Lurasidone (Latuda)

Class

Second-generation (atypical) antipsychotic

Mechanism

Antagonist at dopamine D2 and serotonin 5-HT2A receptors; also acts as a 5-HT7 antagonist and partial agonist at 5-HT1A receptors, which may contribute to antidepressant and cognitive effects

FDA-Approved Use

Schizophrenia, bipolar depression (as monotherapy or adjunct to lithium/valproate)

Off-Label Use

Major depressive disorder (MDD) with mixed features, postpartum psychosis, psychotic depression

Formulation

Oral tablets (20 mg, 40 mg, 60 mg, 80 mg, 120 mg)

Titration

20 mg p.o. daily with food (≥350 calories); titrate in 20 mg increments based on response and tolerability

Dose Range

20–160 mg/day

Kinetics

Half-life ~18 hours; metabolized via CYP3A4; steady state in ~7 days

Common AEs

Akathisia, nausea, somnolence, restlessness, extrapyramidal symptoms (EPS), insomnia

Serious/Rare AEs

Tardive dyskinesia, neuroleptic malignant syndrome (NMS), orthostatic hypotension

Monitoring

Monitor weight, fasting glucose, lipids, and EPS symptoms every 3–6 months; assess for adherence to food requirement for absorption

Black Box Warning

Increased risk of mortality in elderly patients with dementia-related psychosis; increased risk of suicidality in children, adolescents, and young adults with mood disorders

Considerations

Lurasidone is often favored in patients with metabolic syndrome, obesity, or diabetes due to its minimal effects on weight, glucose, and lipid parameters. While it is sometimes used off-label in elderly patients with dementia-related psychosis or agitation, it carries the same increased mortality risk as other antipsychotics in this population and should be used with caution. It may be a reasonable choice in younger individuals or those with bipolar depression and cognitive symptoms due to its serotonergic profile. Lurasidone is contraindicated with strong CYP3A4 inhibitors or inducers, and clinicians should monitor for EPS, especially in patients with a history of sensitivity to extrapyramidal side effects.