Paliperidone, the major active metabolite of the atypical antipsychotic risperidone, is available in an oral extended-release (ER) formulation (Invega(R)) and is indicated for the acute and maintenance treatment of schizophrenia in adults in the US and the EU. Once-daily paliperidone ER provides stable plasma drug concentrations over a 24-hour period and may be initiated at therapeutically effective dosages without the need for titration. Paliperidone ER 3-12 mg/day improved Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint) from baseline to study end to a significantly greater extent than placebo in 6-week, double-blind trials in patients with acute symptoms of schizophrenia. The significant improvement in PANSS total score was seen after 4 days of treatment in some trials and paliperidone ER was effective against both positive and negative symptoms of the disease. End of treatment clinical response rates were significantly higher in paliperidone ER recipients than in those who received placebo. The efficacy of paliperidone ER was maintained with longer-term treatment (up to 52 weeks) in open-label extensions of placebo-controlled trials. When compared with quetiapine, paliperidone ER was associated with significantly greater improvements in PANSS total scores from baseline at 2 weeks (primary endpoint) in patients with acute schizophrenia, and at 6 weeks. The two drugs did not significantly differ in terms of clinical response rates. In the only trial to evaluate paliperidone ER for the prevention of symptom recurrence, paliperidone ER recipients had a significantly longer time to recurrence than did placebo recipients, as well as significantly less deterioration of symptom severity. In a 6-month, open-label trial in patients with non-acute schizophrenia, PANSS total scores, PANSS subscale scores and all five Marder factor scores did not significantly differ between paliperidone ER and olanzapine, but were significantly reduced from baseline at endpoint in both treatment groups. In adults with non-acute schizophrenia who were previously unsuccessfully treated with other oral antipsychotics and switched to paliperidone ER, PANSS total scores, PANSS subscale scores and all five Marder factor scores were significantly decreased from baseline at week 26 or endpoint. Paliperidone ER was generally well tolerated during short- and longer-term use and had a tolerability profile generally similar to that of its parent drug, risperidone. There were no unexpected tolerability findings during treatment of up to 52 weeks in duration. Paliperidone ER appeared to have little pro-arrhythmic potential and little effect on plasma glucose, lipid or insulin levels, but increased plasma prolactin levels over both short- and longer-term treatment periods. Clinically significant gains in bodyweight were seen in 15% of patients treated with paliperidone ER during the extension phase of placebo-controlled trials. Pooled analyses revealed that extrapyramidal symptoms occurred in approximately a quarter of the p...
