Predicting a 'combined treatment outcome' in chronic schizophrenia: the role of demographics, symptomatology, functioning and subjective well-being.

OBJECTIVES: The aim of this study was to determine what variables predict a 'combined treatment outcome' (COMBOUT) in patients with chronic schizophrenia. METHODS: This analysis (n=522) was based on a randomized, double-blind, flexible-dose, 12-week study that enrolled chronically-ill patients diagnosed with schizophrenia or a related disorder. COMBOUT was assessed using the PANSS for symptoms, CGI-S for overall clinical status, MADRS for depressive symptoms, QLS for functioning/QOL, and SWN-K for subjective well-being. Possible predictors included demographics as well as baseline scores (Model I), and early change (week 2) scores (Model II). RESULTS: Model I: significantly better outcome (higher COMBOUT score) was observed in patients with lower MADRS (T= - 6.36; p<0.001) or higher QLS (T=5.05; p<0.001) scores at baseline. Model II: significantly better COMBOUT was observed in patients with early improvement of QLS (T=4.93; p<0.001), SWN-K (T=3.88; p<0.001), PANSS (T= - 2.32; p=0.021) and CGI-S scores (T= - 2.22; p=0.027). Changes in EPS were not predictors of COMBOUT in the models tested. CONCLUSION: COMBOUT at endpoint was predicted by lower depressive symptom score and higher QOL at baseline and by early improvement in psychopathology, quality of life and subjective well-being.

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

AIMS: 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. METHODS: This post hoc analysis of a one-year, multicentre, prospective, observational study included outpatients with schizophrenia who required a change in their antipsychotic medication because of a physician-perceived risk of medication non-adherence. Patients were matched 1 : 1 using an optimal algorithm with rank-based Mahalanobis distances. All-cause medication discontinuation was compared using the Klein and Moeschberger test for survival and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a Cox proportional hazards model, stratifying on matched pairs. RESULTS: Forty patients who initiated a depot antipsychotic could be matched to patients who initiated an oral antipsychotic. Fewer depot-treated patients discontinued their antipsychotic medication at least once compared with oral-treated patients [20% (8/40) vs. 40% (16/40)]. Depot-treated patients discontinued their medication later (Klein and Moeschberger test p = 0.025) and were less likely to discontinue their initial antipsychotic medication [HR = 0.33 (95% CI, 0.12-0.92), p = 0.033] than oral-treated patients. There were few differences in resource use and no differences in clinical and functional outcomes between cohorts. CONCLUSION: In this matched-cohort analysis, patients with schizophrenia who were considered to be non-adherent with their prior oral antipsychotics were less likely to discontinue their medication for any cause if they were initiated on depot compared with oral antipsychotics.

Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia.

OBJECTIVE: Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine. SUBJECTS AND METHODS: We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N=931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed. RESULTS: Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p<0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American. CONCLUSION: Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.

The heterogeneity of antipsychotic response in the treatment of schizophrenia.

BACKGROUND: Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response. METHOD: Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine. RESULTS: Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified. CONCLUSIONS: This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.

The number needed to treat for all-cause medication discontinuation in the treatment of schizophrenia: consistency across world geographies and study designs.

INTRODUCTION: The number needed to treat (NNT) for all-cause medication discontinuation in large, industry-sponsored, non-randomized, observational studies conducted across world geographies was compared with NNTs from CATIE, an 18-month, NIMH-sponsored, randomized study. METHODS: NNTs (with 95% confidence intervals) were calculated using data from 3 large Lilly-sponsored, non-randomized, observational studies (EU-SOHO, IC-SOHO, and US-SCAP, n=20 957). Group differences at medication initiation were adjusted by Cox regression modeling. These NNTs were compared with published NNTs for CATIE (phase 1). RESULTS: NNTs for olanzapine vs. risperidone and for olanzapine vs. quetiapine were similar across the observational studies and similar to those of CATIE. The NNTs for olanzapine vs. oral typical antipsychotics were similar across the observational studies but demonstrated a somewhat stronger effect size than the NNT reported for olanzapine vs. perphenazine in CATIE. DISCUSSION: NNTs for all-cause treatment discontinuation (a proxy measure of a medication's effectiveness from patients' and clinicians' perspectives) appear to be consistent across study designs (non-interventional, observational vs. RCT), study sponsorship (industry vs. independent), and across world geographies, suggesting that antipsychotics differ in this measure.

Patient education about schizophrenia: initial expectations and later satisfaction.

This study investigated patients' expectations prior to participation in an education program about coping with schizophrenia, and their evaluations of the program upon its completion. Adult inpatients diagnosed with schizophrenic disorders (N = 123) responded anonymously to a preintervention expectation measured and a postintervention evaluation questionnaire. Results point to high expectations of this illness self-management education program, and a high level of satisfaction upon its completion, with a self-fulfilling prophecy effect, in which those with high expectations later reported greater satisfaction. Patients perceived, however, a differential level of helpfulness of the program's nine content areas, and rated learning about diagnosis and medication management as most helpful. Content areas that were rated less helpful included prevalence of schizophrenia, its psychosocial rehabilitation, and use of community resources. Implications for clinical practice in patient education are identified and discussed.

A randomized controlled study of two styles of group patient education about schizophrenia.

OBJECTIVE: The therapeutic specificity of patient education about schizophrenia was investigated in a randomized controlled study comparing the effects of two styles of group educational intervention. METHODS: Thirty-three adult inpatients with schizophrenia were assigned in a stratified random manner either to an experimental patient education group that used a didactic format to cover a range of topics on the characteristics and treatment of schizophrenia (N = 16) or to a control group in which participants discussed their subjective experiences with schizophrenia and its treatment (N = 17). Before and after the group interventions, participants responded to measures of knowledge about schizophrenia, insight into illness, and cognitions about medication intake. RESULTS: The two groups did not differ significantly in postintervention scores on measures. CONCLUSIONS: The benefits of patient education may not be due to specific active therapeutic educational ingredients but may be due instead to the presence of nonspecific treatment effects.

Development and validation of a measure of patients' knowledge about schizophrenia.

The Knowledge About Schizophrenia Questionnaire (KASQ), a 25-item multiple-choice test, was developed to assess patients' knowledge about their illness and its management. A total of 136 inpatients participated in four studies, including one cross-validation study, to examine the reliability and validity of the KASQ. Reliability was assessed by measuring the test's precision, internal consistency, and stability of scores. Validity was investigated by comparing patients' scores before and after participation in an educational intervention, and by comparing these scores with those of a waiting-list control group. Results indicate that the KASQ has sound psychometric properties and support its use as an outcome measure.

Educational needs of families of mentally ill adults.

A total of 197 family members of mentally ill adults in Indiana responded to a survey about their preferences for family psychoeducation programs, including type of information, format, presenter, frequency and length of educational programs, setting, and cost. The findings of the survey, which was sent only to persons who were not members of the National Alliance for the Mentally Ill, indicated that family members throughout the state have consistent and persistent needs and clear preferences about educational programs. Of 11 educational topics listed, family members expressed the least interest in learning about their relative's substance abuse. They were ambivalent about whether to include patients in family education programs, but they clearly supported patient education.