Michael D. Stensland

Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia.

BackgroundPrevious research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol).MethodsData were drawn from the acute phase (first 6-weeks) of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative) were measured with the Brief Psychiatric Rating Scale (BPRS), depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration.ResultsWeight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom), given a clinically significant weight gain (at least 7% of baseline weight), showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic response and weight gain were similar for the olanzapine and haloperidol treatment groups. Improved outcomes were, however, more pronounced for the olanzapine-treated patients, and more olanzapine-treated patients gained weight.ConclusionsThe findings of significant relationships between treatment-emergent weight gain and improvements in clinical and functional status at 6-weeks suggest that patients who have greater treatment-emergent weight gain are more likely to benefit from treatment with olanzapine or haloperidol regardless of gender.

Assessing the Value of Antipsychotics for Treating Schizophrenia: The Importance of Evaluating and Interpreting the Clinical Significance of Individual Service Costs

Schizophrenia is a serious and complex disorder, with treatment requiring a large number and wide range of health and social service resources. This paper addresses one challenge for assessing the direct costs of antipsychotic treatments — that of interpreting both cost and effectiveness implications of specific components of service use.Information collected on direct component costs has frequently been analysed and reported only in total. Results of several published studies provide evidence that the total direct medical costs associated with atypical antipsychotics appear to be at least equivalent to, and in some cases lower than, those associated with conventional agents. An important implication of this cost-equivalency finding is that treatment involving higher medication costs have led to offsets in certain medical service costs.Results from several studies demonstrate a shift of cost components, primarily from more expensive inpatient to less expensive outpatient care. Although the common inpatient versus outpatient dichotomy is useful, the complexities of schizophrenia and the heterogeneity of outpatient service provision are likely to warrant greater specificity.Published schizophrenia treatment guidelines can assist researchers to more fully understand and meaningfully interpret the possible relationship of antipsychotic effectiveness to the use of particular outpatient services. Because the disease requires comprehensive and continuous care, outpatient treatment costs may be better conceptualised as baseline or expectable costs necessary in the maintenance phase of treatment. Lack of expectable costs may represent poor patient outcomes and increased intangible costs. In contrast, reductions in acute outpatient service costs may provide important markers of treatment effectiveness. A small number of studies have examined the use of crisis services, but additional work is needed to differentiate treatments vis-à-vis the need for intensive (acute) interventions.The assessment and clinical interpretation of individual cost components may offer an important opportunity to build upon initial results focusing on total costs and tailor analyses to the complexities of the disorder and the treatment process. Research able to incorporate clinical acumen into cost analyses will enhance the ability of healthcare policy makers to make informed decisions regarding the value of different antipsychotic medications for the treatment of schizophrenia.

Weight gain as a prognostic indicator of therapeutic improvement during acute treatment of schizophrenia with placebo or active antipsychotic

Treatment-emergent weight gain may be a general marker of therapeutic improvement, even when improvements occur in the absence of active antipsychotic treatment. To investigate the association between treatment-emergent weight gain and therapeutic improvement across placebo and active treatments, and to examine the association between reported treatment-emergent weight changes and the treatments’ reported efficacy. Data from a randomized, double-blind trial comparing treatment of schizophrenia with placebo and olanzapine were used to correlate weight change and change in psychopathology. Additionally, we correlated effect sizes of the efficacy of clozapine, olanzapine, risperidone, haloperidol and placebo (reported in meta-analytical reviews), with their reported weight changes. Weight gain significantly correlated with clinical improvements for placebo and olanzapine. The correlation between treatments’ efficacy and corresponding weight changes was high (r 0.88, p 0.05). Treatment-emergent weight gain appears to be an important marker of symptom reduction, and may not be exclusively attributable to pharmacological perturbations.

Direct and indirect costs of employees with treatment-resistant and non-treatment-resistant major depressive disorder

Abstract Objective: Treatment-resistant depression (TRD) imposes substantial cost from the perspective of employers. The objective of this study was to assess direct healthcare costs and indirect (disability and medical-related absenteeism) costs associated with TRD compared with non-treatment-resistant major depressive disorder (MDD). Methods: Employees with one or more inpatient, or two or more outpatient/other MDD diagnoses (ICD-9-CM: 296.2x, 296.3x) from 2004 through 2007, ages 18–63 years, were selected from a claims database. Employees who initiated a third antidepressant following two antidepressant treatments of adequate dose and duration or who met published TRD criteria were classified as TRD likely (N = 2312). The index date was the date of the first antidepressant, starting 1/1/2004. The control group was an age- and sex-matched cohort of employees with MDD but without TRD. All had continuous eligibility during the 6-month pre-index (baseline) and 24-month post-index (study) period. McNemar tests were used to compare baseline comorbidities. Wilcoxon signed-rank tests were used to compare costs from employer perspective. Results: TRD-likely employees were on average 48 years old, and 64.8% were women. Compared with MDD controls, TRD-likely employees had significantly higher rates of mental-health disorders, chronic pain, fibromyalgia, and higher Charlson Comorbidity Index. Average direct 2-year costs were significantly higher for TRD-likely employees (

Comparing the treatment patterns of patients with schizophrenia treated with olanzapine and quetiapine in the Pennsylvania Medicaid population

22,784) compared with MDD controls (

American Headache Society Members' Assessment of Headache Diagnostic Criteria

11,733), p < 0.0001. Average indirect costs were also higher among TRD-likely employees (

Measuring use and cost of care for patients with mood disorders: the utilization and cost inventory.

12,765) compared with MDD controls (

Resource Utilization and Costs of Schizophrenia Patients Treated with Olanzapine versus Quetiapine in a Medicaid Population

6885), p < 0.0001. Limitations: Limitations of claims data related to accuracy of diagnosis coding and lack of clinical information apply to this study. Conclusions: Based on comorbidities and healthcare resources used, patients with TRD appeared to represent a clinically complex subgroup of individuals with MDD. TRD was associated with significant cost burden.

Service utilization and associated direct costs for bipolar disorder in 2004: An analysis in managed care

ABSTRACT Objective: Compare treatment patterns for patients with schizophrenia treated with olanzapine versus quetiapine in the Pennsylvania Medicaid population. Methods: Patients (18–64 years) with a diagnosis of schizophrenia (ICD-9-CM: 295.xx) and treated with olanzapine or quetiapine were identified from the Pennsylvania Medicaid claims database (1999–2003). Patients were continuously enrolled in the 12-month pre- and 12-month post-initiation periods. To control for selection bias, propensity score method with optimal matching algorithm was used to match patients from the two treatment groups. The key study outcomes including rates of augmentation, polypharmacy, discontinuation, and switching were analyzed using Kaplan-Meier survival analysis. Medication possession ratio and use of concurrent psychotropic drugs were also compared between the two groups. Results: A total of 2321 quetiapine and 6929 olanzapine patients were identified. In all, 2321 pairs of patients were matched between the two groups and they had similar baseline characteristics. Over the 12-month study period, olanzapine patients had a better medication adherence (0.47 vs. 0.43; p < 0.0001), and were less likely to use other psychotropic medications concomitantly (all p < 0.05). Olanzapine patients had a significantly lower risk of augmentation and polypharmacy with other antipsychotics. The 6-month augmentation rates with antipsychotics were 12.9% and 16.7% for olanzapine and quetiapine, respectively (p < 0.05); the polypharmacy rates with any antipsychotics were 12.5% and 18.6% for olanzapine and quetiapine, respectively (p < 0.001). No significant differences were observed for discontinuation and switching between the two treatment groups. Sensitivity analysis with a 60-day minimum monotherapy requirement showed similar results. Limitations: This studys limitations include the analysis of a single Medicaid state, which may limit the generalizability to the entire Medicaid population with schizophrenia or to all patients with schizophrenia. Conclusion: This large Medicaid claims database analysis showed that olanzapine patients were significantly more compliant to treatment and less likely to augment or have polypharmacy with antipsychotics during the course of treatment compared to quetiapine patients.

Diagnosis of Unipolar Depression Following Initial Identification of Bipolar Disorder : A Common and Costly Misdiagnosis

Objective.—We assessed the views of physicians interested in headache as to the diagnosis of the most commonly occurring and currently controversial headaches.