Background:
To compare the efficacy and tolerability of paliperidone extended-release (ER) with risperidone immediate-release using propensity score methodology.
Methods:
Six double-blind, randomized, placebo-controlled, short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified (3 per compound). Propensity score pairwise matching was used to balance observed covariates between the paliperidone ER and risperidone patient populations. Scores were generated using logistic regression models, with age, body mass index, race, sex, baseline Positive and Negative Syndrome Scale (PANSS) total score and baseline Clinical Global Impressions-Severity (CGI-S) score as factors. The dosage range of paliperidone ER (6-12 mg/day) was compared with 2 risperidone dosage ranges: 2-4 and 4-6 mg/day. The primary efficacy measure was change in PANSS total score at week 6 end point. Tolerability end points included adverse event (AE) reports and weight. AEs with rates [greater than or equal to]5% and with a [greater than or equal to]2% difference between paliperidone ER and risperidone were identified.
Results:
Completion rates for placebo-treated subjects in paliperidone ER trials (n=95) and risperidone trials (n=122) groups were 36.8% and 51.6%, respectively; end point changes on PANSS total scores were similar (p=0.768). Completion rates for subjects receiving paliperidone ER 6-12 mg/day (n=179), risperidone 2-4 mg/day (n=113) or risperidone 4-6 mg/day (n=129) were 64.8%, 54.0% and 66.7%, respectively (placebo-adjusted rates: paliperidone ER vs risperidone 2-4 mg/day, p=0.005; paliperidone ER vs risperidone 4-6 mg/day, p=0.159). PANSS total score improvement with paliperidone ER was greater than with risperidone 2-4 mg/day (difference in mean change score, -6.7; p<0.05) and similar to risperidone 4-6 mg/day (0.2; p=0.927). Placebo-adjusted AEs more common with paliperidone ER were insomnia, sinus tachycardia and tachycardia; more common with risperidone were somnolence, restlessness, nausea, anxiety, salivary hypersecretion, akathisia, dizziness and nasal congestion. Weight changes with paliperidone ER and risperidone were similar (paliperidone ER vs risperidone 2-4 mg/day, p=0.489; paliperidone ER vs risperidone 4-6 mg/day, p=0.236).
Conclusions:
This indirect database analysis suggested that paliperidone ER 6-12 mg/day may be more efficacious than risperidone 2-4 mg/day and as efficacious as risperidone 4-6 mg/day. The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients. Additional randomized, direct, head-to-head clinical trials are needed to confirm these findings.