Rexulti Titration from 1 mg to 3 mg
For adjunctive treatment of major depressive disorder, increase Rexulti from 1 mg to 2 mg after one week, then to 3 mg after another week if clinically indicated, with the maximum dose being 3 mg daily. 1
FDA-Approved Titration Schedule for MDD
The official FDA labeling provides clear guidance for dose escalation in major depressive disorder 1:
- Starting dose: 0.5 mg or 1 mg once daily
- Week 1: Titrate to 1 mg once daily (if started at 0.5 mg)
- Week 2: Increase to target dose of 2 mg once daily
- Subsequent weeks: May increase to maximum of 3 mg once daily based on clinical response and tolerability, with increases at weekly intervals 1
Clinical Context and Evidence
The recommended target dosage for MDD is 2 mg daily, with 3 mg representing the maximum approved dose rather than a routine target. 1 In the pivotal Phase III trials for MDD, both 2 mg and 3 mg doses demonstrated efficacy, with pooled responder rates of 23.2% versus 14.5% for placebo (NNT = 12) 2. The 2 mg dose is generally preferred as it balances efficacy with tolerability 3.
Important Considerations for Dose Escalation
- Weekly intervals are recommended between dose increases to allow assessment of clinical response and tolerability at each dose level 1
- Akathisia risk increases with dose: In MDD trials, akathisia occurred in 8.6% of brexpiprazole-treated patients versus 3.9% on placebo (NNH = 15), making monitoring essential during titration 4, 2
- Weight gain is modest but dose-related: Approximately 10% of patients on 1-4 mg/day gained ≥7% body weight versus 4% on placebo (NNH = 17) in short-term studies 4
Dosage Modifications Required
Reduce maximum dose to 2 mg daily if the patient has: 1
- Moderate to severe hepatic impairment (Child-Pugh score ≥7)
- Renal impairment (CrCl <60 mL/minute)
- Known CYP2D6 poor metabolizer status (administer half the usual dose)
- Concurrent strong CYP3A4 or CYP2D6 inhibitors (administer half the usual dose)
Common Pitfalls to Avoid
- Never escalate faster than weekly intervals, as this increases the risk of activation-like adverse effects including akathisia and agitation 1, 4
- Do not routinely target 3 mg in all patients—the 2 mg dose is the recommended target, with 3 mg reserved for patients with inadequate response at 2 mg after adequate trial duration 1
- Avoid underdosing by stopping at 1 mg—the therapeutic range begins at 2 mg daily for MDD based on clinical trial evidence 3, 2
- Monitor for paradoxical anxiety or agitation during the first 2-4 weeks, as approximately 10% of patients experience paradoxical reactions with aripiprazole-class medications 5