Lurasidone – Psychopharmacology, Side Effects and Clinical Pearls

Lurasidone is an Atypical antipsychotic / Second Generation antipsychotic which is metabolically friendly. It has D2-5HT2A antagonistic properties.

It also acts on the following receptors

1. 5HT-7 antagonism which gives it procognitive and antidepressant effect

2. Alpha 2 A and C antagonism – antidepressant properties

3. 5HT1A partial agonism – antidepressant properties

Side effects –

Akathisia should be carefully monitored for.

Pharmacokinetics: 

• Half-life of 18 hrs.
• Metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, and voriconazole) and strong CYP3A4 inducers (e.g., rifampin, St. John’s wort, phenytoin, and carbamazepine)
• Grapefruit and grapefruit juice should be avoided in patients taking Lurasidone, as these may inhibit CYP3A4.

Dose range : 40 mg – 160 mg.

Important pearls:

• Switch from Olanzapine and Quetiapine should be done gradually to avoid antihistaminergic and anticholinergic rebound.
• The dose should be given in the evening to minimise akathisia.
• Useful as an augmentation agent to treat mixed features
• Useful as an augmentation agent to treat psychotic depression or melancholic depression with agitation 
• Anecdotal case of a patient with severe treatment-resistant schizophrenia with lurasidone as an augmentation strategy with clozapine.
• Lurasidone and Clozapine as an augmentation strategy.
• Lurasidone and olanzapine combination in psychosis.

Read more on the mechanism of action of Lurasidone and other oral antipsychotics