paliperidone

Paliperidone is an atypical antipsychotic used primarily in the treatment of schizophrenia. It is the main active metabolite of risperidone and is available in oral extended-release form as well as in long-acting injectable formulations for maintenance therapy.

Mechanism of action and profile: Paliperidone acts mainly as an antagonist of dopamine D2 receptors and serotonin 5-HT2A receptors, which helps reduce psychotic symptoms while aiming to minimize certain motor side effects. It has lower affinity for muscarinic receptors than some older antipsychotics, which can reduce anticholinergic effects, though it can still cause adverse effects related to other receptor interactions, such as alpha-1 adrenergic and histamine H1 antagonism.

Pharmacokinetics and dosing considerations: The oral extended-release form provides steady plasma levels with once-daily dosing. Paliperidone is not extensively metabolized by cytochrome P450 enzymes and is largely excreted unchanged in the urine, making renal function an important consideration for dosing. Drug interactions via CYP enzymes are limited, but dose adjustments may be needed in renal impairment.

Routes of administration and regimens: In addition to oral tablets, paliperidone is available as long-acting injectables for maintenance. The injectable forms are given on a schedule that involves loading injections followed by regular maintenance injections (monthly or every three months, depending on the product and treatment plan) under clinical supervision.

Safety and adverse effects: Common adverse effects include extrapyramidal symptoms, weight gain, metabolic changes, insomnia, and hyperprolactinemia. Less common risks include QT prolongation, orthostatic hypotension, and sedation. Paliperidone should be used with caution in elderly patients with dementia-related psychosis, and pregnancy should be considered only if clearly needed.