Is aripiprazole (atypical antipsychotic) suitable for treating major depressive disorder?

Aripiprazole for Major Depressive Disorder

Aripiprazole is suitable as an adjunctive treatment for major depressive disorder in patients who have had an inadequate response to antidepressant monotherapy, but should not be used as first-line or monotherapy for MDD. 1, 2

Efficacy and Indications

• Aripiprazole is FDA-approved as an adjunctive therapy for major depressive disorder in adults who have had an inadequate response to standard antidepressant therapy 2, 3
• It should be considered as a second-step treatment option for patients who have not responded adequately to first-line antidepressant therapy 1
• Clinical trials have demonstrated that aripiprazole augmentation significantly improves Montgomery Asberg Depression Rating Scale (MADRS) scores compared to placebo when added to standard antidepressants 4
• Benefits of aripiprazole augmentation can be observed as early as 1-2 weeks after initiation 4

Dosing and Administration

• Starting dose should be low (2.5 mg/day) to minimize side effects, particularly akathisia 5
• Dose can be gradually titrated based on response and tolerability to 2-15 mg/day 3
• Higher starting doses (e.g., 10 mg/day) are associated with higher discontinuation rates due to side effects 5
• Treatment should be regularly assessed, with monitoring beginning within 1-2 weeks of initiation 1

Safety Considerations

Important Warnings

• Aripiprazole carries an FDA black box warning for increased risk of suicidality in children, adolescents, and young adults with major depressive disorder 2
• The risk appears to be highest in patients under 25 years of age, with 14 additional cases of suicidality per 1000 patients treated in those under 18, and 5 additional cases per 1000 in those aged 18-24 2
• Patients should be monitored closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of treatment or during dose changes 2

Common Adverse Effects

• Akathisia is a common side effect that may lead to discontinuation if not properly managed 6, 5
• Other common adverse events include restlessness, insomnia, fatigue, blurred vision, and weight gain 4
• Most treatment-emergent adverse events are mild to moderate in severity 4

Special Populations

• Aripiprazole is not approved for the treatment of depression in pediatric populations 2
• In elderly patients (≥65 years), there appears to be a decreased risk of suicidality compared to placebo (6 fewer cases per 1000 patients) 2

Monitoring Recommendations

• Patients should be monitored for:
  • Emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, or mania 2
  • Suicidal ideation, especially early in treatment and with dose adjustments 2
  • Treatment response and need for medication adjustments if inadequate response after 6-8 weeks 1
  • Metabolic parameters, as aripiprazole may cause weight gain 1

Clinical Approach

1. Start with standard antidepressant monotherapy for initial treatment of MDD 1
2. If inadequate response after 6-8 weeks of optimized antidepressant therapy, consider aripiprazole augmentation 1, 3
3. Begin with a low dose (2.5 mg/day) to minimize side effects 5
4. Gradually titrate dose based on response and tolerability 3
5. Monitor closely for emergence of suicidality and other adverse effects 2
6. Assess response after 6-8 weeks of combined therapy 1

Common Pitfalls to Avoid

• Using aripiprazole as first-line monotherapy for MDD (not FDA-approved for this indication) 2, 3
• Starting with too high a dose, which increases risk of akathisia and discontinuation 5
• Failing to monitor for emergence of suicidality, especially in younger patients 2
• Not providing adequate patient education about potential side effects and warning signs 2
• Continuing ineffective treatment without reassessment after 6-8 weeks 1