What are the next steps for a patient with severe depression on Lexapro (escitalopram) 20mg and Mirtazapine (mirtazapine) 45mg?

Management of Severe Depression After Inadequate Response to Lexapro and Mirtazapine

For a patient with severe depression who has not responded adequately to escitalopram 20mg and mirtazapine 45mg, the next step should be augmentation with cognitive behavioral therapy (CBT) or switching to a different antidepressant medication. 1

Current Treatment Assessment

The patient is currently on:

• Escitalopram (Lexapro) 20mg - maximum FDA-approved dose
• Mirtazapine 45mg - maximum recommended dose

This combination provides both SSRI action (escitalopram) and noradrenergic/specific serotonergic action (mirtazapine), yet the patient remains severely depressed.

Next Treatment Options (Algorithm)

First-line options:

1. Add cognitive behavioral therapy (CBT)

   • Strong evidence supports CBT as an effective augmentation strategy for patients who don't respond to antidepressants 1, 2
   • CBT has shown comparable efficacy to medication switches in treatment-resistant depression

2. Switch one medication:

   • Consider switching escitalopram to another antidepressant class:
     • SNRI (venlafaxine, duloxetine)
     • Atypical antidepressant (bupropion)
     • Different SSRI (sertraline)

Second-line options:

1. Add a third medication:

   • Consider adding bupropion (which has a different mechanism of action)
   • Low-dose atypical antipsychotic (aripiprazole, quetiapine)
   • Lithium augmentation

2. Consider referral for ECT evaluation if depression is severe with suicidal ideation or psychotic features

Evidence-Based Rationale

The American College of Physicians (ACP) guidelines suggest that for patients who don't respond to initial treatment with an adequate dose of a second-generation antidepressant, switching to or augmenting with CBT is a recommended option 2. The ACP also supports switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment.

The American Society of Clinical Oncology (ASCO) guidelines (which address depression management) recommend that "combined treatment using CBT or interpersonal psychotherapy with a pharmacologic agent may be an option for partial or nonresponders to initial psychological interventions" 1.

Important Considerations

Monitor for adverse effects

• Mirtazapine can cause significant sedation, increased appetite, and weight gain 3, 4
• Risk of serotonin syndrome with the current combination 3
• Monitor for suicidal thoughts, especially during medication changes 3

Assess for specific symptoms

• Sleep disturbance (mirtazapine is often helpful for insomnia)
• Anxiety (may require specific targeting)
• Appetite/weight changes
• Energy levels

Rule out medical causes

• Thyroid dysfunction
• Vitamin deficiencies (B12, folate, vitamin D)
• Anemia
• Medication side effects

Common Pitfalls to Avoid

1. Failing to optimize current medications before adding new ones

   • Ensure patient has been on current doses for adequate duration (6-8 weeks)
   • Assess medication adherence

2. Overlooking bipolar disorder

   • Antidepressants can trigger mania in undiagnosed bipolar disorder 5
   • Screen for history of manic/hypomanic episodes

3. Missing medical comorbidities

   • Cardiovascular disease can limit medication options 1
   • Renal/hepatic dysfunction may require dose adjustments

4. Neglecting psychosocial factors

   • Substance use disorders
   • Psychosocial stressors
   • Inadequate social support

Remember that approximately 38% of patients do not achieve treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1. This underscores the importance of considering alternative strategies when initial treatments fail.