Can Lexapro (escitalopram) be added to a patient's current Remeron (mirtazapine) regimen for emotional disturbances and sleep disturbances following a traumatic event?

Can Lexapro Be Added to Mirtazapine for This Patient?

Yes, you can add Lexapro (escitalopram) to the current Mirtazapine regimen, but monitor closely for serotonin syndrome during initiation and dose titration, as both medications have serotonergic activity. 1

Key Safety Considerations When Combining These Medications

Serotonin Syndrome Risk

• The FDA label for escitalopram explicitly warns about serotonin syndrome when combining with other serotonergic drugs, though mirtazapine is not specifically listed among the highest-risk combinations (unlike MAOIs, triptans, or tramadol) 1
• Monitor for mental status changes (agitation, confusion), autonomic instability (tachycardia, labile blood pressure, diaphoresis), neuromuscular symptoms (tremor, rigidity, hyperreflexia), and GI symptoms (nausea, vomiting) 1
• The risk is highest during treatment initiation and dose increases, so educate the patient about these warning signs 1

Practical Monitoring Strategy

• Start Lexapro at 5-10mg daily while maintaining Mirtazapine at the current dose 1
• Assess for serotonin syndrome symptoms at 1-2 weeks after initiation 1
• If tolerated, increase Mirtazapine to 15mg as planned, waiting at least 1-2 weeks before making further adjustments 2
• Check orthostatic blood pressures if the patient is elderly or on other medications affecting blood pressure 2

Evidence for This Combination in Trauma-Related Symptoms

Mirtazapine for Sleep and Trauma

• Mirtazapine 7.5mg at bedtime is appropriate for sleep promotion, with titration to 15-30mg based on response 2
• The medication is "potent and well tolerated" and specifically "promotes sleep, appetite, and weight gain" 2
• For trauma-related sleep disturbances, mirtazapine addresses insomnia but has limited specific evidence for PTSD nightmares 3

SSRIs as First-Line for PTSD Core Symptoms

• Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline) and venlafaxine effectively treat primary PTSD symptoms including intrusive thoughts, avoidance, and hyperarousal 4
• While escitalopram is not specifically mentioned in PTSD guidelines, it is a well-tolerated SSRI that can address the emotional disturbances and mood symptoms following trauma 4
• SSRIs require 4-8 weeks for full therapeutic response, so reassess at 4 weeks minimum 2

What This Combination Does NOT Address Well

• Neither mirtazapine nor escitalopram has strong evidence for treating PTSD-related nightmares specifically 3
• If nightmares emerge or worsen as sleep architecture normalizes and dream recall returns, prazosin should be added, starting at 1mg at bedtime and titrating to 3-4mg for civilians 2, 4
• Recent network meta-analysis found prazosin may be the most effective treatment for insomnia (SMD = -0.88), nightmares (SMD = -0.44), and poor sleep quality (SMD = -0.55) in PTSD 3

Alternative Considerations if This Approach Fails

If Sleep Remains the Primary Problem

• Trazodone 25-200mg decreased nightmares in 72% of veterans, though 60% experienced side effects including orthostatic hypotension and daytime sedation 5
• Prazosin remains the gold standard for PTSD nightmares with medium-to-large effect sizes 2

If Emotional Symptoms Predominate

• Consider switching to paroxetine or sertraline, which have more robust PTSD-specific evidence than escitalopram 4
• Pharmacotherapy is most effective when combined with trauma-focused cognitive behavioral therapy 4

Common Pitfalls to Avoid

• Do not abruptly discontinue either medication - both can cause discontinuation syndromes with dysphoric mood, irritability, dizziness, and sensory disturbances 1
• Screen for bipolar disorder before starting escitalopram - SSRIs can precipitate manic/mixed episodes in undiagnosed bipolar disorder 1
• Monitor sodium levels in elderly patients - both SSRIs and mirtazapine can cause SIADH and hyponatremia 1
• Assess for obstructive sleep apnea - many patients with PTSD-related sleep disturbance have undiagnosed OSA that will not respond to medication alone 4
• Do not expect immediate results - allow 4-8 weeks for full antidepressant effect before declaring treatment failure 2