Long-acting injectable (LAI) medications offer the advantage of administration every 2 to 4 weeks instead of daily, providing more consistent serum levels and potentially fewer side effects compared to oral alternatives. Paliperidone palmitate, an LAI, generally begins to show effects within 8 days, with peak plasma concentrations occurring around 13 days after the initial dose. Treatment initiation involves two injections one week apart, followed by a maintenance dose every four weeks.

Paliperidone has been shown to improve acute psychotic symptoms associated with schizophrenia. In a double-blind RCT involving 652 patients with acute psychosis, those who received paliperidone injections on day 1, day 8, and monthly thereafter demonstrated greater symptom improvement than those on placebo, reaching appropriate drug levels within 8 days. Reported side effects included injection site pain (7.6%), dizziness (2.5%), and sedation (2.3%), with no significant differences in extrapyramidal symptoms (EPS) compared to placebo.

Paliperidone is considered a safe and effective treatment for acute schizophrenia exacerbations, with a favorable side-effect profile. When compared to oral antipsychotics, LAI treatment was associated with lower rates of treatment failure, improved medication adherence, and reduced hospitalization rates. Additionally, paliperidone injections typically achieve a steady state rapidly, reducing the need for concurrent oral medication.