Robert J. Valuck

Metabolic Testing Rates in 3 State Medicaid Programs After FDA Warnings and ADA/APA Recommendations for Second-Generation Antipsychotic Drugs

CONTEXT In 2003, the Food and Drug Administration (FDA) required a warning on diabetes risk for second-generation antipsychotic (SGA) drugs. The American Diabetes Association (ADA) and American Psychiatric Association (APA) recommended glucose and lipid testing for all patients starting to receive SGA drugs. OBJECTIVE To characterize associations between the combined warnings and recommendations and baseline metabolic testing and SGA drug selection. DESIGN Interrupted time-series analysis. SETTING California, Missouri, and Oregon. Patients A total of 109 451 individuals receiving Medicaid who began taking SGA medication and a control cohort of 203 527 patients who began taking albuterol but did not receive antipsychotic medication. INTERVENTIONS Prewarning and postwarning trends in metabolic testing were compared using laboratory claims for the cohort collected January 1, 2002, through December 31, 2005. Changes in SGA prescribing practices were similarly evaluated. MAIN OUTCOME MEASURES Monthly rates of baseline serum glucose and lipid testing for SGA-treated and propensity-matched albuterol-treated patients and monthly share of new prescriptions for each SGA drug. RESULTS Initial testing rates for SGA-treated patients were low (glucose, 27%; lipids, 10%). The warning was not associated with an increase in glucose testing among SGA-treated patients and was associated with only a marginal increase in lipid testing rates (1.7%; P = .02). Testing rates and trends in SGA-treated patients were not different from background rates observed in the albuterol control group. New prescriptions of olanzapine (higher metabolic risk) declined during the warning period (annual share decline, 19.9%; P < .001). New prescriptions of aripiprazole (lower metabolic risk) increased during the warning period (share increase, 12.1%; P < .001) but may be attributable to the elimination of prior authorization in California during the same time frame. Quetiapine, risperidone, and ziprasidone use were not associated with the warning. CONCLUSIONS In a Medicaid-receiving population, baseline glucose and lipid testing for SGA-treated patients was infrequent and showed little change following the diabetes warning and monitoring recommendations. A change in SGA drug selection consistent with intentions to reduce metabolic risk was observed.

Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: a propensity-adjusted retrospective cohort study.

AbstractContext: The US FDA has issued an advisory warning of a possible link between antidepressant treatment for paediatric patients with major depressive disorder (MDD) and an increased risk of suicidal behaviour. A large database of paid health insurance claims for adolescents with MDD provided the opportunity to examine this possible relationship. Objective: To examine the potential empirical link between antidepressant treatment and suicide attempts among adolescents aged 12–18 years using a community sample of managed care enrollees across the US. Design: A retrospective longitudinal cohort using paid insurance claims for all healthcare and prescription fills for adolescents who were newly diagnosed with MDD and had at least 6 months of follow-up data. A multivariate Cox proportional hazards regression analysis was used to test the hypothesis that antidepressant use increased the risk of suicide attempt, adjusting for propensity for allocation to each treatment group and for demographic and clinical characteristics. Setting: Managed care plans including both commercial and Medicaid plans in the east, midwest, south and western regions of the US from January 1997 to March 2003. Participants: All adolescent insurance members aged 12–18 years at first diagnosis of MDD. Main outcome measures: Suicide attempts as indicated by medical utilisation with International Classification of Diseases (9th edition) [ICD-9] or 10th edition (ICD-10) codes in any healthcare setting or by any covered provider. Results: 24 119 adolescents met inclusion criteria (63% female). Crude suicide attempt rates ranged from 0.0-2.3% by index treatment group. Treatment with SSRIs (hazard ratio) [HR] = 1.59; CI 0.89, 2.82), other antidepressants (HR = 1.03; CI 0.43, 2.44), or multiple antidepressants (HR = 1.43; CI 0.70, 2.89) after index MDD diagnosis resulted in no statistically increased risk of suicide attempt. Treatment with antidepressant medication for at least 180 days (6 months) reduced the likelihood of suicide attempt compared with antidepressant treatment for <55 days (8 weeks) [HR = 0.34; CI 0.21, 0.55]. Other variables that were independently associated with greater risk of suicide attempts included female gender, severity of illness indicators, younger age at time of MDD diagnosis, and living in the midwest or west. Conclusions: Antidepressant medication use had no statistically significant effect on the likelihood of suicide attempt in a large cohort of adolescents across the US after propensity adjustment for treatment allocation and controlling for other factors. The relationship between suicidal behaviour and antidepressant medication use is complex and requires further investigation.

Clinical and Economic Impact of Ambulatory Care Clinical Pharmacists in Management of Dyslipidemia in Older Adults: The IMPROVE Study

We examined the impact of ambulatory care clinical pharmacist interventions on clinical and economic outcomes of 208 patients with dyslipidemia and 229 controls treated at nine Veterans Affairs medical centers. This was a randomized, controlled trial involving patients at high risk of drug‐related problems. Only those with dyslipidemia are reported here. In addition to usual medical care, clinical pharmacists were responsible for providing pharmaceutical care for patients in the intervention group. The control group did not receive pharmaceutical care. Seventy‐two percent of the intervention group and 70% of controls required secondary prevention according to the National Cholesterol Education Program guidelines. Significantly more patients in the intervention group had a fasting lipid profile compared with controls (p=0.021). The absolute change in total cholesterol (17.7 vs 7.4 mg/dl, p=0.028) and low‐density lipoprotein (23.4 vs 12.8 mg/dl, p=0.042) was greater in the intervention than in the control group. There were no differences in patients achieving goal lipid values or in overall costs despite increased visits to pharmacists. Ambulatory care clinical pharmacists can significantly improve dyslipidemia in a practice setting designed to manage many medical and drug‐related problems.

Persisting Decline in Depression Treatment After FDA Warnings

CONTEXT In October 2003 the Food and Drug Administration (FDA) issued a Public Health Advisory about the risk of suicidality for pediatric patients taking antidepressants; a boxed warning, package insert, and medication guide were implemented in February 2005. The warning was extended to young adults aged 18 to 24 years in May 2007. Immediately following the 2003 advisory, unintended declines in case finding and non-selective serotonin reuptake inhibitor substitute treatment were shown for pediatric patients, and spillover effects were seen in adult patients, who were not targeted by the warnings. OBJECTIVE To determine whether the unintended declines in depression care persisted for pediatric, young adult, and adult patients. DESIGN Time series analyses. SETTING Ambulatory care settings nationally. Patients Pediatric, young adult, and adult cohorts of patients with new episodes of depression (n = 91 748, 70 311, and 630 748 episodes, respectively). INTERVENTIONS Post-FDA advisory trends were compared with expected trends based on preadvisory patterns using a national integrated managed care claims database from July 1999 through June 2007. MAIN OUTCOME MEASURES Depression diagnosis; antidepressant, antipsychotic, and anxiolytic prescriptions; and psychotherapy visits. RESULTS Changes in pediatric depression care were similar to changes for adults. National diagnosis rates of depression returned to 1999 levels for pediatric patients and below 2004 levels for adults. Primary care providers continued significant reductions in new diagnoses of depression (44% lower for pediatric, 37% lower for young adults, 29% for adults); diagnoses by mental health providers who were not psychiatrists increased. Numbers of prescriptions of anxiolytic and atypical antipsychotic medications did not significantly change from preadvisory trends. Psychotherapy increased significantly for adult, though not pediatric, cases. Selective serotonin reuptake inhibitor use decreased in all cohorts; serotonin-norepinephrine reuptake inhibitor increased for adults. CONCLUSIONS Diagnosing decreases persist. Substitute care did not compensate in pediatric and young adult groups, and spillover to adults continued, suggesting that unintended effects are nontransitory, substantial, and diffuse in a large national population. Policy actions are required to counter the unintended consequences of reduced depression treatment.

Metabolic Screening in Children Receiving Antipsychotic Drug Treatment

OBJECTIVES To estimate metabolic screening rates, predictors of screening, and incidence of metabolic disturbances in children initiating second-generation antipsychotic (SGA) drug treatment. DESIGN A retrospective, new-user cohort study (between July 1, 2004, and June 30, 2006) using Medicaid claims data. SETTINGS California, Missouri, and Oregon. PATIENTS A total of 5370 children (aged 6-17 years) without diabetes mellitus taking SGA drugs and 15,000 children without diabetes taking albuterol (control individuals) [corrected] but no SGA drugs. INTERVENTION Findings 1 year after recommendations from the American Diabetes Association and American Psychiatric Association called for metabolic screening of patients receiving SGA drugs. OUTCOME MEASURES Serum glucose and lipid testing, 6-month incidence of diabetes, and dyslipidemia disturbances. RESULTS Glucose screening was performed in 1699 (31.6% [95% confidence interval (CI), 30.4%-32.9%]) SGA-treated children vs 1891 (12.6% [12.1%-13.2%]) control individuals. Lipid testing was performed in 720 (13.4% [95% CI, 12.5%-14.4%]) SGA-treated children vs 458 (3.1% [2.8%-3.3%]) controls. In multivariate logistic regression analysis, children with serious and/or multiple psychiatric diagnoses and those who used health care services more intensively were more likely to receive metabolic screening. The case incidence of glucose and lipid disorders was higher in SGA-treated vs albuterol-treated children (8.9 per 1000 children [95% CI, 6.6%-11.8%] vs 4.9 per 1000 children [3.9%-6.2%]; and 9.7 per 1000 children [95% CI, 7.2%-12.7%] vs 4.6 per 1000 children [95% CI, 3.6%-5.8%], respectively). CONCLUSION Most children starting treatment with SGA medications in this public sector sample did not receive recommended glucose and lipid screening.

A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives.

With the recent introduction and growing popularity of Depo-Provera Contraceptive Injection, concern about the potential for weight gain during treatment has been raised. The purpose of the present study was to determine whether or not Depo-Provera Contraceptive Injection is associated with greater weight gain, and incidence thereof, than Norplant implants or oral contraceptives. A retrospective chart review of patients seen at a state- and federally-funded clinic was conducted. Fifty women in each treatment group who met the study criteria were identified and included in the study evaluation. Mean one-year weight gain for subjects in each group was as follows: -2.0 pounds in the oral contraceptive group, -1.8 pounds in the Norplant implants group, and +0.1 pounds in the Depo-Provera Contraceptive Injection group. While results among treatment groups differed slightly, no significant weight change occurred in any of the treatment groups.

A Comparison of the Direct Costs and Cost Effectiveness of Serotonin Reuptake Inhibitors and Associated Adverse Drug Reactions

AbstractBackground: The economic burden of depression is known to be high and was estimated to be

Vitamin B12 Deficiency Associated with Histamine2-Receptor Antagonists and a Proton-Pump Inhibitor

US83.1 billion in 2000. Serotonin reuptake inhibitors (SRIs), including both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have a superior adverse effect and safety profile relative to traditional agents (e.g. TCAs), and as a result have demonstrated superior cost effectiveness. Although efficacy across the SRIs is similar, the incidence of adverse drug reactions (ADRs) within SRIs remains significant and varies by agent. Patients who experience ADRs from SRIs may seek medical care, require additional treatment, and even discontinue treatment altogether, leading to increased utilisation and cost of therapy. Objective: This study estimates the direct cost and cost effectiveness, taking into account the impact of treatment-related ADRs, of eight currently marketed SRIs (citalopram, escitalopram, generic fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, venlafaxine and venlafaxine extended release [XR]) used as initial treatment for depression. Methods: A decision analytic model with a 6-month treatment goal was used to estimate the direct cost and cost effectiveness of treatment from the managed care/ payer perspective. Estimates of SRI-related ADRs, associated treatments and costs were derived from the US FDA-approved prescribing information and published literature. Efficacy was assumed to be similar across all SRIs. Effectiveness was measured using quality-adjusted life years (QALY) based on EuroQol EQ-5D scores derived from the 2000 Medical Expenditure Panel Survey (MEPS). Censored least absolute deviations (CLAD) regression analysis was used to derive age-adjusted estimates of utility for all health states. Univariate and Bayesian second-order multivariate probabilistic sensitivity analyses were conducted to examine the impact of uncertainty in the parameter estimates. Results: The expected direct cost and cost effectiveness of treatment from least to most expensive were: escitalopram (

An Electronic Practice-Based Network for Observational Comparative Effectiveness Research

US3891; 0.341), citalopram (

An economic analysis of a randomized, controlled, multicenter study of clinical pharmacist interventions for high-risk veterans: The IMPROVE study

US3938; 0.340), generic fluoxetine (