Potential for increased blood pressure (particularly if the patient is on other antihypertensive medications) 5
Clinical Evidence
A 2018 study (MIR trial) investigated adding mirtazapine to SSRI/SNRI treatment for treatment-resistant depression and found no convincing evidence of clinically important benefit over placebo, with more participants in the mirtazapine group withdrawing due to adverse effects 6. However, other studies suggest that mirtazapine combinations may reduce the latency of antidepressant response and enhance therapeutic effects 3.
Conclusion
While escitalopram and mirtazapine can be prescribed together, the combination should be approached with careful monitoring for adverse effects, particularly serotonin syndrome. The benefit-to-risk ratio should be evaluated based on the individual patient's response to monotherapy and specific symptom profile.