Rexulti Starting Dose for Older Adults
For older adults, start Rexulti (brexpiprazole) at 0.5 mg once daily, then titrate gradually to the target dose of 2-3 mg/day based on tolerability and response. 1, 2
Initial Dosing Strategy
- Begin with 0.5 mg once daily for the first 4 days in older or frail patients 1
- After the initial period, increase to 1 mg daily on days 5-7 3
- Subsequently titrate to 2 mg daily on day 8 and beyond, which is the recommended target dose 3, 2
- The maximum recommended dose is 3 mg/day, though most older adults respond adequately to 2 mg/day 2, 4
Rationale for Lower Starting Doses
Older adults require lower initial doses due to increased vulnerability to antipsychotic side effects, including orthostatic hypotension, sedation, and extrapyramidal symptoms 5. The American Society of Clinical Oncology specifically recommends using lower starting doses in older or frail patients when prescribing atypical antipsychotics 1.
Titration Considerations
- Titrate slowly over 1-2 weeks to minimize adverse effects, particularly akathisia and restlessness 2, 6
- Monitor closely during the first weeks of treatment when akathisia is most likely to occur 1
- In a 26-week study of elderly patients with major depressive disorder, flexible dosing of 1-3 mg/day was generally well tolerated, with 66.7% completing the full study 2
Special Population Adjustments
For older adults who are CYP2D6 poor metabolizers, reduce the dose by 50% from the standard recommendation 1. Additionally, when brexpiprazole is combined with strong CYP3A4 or CYP2D6 inhibitors, dosage adjustments are mandatory 1.
Safety Profile in Older Adults
- In pooled analyses of over 1,000 participants with dementia-related agitation, brexpiprazole was generally well tolerated for up to 24 weeks 5
- The most common adverse events in elderly patients were fatigue (15.2%) and restlessness (12.9%), which were mostly mild to moderate in severity 2
- Weight gain appears modest in short-term use, though more outliers with ≥7% body weight increase were evident in 52-week studies 4
- Minimal effects on prolactin, glucose, lipids, and QT interval were observed 4
- Extrapyramidal symptom-related adverse events occurred in 5.3% of brexpiprazole-treated patients versus 3.1% on placebo 5
Common Pitfalls to Avoid
- Do not start at the standard adult dose of 1 mg daily—this increases the risk of akathisia and early discontinuation in older adults 1, 2
- Avoid rapid titration—the elderly population requires slower dose escalation to assess tolerability 1
- Monitor for orthostatic hypotension, particularly during the first weeks of treatment 5
- Screen for cognitive dysfunction at baseline and during treatment, though brexpiprazole does not appear to worsen cognition 5