Latuda
Latuda
Generic Name
Latuda
Mechanism
Latuda (lurasidone) is a second‑generation antipsychotic that exerts its therapeutic effects primarily through receptor antagonism and selective partial agonism:
• Dopamine D₂/D₃ blockade: Key for antipsychotic activity in schizophrenia and bipolar depression.
• Serotonin 5‑HT₂A and 5‑HT₂C antagonism: Contributes to efficacy and a lower risk of hyperprolactinemia.
• Serotonin 5‑HT₇ antagonism: Enhances serotonergic neurotransmission, potentially improving mood and cognition.
• Serotonin 5‑HT₁A partial agonism: May alleviate anxiety and depressive symptoms without significant motor side effects.
• Low affinity for muscarinic and histamine receptors → minimal anticholinergic and sedative effects.
These actions together provide antipsychotic, antidepressant, and mood‑stabilizing benefits with a favorable metabolic profile.
Pharmacokinetics
Latuda demonstrates the following pharmacokinetic attributes:
• Absorption: Oral bioavailability ≈ 70 %; absorption not significantly affected by food.
• Distribution: Highly protein‑bound (~ 98 %), predominantly to albumin and α‑1‑acid glycoprotein.
• Metabolism: Primarily hepatic via CYP3A4 (~ 80 %); minimal CYP2D6 involvement.
• Elimination: Half‑life ~ 18 h (steady‑state 30–40 h); renal excretion ~ 8 % unchanged drug.
• Drug interactions: Strong CYP3A4 inhibitors/inducers alter exposure; co‑administration with valproate modestly increases lurasidone levels.
Patients with moderate hepatic impairment may require dose adjustment; renal impairment does not significantly alter dosage.
Indications
Latuda is approved for:
• Schizophrenia (adult and adolescent 12 + years)
• Bipolar depression (adult and adolescent 12 + years) – as monotherapy or adjunct to lithium/valproate.
It is also used off‑label for acute mania, psychotic disorders, and as maintenance therapy.
Contraindications
- Contraindications
- Hypersensitivity to lurasidone or any excipients.
- Severe hepatic impairment (Child‑Pugh C).
- Warnings
- Metabolic syndrome: Weight gain, dyslipidemia, and glucose intolerance (rare but increased compared to other atypicals).
- QTc prolongation: Risk in patients with cardiac disease, electrolyte abnormalities, or on QT‑prolonging drugs.
- Seizure threshold: Close monitoring in seizure‑prone patients (low, but noted).
- Interaction with valproate: Elevated lurasidone concentrations may potentiate CNS effects.
Patients should receive routine metabolic assessment and cardiac screening as indicated.
Dosing
Latuda dosing follows an initial titration, then maintenance:
| Condition | Starting dose | Titration | Max dose | Administration |
| Schizophrenia | 10 mg once daily (with food) | ↑10 mg weekly as tolerated | 30 mg/day | Oral, 1‑2 × per day |
| Bipolar depression | 20 mg once daily (with food) | ↑10 mg weekly as tolerated | 30 mg/day | Oral, 1‑2 × per day |
• Titration schedule: 10 mg (first week), 20 mg (second week), 30 mg (third week).
• Split dosing: Allowed to improve tolerability (e.g., 15 mg + 15 mg).
• Food effect: No significant change; medications may be taken with or without food.
Patients on CYP3A4 inhibitors should have dose adjustments (e.g., reduce to 15 mg once daily).
Adverse Effects
Common
• Nausea, vomiting, and abdominal discomfort
• Akathisia, restlessness
• Insomnia & agitation
• Headache
• Minimal sedation
Serious
• Weight gain and metabolic disorders (↑ plasma lipids, hyperglycemia)
• QTc prolongation – monitor ECG in high‑risk patients
• Rare still life‑threatening metabolic syndrome (e.g., severe hyperglycemia)
• Agranulocytosis – very rare, similar to other antipsychotics
Adverse effects are dose‑dependent and generally improve with time or dose adjustment.
Monitoring
| Parameter | Frequency | Rationale |
| Body weight & BMI | Baseline, 4 weeks, then every 3 months | Detect weight gain |
| Fasting glucose & HbA1c | Baseline, 3 months, then annually | Monitor for diabetes |
| Lipid profile | Baseline, 3 months, then annually | Screen for dyslipidemia |
| Electrocardiogram (QTc) | Baseline & as clinically indicated | Detect QT prolongation |
| Liver function tests | Baseline, 3 months | Evaluate hepatic metabolism |
| Psychiatric assessment | Week 4, 8, then monthly | Ensure efficacy & safety |
| Treatment‑emergent SRI‑related symptoms | At each visit | Detect emergent mania or agitation |
Patients taking CYP3A4 inhibitors/inducers should have higher vigilance for dose‑adjusted therapy.
Clinical Pearls
- Low metabolic burden: Compared to olanzapine and clozapine, lurasidone exhibits a markedly lower incidence of weight gain and metabolic derangements.
- Rapid titration: The recommended 3‑week titration is faster than many other atypicals, allowing earlier therapeutic benefit.
- Safety in older adults: Due to minimal anticholinergic activity, *Latuda* is preferable when cognitive side‑effects are a concern.
- Use in mania: Though not labeled for acute mania, small studies suggest efficacy when combined with mood stabilizers; consider in treatment‑resistant cases.
- Serotonin‑biased profile: The 5‑HT₁A partial agonist confers a mild anxiolytic effect, helpful in comorbid anxiety disorders.
- Limited drug–drug interactions: Lurasidone’s minimal CYP2D6 interaction allows safe use with many psychotropics; still watch for CYP3A4 modulators.
- Avoid with taking valproate without dose adjustment: Co‑administration often raises lurasidone levels; consider 15 mg instead of 20 mg or add a metabolic monitor.
These pearls can act as quick reference points for clinical decision‑making and flow‑chart integration in practice guidelines.