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Haya Ascher-Svanum1, William S Montgomery2, David P McDonnell3, Kristina A Coleman4, Peter D Feldman11Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly Australia Pty Ltd, West Ryde, New South Wales, Australia; 3Eli Lilly and Company, Cork, Ireland; 4OptumInsight, Lilyfield, New South Wales, AustraliaBackground: Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia.Methods: Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication's effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study) with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates.Results: Comparison of olanzapine long-acting injection data (931 patients) with the pooled data from the nine risperidone long-acting injection studies (3950 patients) provided almost identical 12-month treatment-completion rates (72.7% versus 72.4%; P = 0.87). When the two most similar studies were compared, the 12-month completion rate for olanzapine long-acting injection was significantly higher than for risperidone long-acting injection (81.3% versus 47.0%; P < 0.001). However, any conclusions drawn from this comparison may be limited by differences in the studies' geographic catchment areas.Conclusion: Using treatment-completion rates as a proxy measure of medication effectiveness, olanzapine long-acting injection did not differ significantly from risperidone long-acting injection when including all eligible studies. However, the findings of this exploratory analysis should be interpreted with caution, considering the methodological limitations of these indirect, cross-study comparisons.Keywords: antipsychotic drugs, intramuscular injection, olanzapine, risperidone, schizophrenia

Haya Ascher-Svanum, Alan JM Brnabic, Anthony H Lawson, Bruce J Kinon, Virginia L Stauffer, Peter D Feldman, Katarina KelinLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USAAbstract: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients’ clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0–14 days prior) and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%). Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions–Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient’s worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians’ stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research.Keywords: augmentation, drug substitution, polypharmacy, schizophrenia, switching

The color-magnitude relation has been determined for the RDCS J0910+5422 cluster of galaxies at redshift z = 1.106. Cluster members were selected from HST ACS images, combined with ground--based near--IR imaging and optical spectroscopy. The observed early--type color--magnitude relation (CMR) in (i_775 -z_850) versus z_850 shows intrinsic scatters in color of 0.042 +/- 0.010 mag and 0.044 +/- 0.020 mag for ellipticals and S0s, respectively. From the scatter about the CMR, a mean luminosity--weighted age t > 3.3 Gyr (z > 3) is derived for the elliptical galaxies. Strikingly, the S0 galaxies in RDCS J0910+5422 are systematically bluer in (i_775 - z_850) by 0.07 +/- 0.02 mag, with respect to the ellipticals. The ellipticity distribution as a function of color indicates that the face-on S0s in this particular cluster have likely been classified as elliptical. Thus, if anything, the offset in color between the elliptical and S0 populations may be even more significant. The color offset between S0 and E corresponds to an age difference of ~1 Gyr, for a single-burst solar metallicity model. A solar metallicity model with an exponential decay in star formation will reproduce the offset for an age of 3.5 Gyr, i.e. the S0s have evolved gradually from star forming progenitors. The early--type population in this cluster appears to be still forming. The blue early-type disk galaxies in RDCS J0910+5422 likely represent the direct progenitors of the more evolved S0s that follow the same red sequence as ellipticals in other clusters. Thirteen red galaxy pairs are observed and the galaxies associated in pairs constitute ~40% of the CMR galaxies in this cluster., ApJ, in press