Paliperidone palmitate for schizophrenia

Paliperidone palmitate is a long-acting intramuscular formulation of paliperidone, an active metabolite of risperidone that was previously available only in an oral formulation. We evaluated the efficacy, adverse effects, and safety of paliperidone palmitate in the treatment of people with schizophrenia and schizophrenia-like illnesses. In short-term studies, paliperidone palmitate is a more effective antipsychotic than placebo. The adverse effects of paliperidone palmitate are similar to those of oral paliperidone, oral risperidone, and risperidone long-acting injection. In two short-term studies, flexibly-dosed paliperidone palmitate is roughly equivalent in efficacy and tolerability to flexibly-dosed risperidone long-acting injection.

Authors' conclusions: 

In short-term studies, paliperidone palmitate is an antipsychotic drug that is more efficacious than placebo. We found its adverse effects to be similar to those of its related compounds, paliperidone and risperidone, with extrapyramidal movement disorders, weight gain, and tachycardia all more common with paliperidone palmitate than placebo. While no difference was found in the incidence of reported adverse sexual outcomes, paliperidone palmitate is associated with substantial increases in serum prolactin. When flexibly dosed with a mean doses of approximately 70 to 110 mg every four weeks, paliperidone palmitate appears comparable in efficacy and tolerability to risperidone long-acting injection flexibly dosed with mean doses of approximately 35 mg every two weeks.  

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Background: 

Paliperidone palmitate, a long-acting, intramuscular formulation of paliperidone, is now available for clinical use. Paliperidone is an active metabolite of risperidone and it is also available in an oral formulation for daily use.

Objectives: 

To compare the effects of paliperidone palmitate with any other treatment for people with schizophrenia and schizophrenia-like illnesses.

Search strategy: 

We searched the Cochrane Schizophrenia Group's Register (November 2009) and inspected references of identified studies for further trials. We contacted the manufacturers of paliperidone palmitate, the Food and Drug Administration, and authors of relevant trials for additional material.

Selection criteria: 

We included randomised controlled trials (RCTs).

Data collection and analysis: 

We independently selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate, we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to benefit/harm statistic (NNB/H). We calculated mean differences (MD) for continuous data.

Main results: 

Five studies with 2215 participants compared paliperidone palmitate with placebo. Fewer people left studies early if they were randomised to paliperidone palmitate (n = 2183, 5 RCTs, RR 0.76 CI 0.70 to 0.84, NNTB 9 CI 7 to 14) and those receiving any dose of paliperidone palmitate were significantly less likely to show no improvement in global state (n = 1696, 4 RCTs, RR 0.79 CI 0.74 to 0.85, NNTB 7 CI 5 to 9). People randomised to paliperidone palmitate were less likely to experience a recurrence of psychosis (n = 312, 1 RCT, RR 0.28 CI 0.17 to 0.48, NNTB 5 CI 4 to 6) than those allocated to placebo in a single trial specifically designed to study recurrence. In the other studies where recurrence was recorded only as an adverse event, we found that people who received paliperidone palmitate were also less likely to experience a recurrence of psychotic symptoms (n = 1837, 4 RCTs, RR 0.55 CI 0.44 to 0.68, NNTB 10 CI 8 to 14).  Paliperidone palmitate was associated with fewer reports of agitation or aggression (n = 2180, 5 RCTs, RR 0.65 CI 0.46 to 0.91, NNTB 39 CI 25 to 150) and of using anxiolytic medications (n = 2170, 5 RCTs, RR 0.89 CI 0.83 to 0.96, NNTB 16 CI 11 to 44). A consistent, significant elevation in serum prolactin (ng/mL) was found for both men and women receiving paliperidone palmitate, but the data were too heterogenous to sum. We found no evidence of sexual dysfunction in these short-term trials. People receiving paliperidone palmitate had a significantly greater increase in weight (n = 2052, 5 RCTs, MD 1.34 CI 0.97 to 1.70) in comparison with people who received placebo.

Two studies with 1969 participants compared flexibly-dosed paliperidone palmitate with flexibly-dosed risperidone long-acting injection. The mean doses of paliperidone palmitate in these trials were 73.3 and 104.6 mg every four weeks compared with risperidone long-acting injection at mean doses, respectively, of 35.3 and 31.7 mg every two weeks. We found no differences between paliperidone palmitate and risperidone long-acting injection for leaving these studies early for any reason (n = 1969, 2 RCTs, RR 1.12 CI 1.00 to 1.25). Those receiving paliperidone palmitate were statistically no more likely to have a recurrence of psychotic symptoms than those receiving risperidone long-acting injection (n = 1961, 2 RCTs, RR 1.23 CI 0.98 to 1.53). While we found no significant difference in the occurrences of deaths in the pooled trials (n = 1967, 2 RCTs, RR 3.62 CI 0.60 to 21.89), we note that a total of six deaths occurred in these two trials, with five deaths among people who received paliperidone palmitate and one death among people who received risperidone long-acting injection. Although death is the most serious of adverse events, the small number of these events in these trials makes it unclear if this finding is meaningful. We found that participants randomised to paliperidone palmitate were significantly less likely to use anticholinergic medications in these trials (n = 1587, 2 RCTs, RR 0.67 CI 0.55 to 0.82, NNTB 13 CI 10 to 24).

We found no data regarding paliperidone palmitate relating to services use, quality of life, behaviour, patient satisfaction, cognitive functioning or cost.

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