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In short-term studies, oral paliperidone is an antipsychotic 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. In addition, paliperidone is associated with substantial increases in serum prolactin that may be associated with sexual dysfunction, although sexual functioning outcomes were not reported. At doses greater than 3 mg per day, oral paliperidone appears comparable in efficacy to oral olanzapine 10 mg per day. Regarding the critical comparison of oral paliperidone to risperidone, we have no information and are thus unable to determine if paliperidone has any advantages or disadvantages compared to its well-known parent compound.
Paliperidone, 9-hydroxy-risperidone, is an active metabolite of risperidone that is now commercially available in an oral formulation. A long-acting intramuscular formulation may be commercially available soon.
To compare the effects of paliperidone with any other treatment, including placebo, for people with schizophrenia and schizophrenia-like illnesses.
We searched the Cochrane Schizophrenia Group's Register (December 2006) 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.
We included all randomized clinical trials (RCTs) comparing paliperidone to any treatment for schizophrenia and schizophrenia-like illnesses.
We independently selected and critically appraised studies, extracted data, and analyzed on an intention-to-treat basis. Where possible and appropriate, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs) with the number needed to treat/harm (NNT/NNH). We calculated weighted mean differences (WMDs) for continuous data.
Five studies compared paliperidone with placebo. Fewer people left the studies early if they were randomized to paliperidone as shown in Figure 1 (n=1647, 5 RCTs, RR = 0.68, CI = 0.61 to 0.76; NNT = 7, CI = 6 to 9), and those receiving any dose of paliperidone were significantly more likely to have an improvement in global state as indicated by at least 30% improvement in Positive and Negative Syndrome Scale total score (n=1420, 4 RCTs, RR = 0.69, CI = 0.63 to 0.75; NNT = 5, CI = 4 to 6). People randomized to paliperidone were less likely to experience a recurrence (n=1638, 5 RCTs, RR = 0.45, CI = 0.31 to 0.66; NNT = 16, CI = 13 to 26) than those allocated to placebo. Adverse effect data were not well reported, but paliperidone does seem to produce 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 was found for both men (n=413, 3 RCTs, WMD = 27.68, CI = 23.66 to 31.69) and women (n=252, 3 RCTs, WMD = 87.39, CI = 74.27 to 100.51). People receiving paliperidone were more likely to experience extrapyramidal disorders (n=1638, 5 RCTs, RR = 2.21, CI = 1.26 to 3.88; NNH = 28, CI = 12 to 129) and weight gain (n=769, 4 RCTs, WMD = 1.07, CI = 0.65 to 1.49). In our sensitivity analyses examining dose, the results for leaving the study early for any reason were favorable for all specific doses of paliperidone.
Three studies compared various doses of paliperidone with olanzapine 10 mg daily. We found no differences between paliperidone and olanzapine for leaving the study early as shown in Figure 2 (n=1332, 3 RCTs, RR = 1.04, CI = 0.89 to 1.21; ca. 40% in both groups left by 6 weeks). Those receiving any dose of paliperidone were no more likely to have a recurrence of psychotic symptoms than those receiving olanzapine 10 mg daily (n=1327, 3 RCTs, RR = 1.07, CI = 0.64 to 1.76). People who received paliperidone experienced less weight gain than those who received olanzapine (n=660, 3 RCTs, WMD = −0.88, CI = −1.38 to −0.37). Results for various movement disorders all favored olanzapine (extrapyramidal disorder: n=1327, 3 RCTs, RR 2.99 CI 1.44 to 6.18; hyperkinesias: n=1327, 3 RCTs, RR 3.14 CI 1.53 to 6.42; and hypertonia: n=836, 2 RCTs, RR 9.28 CI 1.26 to 68.5). In our sensitivity analyses examining dose, those randomized to paliperidone 3 mg daily were more likely to leave early (n=255, 1 RCT, RR = 1.44, CI = 1.04 to 1.98, NNH = 7) compared with those randomized to olanzapine 10 mg daily. However, there was no difference in numbers leaving early for 6 (n=473, 2 RCTs, RR = 1.05, CI = 0.86 to 1.28, NNH = 54), 9 (n=503, 2 RCTs, RR = 1.11, CI = 0.86 to 1.43, NNH = 25), 12 (n=480, 2 RCTs, RR = 0.89, CI = 0.72 to 1.11, NNT = 25), or 15 mg (n=243, 1 RCT, RR = 0.92, CI = 0.62 to 1.35, NNT = 34).
Oral paliperidone is an effective antipsychotic whose optimal dose appears to be between 6 and 12 mg per day, a dose range in which its effectiveness is comparable to olanzapine 10 mg per day. We found its adverse effects to be similar to those of its parent compound, risperidone, with higher doses more likely to cause movement disorders than lower doses. We observed that people who received paliperidone 3, 6, or 9 mg per day experienced less weight gain than those receiving olanzapine 10 mg per day, but found no difference for people receiving paliperidone 12 or 15 mg per day. People who received paliperidone 9, 12, or 15 mg per day experienced more movement disorders than those who received olanzapine 10 mg per day, but we identified no difference for those receiving paliperidone 3 or 6 mg per day. Paliperidone is associated with substantial increases in serum prolactin in men and women, with larger effects in women than men; the incidence of amenorrhea, anorgasmia, erectile dysfunction, galactorrhea, and other sexual dysfunction, were not reported in these studies.
While no direct comparisons with its parent molecule risperidone are available, we suspect that oral paliperidone will affect people with schizophrenia in a similar fashion to risperidone. For individual clinicians to select paliperidone over risperidone on the basis of appropriate evidence, researchers will need to conduct pragmatic studies that more closely resemble the lived experience of patients with schizophrenia and include comparisons with risperidone. Clinicians would also benefit from studies that assess the efficacy, adverse effects, and safety of long-term use of paliperidone, including behavior, mortality, satisfaction with treatment, and cost-effectiveness in comparisons to older and newer generation antipsychotics.
The authors received no financial consideration from any parties for the preparation of this review. Dr Stroup has been a consultant for AstraZeneca, Janssen, Lilly, and Pfizer and has spoken at events sponsored by Lilly, Lundbeck, and Pfizer.