Oral paliperidone for schizophrenia

Paliperidone, 9-hydroxy-risperidone, is an active metabolite of risperidone that is now commercially available in an oral formulation. We evaluated the efficacy, adverse effects, and safety of oral paliperidone in the treatment of people with schizophrenia and schizophrenia-like illnesses. In short-term studies, oral paliperidone is a more effective antipsychotic than placebo. The adverse effects of paliperidone are similar to those of risperidone. No data comparing the efficacy of paliperidone to risperidone over a meaningful period of time was available for this review; in a six-day trial comparing paliperidone to risperidone we identified no difference in recurrence of psychotic symptoms or adverse effects. The manufacturer is also developing an intramuscular long-acting formulation, but it is not yet commercially available; its use in the treatment of schizophrenia will be considered in a separate review.

Authors' conclusions: 

In short-term studies, oral paliperidone is an antipsychotic drug that is more efficacious than placebo. We found its adverse effects to be similar to those of its parent compound, risperidone, with movement disorders, weight gain and tachycardia all more common with paliperidone than placebo. While no difference was found in the incidence of reported adverse sexual outcomes, paliperidone is associated with substantial increases in serum prolactin. When used at doses of 6 mg per day or higher, oral paliperidone appears comparable in efficacy to olanzapine 10 mg/day. A single study of six days duration found neither an advantage nor disadvantage of paliperidone compared to risperidone. When dosed flexibly with other psychotropics available, it appears to be comparable in efficacy to flexible doses of quetiapine with other psychotropics available.

Read the full abstract...

Paliperidone, an active metabolite of risperidone, is now available in an oral formulation for daily use; an intramuscular formulation for monthly administration is expected to follow shortly. Oral paliperidone is available commercially only in an extended release formulation that was used in all of the clinical trials we examined in this review.


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

Search strategy: 

We searched the Cochrane Schizophrenia Group's Register (November 2008) and inspected references of identified studies for further trials. We contacted the manufacturers of paliperidone, the Food and Drug Administration, and authors of relevant trials for additional material.

Selection criteria: 

We included all relevant 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 treat (NNT). We calculated Weighted Mean Differences (WMD) for continuous data.

Main results: 

Eight studies with 2567 participants compared paliperidone with placebo. Fewer people left studies early if they were randomised to paliperidone (n=1926, 7 RCTs, RR 0.68 CI 0.61 to 0.75, NNT 7 CI 6 to 10) and those receiving any dose of paliperidone were significantly more likely to have an improvement in global state (n=1420, 4 RCTs, RR 0.69 CI 0.63 to 0.75, NNT 5 CI 4 to 6). People randomised to paliperidone were less likely to experience a recurrence of psychosis (n=1918, 7 RCTs, RR 0.47 CI 0.34 to 0.66, NNT 17 CI 14 to 26) than those allocated to placebo. Paliperidone was associated with a greater incidence of tachycardia than placebo (n=1638, 5 RCTs, RR 1.88 CI 1.28 to 2.76, NNH 21 CI 11 to 90) and a consistent, significant elevation in serum prolactin (ng/mL) for both men (n=413, 4 RCTs, WMD 27.68 CI 23.66 to 31.69) and women (n=252, 4 RCTs, WMD 87.39 CI 74.27 to 100.51). People receiving paliperidone were more likely to experience extrapyramidal disorders (n=1680, 6 RCTs, RR 2.27 CI 1.31 to 3.95, NNH 28 CI 12 to 111) and weight gain (n=769, 4 RCTs, WMD 1.07 CI 0.65 to 1.49, I-squared 78%) compared with those allocated to placebo.

Three studies with 1692 participants compared paliperidone with 10 mg/day olanzapine. We found no differences between paliperidone and olanzapine for leaving in the short term (n=1332, 3 RCTs, RR 1.04 CI 0.89 to 1.21; ~40% in both groups left by six weeks). Those receiving any dose of paliperidone were no more likely to have a recurrence of psychotic symptoms than those receiving olanzapine (n=1327, 3 RCTs, RR 1.07 CI 0.64 to 1.76). Data from all three studies found that paliperidone was associated with less weight change than olanzapine (n=660, 3 RCTs, WMD -0.88 CI -1.38 to -0.37). Results for various movement disorders all favoured olanzapine.

One study lasting less than a week compared paliperidone with risperidone. When participants taking paliperidone were compared with participants taking 4 mg/day risperidone in this brief study, we found no significant difference in the recurrence of psychotic symptoms or in the incidence of adverse events.

One study compared paliperidone, with a mean dose of 9.8 mg daily, versus quetiapine, with a mean dose of 599.1 mg daily, over six weeks. Patients receiving paliperidone were less likely to leave the study early (n=314, 1 RCT, RR 0.64 CI 0.44 to 0.93, NNT 9 CI 6 to 43). No significant difference was observed in the recurrence of psychotic symptoms (n=317, 1 RCT, RR 0.65 CI 0.29 to 1.45, NNT 52 CI Not Significant). Participants receiving paliperidone were more likely to experience hypertonia (n=317, 1 RCT, RR 3.19 CI 1.31 to 7.77, NNH 13 CI 4 to 86) and tremor (n=317, 1 RCT, RR 2.60 CI 1.39 to 4.88, NNH 9 CI 4 to 34).

There are no clear data regarding oral paliperidone relating to social functioning, services use, quality of life, patient satisfaction or cost.