Lurasidone
Lurasidone
Generic Name
Lurasidone
Mechanism
- Potent D₂ & 5‑HT₂A antagonist – high‑affinity binding reduces psychotic symptoms without typical extrapyramidal effects.
- Partial agonism at 5‑HT₁A – contributes to antidepressant and anxiolytic activity.
- Weak affinity for α₁, α₂, M₁ / M₂ muscarinic, and H₁ histamine receptors – minimal sedation and anticholinergic side effects.
- Moderate 5‑HT₂C blockade – may help with weight stabilization but rarely causes significant weight gain.
Pharmacokinetics
| Parameter | Details |
| Absorption | Fast; peak serum concentration 90–120 min post‑dose. Food ↑ (≈1.5 ×) but does not change the therapeutic window. |
| Distribution | Highly lipophilic, ~62 % plasma protein bound; CNS penetration adequate for antipsychotic action. |
| Metabolism | Predominantly CYP3A4; minor CYP2D6 contribution. Drugs that strongly inhibit or induce CYP3A4 may alter levels. |
| Elimination | Primarily hepatic (≈65 %) with a half‑life of 18–34 h. Renal excretion <25 %. Dose adjustments not required for mild–moderate renal impairment. |
| Drug‑Drug Interactions | Potentiated by CYP3A4 inhibitors (e.g., ketoconazole). Inhibitor potential with strong CYP3A4 inducers (e.g., rifampin). |
Indications
- Schizophrenia – adjunct or monotherapy for acute or maintenance therapy.
- Bipolar I Disorder – Depressive Episode – effective as monotherapy or adjunct to mood stabilizer.
- Off‑label use: schizoaffective disorder, other mood disorders (under specialist supervision).
Contraindications
- Absolute Contraindications – hypersensitivity to lurasidone or any excipients; use in patients with known prolonged QTc (>450 ms).
- Pregnancy – Category C; consider risk/benefit.
- Pediatric – not approved for <18 yrs.
- Warnings
- QT prolongation – monitor ECG, especially with other QT‑prolonging agents.
- Orthostatic hypotension – monitor BP in the first 48 h, particularly with concurrent antihypertensives.
- Seizure risk – increase for patients on AEDs that lower the seizure threshold.
- Metabolic disturbances – minimal but monitor weight, lipids, glucose.
- Neuroleptic malignant syndrome – watch for fever, rigidity, autonomic instability.
Dosing
| Phase | Dose | Schedule | Notes |
| Initial | 20 mg/day | Once daily | Start after a 3‑day dose‑titration period to mitigate nausea. |
| Maintenance | 20–120 mg/day | Once daily | Typical therapeutic range 40–80 mg/day. |
| Escalation | Up to 120 mg/day | Gradual; every 1–3 days | In bipolar depression, titrate to 80–120 mg/day. |
| Administration | With food | Yes, improves bioavailability | Avoid high-fat meals that may alter absorption patterns slightly. |
| Discontinuation | Taper over 2–4 weeks | In bipolar depression, 4–6 weeks | Rapid cessation may precipitate withdrawal symptoms. |
Adverse Effects
- Common (≤10 %)
- Nausea, dizziness, somnolence, fatigue
- Mild agitation or anxiety
- Diarrhea, constipation, dry mouth
- Moderate (1–5 %)
- Weight change (usually neutral or slight gain)
- Elevated prolactin (rare, dose‑dependent)
- Orthostatic hypotension
- Serious (>1 %)
- QT prolongation → arrhythmia
- Neuroleptic malignant syndrome
- Severe metabolic syndrome (rare)
- Severe allergic reactions (rash, anaphylaxis)
Monitoring
- Baseline – ECG (QTc), CBC, CMP, fasting lipid profile, fasting glucose, weight, height, BMI.
- During Therapy –
- Weight/BMI every 4–6 weeks; follow NICE guidelines once per year.
- Lipids/glucose at 3, 6, 12 months if risk factors present.
- ECG if QTc >450 ms or added QT‑prolonging drugs.
- Monitor for signs of NMS: fever, rigidity, autonomic instability.
Clinical Pearls
- Food Interaction – A 1‑hour pre‑meal timing reduces peak nausea; avoid meals >800 kcal.
- CYP3A4 Consideration – If co‑administering strong inhibitors, limit dose to 20 mg/d and monitor serum levels by measuring clinical response.
- Weight Neutrality – Lurasidone’s high 5‑HT₁A/5‑HT₂C profile can modestly attenuate weight gain seen with other SGAs—an advantage in metabolic‑sensitive populations.
- Pregnancy & Lactation – Limited data support use only when no safe alternatives; minimal excretion into breast milk.
- Mood Stabilization – Combining lurasidone with lithium or valproate may require lithium dose adjustment due to increased serum levels via CYP3A4 inhibition.
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• Key Takeaway: Lurasidone offers robust antipsychotic and antidepressant activity with a favorable metabolic profile, making it a strong candidate in first‑line management of schizophrenia and bipolar depression when metabolic risk must be balanced.
