Is Rexulti (brexpiprazole) safe for treating depression?

Safety Profile of Rexulti (Brexpiprazole) for Depression Treatment

Brexpiprazole (Rexulti) has demonstrated an acceptable safety profile for depression treatment as an adjunctive therapy, but requires careful monitoring for specific side effects including akathisia, weight gain, and somnolence. 1

Efficacy and Indication

Brexpiprazole is FDA-approved as an adjunctive (add-on) treatment for major depressive disorder (MDD) in patients with inadequate response to antidepressant therapy. It belongs to the class of atypical antipsychotics and functions as a serotonin-dopamine activity modulator.

Clinical studies have shown that:

• Brexpiprazole 1-2 mg daily is effective as adjunctive therapy for patients with MDD who have had inadequate response to antidepressant treatment 2
• It demonstrates significant improvement in depression scores compared to placebo when added to existing antidepressant therapy 2

Safety Profile

Common Side Effects

• Akathisia: Occurs in approximately 9% of patients receiving brexpiprazole plus antidepressant therapy versus 2% with placebo plus antidepressant 1
• Weight gain: Reported in 7% of brexpiprazole-treated patients versus 2% in placebo 1
• Somnolence/sedation: Occurs in 5% of patients (including hypersomnia) versus 1% with placebo 1
• Other common side effects:
  • Fatigue (3%)
  • Headache (7%)
  • Tremor (4%)
  • Restlessness (3%)
  • Anxiety (3%)
  • Nasopharyngitis (4%) 1

Serious Safety Concerns

Brexpiprazole carries several boxed warnings and serious safety concerns that require monitoring:

1. Increased mortality risk in elderly patients with dementia-related psychosis (boxed warning) 1
2. Suicidal thoughts and behaviors in adolescents and young adults (boxed warning) 1
3. Metabolic changes: Weight gain, hyperglycemia, and lipid abnormalities 1
4. Neuroleptic malignant syndrome: A rare but potentially fatal reaction 1
5. Tardive dyskinesia: Risk of potentially irreversible involuntary movements 1
6. Orthostatic hypotension and syncope: Particularly in patients with cardiovascular or cerebrovascular disease 1
7. Leukopenia, neutropenia, and agranulocytosis: Requires monitoring in patients with pre-existing low white blood cell counts 1
8. Seizures: May lower seizure threshold 1
9. Cognitive and motor impairment: May affect judgment, thinking, and motor skills 1

Special Populations and Considerations

• Elderly patients: Higher risk of adverse effects, especially if dementia is present 1
• Pregnancy: Limited data available; potential risks should be weighed against benefits
• Patients with anxiety: Brexpiprazole has shown efficacy in MDD patients with concurrent anxiety symptoms 3

Monitoring Recommendations

When initiating brexpiprazole for depression:

1. Baseline assessment: Obtain weight, BMI, waist circumference, blood pressure, fasting glucose, and lipid profile
2. Regular monitoring:
   • Monitor for emergence of akathisia, especially in the first few weeks
   • Track weight changes regularly
   • Assess for sedation and cognitive effects
   • Monitor for extrapyramidal symptoms using standardized scales
3. Dose considerations: Start with lower doses (1 mg daily) and titrate as needed, with 2 mg daily being the target dose for most patients 2

Practical Recommendations

• Start low: Begin with 1 mg daily and increase to 2 mg daily if needed and tolerated
• Take with or without food: Administration can be with or without meals
• Monitor closely during the first 1-2 weeks for akathisia and other side effects
• Consider discontinuation if intolerable side effects occur despite dose adjustment
• Avoid abrupt discontinuation: Taper gradually when stopping treatment

Brexpiprazole represents an additional option for patients with depression who have had inadequate response to antidepressant monotherapy, but the risk-benefit profile should be carefully considered for each patient, with particular attention to monitoring for metabolic effects, akathisia, and sedation.