Jamie Karagianis

Worldwide‐Schizophrenia Outpatient Health Outcomes (W‐SOHO): baseline characteristics of pan‐regional observational data from more than 17,000 patients

Objective:u2002 To describe the Worldwide‐Schizophrenia Outpatient Health Outcomes (W‐SOHO) patient population at study entry, focusing on illness burden and prescribing practices across regions.

Changes in weight and metabolic parameters during treatment with antipsychotics and metformin: do the data inform as to potential guideline development? A systematic review of clinical studies.

Background:u2002 Changes in weight and metabolic parameters have been commonly reported in patients with schizophrenia. Metformin has been evaluated in clinical studies to prevent or reduce weight gain and changes in metabolic parameters in non‐diabetic subjects. We undertook a systematic review of the efficacy and safety of metformin in reducing weight gain and metabolic abnormalities in non‐diabetic subjects with schizophrenia or bipolar disorder taking antipsychotic medication to establish if these data could potentially drive guideline development.

A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: The PLATYPUS Study

BACKGROUNDnPatients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine (ODO) tablets. The primary objective of this study was to investigate the change in body mass index (BMI) in patients who had previously gained weight with SOT and continued with this therapy during the study period, compared with those patients who switched to ODO during the study period.nnnMETHODSnThis was a 16-week, multicentre, randomized, double-blind, double-dummy, study of outpatients diagnosed with schizophrenia, schizoaffective disorder, related psychotic disorder or bipolar disorder, who were taking 5-20 mg SOT daily. Patients continued treatment with 5-20 mg olanzapine in a flexible single daily dose, and were randomized to either receive sublingual ODO plus an oral placebo, or sublingual placebo plus SOT.nnnRESULTSnNo statistically significant between group differences in mean change from baseline in BMI, weight or waist circumference were observed. Analysis of change in body weight from baseline, by pre-specified category (no change, loss of >or=1.5 kg, gain of >or=1.5 kg), revealed a significant difference between groups, favoring ODO patients, who also experienced a significant reduction in subjective appetite and better treatment compliance, compared to patients in the SOT group.nnnCONCLUSIONSnIn this study, patients treated with ODO experienced a similar mean change in BMI and weight from baseline, to those patients treated with SOT.

Relative association of treatment-emergent adverse events with quality of life of patients with schizophrenia: post hoc analysis from a 3-year observational study

To explore the relative association of adverse events with health‐related quality of life (HRQL) in patients (Nu2009=u200916u2009091) with schizophrenia, treated with antipsychotic medication.

Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia

BackgroundIn a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes.MethodsOutpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to low (150 mg/2 weeks; N = 140), medium (405 mg/4 weeks; N = 318), or high (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data).ResultsSafety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose.ConclusionsAnalyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient.Trial RegistrationClinicalTrials.gov: NCT00088491

Medication discontinuation with depot and oral antipsychotics in outpatients with schizophrenia: comparison of matched cohorts from a 12-month observational study.

Aims:u2002 This study compared all‐cause medication discontinuation (any switch, augmentation or medication discontinuation) in matched cohorts of patients with schizophrenia who were initiated on depot or oral antipsychotics. Other objectives included between‐group comparisons of resource use, and clinical and functional outcomes.

Orally disintegrating olanzapine and potential differences in treatment-emergent weight gain

Several papers and communications have reported possible weight reduction or less weight gain when patients start or switch to orally disintegrating olanzapine, as contrasted with standard oral olanzapine tablets. In this paper, the current literature is reviewed and hypothesized mechanisms of action are discussed. The data are still preliminary and mechanisms of action are not well understood. Randomized controlled trials are needed to further evaluate change in weight during treatment with orally disintegrating olanzapine. Copyright

Regional differences in treatment response and three year course of schizophrenia across the world.

Data from the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) study was used to determine the frequency of response and describe the course of disease in outpatients with schizophrenia in different regions of the world. The W-SOHO study was a 3-year, prospective, observational study that included over 17,000 outpatients with schizophrenia from 37 countries classified into six regions (Northern Europe, Southern Europe, Latin America, East Asia, Central & Eastern Europe, North Africa & Middle East). Cox proportional-hazards regression was employed to assess the factors associated with response. Multinomial logistic regression was used to assess the correlates of disease course. We found that approximately two-thirds of the patients (66.4%) achieved response during the 3-year follow up. Response rates varied across regions, and were highest in North Africa & Middle East (84.6%) and Latin America (78.6%) and lowest in Southern Europe (62.1%) and East Asia (60.9%). There were significant differences between the regions in the proportion of patients experiencing continuous remission, remission plus relapse and a persistent symptomatic course, and between the regions in the duration of remission. Overall, Latin America, East Asia, and North Africa & Middle East had more favorable outcomes because they had the largest proportion of people who achieved continuous remission, the longest time in remission and lowest percentage with a persistent symptomatic course. Having good social functioning at baseline was consistently associated with better clinical outcome. These results seem to indicate that patients from Latin America, East Asia, North Africa & Middle East may have a more favorable disease course than patients from European nations.

Clinical consequences of switching from olanzapine to risperidone and vice versa in outpatients with schizophrenia: 36-month results from the worldwide schizophrenia outpatients health outcomes (W-SOHO) study

BackgroundWith many atypical antipsychotics now available in the market, it has become a common clinical practice to switch between atypical agents as a means of achieving the best clinical outcomes. This study aimed to examine the impact of switching from olanzapine to risperidone and vice versa on clinical status and tolerability outcomes in outpatients with schizophrenia in a naturalistic setting.MethodsW-SOHO was a 3-year observational study that involved over 17,000 outpatients with schizophrenia from 37 countries worldwide. The present post hoc study focused on the subgroup of patients who started taking olanzapine at baseline and subsequently made the first switch to risperidone (n=162) and vice versa (n=136). Clinical status was assessed at the visit when the first switch was made (i.e. before switching) and after switching. Logistic regression models examined the impact of medication switch on tolerability outcomes, and linear regression models assessed the association between medication switch and change in the Clinical Global Impression-Schizophrenia (CGI-SCH) overall score or change in weight. In addition, Kaplan-Meier survival curves and Cox-proportional hazards models were used to analyze the time to medication switch as well as time to relapse (symptom worsening as assessed by the CGI-SCH scale or hospitalization).Results48% and 39% of patients switching to olanzapine and risperidone, respectively, remained on the medication without further switches (p=0.019). Patients switching to olanzapine were significantly less likely to experience relapse (hazard ratio: 3.43, 95% CI: 1.43, 8.26), extrapyramidal symptoms (odds ratio [OR]: 4.02, 95% CI: 1.49, 10.89) and amenorrhea/galactorrhea (OR: 8.99, 95% CI: 2.30, 35.13). No significant difference in weight change was, however, found between the two groups. While the CGI-SCH overall score improved in both groups after switching, there was a significantly greater change in those who switched to olanzapine (difference of 0.29 points, p=0.013).ConclusionOur study showed that patients who switched from risperidone to olanzapine were likely to experience a more favorable treatment course than those who switched from olanzapine to risperidone. Given the nature of observational study design and small sample size, additional studies are warranted.

An exploratory analysis of factors associated with weight change in a 16-week trial of oral vs. orally disintegrating olanzapine: the PLATYPUS study

Background:u2002 We conducted exploratory analyses of the data from a multinational, randomised study to identify factors associated with weight change after 16u2003weeks of treatment with standard olanzapine tablets (SOT) or sublingual orally disintegrating olanzapine (ODO).