Movement disorder profile and treatment outcomes in a one-year study of patients with schizophrenia.

BACKGROUND: This study identified subgroups of patients with schizophrenia who differed on their movement disorder profile and compared their treatment outcomes. METHODS: Data from a randomized, open-label, one-year study of patients with schizophrenia who were treated with antipsychotics in usual clinical care settings were analyzed (n = 640). Five measures of movement disorder were incorporated into a single Movement Disorder Index (MDI). Subgroups that differed in their movement disorder profile over the one-year study period were compared on clinical and functional outcomes. RESULTS: THREE SUBGROUPS WERE IDENTIFIED: a worsening of MDI in 15% of patients, an improvement in 33%, and no change in 53%. Compared with the other two subgroups, the MDI-worsened subgroup had poorer symptom improvement measured by the Positive and Negative Syndrome Scale (PANSS) total score (mean changes of -11.0, -18.4, and -16.8 for the patients who had a worsening of MDI, no change, and an improvement, respectively), poorer symptom improvement on the PANSS positive and anxiety/depression subscale scores, worsening on the 36-Item Short Form Health Survey (SF-36) physical component summary score, and a higher rate of hospitalization (P < 0.05). CONCLUSION: Patients with schizophrenia who experience worsening of their MDI score appear to have poorer clinical and functional outcomes, suggesting that such worsening may be a marker of poorer prognosis.

Time to all-cause treatment discontinuation of olanzapine compared to other antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis.

OBJECTIVE: This comprehensive review and meta-analysis compared the effectiveness of olanzapine and other antipsychotics in schizophrenia treatment, defining effectiveness as time to all-cause medication discontinuation (primary) and as all-cause treatment discontinuation rates. This study examined randomized clinical trials (RCTs) and observational non-interventional studies. EXPERIMENTAL PROCEDURES: Schizophrenia studies that compared olanzapine with individual first- (FGAs) and/or second-generation antipsychotics (SGAs) were included in the meta-analyses. Hazard ratios (HR), risk ratios (RR), and their associated 95% confidence intervals were extracted for RCTs and observational studies. Sensitivity analyses assessed the impact of sources of funding, dose of olanzapine, and allocation concealment method on final results. RESULTS: There were 60 RCTs (N=33,360) and 27 observational studies (N=202,591) included. On time to all-cause medication discontinuation, olanzapine was significantly better than aripiprazole, quetiapine, risperidone, ziprasidone and perphenazine for RCTs and better than amisulpride, risperidone, haloperidol, and perphenazine for observational studies. There were no significant differences between olanzapine and clozapine in RCTs or observational studies. All-cause discontinuation rates in RCTs were significantly lower for olanzapine compared to all comparators except amisulpride and clozapine. In observational studies, olanzapine was less effective than clozapine. Industry-sponsored studies favored olanzapine when compared to haloperidol and perphenazine; higher dose of olanzapine favored quetiapine and perphenazine when compared to olanzapine; method of allocation concealment did not generally affect the results. CONCLUSION: Using a global measure of medication effectiveness (time to all-cause medication discontinuation), olanzapine appears to be more effective - in both RCTs and observational studies - than most SGAs and FGAs, except for clozapine.

Comparison of patients undergoing switching versus augmentation of antipsychotic medications during treatment for schizophrenia.

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.

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States.

OBJECTIVE: Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations. METHODS: Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained. RESULTS: Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations. LIMITATIONS: Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study. CONCLUSIONS: This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications.

Treatment response trajectories and antipsychotic medications: examination of up to 18 months of treatment in the CATIE chronic schizophrenia trial.

BACKGROUND: Trajectory studies highlight heterogeneity in treatment response, although they are yet to systematically differentiate between antipsychotic medications. AIMS: To compare treatment response trajectories across antipsychotic medication groups. METHOD: Data were analyzed from Phase 1 of CATIE, an 18-month double-blind randomized controlled trial of chronic schizophrenia. Change on recurrent Positive and Negative Syndrome Scale (PANSS) administrations for 1124 patients was used to index treatment response trajectories up to 18 months. Trajectory groups were identified with mixed-mode latent class regression modeling. Groups were derived for all participants, and separately for completers, dropouts, and each antipsychotic medication (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone) and then characterized. RESULTS: Trajectory analysis of the entire sample identified that 18.9% of participants belonged to a group of responders. This figure increased to 31.5% for completers, and fell to 14.5% for dropouts. Olanzapine treated patients were significantly more likely than other treatment groups to belong to the trajectory of responders (n=69, 32.55%; Chi=20.13, df=2, p<.01). Separate trajectory analyses of each medication group showed that all medication groups showed two trajectories except olanzapine that had three trajectories and the only trajectory that attained a 20% PANSS reduction by endpoint. CONCLUSIONS: Trajectories of treatment response differ between antipsychotic medications and demonstrate substantial heterogeneity in chronic schizophrenia.

Updating and confirming an industry-sponsored pharmacoeconomic model: comparing two antipsychotics in the treatment of schizophrenia.

OBJECTIVE: This study updated a 2001 decision economic model that used indirect data and confirmed its findings by developing a new cost-effectiveness model by using now available head-to-head data. The models compared olanzapine with ziprasidone in the treatment of schizophrenia in the United States. METHODS: A decision analytic modeling approach was used to estimate annual health-care costs and health outcomes, incorporating events such as response, relapse, and suicide. Patients without response to first-line treatment switched to the other comparator. Decision tree probabilities were extracted from head-to-head studies and other published clinical literature. Direct health-care costs and quality-adjusted life-years (QALYs) were estimated on the basis of resource use and utility weights for initial and relapse episodes, maintenance therapy, and extended episodes of illness. Disutilities associated with treatment-emergent adverse events were included. RESULTS: Consistent with the 2001 model, this model found that first-line treatment with olanzapine is associated with fewer hospital days, fewer days with extrapyramidal symptoms, and higher QALYs than is first-line treatment with ziprasidone. Total costs were lower for the olanzapine pathway ($70,232-$72,776 vs. $73,086-$73,310 in the Positive and Negative Syndrome Scale analysis) due to the cost savings associated with reduced health-care resource use. The incremental cost per QALY gained indicated that the olanzapine pathway dominated the ziprasidone pathway. CONCLUSIONS: Decision analytic models should be continuously assessed against new data. This case study shows that incorporating new data confirmed results of a previously published model in which olanzapine was associated with better expected health outcomes and lower total health-care costs than was ziprasidone.

Extent of attaining and maintaining symptom remission by antipsychotic medication in the treatment of chronic schizophrenia: evidence from the CATIE study.

BACKGROUND: Data on attaining and maintaining symptom remission associated with specific antipsychotic medications are rare and variant. AIMS: To examine remission rates and their variation by antipsychotic medication in chronic schizophrenia in the National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) given it has an 18-month duration and representative antipsychotic medications. METHODS: Symptom remission was examined using the Remission in Schizophrenia Working Group remission criteria of attaining and maintaining for 6 months with mild ratings on 8 specific Positive and Negative Syndrome Scale (PANSS) items. Remission rates were assessed (a) up to 18 months across CATIE's switching phases (n = 1332); and (b) in phase 1 (that involved double-blind randomization to one of five antipsychotic medications) to compare antipsychotic medication differences in attaining and maintaining remission among patients not in remission at baseline (n = 941). RESULTS: At baseline 16.2% of patients were in symptomatic remission. Across the medication phases of CATIE only 11.7% attained and then maintained at least 6 months of symptomatic remission, and 55.5% (n = 623) experienced no symptom remission at any visit. During the first medication randomization phase, attaining and maintaining remission for 6 months was highest for the olanzapine (12.4%) medication group followed by the quetiapine (8.2%), perphenazine (6.8%), ziprasidone (6.5%), and risperidone (6.3%) groups. CONCLUSIONS: As currently defined, remission appears to be a very difficult therapeutic target to attain and maintain in chronic schizophrenia and may differ by antipsychotic medication. Pragmatically, remission gradients may be effectively studied by applying modified duration and symptom criteria.

Early response predicts subsequent response to olanzapine long-acting injection in a randomized, double-blind clinical trial of treatment for schizophrenia.

BACKGROUND: In patients with schizophrenia, early non-response to oral antipsychotic therapy robustly predicts subsequent non-response to continued treatment with the same medication. This study assessed whether early response predicted later response when using a long-acting injection (LAI) antipsychotic. METHODS: Data were taken from an 8-week, randomized, double-blind, placebo-controlled study of olanzapine LAI in acutely ill patients with schizophrenia (n = 233). Early response was defined as ≥ 30% improvement from baseline to Week 4 in Positive and Negative Syndrome Scale (PANSS0-6) Total score. Subsequent response was defined as ≥ 40% baseline-to-endpoint improvement in PANSS0-6 Total score. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and predictive accuracy were calculated. Clinical and functional outcomes were compared between Early Responders and Early Non-responders. RESULTS: Early response/non-response to olanzapine LAI predicted later response/non-response with high sensitivity (85%), specificity (72%), PPV (78%), NPV (80%), and overall accuracy (79%). Compared to Early Non-responders, Early Responders had significantly greater improvement in PANSS0-6 Total scores at all time points and greater baseline-to-endpoint improvement in PANSS subscale scores, Quality of Life Scale scores, and Short Form-36 Health Survey scores (all p ≤ .01). Among Early Non-responders, 20% demonstrated response by Week 8. Patients who lacked early improvement (at Week 4) in Negative Symptoms and Disorganized Thoughts were more likely to continue being non-responders at Week 8. CONCLUSIONS: Among acutely ill patients with schizophrenia, early response predicted subsequent response to olanzapine LAI. Early Responders experienced significantly better clinical and functional outcomes than Early Non-responders. Findings are consistent with previous research on oral antipsychotics. CLINICAL TRIALS REGISTRY: F1D-MC-HGJZ: Comparison of Intramuscular Olanzapine Depot With Placebo in the Treatment of Patients With Schizophrenia http://clinicaltrials.gov/ct2/show/NCT00088478?term=olanzapine+depot&rank=3Registry identifier - NCT00088478.

Evaluation of the Reliability of Electronic Medical Record Data in Identifying Comorbid Conditions among Patients with Advanced Non-Small Cell Lung Cancer.

Background. Traditional methods for identifying comorbidity data in EMRs have relied primarily on costly and time-consuming manual chart review. The purpose of this study was to validate a strategy of electronically searching EMR data to identify comorbidities among cancer patients. Methods. Advanced stage NSCLC patients (N = 2,513) who received chemotherapy from 7/1/2006 to 6/30/2008 were identified using iKnowMed, US Oncology's proprietary oncology-specific EMR system. EMR data were searched for documentation of comorbidities common to advanced stage cancer patients. The search was conducted by a series of programmatic queries on standardized information including concomitant illnesses, patient history, review of systems, and diagnoses other than cancer. The validity of the comorbidity information that we derived from the EMR search was compared to the chart review gold standard in a random sample of 450 patients for whom the EMR search yielded no indication of comorbidities. Negative predictive values were calculated. Results. The overall prevalence of comorbidities of 22%. Overall negative predictive value was 0.92 in the 450 patients randomly sampled patients (36 of 450 were found to have evidence of comorbidities on chart review). Conclusion. Results of this study suggest that efficient queries/text searches of EMR data may provide reliable data on comorbid conditions among cancer patients.

Increased olanzapine discontinuation and health care resource utilization following a Medicaid policy change.

OBJECTIVE: To assess the short-term impact of Florida Medicaid's policy change on olanzapine discontinuation and health care resource utilization among olanzapine-treated patients with schizophrenia or bipolar diagnoses. The announced policy change, effective on July 11, 2005, but rescinded on September 9, 2005, reclassified olanzapine as nonpreferred and gave physicians 60 days to change antipsychotics for current users. METHOD: Prescription patterns, health care resource utilization, and Medicaid payments were compared between patients using olanzapine on July 11, 2005, and matched prior-year controls. For reference, parallel analyses were conducted in New Jersey Medicaid, where access to olanzapine remained constant. The effect of Florida's policy change was also estimated among policy-sensitive olanzapine users by treating year (2004 vs 2005) as an instrumental variable. RESULTS: Matched Florida cohorts (N = 4,255) showed increases from 2004 to 2005 in 6-month rates of switching from olanzapine (+326%), hospitalization (+19.8%), and emergency room visits (+19.7%) (all P values < .001). Concurrently in the matched New Jersey cohorts (N = 2,680), there were no significant changes in these outcomes from 2004 to 2005. Among matched Florida policy-sensitive olanzapine users, an additional 9.3% experienced hospitalization in 2005 versus 2004 (P < .001), and increased payments for medical services and other antipsychotics largely offset decreased payments for olanzapine. CONCLUSIONS: The announced reclassification of olanzapine to nonpreferred status substantially disrupted the continuity of olanzapine therapy for many Florida Medicaid recipients diagnosed with schizophrenia or bipolar disorder and was associated with increased hospitalization and emergency room visits. During the 6 months following the policy change, increased payments for medical services largely offset reduced payments for olanzapine.

Cost-effectiveness of olanzapine long-acting injection in the treatment of patients with schizophrenia in the United States: a micro-simulation economic decision model.

OBJECTIVE: To compare, from the perspective of third-party payers in the United States health care system, the cost-effectiveness of olanzapine long-acting injection (LAI, depot) with alternative antipsychotic agents including risperidone-LAI, paliperidone-LAI, haloperidol-LAI, and oral olanzapine, in the treatment of patients with schizophrenia who have been non-adherent or partially adherent with oral antipsychotics. RESEARCH DESIGN AND METHODS: A 1-year micro-simulation economic decision model was developed to simulate the dynamics of usual care of patients with schizophrenia who continue, discontinue, switch, or restart their medication. The model uses a range of clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation rates by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct health care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. OUTCOME MEASURES: Key model outputs include annual total direct cost (US$) per treatment and incremental cost-effectiveness values per additional QALY gained. RESULTS: Model results found that the olanzapine-LAI treatment strategy was more effective (greater QALYs) and less costly than risperidone-LAI, paliperidone-LAI, and haloperidol-LAI. In addition, olanzapine-LAI was both more effective and more costly, with an estimated incremental cost/QALY of $26,824 compared to oral olanzapine. The base-case and multiple sensitivity analyses found olanzapine-LAI to remain within acceptable cost-effective ranges (<$50,000) in terms of incremental cost/QALY gained. CONCLUSIONS: This micro-simulation model finds the olanzapine-LAI treatment strategy to result in better effectiveness and to be a cost-effective alternative compared to oral olanzapine and the LAI formulations of risperidone, paliperidone, and haloperidol in the treatment of non-adherent and partially adherent patients with schizophrenia in the United States. A key limitation is the assumption how LAI therapies compare to oral counterparts due to sparse head-to-head data. Further research is needed to verify baseline assumptions.

Cost-effectiveness of pemetrexed as first-line maintenance therapy for advanced nonsquamous non-small cell lung cancer.

INTRODUCTION: The primary objective was to estimate the cost-effectiveness of maintenance therapy with pemetrexed (Pem) compared with observation, each with best supportive care, in patients with advanced non-small cell lung cancer (NSCLC) who have completed, without progression, at least four cycles of first-line platinum chemotherapy, particularly in those with nonsquamous cell histology. Secondary comparisons included Pem with erlotinib (Erl) or Pem with bevacizumab (Bev). METHODS: A semi-Markov model was developed to compare the 3-year impact of Pem with three other alternatives for maintenance therapy from a United States payer perspective. Data from randomized controlled clinical trials provided clinical inputs. Medicare reimbursement rates were used to determine drug costs. A retrospective claims database analysis was used to obtain estimates of other direct NSCLC-related costs. RESULTS: In the prespecified subset of patients with nonsquamous cell histology only, the incremental cost per life-year gained was $122,371 for Pem to observation and $150,260 for Pem to Erl, and Bev was dominated by Pem. In all patients with advanced NSCLC regardless of histologic subtype, using Pem as maintenance therapy led to an incremental cost per life-year gained of $205,597 compared with observation and $312,341 compared with Erl. CONCLUSIONS: Compared with observation and other agents used and/or reimbursed for maintenance therapy in advanced NSCLC, Pem may be considered cost-effective, particularly in patients with nonsquamous cell histology. This analysis is the first to evaluate the cost-effectiveness of maintenance therapy in advanced NSCLC and emphasizes the importance of histology in identifying the appropriate patient for Pem maintenance therapy.

Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States.

BACKGROUND: Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator), quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. METHODS: A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. RESULTS: The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544) followed by generic risperidone ($9,080). In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719). The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. CONCLUSION: The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and aripiprazole. Olanzapine may, therefore, be a cost-effective therapeutic option for patients with schizophrenia.

HIV prevention services for adults with serious mental illness in public mental health care programs.

Despite well-documented need, little is known about the HIV prevention services provided to adults with serious mental illness in the public mental health system. This study examined the types, frequency, and client-level correlates of HIV prevention services provided to a representative sample of clients in five public mental health care programs. Although results indicate that HIV prevention care is infrequent, clients identified as being at higher risk for HIV infection reported receiving prevention interventions more frequently. However, both the clients' gender and the service setting influenced the types and frequency of services that clients received.