What is the next step in treatment for a patient with depressive symptoms who has shown significant improvement in mood, energy, and social engagement while taking Rexulti (brexpiprazole) and Lexapro (escitalopram) 20 mg?

Continue Rexulti and Taper Lexapro in Responding Patient

Continue the Rexulti trial at the current dose and proceed with the planned Lexapro taper, as the patient has demonstrated significant clinical improvement with the combination therapy and adjunctive brexpiprazole has proven efficacy for maintaining response in major depressive disorder. 1, 2

Rationale for Continuing Rexulti

• Adjunctive brexpiprazole has demonstrated sustained efficacy across multiple symptom domains including mood, energy, and social engagement (anhedonia cluster), with effect sizes of 0.36-0.43 versus placebo when added to antidepressants 2
• The patient's reported improvements in mood, energy, and social engagement align precisely with brexpiprazole's documented benefits on core depressive symptoms, anhedonia, and lassitude clusters 2
• Clinical improvements with adjunctive brexpiprazole typically emerge early (Week 1) and are maintained through 6 weeks and beyond, supporting continuation of the current regimen 2, 3

Lexapro Taper Strategy

• Implement gradual dose reduction of escitalopram rather than abrupt cessation to minimize discontinuation syndrome, which can include dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, and emotional lability 4
• The FDA label explicitly recommends gradual dose reduction whenever possible, and if intolerable symptoms occur, resuming the previous dose and decreasing more gradually 4
• Monitor specifically for discontinuation symptoms during the taper: dizziness, anxiety, irritability, sensory disturbances (electric shock sensations), and sleep disturbances 4

Monitoring Protocol During Transition

• Assess treatment response every 2-4 weeks during the taper using standardized depression and anxiety rating scales to objectively track symptom stability 5
• Monitor closely for suicidal ideation during the first 1-2 months after medication changes, as suicide risk is greatest during treatment transitions 5, 4
• Watch for behavioral activation, agitation, or worsening mood that could indicate destabilization during the escitalopram taper 4

Evidence Supporting This Approach

• Switching from inadequate adjunctive therapy to brexpiprazole adjunctive treatment resulted in 83.6% completion rates and significant improvements in Montgomery-Åsberg Depression Rating Scale scores (mean change -17.3 points, P<0.0001) 1
• Patients switching to adjunctive brexpiprazole showed improvements in general functioning (Sheehan Disability Scale mean change -3.1, P<0.0001) and cognitive function 1
• Adjunctive brexpiprazole demonstrated efficacy across all MDD symptom clusters with improvements maintained over 6-12 weeks, supporting its use as ongoing adjunctive therapy 2, 3

Common Pitfalls to Avoid

• Do not taper escitalopram too rapidly (faster than every 1-2 weeks per dose reduction), as this increases risk of discontinuation syndrome and symptom destabilization 5, 4
• Do not discontinue brexpiprazole prematurely based on the assumption that improvement was solely due to the SSRI, as the adjunctive antipsychotic likely contributed significantly to the observed response 1, 2
• Do not exceed escitalopram 20 mg daily during any phase due to QT prolongation risk, though this is not relevant during tapering 5

Safety Considerations

• The most common adverse events with adjunctive brexpiprazole are fatigue (14.8%) and akathisia (8.2%), which should be monitored during continuation 1
• Brexpiprazole has low rates of akathisia (6.4-8.2%) and clinically relevant weight gain (10.5% with ≥7% increase) in clinical trials 1, 3
• Continue monitoring for serotonin syndrome during the taper period, though risk decreases as escitalopram dose is reduced 4

Duration of Continuation Therapy

• Continue antidepressant treatment for 4-9 months after satisfactory response in first-episode major depression, and for recurrent depression (2+ episodes), consider years to lifelong maintenance therapy 5
• The evidence supports maintaining adjunctive brexpiprazole as the primary ongoing therapy if escitalopram is successfully tapered, given the patient's robust response to the combination 1, 2