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. This review will also address the gaps in reporting of pediatric psychotropic polypharmacy.
Methods:
An electronic literature search was undertaken for the period 2000 through 2020 using keywords such as “pediatric,” “concomitant,” “polypharmacy,” “multiple medications,” and “concurrent psychotropic”; Relevant references in textbooks were also used. Only English language and U.S. studies were included, resulting in 35 inter-class studies.
Results:
Studies were organized into seven groups according to data sources and clinical topics: (1) population surveys; (2a) multi-state publicly insured populations; (2b) single/two state studies; (3) privately insured populations; (4) diagnosed populations; (5) foster care populations; (6) special settings. Across 20 years it is apparent that pediatric psychotropic polypharmacy affects substantially more children and adolescents today than had been the case. As many as 300,000 youth now receive 3 or more classes concomitantly. The duration of concomitant use is relatively long, e.g., 69–89% of annual medicated days. Finally, more adverse event reports were associated with 3-class compared with 2-class drug regimens.
Discussion:
Factors that contribute to the growth of pediatric psychotropic polypharmacy include: (1) predominance of the biological model in psychiatric practice; (2) invalid assumptions on efficacy of combinations, (3) limited professional awareness of metabolic and neurological adverse drug events, and (4) infrequent use of appropriate deprescribing.
Conclusion:
A review of publications documenting U.S. pediatric psychotropic polypharmacy written over the last 20 years supports the need to standardize the methodologies used. The design of population-based studies should maximize information on the number of youth receiving regimens of 3-, 4-, and 5 or more concomitant classes and the duration of such use. Next, far more post-marketing research is needed to address the effectiveness, safety and tolerability of complex drug regimens prescribed for youngsters.
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 across a 5-year span.
Ambulatory care prescription records from 2 state Medicaid programs and a salaried group-model health maintenance organization (HMO) were used to perform a population-based analysis of three 1-year cross-sectional data sets (for the years 1991, 1993, and 1995).
From 1991 to 1995, the number of enrollees aged 2 through 4 years in a Midwestern state Medicaid (MWM) program ranged from 146,369 to 158,060; in a mid-Atlantic state Medicaid (MAM) program, from 34,842 to 54,237; and in an HMO setting in the Northwest, from 19,107 to 19,322.
Total, age-specific, and gender-specific utilization prevalences per 1000 enrollees for 3 major psychotropic drug classes (stimulants, antidepressants, and neuroleptics) and 2 leading psychotherapeutic medications (methylphenidate and clonidine); rates of increased use of these drugs from 1991 to 1995, compared across the 3 sites.
The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM program was: stimulants (12.3), 90% of which represents methylphenidate (11.1); antidepressants (3.2); clonidine (2.3); and neuroleptics (0.9). A similar rank order was observed for the MAM program, while the HMO had nearly 3 times more clonidine than antidepressant use (1.9 vs 0.7). Sizable increases in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine, stimulants, and antidepressants, while neuroleptic use increased only slightly. Methylphenidate prevalence in 2- through 4-year-olds increased at each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in the relative proportions of previously dominant psychotherapeutic agents in the stimulant and antidepressant classes, while increases occurred for newer, less established agents.
In all 3 data sources, psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995. The predominance of medications with off-label (unlabeled) indications calls for prospective community-based, multidimensional outcome studies.
Detailed research on long-term antidepressant (AD) trends within a single large US Medicaid population of youth has not heretofore been reported.
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 mid-Atlantic state Medicaid program. Total annual AD prevalence and age-, gender-, race-, eligibility group-, and diagnosis-specific prevalence were formed from bivariate analyses; logistic regression assessed the change in use (2007-2014) adjusted for covariates. AD-polypharmacy data were assessed in 2014.
The major findings are: 1) AD use in state Medicaid enrollees grew 14-fold between 1987 and 2014. Data from 2014 revealed significantly increased odds of youth with SSRI/SNRI dispensings compared to 2007 (AOR=1.15 95% CI 1.11-1.19), representing 78% of total AD users. 2) Recent AD increases were greatest for 15-19-year olds. 3) AD use in girls passed up AD use in boys for the first time in 2014. 4) In 2014, ADs for foster care (12.7%) were 6 times greater than for their income-eligible Medicaid-counterparts. 5) In 2014, a quarter of AD-medicated youth were diagnosed with a behavior disorder. 6) More than 40 percent of AD medicated youth had >=1 other concomitant psychotropic classes for 60 or more days.
Second-generation antidepressant use in Medicaid-insured youth has increased despite growing questions that pediatric AD benefits may not outweigh harms. These patterns support the call for publicly funded, independent investigator-conducted post-marketing outcomes research.
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).
Medicaid Analytic eXtract data were used to conduct a retrospective cohort study of youth (aged 5-20 years) who initiated AAP treatment. In AAP-treated youth, concomitant antidepressant (selective serotonin reuptake inhibitors SSRI/serotonin-norepinephrine reuptake inhibitors SNRIs, tricyclic/other cyclic antidepressants TCAs, and other antidepressants) or stimulant use was assessed. The risk of incident T2DM was estimated using discrete time failure models, adjusting for disease risk score estimated using >125 baseline and time-dependent covariates.
Among 73,224 AAP initiators, 43.0% had concomitant antidepressant use (76.4% were SSRI/SNRIs) and 43.8% had concomitant stimulant use. The study cohort had an average follow-up of 24.8 months (median = 22.0 months, interquartile range IQR = 10.0-38.0 months). In current AAP-treated youth, concomitant SSRI/SNRI (relative risk RR = 1.84, 95% CI = 1.30-2.59) or TCA use (RR = 2.75, 95% CI = 1.28-5.87) was associated with an increased risk of T2DM. By contrast, concomitant use of other antidepressants or stimulants with AAPs was not associated with an increased risk of T2DM. In concomitant users of AAPs and SSRI/SNRIs, the risk of T2DM increased with the duration of SSRI/SNRI use (RR = 2.35, 95% CI = 1.15-4.83 for ≥180 days vs. 1-180 days) as well as with the cumulative SSRI/SNRI dose (RR = 1.99, 95% CI = 1.08-3.67 for >2,700 mg vs. 1-2,700 mg fluoxetine dose equivalents), after adjusting for the duration and cumulative dose of AAP use. By contrast, in concomitant users of AAPs and stimulants, neither duration nor cumulative dose of stimulants was associated with an increased risk of T2DM.
In AAP-treated Medicaid-insured youth, concomitant SSRI/SNRI use was associated with a heightened risk of T2DM, which intensified with increasing duration and dose.
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 concomitant use. The data include insured youth aged 0-19 in the year 2000 from the Netherlands (n = 110,944), Germany (n = 356,520) and the United States (n = 127,157).
The annual prevalence of any psychotropic medication in youth was significantly greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%). Antidepressant and stimulant prevalence were 3 or more times greater in the US than in the Netherlands and Germany, while antipsychotic prevalence was 1.5-2.2 times greater. The atypical antipsychotic subclass represented only 5% of antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents generally followed the ranking of US>Dutch>German youth with very rare (less than 0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice as common in Dutch as in US and German youth. Prescription hypnotics were half as common as anxiolytics in Dutch and US youth and were very uncommon in German youth. Concomitant drug use applied to 19.2% of US youth which was more than double the Dutch use and three times that of German youth.
Prominent differences in psychotropic medication treatment patterns exist between youth in the US and Western Europe and within Western Europe. Differences in policies regarding direct to consumer drug advertising, government regulatory restrictions, reimbursement policies, diagnostic classification systems, and cultural beliefs regarding the role of medication for emotional and behavioral treatment are likely to account for these differences.
Atypical antipsychotic drugs have been used off label in clinical practice for treatment of serious dementia-associated agitation and aggression. Following reports of cerebrovascular adverse events ...associated with the use of atypical antipsychotics in elderly patients with dementia, the U.S. Food and Drug Administration (FDA) issued black box warnings for several atypical antipsychotics titled "Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients With Dementia." Subsequently, the FDA initiated a metaanalysis of safety data from 17 registration trials across 6 antipsychotic drugs (5 atypical antipsychotics and haloperidol). In 2005, the FDA issued a black box warning regarding increased risk of mortality associated with the use of atypical antipsychotic drugs in this patient population.
Geriatric mental health experts participating in a 2006 consensus conference (Bethesda, Md., June 28-29) reviewed evidence on the safety and efficacy of antipsychotics, as well as nonpharmacologic approaches, in treating dementia-related symptoms of agitation and aggression. EVIDENCE/CONSENSUS PROCESS: The participants concluded that, while problems in clinical trial designs may have been one of the contributors to the failure to find a signal of drug efficacy, the findings related to drug safety should be taken seriously by clinicians in assessing the potential risks and benefits of treatment in a frail population, and in advising families about treatment. Information provided to patients and family members should be documented in the patient's chart. Drugs should be used only when nonpharmacologic approaches have failed to adequately control behavioral disruption. Participants also agreed that there is a need for an FDA-approved medication for the treatment of severe, persistent, or recurrent dementia-related symptoms of agitation and aggression (even in the absence of psychosis) that are unresponsive to nonpharmacologic intervention.
This article outlines methodological enhancements to better evaluate treatment approaches in future registration trials and provides an algorithm for improving the treatment of these patients in nursing home and non-nursing home settings.
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