Daniel Safer

• Johns Hopkins Medicine

Background: Psychotropic concomitant medication use for the treatment of youth with emotional and behavioral disorders has grown significantly in the U.S. over the past 25 years. The use of pharmacy claims to analyze these trends requires the following: age of the selected population, overlapping days of use, and precision of the outcome itself. Th...

Background Detailed research on long-term antidepressant (AD) trends within a single large US Medicaid population of youth has not heretofore been reported. Methods Administrative claims data for eight annual timepoints across 28 years (1987–2014) were organized for youth (<20 years old) who were continuously enrolled during each study year in a m...

The diagnosis of major depressive disorder (MDD) in U.S. youth is increasing as is the rate of antidepressant medication (ADM) treatment for the disorder. Fluoxetine and escitalopram are FDA approved for the short term and maintenance treatment of MDD in youth. Placebo-controlled short-term ADM trials represent the basis for Food and Drug Administr...

To understand possible medication overprescribing, it would be important to know which classes are the most prescribed, for which indications, for what duration, and for which age groups. Among the 10 most frequently prescribed medication classes for US adults, four were evaluated for overprescribing, and systematically assessed in relation to thei...

Objective: To assess the risk of incident cardiovascular events that led to hospitalizations or emergency department visits following atypical antipsychotic (AAP) treatment initiation in youth according to dose, duration of use, and concomitant use of leading psychotropic medication classes. Methods: We used computerized Medicaid claims to condu...

Objective: To describe psychotropic medication prescribing practices of nurse practitioners (NP) and physicians for Medicaid-insured youths in 2012-2014 in a mid-Atlantic state where NP independent prescribing is authorized. Method: From annual computerized administrative claims data in a mid-Atlantic state, we analyzed 1,034,798 dispensed psych...

Objective: This cross-sectional study assessed the impact of a peer-review program on the prevalence of pediatric antipsychotic use among Medicaid-insured youths in a Mid-Atlantic state. Methods: Medicaid claims (2010-2014) were assessed among continuously enrolled youths in the 12 months before and after implementation of peer review. The study...

Importance Antidepressants are one of the most commonly prescribed classes of psychotropic medications among US youths. For adults, there is emerging evidence on the increased risk of type 2 diabetes in association with antidepressant use. However, little is known about the antidepressant treatment–emergent risk of type 2 diabetes among youths. Ob...

Background: The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate o...

Objective: Little is known about how nurse practitioner independent practice authority (NP-IPA) influences patient care. This study examined the effect of NP-IPA on patterns of mental health-related visits provided by NPs in U.S. community health centers (CHCs). Methods: State NP regulatory information was linked to National Ambulatory Medical C...

Objective More than half of youth treated with atypical antipsychotic (AAP) medications are also treated with concomitant antidepressants or stimulants. This study assessed the association between antidepressant or stimulant use concomitant with AAPs and the risk of incident type 2 diabetes mellitus (T2DM). Method Medicaid Analytic eXtract data we...

Objective: This study aimed to evaluate a conceptual framework that assessed the effect of Hispanic residential isolation on Attention Deficit Hyperactivity Disorder (ADHD) health service utilization among 2.2 million publicly insured youth. Design: Cross-sectional. Setting: Medicaid administrative claims data for ambulatory care services from...

This review focuses on the dose-response of serotonin reuptake inhibitor (SRI) antidepressants for efficacy and for adverse drug events (ADEs). Dose-response is identified by placebo-controlled, double-blind, fixed-dose clinical trials comparing various doses for efficacy and for ADEs. Reports from the great majority of clinical trials have consist...

This pharmacoepidemiology study uses BCBS claims data to characterize recent trends in use of methylphenidate and amphetamine-related products in 4 US states between 2010 and 2014.Stimulants are the most commonly prescribed treatment of attention-deficit/hyperactivity disorder (ADHD) in youths, and according to a nationally representative US househ...

Objectives: The study objective was to assess national trends in the diagnosis of attention-deficit hyperactivity disorder (ADHD) in outpatient visits by comparing adults and youths. Also examined were recent stimulant prescribing patterns for ADHD visits by youths and adults. Methods: Databases from the 1999-2010 National Ambulatory Medical Car...

Objective: This study examined national trends between 1999 and 2010 in not otherwise specified (NOS) DSM-IV psychiatric diagnoses and in related medication treatment patterns reported for adults during outpatient physician office visits. Methods: Data on physician office visits by adults (ages 18-64) with a psychiatric diagnosis were from the N...

Purpose: To assess antipsychotic prescribing patterns according to insurance coverage type and physician specialty in the outpatient treatment of behavioral disorders (BD) in US youth. Methods: We used 2003-2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data to compare antipsychotic prescribing...

Objective: In the last decade, dramatic changes have occurred in stimulant medication prevalence and in patterns of stimulant treatment. The resultant trends merit analysis. Method: Usage patterns of stimulant medication, specifically amphetamine and methylphenidate, were analyzed for trends. The data were obtained from datasets including pharmacy...

Objective: It would be useful to compare temporal changes in the diagnostic prevalence of ADHD obtained from identical population surveys with time-trend survey findings based on individual ADHD features. Method: Changes in the diagnostic prevalence of ADHD over time were recorded from parent reports and from physician office visit data. Associated...

Patterns and trends of subthreshold DSM-IV mental health diagnoses for youth within US community treatment settings merit systematic research. To quantify and assess temporal patterns of DSM-IV diagnoses not otherwise specified (NOS) among youth during physician office visits. We conducted a retrospective study using psychiatric diagnostic data fro...

The main objective of this study is to explore the relationship of psychotropic medication use patterns and clinician-reported maltreatment status in Medicaid-insured youth. This cross-sectional study analyzed computerized outpatient claims for youth aged 2–17 years who were continuously enrolled for ≥10 months in a mid-Atlantic state Medicaid prog...

The sharply differing perspectives of the various stakeholders on the benefit-to-risk assessment of selective serotonin reuptake inhibitors (SSRIs) have generated much confusion. To make these issues clearer, this chapter aims to provide a review and critique of the following topics: (1) published randomized pediatric clinical trials on the efficac...

Objective: Over the last two decades, the increased use of atypical antipsychotic medications, often for unlabeled indications including attention-deficit/hyperactivity disorder (ADHD), has been profound. This study aims to characterize duration of atypical antipsychotic use by age group and Medicaid eligibility category, and among youth with nonc...

The diagnosis of pediatric bipolar disorder (PBD) has increased dramatically in community-treated youth in the past 20 years. No previous study has assessed the trend in PBD subtype diagnoses or the impact of clinician-reported behavioral comorbidities (BC) on psychotropic medication prescribing patterns. This study aims: (1) to characterize nation...

Commonly used statistical measures to quantify the likelihood of an adverse drug event (ADE) from clinical trials include risk ratio; odds ratio; and number needed to harm (NNH), the reciprocal of absolute risk. This critical review focused on NNH, specifically on its limitations in controlled trials with psychotropic medication. Data for this eval...

Commonly used statistical measures to quantify the likelihood of an adverse drug event (ADE) from clinical trials include risk ratio; odds ratio; and number needed to harm (NNH), the reciprocal of absolute risk. This critical review focused on NNH, specifically on its limitations in controlled trials with psychotropic medication. Data for this eval...

Objective: This study aimed to: document the extent of the reduction of serum prolactin (PRL) levels induced by aripiprazole (ARI) treatment in children and adolescents, compare this effect by age group, and shed light on this phenomenon. Methods: PRL serum levels in unmedicated subjects were compared to those in subjects treated with aripiprazo...

Objective: This cross-sectional study evaluated the impact of Medicaid-eligibility category on the increased use of antipsychotic medication by Medicaid-insured youths across a decade. Methods: The authors analyzed computerized administrative claims data for 456,315 youths aged two to 17 years who were continuously enrolled in Medicaid in a mid-...

Objective: This research study aimed to assess national trends in pediatric use of anticonvulsants for seizures and psychiatric disorders. Methods: In a cross-sectional design, data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey were analyzed. Outpatient visit information for youths (age...

Objective: This review of published studies compares scores on individual items of mania rating scales that systematically recorded symptom severity in persons diagnosed with bipolar disorder to identify age-grouped differences. Methods: An extensive literature search identified item scores from mania rating scales, with a particular emphasis on...

Objectives The primary purpose of this study was to determine whether youth with a clinical diagnosis of cancer are subsequently more likely to be prescribed antidepressants than their counterparts without cancer in a multi-state Medicaid-enrolled population. Methods Data on youth, ages 2–17 years, who were continuously enrolled in Medicaid for 3 o...

Large community-based, computerized administrative datasets comprised of enrollment data, socio-demographic characteristics, and diagnostic and treatment information on all individuals in populations or a health insurance plan constitute the major resource for pharmacoepidemiologic research. Investigators use such data to estimate prevalence or new...

Background. Anticonvulsant (ATC) use for psychiatric disorders in youth dramatically increased during the last decade. This off-label use, particularly by divalproex, is a growing concern because of its doubtful efficacy (Pavuluri MN et al. 2010; Wagner KD, et al. 2006) and safety concerns (Bryant AE, et al. 1996; Wisner et al. 2011). Objectives. T...

This review aims to detail specific psychotropic medication treatment differences in adverse drug events (ADEs) between children, adolescents, and adults. A thorough data-based search of ADEs was made, augmented by findings from approved and updated U.S. Food and Drug Administration (FDA) drug labels, controlled clinical trial reports, and from FDA...

To assess the national impact of the March 2004 Food and Drug Administration (FDA) antidepressant suicidality warning on the outpatient treatment of new-onset depression in youth. A repeated measures, longitudinal design in a cohort of youth diagnosed with new-onset depression was used to assess pre- and post-FDA warning effects. US commercial insu...

In the DSM-IIIR in 1987, the category title for depressive and bipolar disorders was changed from affective disorders to mood disorders. Within a short period of time thereafter, mood swing and mood stabilizer became very commonly used terms in psychiatry with bipolar implications. Terms and definitions in recent texts, articles, and dictionaries p...

Introduction: Over the past 20 years, there has been a substantial increase in the prevalence of psychotropic medications prescribed for the treatment of behavioral and emotional problems in youth. Despite the increased use in psychotropic medications in U.S. youth, African American and Hispanic youth are significantly less likely to be dispensed p...

The terms 'irritable mood' and 'irritability' have been applied to describe and define a variety of different categories in the Diagnostic and Statistical Manual of Mental Disorders (DSM). More precise diagnostic terms and concepts are needed. A concise critical historical review of DSM categories characterized by irritability, anger, and aggressio...

The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warr...

The study aims to compare cross-national prevalence of psychotropic medication use in youth. A population-based analysis of psychotropic medication use based on administrative claims data for the year 2000 was undertaken for insured enrollees from 3 countries in relation to age group (0-4, 5-9, 10-14, and 15-19), gender, drug subclass pattern and c...

Studies have revealed that youth in foster care covered by Medicaid insurance receive psychotropic medication at a rate > 3 times that of Medicaid-insured youth who qualify by low family income. Systematic data on patterns of medication treatment, particularly concomitant drugs, for youth in foster care are limited. The purpose of this work was to...

To update knowledge of the prevalence of the use of psychotherapeutic medications in preschoolers with Medicaid insurance as requested by the Best Pharmaceuticals for Children Act of 2002 (BPCA). Prescription, enrollment, and outpatient visit data from 7 state Medicaid programs were used to identify 274,518 youths continuously enrolled in 2001 and...

Investigators from a number of countries have linked temporal declines in the rate of completed suicide in children and adults to the increasing utilization of selective serotonin reuptake inhibitor (SSRI) antidepressants. They suggest that the relationship is causal. We undertook a thorough literature search of the rates of completed suicide using...

IntroductionEfficacy from Published TrialsMeta-Analysis of Published and Unpublished StudiesSafety from Clinical Trial DataSafety from Observational StudiesNew Studies to Address the Research QuestionImproving the Safety InfrastructureRecent FDA Actions and ConsequencesConclusions References

To compare antidepressant prevalence data in youths across three western European countries (Denmark, Germany, and the Netherlands) with US regional data in terms of age and gender and to show proportional subclass antidepressant (ATD) use. A population-based analysis of administrative claims data for the year 2000 was undertaken in 0 to 19-year-ol...

This study compared the prevalence of anticonvulsant treatment for youths with a diagnosis of a psychiatric disorder to youths with a diagnosis of a seizure disorder. Administrative claims from outpatient visits and prescriptions were organized for a data set of 258,472 youths who were younger than 18 years of age in a mid-Atlantic state Medicaid p...

The aim of this study was to report the frequency of common treatment-emergent adverse events (AEs) from selective serotonin reuptake inhibitors (SSRIs) in children, adolescents, and adults. AE data were obtained from all published double-blind, placebo-controlled SSRI studies of children and adolescents that separated AE findings by age group. The...

The aim of this study was to compare multiple psychotropic use among youths enrolled in two U.S. mid-Atlantic state Medicaid and state Children's Health Insurance Programs (SCHIP). Administrative data were used to examine multiple psychotropic use among youths less than 20 years of age and who were continuously enrolled in Medicaid or SCHIP program...

This study sought to determine the degree to which Medicaid eligibility categories modify disparities between black and white youths in the prevalence of psychotropic medication. Computerized claims for 189,486 youths aged two to 19 years who were continuously enrolled in a mid-Atlantic state Medicaid program for the year 2000 were analyzed to dete...

The one-year prevalence of use of psychotropic medications among youths enrolled in a Mid-Atlantic State Children's Insurance Program (SCHIP) in 1999 or 2000 was compared with the 1998-2000 prevalence findings for youths enrolled in four large multistate private medical insurance programs. Prevalence was significantly higher among youths enrolled i...

A systematic and comprehensive literature search was performed to determine the extent of weight gain induced by risperidone (RIS) treatment across the age span. The review and pooled data analyses were based on double-blind, open trial, and case series studies containing findings on drug dose, age of subjects, weight gain, duration of treatment, a...

Few reports have documented parental perceptions of stimulants for attention-deficit hyperactivity disorder (ADHD), despite the recent increased use of stimulants among youths. Of 302 parents recruited from six pediatric primary care clinics, 84% completed a survey of their knowledge, attitudes, and satisfaction with the medication their child was...

This study reviewed the clinical research and practice literature relating to the prevalence and patterns of concomitant psychotropic medication given to youths with emotional and behavioral disorders. A MEDLINE search from 1996 through spring 2002, including a review of references from relevant published articles and reports, was undertaken to ide...

To examine changes in the full spectrum of psychotropic medication treatment for youths from 1987 to 1996. A population-based analysis of community treatment data on nearly 900,000 youths enrolled in 2 US health care systems included (1) computerized Medicaid data from 2 states (a midwestern state and a mid-Atlantic state) composed of outpatient pr...

This review of recently published pharmaceutical industry-sponsored comparative psychotropic drug trials aims to classify apparent design and reporting modifications that favor the sponsor's product. The modifications have been grouped into 13 discrete categories, and representative examples of each are presented. Strong circumstantial evidence sug...

To examine changes in antidepressant (ATD) prevalence and the sociodemographic and clinical correlates of ATD use among youths who are treated in community practice settings. A retrospective study was undertaken using large data sets from 3 US sites. Outpatient prescription and clinical service records of youths who were aged 2 to 19 and enrolled i...

This study assessed whether mental health services for youths differ with respect to medical assistance aid category. Computerized claims for 15,507 youths with Medicaid insurance in a populous county of a mid-Atlantic state were used to establish population-based prevalence estimates of mental disorders and psychotherapeutic treatments during 1996...

Between 1988 and 1994, data from 3 large sites revealed a 3-5 fold increase in the prevalence of antidepressant (ATD) treatment for U.S. youths aged 2-19 years. In 1994, the ATD prevalence for youths of this age ranged from 13 per 1000 (in the HMO) to 18 per 1000 (in 2 state Medicaid systems). Males predominated in the 10-14-year-olds treated with...

To review the numerous reports of hepatotoxic adverse drug reactions (ADRs) ascribed to pemoline that were sent to the U.S. Food and Drug Administration (FDA) between 1975 and 1996 and to describe the medical community's lack of awareness of these reports. All ADR reports from 1975 through 1996 wherein pemoline was the suspect agent were obtained f...

This review of antidepressant treatments in children and adolescents emphasizes the gap between efficacy data derived from randomized clinical trials (RCTs) and the limited effectiveness data from community-based practices. Part one is a brief review of data from randomized, double-blind clinical trials to assess the evidence base for the major app...

A statewide school survey was performed to provide naturalistic data on the prevalence of medication administered to Maryland public school students for the treatment of attention deficit hyperactivity disorder (ADHD) to clarify the concern of some state legislators about stimulant treatment for youths. In April 1998, school nurses supervised a sur...

Critics of stimulant treatment for youths with attention deficit hyperactivity disorder (ADHD) have increased their rhetoric of late, contending that the leading medication for it, Ritalin, is vastly overprescribed. Additionally, they claim that Ritalin (methylphenidate) is inherently dangerous and that the entire system of the diagnosis and treatm...

Recent reports on the use of psychotropic medications for preschool-aged children with behavioral and emotional disorders warrant further examination of trends in the type and extent of drug therapy and sociodemographic correlates. To determine the prevalence of psychotropic medication use in preschool-aged youths and to show utilization trends acr...

(1) To describe temporal patterns of office visits for attention-deficit/hyperactivity disorder (ADHD) and stimulant treatment for 5- to 14-year-old US youths; (2) to compare youth visits for ADHD with and without melication according to patient demographics, physician specialty, reimbursement source, and comorbid diagnoses; and (3) to compare offi...

Psychotropic medication treatment of attention deficit hyperactivity disorder (ADHD) has prominently increased over the last three decades such that an estimated 2 to 2.5 million youths in the United States now receive this treatment. Stimulants have been and remain the primary prescribed medication group to treat this disorder, even though the var...

A retrospective analysis was conducted using state Medicaid prescription drug reimbursement claims for youths aged 5 through 14 years according to the race of the recipients of psychotropic and medical drugs. A person-based data set was created from Medicaid administrative data for fiscal year 1991 from the state of Maryland to yield the following:...

This study was undertaken to clarify several aspects of the estimation of prevalence of three commonly use pediatric psychotropic agents, namely, methylphenidate, desipramine, and imipramine. The study aims are threefold: (1) to show the variability of drug prevalence by comparing estimates from three data sources; (2) to show the misleading impres...

A thorough medical literature review of adolescent self-reported suicide attempts focused on comparing the following: (1) the prevalence of attempts in anonymous vs. face-to-face surveys; (2) the prevalence rates in the United States and Canada vs. those reported elsewhere; and (3) the prevalence of attempt findings vs. self-harm behavior in anonym...

A comprehensive literature review compared the patterns of suicide and suicidal behavior for adolescents and adults to identify age-related similarities and differences. Particular attention was given to follow-up rates of suicide by psychiatrically treated persons in these age groups. The major findings were that (1) adults and adolescent suicide...

The use of CNS stimulants for the treatment of attention deficit hyperactivity disorder (ADHD) in children has steadily increased in most areas of the world over the last 30 years. In mid-1995, at least 1.5 million US children were receiving methylphenidate or dexamphetamine (dextroamphetamine). However, in other countries these agents are not used...

Treatment of attentional disorders in America has increased dramatically in recent years. This trend is accounted for partly by lengthening the duration of treatment into adulthood for some individuals as well as by increased treatment among girls. Beyond these factors, the role of economic status, race, and geographic region to explain the variati...

To estimate the increased use and the prevalence of methylphenidate (Ritalin) treatment of youth with attention deficit disorder (ADD) during the 1990s. Using time-trend findings from two large population-based data sources, three pharmaceutical databases, and one physician audit, a best-fit estimate of the usage and the usage trends for methylphen...

In view of the dramatic shift to managed care models for United States health care delivery, reliable information on the prevalence and variations in psychopharmacological drug therapies for youth in community practice settings is essential. Pharmacoepidemiology, the study of medication use in large populations, aims to accomplish that challenging...