Rexulti
Rexulti
Generic Name
Rexulti
Brand Names
for *brexpiprazole*) is a second‑generation antipsychotic indicated for schizophrenia and adjunctive treatment of major depressive disorder (MDD) in adults. It is available in oral tablets (1 mg, 2 mg, 4 mg) and a nasally administered suspension (25 mg).
Mechanism
Brexpiprazole is a *partial agonist* at the dopamine D₂ and serotonin 5‑HT₁A receptors and an *antagonist* at the serotonin 5‑HT₂A receptor.
• D₂ partial agonism: stabilizes dopamine neurotransmission in both hypo‑ and hyper‑dopaminergic states, reducing positive psychotic symptoms without the high risk of extrapyramidal side effects.
• 5‑HT₁A partial agonism: confers anxiolytic/antidepressant properties and contributes to mood stabilization.
• 5‑HT₂A antagonism: mitigates negative symptoms and cognitive deficits of schizophrenia, while also limiting hyperprolactinemia.
The drug’s partial agonist/antagonist profile promotes *functional selectivity*, offering a balanced pharmacodynamic effect.
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability ~50 %; peak plasma concentration (Tmax) at 5–6 h. |
| Distribution | Protein‑bound ~67 %; crosses the blood–brain barrier. |
| Metabolism | Primarily hepatic via CYP3A4 & CYP2D6; active metabolite M1 exists. |
| Elimination | 70 % excreted renally as metabolites; terminal half‑life ~61 h. |
| Drug–Drug Interactions | Strong CYP3A4 inhibitors (e.g., ketoconazole) increase exposure; CYP3A4 inducers (e.g., rifampin) decrease efficacy. |
Indications
- Schizophrenia in adults: *Rexulti* is approved as monotherapy or adjunctive therapy.
- Major Depressive Disorder (MDD): adjunctive to antidepressants for patients with inadequate response after ≥2 antidepressant trials.
Contraindications
- Contraindicated in patients with known hypersensitivity to *brexpiprazole* or any excipient.
- Caution in:
- Pediatric and geriatric patients: lack of adequate safety data.
- Seizure disorder: potential lowering of seizure threshold.
- Cardiovascular disease: monitor for orthostatic hypotension, QT prolongation.
- Metabolic syndrome: risk of weight gain, dyslipidemia, hyperglycemia.
Dosing
| Condition | Starting Dose | Maintenance Dose | Titration |
| Schizophrenia | 1 mg daily | 2–4 mg daily | 1 mg increments every 3–4 days up to max 4 mg |
| MDD Adjunct | 1 mg daily | 2–4 mg daily | Same titration strategy as schizophrenia |
| Nasally administered suspension (MDD) | 25 mg BID | 25 mg BID | No titration; monitor for tolerance |
• Take orally with or without food; adherence facilitated by once‑daily dosing.
• For the nasal formulation, instruct patient to aspirate 1 cc of the suspension and hold for 5 min before rinsing.
Missed dose: skip; do not double dose next day.
Switching from other atypicals: taper previous drug over 2–3 weeks before initiating *brexpiprazole*.
Adverse Effects
| Adverse Effect | Frequency | Notes |
| Somnolence | 20–25 % | Dose‑dependent; often resolves within weeks. |
| Weight gain | 10–15 % | Monitor BMI; initiate lifestyle counseling. |
| Akathisia | 5–8 % | Treat with propranolol/lorazepam; dose adjustment may reduce. |
| Sedation | 15–20 % | Consider dose titration or nighttime dosing. |
| Orthostatic hypotension | 5–10 % | Assess BP pre‑ and post‑dose in first week. |
| QTc prolongation | Rare (<1 %) | Baseline ECG recommended if QT‑prolonging medications are used. |
| Metabolic syndrome | 5–10 % | Periodic fasting glucose, lipids. |
| Extrapyramidal symptoms (EPS) | <5 % | Lower than other antipsychotics but remain vigilant. |
Serious:
• Neuroleptic malignant syndrome (NMS): rare; monitor for rigidity, hyperthermia, autonomic instability.
• Seizures: risk ↑ in patients with epilepsy or on valproate; monitor neurological status.
• Hyponatremia (especially in elderly on SSRIs): manage by fluid restriction/rescue meds.
Monitoring
- Baseline: weight/BMI, fasting glucose, lipids, BP, ECG (QTc), serum prolactin (optional).
- Follow‑up:
- Weight/BMI every 4–6 weeks.
- Fasting glucose & lipids at 3 months, then annually.
- BP at each visit for first 6 weeks, then quarterly.
- Assess for akathisia/rigidity at every visit.
- Electrolyte panel if hyponatremia concerns.
- Laboratory: no routine CBC required unless symptomatic.
Clinical Pearls
- “Stability first”: Start at 1 mg; many patients reach therapeutic benefit at 1–2 mg, reducing risk of EPS.
- Adjunctive MDD benefit: *Rexulti* improves depressive symptoms when added to an SSRI, but avoid combining with another dopamine agonist.
- Nasal route advantage: Superior brain penetration for MDD; avoids first‑pass metabolism, giving consistent plasma levels.
- CYP3A4 caution: Co‑administration of strong inducers (e.g., carbamazepine) can significantly reduce *brexpiprazole* serum levels; consider dose escalation or drug switch.
- Weight gain mitigation: Pair therapy with low‑calorie diet and aerobic exercise; consider adding metformin if BMI >30 kg/m² or fasting glucose >100 mg/dL.
- Early akathisia detection: Use Barnes Akathisia Scale at first visit; treat preemptively with beta‑blockers to avoid dose discontinuation.
- Special populations: While data are limited in children and elderly, cautious use in geriatric patients with monitoring for orthostatic hypotension can yield benefits without high EPS risk.
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• *This drug card is for educational purposes and should not replace professional judgment or official prescribing information.*