Clinical Scorecard: Safety Evaluations of Brexpiprazole for Managing Agitation in Alzheimer’s Disease: Analyzing Timing and Duration of Adverse Effects

At a Glance

Key Highlights

• Brexpiprazole 2 or 3 mg/day showed similar timing and duration of adverse events compared to placebo over 12 weeks.
• Participants discontinuing due to adverse events did so earlier with placebo than with brexpiprazole.
• Brexpiprazole was well tolerated up to 24 weeks in extension trials without cognitive worsening.

Guideline-Based Recommendations

Diagnosis

• Diagnose probable Alzheimer’s disease using NINCDS-ADRDA criteria supported by clinical assessment.

Management

• Use brexpiprazole 2 or 3 mg/day for agitation associated with Alzheimer’s dementia as approved.
• Prescribe atypical antipsychotics at the lowest effective dose and with caution regarding treatment duration.
• Avoid off-label use of antipsychotics without clear evidence of efficacy.

Monitoring & Follow-up

• Monitor for adverse events including insomnia, somnolence, nasopharyngitis, urinary tract infections, cerebrovascular and cardiovascular events, extrapyramidal symptoms, orthostatic hypotension, falls, and sedation.
• Observe timing and duration of treatment-emergent adverse events, noting that brexpiprazole adverse events occur similarly to placebo.
• Assess cognition regularly to detect any worsening during treatment.

Risks

• Be aware of boxed warnings for increased mortality risk in older patients with dementia-related psychosis treated with antipsychotics.
• Consider risks of cerebrovascular events, cardiovascular events, extrapyramidal symptoms, orthostatic hypotension, falls, fractures, and sedation.
• Discontinue treatment early if adverse events occur, noting that brexpiprazole discontinuations due to adverse events occur later than placebo.

Patient & Prescribing Data

Older adults with agitation associated with dementia due to Alzheimer’s disease enrolled in phase 3 trials and extension studies.

Brexpiprazole at 2 or 3 mg/day reduces agitation symptoms with a safety profile comparable to placebo over 12 weeks and is well tolerated up to 24 weeks.

Clinical Best Practices

• Confirm diagnosis of agitation related to Alzheimer’s dementia before initiating brexpiprazole.
• Start brexpiprazole at approved doses (2 or 3 mg/day) and monitor closely for adverse events.
• Educate patients and caregivers about potential side effects and timing of adverse events.
• Regularly assess treatment efficacy and tolerability, adjusting or discontinuing therapy as needed.
• Use caution in prescribing antipsychotics to older adults due to increased susceptibility to adverse effects and mortality risk.

References

• NINCDS-ADRDA criteria for Alzheimer's diagnosis
• Brexpiprazole FDA Prescribing Information
• ClinicalTrials.gov NCT01862640
• ClinicalTrials.gov NCT01922258
• ClinicalTrials.gov NCT03548584