Brian Cuffel

Metabolic Screening After the American Diabetes Association's Consensus Statement on Antipsychotic Drugs and Diabetes

OBJECTIVE Several second-generation antipsychotic (SGA) drugs have been associated with weight gain, hyperglycemia, and dyslipidemia. We evaluated whether glucose and lipid testing increased after the American Diabetes Association (ADA) consensus statement recommending metabolic monitoring for SGA-treated patients. RESEARCH DESIGN AND METHODS Laboratory claims for serum glucose and lipid testing were identified for an incident cohort of 18,876 adults initiating SGA drugs in a U.S. commercial health plan (2001–2006) and a control group of 56,522 adults with diabetes not receiving antipsychotics. Interrupted time-series models were used to estimate the effect of ADA recommendations on baseline and annual testing trends after adjusting for differences in age, sex, mental health diagnoses, and cardiovascular risk using propensity score matching. RESULTS Mean baseline testing rates for SGA-treated patients during the study period were 23% (glucose) and 8% (lipids). Among persistent users of SGA medication, annual testing rates were 38% (glucose) and 23% (lipid). Before the ADA statement, screening rates for SGA-treated patients were increasing (glucose: baseline 3.6% per year, annual 7.2% per year; lipid: baseline 1.2% per year, annual 4.8% per year; P < 0.001 for each trend). Increases were similar to background testing trends in control subjects. The ADA statement was not associated with an increase in screening rates. CONCLUSIONS In a commercially insured population, glucose and lipid testing for SGA-treated adults was infrequent. A gradual increase in screening rates occurred over the 6-year period, but the changes were not temporally associated with the ADA statement. More effort is needed to improve diabetes and dyslipidemia screening in these at-risk patients.

Risk of discontinuation of atypical antipsychotic agents in the treatment of schizophrenia

OBJECTIVESnTo compare discontinuation rates of atypical antipsychotic agents in patients with schizophrenia.nnnMETHODnAdult Maryland Medicaid patients with schizophrenia were categorized based on initial atypical antipsychotic drug received: aripiprazole (n=446); olanzapine (n=1705); quetiapine (n=1467); risperidone (n=1580); and ziprasidone (n=700). Discontinuation was measured using refill patterns, allowing 14-day gaps between refill dates. Using olanzapine as the reference drug, the hazard of discontinuation within the first year of follow-up was compared across atypicals using Cox proportional hazard models adjusted for demographic and clinical covariates. Sensitivity analysis tested the robustness of results by using different definitions of the index date.nnnRESULTSnAt one-year follow-up, most patients discontinued their antipsychotic medication (90.4% adjusted mean discontinuation). The hazard ratio (HR) for discontinuing therapy in patients starting treatment on aripiprazole, risperidone, or ziprasidone was not significantly different from olanzapine [HR 1.047, 0.973 and 0.990, respectively]. Quetiapine was associated with significantly higher hazard of discontinuation [HR 1.130] than olanzapine. Covariates associated with significantly lower discontinuation were being male [HR 0.899], older age [HR 0.997] and being on concurrent medication when initiating therapy [HR 0.225]; having a previous hospitalization was associated with significantly higher discontinuation hazard [HR 1.276]. Results were robust in the sensitivity analysis.nnnCONCLUSIONSnDiscontinuation rates were high at one-year follow-up and did not differ significantly for patients on aripiprazole, olanzapine, risperidone, or ziprasidone. The higher hazard of discontinuation associated with quetiapine when compared to olanzapine is consistent with that observed in Phase I of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Patient satisfaction with an injection device for multiple sclerosis treatment

Objectivesu2002–u2002 To develop a measure of treatment satisfaction assessing attributes specific to injected interferon‐beta‐1a (IFN‐β‐1a) for multiple sclerosis (MS), and to test pain and instrument sensitivity to change among patients changing injection devices.

Efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis: a systematic comparison.

The treatment of relapsing-remitting multiple sclerosis (RRMS) has become more effective over the last decade with the advent of the currently available disease-modifying therapies (DMTs). Pivotal clinical studies differ in many characteristics, such that cross-comparisons of relative risk reductions are of limited value and can be misleading. Our objective was to compare the clinical efficacy of currently approved first-line DMTs in patients with RRMS, applying an evidence-based medicine approach. We reviewed all phase III pivotal trials of DMTs. Six clinical trials of Avonex®, Betaseron®, Copaxone®, Rebif® and Tysabri® in patients with RRMS were identified for analysis. Only randomized, placebo-controlled, double-blind studies were included. The clinical efficacy endpoints compared were: proportion of relapse-free patients at 1 and 2 years; annualized relapse rate at 2 years; proportion of progression-free patients at 2 years, and proportion of patients free of gadolinium-enhancing lesions at 1 year or 9 months. Based on these analyses, Betaseron, Rebif, and Tysabri show comparable effects, whereas for several endpoints Avonex or Copaxone did not significantly differ from placebo. In the absence of head-to-head studies for all products used to treat RRMS, it still may be possible to compare treatment effects by applying evidence-based medicine principles.

Metabolic risk status and second-generation antipsychotic drug selection: a retrospective study of commercially insured patients.

Background: Routine metabolic screening and consideration of patient metabolic status in the choice of a second-generation antipsychotic (SGA) medication are recommended. This study evaluated the association between abnormal blood glucose and lipid values and SGA prescribing patterns. Materials and Methods: A retrospective cohort study using administrative data from 2 managed care plans in the United States evaluated 7904 adults initiating SGA therapy between 2001 and 2004. Baseline serum glucose, total cholesterol, and triglyceride values were available for 989 patients (12.5%), and follow-up assessments were done in 699 patients (8.8%). Abnormal values were defined as the following: total cholesterol, 200 mg/dL or higher; triglycerides, 200 mg/dL or higher; and glucose, 126 mg/dL or higher. The likelihood of abnormal laboratory values being associated with selection of a lower metabolic risk SGA drug (aripiprazole or ziprasidone) and with switching decisions was assessed using multivariate logistic regression models. Results: Thirteen percent of the patients had glucose and lipid tests within 6 months of starting SGA therapy. The likelihood of starting a patient on an SGA drug with lower metabolic risk (ziprasidone: odds ratio, 3.26; 95% confidence interval, 1.25-8.47; aripiprazole: odds ratio, 2.13; 95% confidence interval, 0.77-5.88) was higher if the patient had elevated glucose values but was not associated with elevated cholesterol or triglyceride values or if the patient had preexisting diabetes or dyslipidemia. Abnormal glucose and lipid values were not associated with switching SGA medications in the first 6 months of therapy. Among patients who did switch SGA medications, elevated glucose and lipid values were not associated with a greater likelihood of switching to aripiprazole or ziprasidone. Conclusions: Low rates of recommended monitoring were observed. Abnormal metabolic parameters among those who were tested were not consistently associated with the selection of an SGA drug with lower metabolic risk.

Dose trends for second-generation antipsychotic treatment of schizophrenia and bipolar disorder

BACKGROUNDnAntipsychotic dosing used in clinical practice can differ from dosing originally recommended in product labeling. This has been reported for olanzapine and quetiapine, where higher doses are commonly used. This may be the case for ziprasidone as well.nnnMETHODnTo characterize changes over time in dosing for the initial and subsequent prescriptions of first-line second-generation antipsychotics used during treatment episodes for outpatients with schizophrenia and bipolar disorder, the 2001-2005 Thomson MarketScan Medicaid Database (Medicaid) and the 2001-2006 MarketScan Commercial Claims and Encounters Database (Commercial) were analyzed. Dose trends were evaluated using autoregressive time-series models.nnnRESULTSnData were available for 49180 treatment episodes of schizophrenia (4683 Commercial and 44497 Medicaid) and 83289 treatment episodes of bipolar disorder (57961 Commercial and 25328 Medicaid). The initial prescription mean daily and overall mean daily doses of ziprasidone in schizophrenia episodes significantly increased across the Medicaid and Commercial populations, with similar trends observed for bipolar episodes. The first (May 2001) and last (December 2005) observed 3-month mean daily doses for ziprasidone were 112 mg/d and 138 mg/d for patients with schizophrenia and 93 mg/d and 113 mg/d for those with bipolar disorder in the Medicaid cohort, with similar findings for the Commercial cohort. Consistently significant trends in dose changes were not observed for the other medications, although quetiapine and olanzapine doses generally increased while aripiprazole and risperidone doses generally decreased.nnnCONCLUSIONSnThere remains a need for controlled randomized clinical trials that test fixed doses of antipsychotics to ascertain the dose-response relationship within the dose range used in contemporary clinical practice.

Impact of real-world ziprasidone dosing on treatment discontinuation rates in patients with schizophrenia or bipolar disorder

BACKGROUNDnThe purpose of this study is to evaluate the relationship between maximum dose of ziprasidone and time to discontinuation in the treatment of schizophrenia/schizoaffective disorder and bipolar disorder in clinical practice.nnnMETHODnThe 2001-2006 MarketScan Commercial and Medicare Databases were analyzed for maximum ziprasidone doses achieved in patients with schizophrenia/schizoaffective disorder or bipolar disorder. Ziprasidone maximum-dose groups were defined as low (20-60 mg/d), medium (61-119 mg/d), or high (120-160 mg/d). Patients receiving >160 mg/d were excluded. Mean time to discontinuation was evaluated across propensity score-matched dosing groups. Cox proportional hazard models were used to adjust for confounding when comparing the high- and medium-dose groups with the low-dose group.nnnRESULTSnData were available for 33,340 patients with schizophrenia/schizoaffective disorder, of whom 16.6% received low dose of ziprasidone, 22.0% medium dose, and 61.4% high dose. Of those subjects with bipolar disorder (n=27,751), 26.1% were receiving a low dose of ziprasidone, 25.7% a medium dose, and 48.3% a high dose. Among the propensity score-matched dosing groups, the respective mean time to discontinuation for low, medium, and high doses was 90.5, 117.2, and 201.6d within the schizophrenia/schizoaffective disorder cohort and 84.6, 110.7, and 173.2d within the bipolar cohort (p<0.0001 for all comparisons). The hazard ratios for discontinuing therapy were significantly lower for the medium- (0.84, 0.84) and high-dose (0.57, 0.60) groups relative to the low-dose group in schizophrenia/schizoaffective disorder and bipolar disorder, respectively.nnnCONCLUSIONSnPatients with schizophrenia/schizoaffective or bipolar disorders receiving ziprasidone 120-160 mg/d experienced a statistically significant lower discontinuation rate compared with those receiving lower doses.

Outcome assessment of an antipsychotic drug algorithm: effects of the Mississippi State Hospital algorithm project.

OBJECTIVEnThis study evaluated a state psychiatric hospitals algorithm for prescribing antipsychotic drugs for inpatients with schizophrenia to determine whether its emphasis on cost efficiency is compatible with quality of care.nnnMETHODSnOutcomes were compared for patients who received medication that was algorithm adherent or nonadherent. Risperidone and ziprasidone were first-step oral antipsychotics. Documentation of clinical rationale was acceptable for nonpreferred drug use. Outcomes of interest were length of hospitalization and much improved or very much improved status on the Clinical Global Impression severity scale (CGI-S).nnnRESULTSnOf 401 patients, 70% were male. The CGI-S modal rating of severity was markedly ill. Duration of illness was longer for patients given algorithm-nonadherent (17.6±9.7 years) versus -adherent (14.9±11.6 years, p=.013) medication. No statistically significant between-group differences were observed for mean length of stay (51.4±35.5 days versus 43.8±27.4 days, adjusted difference p=.18) or median improvement time (adherent, 41 days; nonadherent, 42 days; CI=34-48 days for both group medians).nnnCONCLUSIONSnPrescription algorithm adherence was not associated with significantly increased length of inpatient stay or delayed time to improvement.

A pilot study of antipsychotic prescribing decisions for acutely-Ill hospitalized patients

BACKGROUNDnEvidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.nnnMETHODSnPrescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.nnnRESULTSnAntipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p<0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists expectations of metabolic risk with selected treatments, we found that patients actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.nnnCONCLUSIONnIn the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines.