Paliperidone Palmitate for Schizophrenia

Summary

A Cochrane review [Abstract] 1 included 7 studies with a total of 4184 subjects with schizophrenia. Five trials compared long-acting intramuscular formulation paliperidone palmitate (PP) with placebo and two trials with risperidone long-acting injection. Paliperidone is an active metabolite of risperidone. One trial lasted 53 weeks, 4 trials lasted 3 months, and 2 trials 2 months and 6 months.

• PP vs placebo: fewer people left studies early if they were randomised to PP (RR 0.76, CI 0.70 to 0.84, NNTB 9, CI 7 to 14; 5 RCTs, n = 2183) and those receiving any dose of PP were significantly less likely to show no improvement in global state (RR 0.79, CI 0.74 to 0.85, NNTB 7, CI 5 to 9; 4 RCTs, n = 1696). Patients on PP were less likely to experience a recurrence of psychosis than those on placebo (RR 0.28, CI 0.17 to 0.48, NNTB 5, CI 4 to 6; 1 RCT, n = 312). In the other studies where recurrence was recorded only as an adverse event, people on PP were also less likely to experience a recurrence of psychotic symptoms (RR 0.55, CI 0.44 to 0.68, NNTB 10, CI 8 to 14; 4 RCTs, n = 1837). PP was associated with fewer reports of agitation or aggression (RR 0.65, CI 0.46 to 0.91, NNTB 39, CI 25 to 150; 5 RCTs, n = 2180) and of using anxiolytic medications (RR 0.89, CI 0.83 to 0.96, NNTB 16, CI 11 to 44; 5 RCTs, n = 2170). A consistent, significant elevation in serum prolactin was found for both men and women receiving PP. People receiving PP had a significantly greater increase in weight (MD 1.34, CI 0.97 to 1.70; 5 RCTs, n = 2052) in comparison with people who received placebo.
• PP (mean doses 73.3 and 104.6 mg every 4 weeks) vs flexibly-dosed risperidone long-acting injection (mean doses 35.3 and 31.7 mg every 2 weeks): there was no difference for leaving the studies early for any reason (RR 1.12, CI 1.00 to 1.25; 2 RCTs, n = 1969). Those receiving PP were statistically no more likely to have a recurrence of psychotic symptoms than those receiving risperidone (RR 1.23, CI 0.98 to 1.53; 2 RCTs, n = 1961). There was no significant difference in the occurrences of deaths (RR 3.62, CI 0.60 to 21.89; 2 RCTs, n = 1967), but a total of 6 deaths occurred, with 5 deaths in the PP group and one death the risperidone group. The small number of events in these trials makes it unclear if this finding is meaningful. The patiets on PP were significantly less likely to use anticholinergic medications (RR 0.67, CI 0.55 to 0.82, NNTB 13, CI 10 to 24; 2 RCTs, n = 1587).

Comment: The quality of the evidence is downgraded by study quality (more than 20% loss to follow-up, short follow-up time).