Switching from Mirtazapine to Escitalopram
Taper mirtazapine gradually over 1-2 weeks before starting escitalopram to minimize withdrawal symptoms, then initiate escitalopram at 10 mg daily after completing the mirtazapine taper. 1, 2
Tapering Mirtazapine
Gradually reduce mirtazapine over 1-2 weeks rather than stopping abruptly to avoid withdrawal symptoms including panic attacks, palpitations, dyspnea, dizziness, nausea, and severe anxiety that can recur every 1-2 hours for days after sudden discontinuation 3, 4
For patients on 30 mg daily, reduce to 15 mg daily for 1 week, then discontinue 5, 4
For patients on 15 mg daily, consider reducing to 7.5 mg for several days before complete discontinuation 5
Monitor closely during the taper period as mirtazapine withdrawal can cause recurrent panic attacks even after medium-duration therapy (10 weeks) 3
Washout Period
Allow a minimum 3-7 day washout period after completely stopping mirtazapine before initiating escitalopram to reduce risk of serotonin syndrome and allow adequate clearance 6, 5
This conservative approach is safer than cross-tapering, which carries higher risk of drug toxicity when combining antidepressants 4
No MAOI washout is required as mirtazapine is not an MAOI, but ensure the patient is not taking MAOIs from other sources 2
Initiating Escitalopram
Start escitalopram at 10 mg once daily after the washout period is complete 2
This is the recommended starting dose for adults with major depressive disorder 2
Maintain 10 mg daily for a minimum of 1 week before considering any dose increase 2
If needed for inadequate response, increase to 20 mg daily (maximum dose) only after at least 1 week at 10 mg 2
Critical Monitoring Requirements
Contact the patient within the first week (in-person or by telephone) after starting escitalopram to assess for adverse effects including nausea, headache, insomnia, nervousness, and sexual dysfunction 1, 2
Monitor closely for behavioral activation and suicide-related events, especially in younger patients, during the first 4 weeks of escitalopram treatment 1
Watch for signs of serotonin syndrome during the transition, including confusion, agitation, tremors, hyperreflexia, tachycardia, and diaphoresis 6
Assess treatment response at 6-12 weeks; if inadequate, consider switching to another agent or augmentation strategies 1
Special Populations
For elderly patients or those with hepatic impairment, maintain escitalopram at 10 mg daily without dose escalation 2
Use caution in patients with severe renal impairment 2
Do not exceed 20 mg daily in any patient due to risk of QT prolongation and cardiac arrhythmias 6
Alternative Strategy: Augmentation Instead of Switching
Consider augmenting mirtazapine with escitalopram rather than switching if the patient had partial response to mirtazapine, as augmentation strategies show similar efficacy to switching 1
However, this approach requires careful monitoring for serotonin syndrome when combining serotonergic agents 6, 4
The STAR*D trial showed that only 25% of patients achieve remission after switching antidepressants, suggesting augmentation may be preferable in partial responders 1
Common Pitfalls to Avoid
Never stop mirtazapine abruptly, even after short-term use, as withdrawal symptoms can be severe and persistent 3
Never combine escitalopram with MAOIs or start escitalopram within 14 days of stopping an MAOI due to fatal serotonin syndrome risk 2
Avoid cross-tapering (overlapping both medications) unless you have specific expertise, as this increases toxicity risk 4
Do not rush the process—conservative tapering and washout periods, while taking longer, are safer than rapid switches 5, 4