How Much Is Too Much? Escalating Psychotropic Class Polypharmacy, Diabetes Risk, and Clinical Complexity in Stimulant New Users.

Background: Mental disorders are common among children and adolescents, worldwide. However, little is known about the patterns of psychiatric diagnoses in Saudi Arabia in general. Moreover, it is crucial to examine the prescribing patterns of psychotropic medications and polypharmacy among children and adolescents as the benefits versus risks are not clear in this population. This study aimed to evaluate the patterns of psychiatric diagnoses as well as prescribing patterns of psychotropic medications and polypharmacy among children and adolescents in the Jazan region of Saudi Arabia. Methods: A retrospective cross-sectional study design was conducted with a sample of children and adolescents (N=647) who attended the outpatient clinics in the psychiatric hospital in the Jazan region, Southwest of Saudi Arabia. Age, gender and clinical outcomes were retrieved from the electronic health records of the sample. Outcome Measures included patterns of psychiatric diagnoses and prescribing patterns of psychotropic medications and polypharmacy (>=2 psychotropic medications). Logistic regression models were conducted to examine the relationships between the explanatory variables and the following: polypharmacy, antidepressants, antipsychotics and stimulants prescriptions. Results: The most prevalent psychiatric diagnosis was attention-deficit hyperactivity disorder (31.5%) followed by autism and pervasive developmental disorders (27.6%) and mental retardation (24%). The most prescribed psychotropic classes were antipsychotics and stimulants. Approximately, a quarter of the children and adolescents were given psychotropic polypharmacy. A higher percentage of adolescents were given polypharmacy than children (31.5% vs 18.2%). In the adjusted analyses, adolescents were more likely to receive psychotropic polypharmacy, antidepressants and stimulants than children. Nevertheless, adolescents were less likely than children to be given antipsychotics. Conclusions: Psychotropic polypharmacy rates in the Jazan region are concerning, especially among adolescents. Healthcare professionals should closely monitor children and adolescents with psychotropic polypharmacy to minimize the risk of drug-drug and/or drug-disease interactions.

Importance: Psychotropic classes concomitant with stimulants (PCCWS) in children and adolescents have shown an inconsistent impact on the risk of diabetes mellitus. PCCWS with 2-5 classes is common but the risk of diabetes subsequent to stimulant initiation is unknown. Objective: To assess the risk of diabetes in youth with PCCWS regimens with 2-5 additional psychotropic classes. Design: A retrospective cohort study was conducted using Medicaid claims data from 2007-2014. Youth aged 2-17 years with 1-7.5 years of continuous enrollment who were new stimulant users with clinician-reported psychiatric diagnosis were followed. Setting: Outpatient clinic and inpatient records for statewide Medicaid-insured youth in a mid-Atlantic state. Participants: The study cohort comprised 30,112 youth with an average follow-up of 6.4 years. Exposures: Among stimulant users, five groups were defined according to concomitant use. Main Outcomes and Measures: The major outcome is diabetes risk and was assessed using discrete-time failure models, after adjustment for disease risk score which was categorized using more than 120 baseline and time-dependent covariates. Results: Among 30,112 new stimulant users, 43 were new diabetes patients and 30,069 were nondiabetes patients. The absolute risk of diabetes in youth had an eight-fold increase from 3 to 5 class PCCWS regimens that included antipsychotics, antidepressants, or anticonvulsant-mood stabilizers (0.5; 1.13; 4.20 per 10,000 person-months, respectively). Compared with stimulant monotherapy, PCCWS with any of these 3 classes were significantly more likely to develop diabetes (adjusted relative risk [ARR], 2.58, (95% CI 1.05-6.82); 5.81, (2.29-14.75); 18.91, (6.07-58.90) for 3, 4 and 5 class PCCWS, respectively). Similarly, there was a significantly greater risk of diabetes for those with 120-779 days of cumulative duration than for shorter exposures, and in 4 and 5 class combined PCCWS including antipsychotics, antidepressants, or anticonvulsant-mood stabilizers [ARR, 3.78, (1.16-12.40)]. Conclusions: In a large Medicaid-insured, long-enrolled youth cohort, the use of PCCWS, particularly concomitant use with antipsychotic, antidepressant, and/or antipsychotic-mood stabilizers, and with long duration of these combinations were associated with an increased risk of diabetes. Relevance: The findings support a call for corroboration in a large national cohort of continuously enrolled Medicaid-insured pediatric youth with long follow-up.

15.1 Long-Term Psychotropic Use Patterns in Very Young, Publicly Insured Youth

People with intellectual disability (ID) are at increased risk of exposure to psychotropic drugs and psychotropic polypharmacy because of the higher prevalence of mental health conditions present and more controversially, the use of these agents to treat challenging behaviours. Despite the fact that many adults with ID are exposed to psychotropic polypharmacy, few studies to date have focused on the patterns of use of multiple psychotropics, or factors associated with psychotropic polypharmacy, particularly in the older population. This study aims to examine the prevalence, patterns and factors associated with psychotropic use in general and psychotropic polypharmacy in particular in a representative sample of ageing people with ID. This was an observational cross-sectional study from Wave 1 of Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing; a nationally representative sample of 753 persons with ID aged between 41 and 90years. Participants/proxy reported medicines (prescription and over the counter) taken on a regular basis; medication data were available for 736 participants (98%). Participants were divided into those with no psychotropic exposure, exposure to 1 psychotropic and psychotropic polypharmacy (2+ psychotropics). Patterns of psychotropic use were analysed. A multinomial logistic regression model identified factors associated with use of 1 psychotropic and psychotropic polypharmacy. Overall, 59.1% (436) of the sample was exposed to any psychotropic; of these, 66.2% reported psychotropic polypharmacy. Antipsychotics were the most frequently reported psychotropic class by 43% of the sample. Living in a residential institution and having a history of reporting a mental health condition or sleep problems were associated with psychotropic polypharmacy after adjusting for confounders, while those with epilepsy were less likely to experience exposure to polypharmacy, but age, gender had no significant effect. Psychotropic use and polypharmacy were commonplace for older adults with ID. Psychotropic use, particularly the use of psychotropic combinations, needs to be regularly reviewed for safety, efficacy and adverse effects, and rationale for use of multiple agents needs to be clear and documented.

This study evaluated psychotropic polypharmacy frequency and patterns of use among Medicaid-enrolled youths. A cross-sectional study of a state Medicaid claims database (2015-2020) focused on youths (≤17 years old) with at least one psychotropic medication claim and ≥90 continuous days of Medicaid enrollment. Psychotropic polypharmacy (claims for three or more therapeutic classes of psychotropics for ≥90 consecutive days) was analyzed as average annual days and annual prevalence of class combinations. Multivariable negative binomial regression models assessed changes in annual psychotropic polypharmacy days. A total of 126,972 unique youths were identified. Almost all youths with psychotropic polypharmacy had three-class combinations, the most common of which included attention-deficit hyperactivity disorder medications, antipsychotics, and antidepressants. The number of polypharmacy days increased from a mean±SD of 227.8±90.3 in 2015 to 235.7±97.5 in 2020. Polypharmacy days significantly increased year over year (rate ratio=1.01, 95% CI=1.00-1.01). Psychotropic polypharmacy regimens reflect chronic use that is increasing over time.

To determine if adverse family factors are associated with a higher likelihood of psychotropic polypharmacy among US youth with a mental health condition. The 2009-2015 Medical Expenditure Panel Survey data were used to identify family characteristics of 5136 youth aged ≤18 years with an emotional or behavioral health condition. Family adversity was based on family size, number of parents in the household, parental education and income, and parent-reported physical and/or cognitive or mental health disability. Cluster analysis identified family adversity subgroups. Polypharmacy was defined as 3 or more psychotropic classes (eg, stimulants, antipsychotics, antidepressants, mood stabilizers, and sedatives) in at least 1 interview round in a calendar year. Weighted logistic regression evaluated associations between family adversity and psychotropic polypharmacy among youth. Nearly half (47.8%) of youth lived with parents who had a disability. Parents in the least socioeconomically disadvantaged cluster mainly had a mental illness, and 94% of parents in the most socioeconomically disadvantaged cluster had a parent-reported physical and/or cognitive disability and mental illness. Among youth, mood disorder (24.2%; 95% confidence interval [CI]: 12.6%-16.0%), antidepressant use (16.0%; 95% CI: 10.6%-21.5%), and antipsychotic use (7.5%; 95% CI: 5.4%-9.6%) were higher in the most socioeconomically disadvantaged cluster relative to the other clusters. Approximately 3% of youth received psychotropic polypharmacy. The odds of psychotropic polypharmacy were 2.7 (95% CI: 1.1-6.4) times greater among youth in the most relative to the least socioeconomically disadvantaged cluster. Higher use of psychotropic polypharmacy among youth with parents who have multiple disabilities raises concerns about oversight and monitoring of complex psychotropic treatment.

THE EFFECTS OF PSYCHOTROPIC MEDICATIONS ON GAIT STABILITY OF OLDER ADULTS WITH DEMENTIA

This study investigates differences in the characteristics of US youths treated with psychotropic polypharmacy and in the psychotropic classes used in combination.

BackgroundDespite limited evidence, psychotropics, such as antipsychotics are commonly used to treat neuropsychiatric symptoms (NPS) in people living with dementia. There are safety concerns on the use of antipsychotics, but co‐prescribing multiple classes of psychotropics (psychotropic polypharmacy) may have a greater and more serious harm to this group. This includes sedation‐induced falls, delirium, hospitalizations, and mortality.In Australia, people with significant NPS, such as agitation and aggression can be referred for free 24/7 support and advise to a national behavior dementia‐specific support service known as Dementia Support Australia (DSA). The aim of this study is to describe the prevalence of psychotropic polypharmacy in DSA referrals.MethodWe used a sample of medication charts from the DSA database to estimate the prevalence of psychotropic polypharmacy in referrals between January and November 2020. A descriptive analysis of psychotropic use was based on the grouping of the World Health Organization Anatomical Therapeutic Classes (ATCs), which included seven classes: antipsychotics, antidepressants, anxiolytics, opioid analgesics, hypnotics, anticonvulsants, and anti‐dementia drugs. Psychotropic polypharmacy was defined as the concomitant use of ≥2 psychotropics overall, whether it is within the same class, subclass, or cross‐class.ResultsOf the 137 referrals [M = 83.6 (SD = 8.5) years of age; 54.0% female], 28 referrals were prescribed medications that could not be nearly categorized into the ATCs (e.g., ibuprofen). For the remaining 109 referrals included in analysis, polypharmacy was common (n = 82, 75.2%; Figure 1A). Polypharmacy was especially common for referrals who were prescribed anxiolytics (n = 25, 100% prescribed additional medication), anticonvulsants (n = 27, 96.4% prescribed additional medication), or anti‐dementia (n = 25, 96.2% prescribed additional medication) medications. Of the 36 different psychotropic medications prescribed to referrals, 23 (63.9%) were prescribed exclusively with additional medications. The most common co‐prescriptions (Figure 1B) were antidepressants+antipsychotics (n = 6, 5.5%), anti‐dementia+opioid analgesic (n = 4, 3.7%), antidepressants+antipsychotics+hypnotics (n = 4, 3.7%), and antipsychotics+hypnotics (n = 4, 3.7%).ConclusionPsychotropic polypharmacy is common in people with dementia related NPS who require external behavioral support. Deprescribing psychotropics should be considered a priority in this group as the risks of these agents outweigh their benefits.

Psychotropic polypharmacy reconsidered: Between-class polypharmacy in the context of multimorbidity in the treatment of depressive disorders

To describe psychotropic polypharmacy in Australia between 2006 and 2015. We used pharmaceutical claims from a national 10% sample of people with complete dispensing histories to estimate the annual prevalence of the combined use (overlap of >60days exposure) of ≥2 psychotropics overall and within the same class or subclass (class and subclass polypharmacy). We also estimated the proportion of polypharmacy episodes involving one, two, three and four or more unique prescribers. The prevalence of class polypharmacy between 2006 and 2015 in people dispensed specific psychotropic classes was 5.9-7.3% for antipsychotics, 2.1-3.7% for antidepressants and 4.3-2.9% for benzodiazepines. The prevalence of antipsychotic polypharmacy was higher than expected given the prevalence of antipsychotic exposure and combinations of sedating agents were notably common. Overall, 26.7% of polypharmacy episodes involved multiple prescribers but having multiple prescribers occurred more frequently for class and subclass polypharmacy and people with four or more concomitant psychotropics. Psychotropic polypharmacy is common, despite limited evidence of risks and benefits. Increases in polypharmacy with multiple prescribers may be due to poor communication with patients and between health care professionals.

To determine longitudinal patterns of dispensing of antidepressant, anxiolytic, antipsychotic, psychostimulant, and hypnotic/sedative medications to children and adolescents in Australia during 2013-2021. Retrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data. People aged 18 years or younger dispensed PBS-subsidised psychotropic medications in Australia, 2013-2021. Population prevalence of dispensing of psychotropic medications to children and adolescents, by psychotropic class, gender, and age group (0-6, 7-12, 13-18 years). The overall prevalence of psychotropic dispensing to children and adolescents was 33.8 per 1000 boys and 25.2 per 1000 girls in 2013, and 60.0 per 1000 boys and 48.3 per 1000 girls in 2021. The prevalence of psychotropic polypharmacy was 5.4 per 1000 boys and 3.7 per 1000 girls in 2013, and 10.4 per 1000 boys and 8.3 per 1000 girls in 2021. Prevalent dispensing during 2021 was highest for psychostimulants (boys, 44.0 per 1000; girls, 17.4 per 1000) and antidepressants (boys, 20.4 per 1000; girls, 33.8 per 1000). During 2021, the prevalence of dispensing was higher than predicted by extrapolation of 2013-2019 data for many classes, including antidepressants (boys: +6.1%; 95% CI, 1.1-11.1%; girls: +22.2%; 95% CI, 17.4-26.9%), and psychostimulants (boys: +14.5%; 95% CI, 8.0-21.1%; girls: +27.7%; 95% CI, 18.9-36.6%). The increases were greatest for girls aged 13-18 years (antidepressants: +20.3%; 95% CI, 16.9-23.7%; psychostimulants: +39.0%; 95% CI, 27.9-50.0%). The prevalence of both psychotropic dispensing and psychotropic polypharmacy for children and adolescents were twice as high in 2021 as in 2013. The reasons and appropriateness of the marked increases in psychotropic dispensing during the COVID-19 pandemic, particularly to adolescent girls, should be investigated.

Objective: Little U.S. pharmacoepidemiologic study is based on treatment during continuous enrollment for periods more than a year. This study aims to show pediatric patterns of stimulant use (alone or with other psychotropic classes) from Medicaid administrative claims data for stimulant patterns of 3- to 8-year continuous enrollees. Methods: A retrospective cohort study was derived from Medicaid enrollment, pharmacy, and diagnosis claims data (2007-2014) in a mid-Atlantic state. Youth aged 2-17 years with 3-8 years of continuous enrollment treated with stimulants were compared with a date-matched comparison group treated without stimulants. Major outcomes include prevalence and duration of stimulant use and patterns of stimulant polypharmacy across relatively long enrollments (3-8 years). Results: Among 264,518 unique 2- to 17-year olds with 3-8 years of continuous enrollment, 16.5% had stimulant prescription dispensings, doubling the annual national prevalence of 8.1%. Subgroup analysis showed that the highest prevalence of stimulant use was for 6- to 11-year olds (20.4%), foster care eligible youth (42.3%), and those with 7-8 years of continuous enrollment (20.1%). Externalizing psychiatric disorders were far more common in those treated with stimulants than in those treated without stimulants. The duration of stimulant exposure overall was a median of 487 days, half that of foster care stimulant users. Stimulant polypharmacy with two or more psychotropic classes concomitantly characterized 29.8% of stimulant users. Among those with three or four or more class polypharmacy, 85% and 88%, respectively, had concomitant stimulant and antipsychotic use. The adjusted odds ratio (AOR) of three or more class polypharmacy significantly increased in 12- to 17-year-old age group (AOR = 1.8), foster care eligibility (AOR = 4.5), and among those with the longest enrollment (AOR = 1.7). Conclusions and Relevance: Stimulant prevalence in Medicaid-insured youth with continuous enrollment of 3-8 years was twice as common as in annual data sets. Future research should investigate three to five interclass stimulant polypharmacy effectiveness in reliably diagnosed community populations.

Objective: Pharmacoepidemiologic research shows increasing use of polypharmacy to manage behavioral treatment of youth. Methods to increase precision, for example, competing risk analysis, to capture psychotropic patterns of concomitant stimulant treatment changes over time have not been explored. Methods: A retrospective cohort study was derived from Medicaid enrollment data, prescription drug, and clinician-reported diagnosis claims data from 2007 to 2014. Youths aged 2-17 years with 1-7.5 years of continuous enrollment who were new users of stimulants were followed. Major outcomes include detailed changes of concomitant use according to the number of psychotropic classes (NPC); competing risk assessment of patient factors according to NPC; and time factors related to changes in NPC. Results: Among 30,294 new stimulant users, 75.5% remained on stimulant monotherapy and 24.5% had stimulant concomitant regimens. Among the latter, great flux was observed, revealing exposure to combinations changed substantially across time. As a proportion of all changes, retention of the maximum NPC was observed for 65.3% of 2 concomitant classes, 56.2% of 3 concomitant classes, and 57.1% and 56.2% of 4 and 5 concomitant classes, respectively. Median duration according to NPC showed a linear decrease in time from 223 days for 2 classes, 172 days for 3 classes, 141 days for 4 classes, and 113 days for 5 classes combinations. By contrast, the path to maximum NPC regimens took median times of 491-833 days as NPC increased from 2 to 4 concomitant classes. Competing risk analysis demonstrated significantly increased hazard ratios according to the number of concomitant classes for 12-17-year-olds, patients with foster care or disability coverage, and those with 3-4 years of continuous enrollment. Conclusions: Detailed NPC changes illustrate great flux in concomitant stimulant patterns among Medicaid-insured youth. Competing risk analysis brings more precise patient characteristics risk information to assess NPC changes compared with a binary model.

Psychotropic medications (e.g., antidepressants, anxiolytics, and neuroleptics) are increasingly prescribed with two or more taken concurrently (polypharmacy), and have been associated with an increased risk of falling. The aim of this study was to examine the association between psychotropic medication use and balance impairment using an objective balance measure. We derived data from participants aged 40years and older in the US National Health and Nutrition Examination Survey (1999/00-2003/04) who completed the Modified Clinical Trial of Sensory Interaction and Balance and indicated current medications (n = 3090). Balance impairment was defined as failing the Modified Clinical Trial of Sensory Interaction and Balance condition4 (standing on foam surface, eyes closed). Medication use included specific psychotropic classes, a count of psychotropic medications, and a count of non-psychotropic medications taken concurrently. Nested multiple logistic regression assessed relationships between medication use and balance impairment, adjusting for covariates and complex sampling. One third of participants had balance impairment. After accounting for medical comorbidities, there was no relationship between individual classes of psychotropic medications and balance impairment. After adjusting for all covariates, there was a dose-response relationship between the number of psychotropic medications taken and balance impairment, with every additional medication associated with a 35% higher odds (odds ratio = 1.35; 95% confidence interval 1.07-1.70). In comparison, there was no increase in the odds of balance impairment associated with each additional medication taken for participants only taking non-psychotropic medications. Psychotropic medication polypharmacy is associated with an increased odds of balance impairment. Clinicians should exercise caution when prescribing combinations of psychotropic medications, and refer to physical therapy for assessment and treatment if balance impairment is detected.