OBJECTIVES To assess the use of oral antipsychotics and other concomitant oral medications – psychotropics and the anticholinergic benztropine - during the 1-year open-label treatment of schizophrenia with olanzapine long-acting injection (OLAI), and to compare with previously published rates for risperidone long-acting injection (RLAI). METHODS One-year rates of concomitant oral medication use were drawn from 2 comparable open-label, single-arm extension studies of patients with schizophrenia treated with long-acting atypical antipsychotic medications: 1 for OLAI (n=931), with extension of 3 OLAI clinical trials, and 1 for RLAI (n=371), with extension of 2 RLAI clinical trials (based on published 1-year data - Lindenmayer et al., Eur Neuropsychopharmacol. 2007;17:138-144). RESULTS Supplementation with oral olanzapine occurred in 21% of OLAI-treated patients (median duration 10 days). Oral risperidone was supplemented – beyond the first 3 weeks of treatment in 45%-83% of RLAI-treated patients (median duration not reported). Use of the anticholinergic benztropine was low among OLAI-treated patients (3%, median duration 14 days) and higher among RLAI-treated patients (31%-44%, median duration not reported). Lorazepam was used by 11% of OLAI-treated patients compared to 24%-55% of RLAI-treated patients. Zolpidem was used by 4% of OLAI-treated patients and 11%-12% of RLAI-treated patients. CONCLUSIONS Atypical antipsychotic therapies in long-acting injection formulations were found in this preliminary analysis to differ on concomitant use of oral atypical antipsychotic and other oral medications. OLAI therapy may require less oral supplementation compared to RLAI, thus offering a simpler treatment regimen. Though limited by cross-study comparisons and the need for replication, the current findings may have important clinical and economic ramifications as depot formulations are often chosen for persons previously nonadherent to oral medication regimens.