Long-Acting Injection in Markedly-to-Severely

Objective: To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects. Methods: This subgroup analysis included 292 subjects with baseline Clinical Global Im-pressions-Severity scores of markedly ill or worse from a 13-week, randomized, double-dummy noninferiority study (NCT00589914). Subjects received either: 1) paliperidone palmitate (PP; 234 mg day 1 and 156 mg day 8 [correspond-ing to 150 and 100 milligram equivalents of paliperidone, respectively], both administered in deltoid muscle, followed by once-monthly flexible dosing in deltoid or gluteal muscle) and risperidone long-acting injection (RLAI)–matched placebo injections; or, 2) RLAI (25 mg, days 8 and 22; followed by biweekly flexible dosing) and PP-matched placebo injections. RLAI subjects received oral risperidone days 1–28; PP subjects received oral placebo. Because of RLAI’s release profile, data through day 22 correspond to oral risperidone. Assessments included Positive and Negative Syn-drome Scale (PANSS) and adverse event (AE) reports. Paired t-tests assessed within-group changes. Results: LS mean (SE) PANSS total scores improved significantly (both p<.001) with PP and oral risperidone by day 4 (-5.0 [0.6] and-3.4 [0.6], respectively) through day 22; and with PP and RLAI through end point (-21.5 [1.9] and-18.6 [1.9], re-spectively). The between-group difference was significant only at day 4 (p=.006). Proportion of subjects with a ≥30% reduction in PANSS total score was not significantly different between the two groups at day 4 and was significantly greater with paliperidone palmitate than oral risperidone at days 15 and 22 (26.1 % versus 12.7%, p=.013; 41.6 % ver-sus 32.0%, p=.048, respectively). Most common AEs (≥5 % in either treatment group): headache (PP 6.3 % and RLA