To treat acute schizophrenia, a long-acting injectable antipsychotic needs a rapid onset of action and therapeutic profile similar to that of oral agents. The present post-hoc analyses compared results from a randomized, double-blind, placebo-controlled trial of olanzapine long-acting injection (LAI) for acute schizophrenia with those observed in similarly designed trials of oral olanzapine.
Six-week results from the olanzapine LAI study (N=404) were compared with those of 3 oral studies (study 1: olanzapine vs. haloperidol vs. placebo [N=335]; study 2: olanzapine vs. haloperidol vs. low-dose olanzapine [N=431]; study 3: olanzapine vs. placebo vs. low-dose olanzapine [N=152]). All patients had baseline Brief Psychiatric Rating Scale (BPRS) scores ≥24 (0–6 scale). Six-week effect sizes were calculated. Efficacy onset, pharmacokinetics, discontinuations, weight gain, and extrapyramidal symptoms were also assessed.
At 6weeks, mean BPRS scores decreased by 14 to 15 points for olanzapine LAI (405mg/4weeks, 210 or 300mg/2weeks), by 8 to 16 for oral olanzapine (10±2.5 or 15±2.5mg/day), and by 12 to 13 for haloperidol (15±5mg/day). For those same dose groups, effect sizes vs. placebo for the BPRS were 0.7 to 0.8 for olanzapine LAI, 0.5 to 0.7 for oral olanzapine, and 0.6 for haloperidol. The first statistically significant separation from placebo on the BPRS occurred at 3days for the olanzapine LAI groups and at 1week for oral olanzapine and haloperidol (15±5mg/day) in oral study 1 although as late as week 6 for the 10-mg/day olanzapine dose in oral study 3. Olanzapine concentrations were similar across studies. Weight gain ≥7% of baseline occurred in up to 35% of olanzapine LAI and oral patients versus up to 12% of haloperidol and placebo patients. Extrapyramidal symptoms were lowest in the olanzapine LAI groups and significantly greater in the haloperidol groups. No post-injection delirium/sedation syndrome events occurred in the olanzapine LAI study.
Patients treated acutely with olanzapine LAI showed a similar pattern of improvement to that seen historically with oral olanzapine. With the exception of injection-related adverse events, the efficacy and tolerability profile of olanzapine LAI is similar to oral olanzapine.
Keywords: Olanzapine, Long-acting injection, Pamoate, Haloperidol, Effect size, Onset, Pharmacokinetics