Lurasidone

Not primarily H1-mediated (lurasidone has minimal H1 binding). The mechanism of lurasidone-related somnolence is not fully established but may involve 5-HT7 antagonism or other pathways. If somnolence occurs, evening dosing converts this side effect into a therapeutic benefit for many patients. If akathisia or insomnia predominate instead, morning dosing may be preferable. Usually most prominent in the first weeks and may attenuate over time.

The most commonly reported EPS with lurasidone. Can be dose-related. Presents as subjective restlessness and inability to sit still. Often misdiagnosed as anxiety (ask about the motor component: do they feel they need to pace or move, not just feel worried?). Management: dose reduction (most effective), propranolol 10-20mg BID-TID, benzodiazepine, or switch agents.

Often occurs early in treatment. Taking with food (which is required anyway) may mitigate. Usually improves within the first 1-2 weeks. If persistent, consider dose reduction.

Acute dystonia and drug-induced parkinsonism are uncommon at standard doses due to the high 5-HT2A/D2 ratio and 5-HT1A partial agonism. Tardive dyskinesia risk is present with chronic use (as with all antipsychotics) but expected to be lower than with high-potency FGAs.

Among the most weight-neutral SGAs. Short-term trials show minimal weight change. Long-term data supports weight neutrality. This is lurasidone's primary metabolic advantage.

No clinically significant changes in fasting glucose, HbA1c, total cholesterol, LDL, or triglycerides in clinical trials. Metabolic monitoring per ADA/APA guidelines is still recommended for all antipsychotic-treated patients.

Less than risperidone, haloperidol, or paliperidone. More than aripiprazole. Usually not clinically significant at standard doses, but some patients do develop symptomatic elevation. Monitor if galactorrhea, menstrual irregularity, or sexual dysfunction develop.

Clinical trials have not shown clinically significant QTc prolongation at standard doses. This is an advantage over ziprasidone for patients with cardiac risk factors, though baseline risk factors should still be considered with any antipsychotic.