Extended-release paliperidone produces significant symptomatic improvement in acutely ill, hospitalized patients with schizophrenia compared with quetiapine and placebo, according to a presentation at the twentieth annual U.S. Psychiatric and Mental Health Congress.

In the study, 399 patients with an acute exacerbation of symptoms of schizophrenia were randomized to receive extended-release paliperidone, quetiapine, or placebo. Patients were either hospitalized or in need of hospitalization at the start of the trial and willing to remain hospitalized for a minimum of 10 days. The study involved two phases: a two-week monotherapy phase (primary endpoint) followed by a four-week additive therapy phase (secondary endpoint). During the four-week phase, patients could be prescribed additional psychotropic therapy as clinically indicated to manage psychiatric symptoms.

Improvement in symptoms was seen as early as five days after beginning treatment with the extended-release formulation and persisted through the end of the two-week, monotherapy study period. The primary efficacy endpoint was total change in Positive and Negative Symptom Scale (PANSS) score from baseline to the end of the monotherapy phase (day 14). The average PANSS score at baseline was 102.8 (plus or minus 13.1) for the paliperidone group, 101.6 (plus or minus 13.5) for the quetiapine group, and 103.8 (plus or minus 15.7) for the placebo group.

At the end of the monotherapy phase (day 14), the change in the total score from baseline was: -23.4 (1.8) for extended-release paliperidone, - 17.1(1.8) for quetiapine, and -15.0 (2.2) for placebo, with paliperidone showing a significant reduction in symptoms over both quetiapine and placebo.

In a separate analysis, the extended-release formulation also produced a statistically significant improvement in reduction in the individual symptom domains of the PANSS, which includes positive symptoms, negative symptoms, disorganized thoughts and uncontrolled hostility/excitement compared with quetiapine and placebo at two weeks. In the additive therapy phase (days 15-42), 52.9 percent of patients taking extended-release paliperidone received optional additive therapy compared with 55.4 percent of patients taking quetiapine.

"In the treatment of patients with an acute exacerbation of schizophrenia, it is important to explore medications that have the potential to achieve effective, acute symptom control. Schizophrenia patients may take two to four weeks to respond fully to treatment, so the fact that noticeable clinical improvement was observed as early as day 5 in these acutely ill patients is very important," said Miranda Chakos, MD, Professor of Psychiatry, State University of New York at Downstate, Brooklyn, N.Y., and one of the investigators of the trial.

"INVEGA (extended-release paliperidone) is an important treatment option for patients diagnosed with schizophrenia. This trial showed beneficial effects in severely ill, hospitalized patients with an acute exacerbation of schizophrenia."

Recent trials in hospitalized patients have suggested the need for higher doses in treatment of acutely ill patients. The current study examined the effects of recommended labeled doses while taking into account common clinical practice for this patient population. The extended-release formulation was initiated at the recommended starting dose of 6 mg/day (days one to three), increasing to 9 mg/day on day four. Because patients were acutely ill, there was an option to increase the dose to 12 mg/day on day eight.

Quetiapine was titrated to 600 mg/day by day five with an option to increase the dose to 800 mg/day on day eight. Because this study enrolled severely ill patients with recent onset of symptoms, patients were more likely to require doses near the upper end of the recommended ranges to control their symptoms. The average doses during the monotherapy phase were 10.4 mg/day for paliperidone and 690.9 mg/day for quetiapine.