What is the best way to switch Rexulti (brexpiprazole) from a 5pm dose to a morning dose?

Switching Rexulti from Evening to Morning Dosing

Direct Recommendation

For most patients, you can switch Rexulti from 5pm to morning administration immediately without any titration period or gradual transition. 1, 2

Rationale for Immediate Switch

• Brexpiprazole (Rexulti) has a long elimination half-life of approximately 91 hours, which means steady-state blood levels are maintained throughout the day regardless of exact dosing time 1
• The extended half-life provides a pharmacokinetic buffer that prevents significant fluctuations in drug levels when switching administration times 2
• Clinical trials have demonstrated that brexpiprazole can be administered once daily at any time of day with consistent efficacy and tolerability 1, 2

Practical Implementation Algorithm

Step 1: Assess Current Tolerability

• If the patient is experiencing sedation or somnolence with evening dosing, morning administration may actually worsen daytime functioning 1
• If the patient has insomnia or activation with evening dosing, morning administration is likely to improve tolerability 3

Step 2: Execute the Switch

• Simply take the next scheduled dose in the morning instead of at 5pm 1
• No dose reduction, splitting, or overlap period is necessary 2
• Maintain the same total daily dose (typically 2-4 mg for schizophrenia) 1, 2

Step 3: Monitor for 1-2 Weeks

• Watch for changes in sedation patterns, particularly if the patient had been tolerating evening dosing well 3
• Assess for any emergence or worsening of akathisia, though brexpiprazole has a relatively low incidence (5.5% in schizophrenia trials) compared to other dopamine partial agonists 2
• Monitor sleep quality, as the timing change may affect sleep architecture differently than the previous evening dose 3

Critical Considerations Based on Side Effect Profile

• Brexpiprazole exhibits stronger antihistaminic activity than aripiprazole, which contributes to sedative effects 3
• If sedation has been problematic, switching to morning dosing may interfere with daytime functioning and work performance 3
• The drug's relatively low propensity for activating adverse events means that morning dosing is unlikely to cause significant agitation or restlessness 1

Common Pitfalls to Avoid

• Do not gradually transition by splitting doses or taking partial doses at different times - this is unnecessary given the long half-life and may confuse the patient 1
• Do not reduce the dose when switching times unless there are specific tolerability concerns unrelated to timing 2
• Do not overlap doses (taking both evening and morning doses) as this would constitute a double dose and increase risk of adverse effects 1
• Do not assume that all patients will tolerate morning dosing better - some patients may have been strategically dosed in the evening to leverage sedative effects for sleep 3

When to Reconsider the Switch

• If the patient experiences increased daytime sedation that impairs functioning after 1-2 weeks, consider switching back to evening dosing 3
• If new-onset insomnia develops with morning dosing, this may indicate the drug's activating properties are more prominent in this individual 1
• Weight gain and metabolic parameters should continue to be monitored regardless of dosing time, as these are not timing-dependent effects 2