The Nurse Is Reviewing the Use of Central Nervous System Stimulants
Changes in medical use of central nervous system stimulants amid US adults, 2013 and 2018: a cantankerous-sectional study
Abstract
Objective To assess the 5-twelvemonth changes in the adult medical use of central nervous organisation (CNS) stimulants with higher gamble of dependence and evaluate the population characteristics of users and their medical and/or neurological conditions.
Design Cross-sectional study.
Setting Almanac US Medical Expenditure Panel Survey, a stratified random sample of approximately xxx 000 persons designed to produce national population estimates. It focuses on reported medical spending, medical services used, health status and prescription medications.
Participants Adults historic period 19 years and older who reported obtaining i or more prescriptions for amphetamine or methylphenidate products during two survey years, 2013 and 2018.
Main outcomes measures Prescriptions obtained, the specific stimulant product and annual treatment days of drug supplied.
Results In 2018, an estimated 4.ane million U.s. adults (95% CI 3.4 million to 4.viii million) reported prescriptions for CNS stimulants, having filled a mean of vii.3 (95% CI 6.8 to vii.eight) prescriptions with a mean of 226 (95% CI 210 to 242) days' supply. Compared with 2013, the estimated number of adults reporting using CNS stimulants in 2018 increased by 1.eight million (95% CI i.0 1000000 to two.7 million) or 79.8%. Nigh 2018 developed stimulant users reported taking psychoactive medication for one or more mental, behavioural or neurodevelopment disorders. Overall, 77.viii% (95% CI 72.half dozen% to 83.0%) reported some medication for adult attention arrears disorder, 26.8% (95% CI 22.2% to 31.5%) took medication for feet, 25.1% (95% CI 19.ix% to xxx.iii%) for depression and 15.3% (95% CI 9.8% to 20.8%) indicated drug treatment for other mental or neurological disorders. Adult CNS stimulant use was higher in females, in younger age cohorts and amongst individuals of white race/ethnicity.
Conclusions Developed medical apply of prescription stimulants increased markedly in 5 years and occurred in a population often reporting multiple mental or neurological disorders. Further action is needed to understand and manage this new resurgence in drugs with high risks of dependence.
- epidemiology
- health policy
- neurology
- mental health
- adult psychiatry
Data availability argument
Data are bachelor in a public, open admission repository. The data for this report are publicly available for research use from the US Agency for Healthcare Research and Quality. https://www.meps.ahrq.gov/mepsweb/
http://creativecommons.org/licenses/past-nc/4.0/
This is an open admission article distributed in accordance with the Artistic Eatables Attribution Not Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, advisable credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/past-nc/iv.0/.
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- epidemiology
- health policy
- neurology
- mental health
- adult psychiatry
Strengths and limitations of this written report
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This assay of adult utilise of prescription amphetamine and methylphenidate stimulants is based on the largest publicly available annual US health survey conducted annually since 1996.
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While the utilisation of these stimulant drug products in 2013 and 2018 was cocky-reported in an annual household survey, the prescription detail was confirmed in chemist's shop records.
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The annual, federally funded survey was designed to support wellness policy assay; its multistage probability design supports population estimates and CIs for the entire US population.
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With an overall survey random sample of approximately 30 000 households and 325 000 dispensed prescriptions for each yr, the number of cases indicating the written report drug products was modest.
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Given stimulant drugs with a higher take a chance of psychological or physical dependence, also as risks of non-medical utilize, the self-reporting feature of this survey could result in underestimating actual exposure among adults.
Introduction
The central nervous system (CNS) stimulants amphetamine and methylphenidate are among the oldest synthetic psychoactive medications however in widespread clinical use. The amphetamine production Benzedrine was showtime marketed in 1933 for nasal congestion and in 1937 for depression and narcolepsy1; in 1954, the US Nutrient and Drug Administration (FDA) approved a methylphenidate product (Ritalin), which was marketed for low, senile behaviour, lethargy and narcolepsy.two
Amphetamine and methylphenidate are strong and structurally related sympathomimetic amines with therapeutic mechanisms that remain unclear but stimulate the release of dopamine and norepinephrine primarily through inhibition of neuronal reuptake.3 Currently, a large number of amphetamine products are licenced based on mixtures of various salts (saccharate, sulfate and aspartate), specific enantiomers (d-), extended release formulations and a prodrug. Methylphenidate has fewer chemic variants but is bachelor in immediate and extended release formulations, d-enantiomer salt mixtures and a transdermal patch. Multiple generics and brand name variants are available for both stimulants. Canonical and off-label uses of these two CNS stimulants take evolved over the many decades. Medical use for depression and weight loss declined in the 1950s and 1960s, and these indications were repealed over business organization virtually growing evidence of misuse and questions nigh effectiveness.ane Still, beginning in 1961, use in children expanded with FDA approving of indications for treating behavioural problems and after for attention deficit hyperactivity disorder (ADHD).4 For many years, new formulations were approved based on studies of ADHD in children. Starting in 2004, the FDA extended the ADHD indication to adults for some branded stimulants (Adderall XR, Concerta, Vyvanse) and in 2015 approved a rampage eating indication for lisdexamfetamine (Vyvanse).5–7 Throughout the decades since initial marketing, the two stimulant products were approved for narcolepsy, and during that fourth dimension, off-characterization use was observed among persons using them to increment alertness or seeking to achieve cognitive enhancement.eight
Amphetamine and methylphenidate have been long restricted globally because of addiction risks including a United Nations Convention on Psychotropic Substances and specific legal controls in many countries, including the Uk, Canada and Australia.9–12 In the USA, these stimulants are classified as Schedule Two Controlled Substances, those declared to accept 'a loftier potential for abuse which may lead to severe psychological or concrete dependence'.13 Other major Schedule II drugs include college authority opioids and the barbiturates. Restrictions for this highest risk class of licit psychoactive drugs include a Drug Enforcement Administration licence to prescribe, limitations on prescribed refills, monitoring at the country and federal levels and secure pharmacy storage measures to foreclose theft and diversion. In add-on to risks of misuse and dependence, other adverse events associated with these stimulants include serious cardiovascular reactions, seizures, tics, tremors, assailment, manic symptoms and psychosis.5–7 14 Given that the increased use of prescription opioids connected for many years earlier failing in response to numerous public wellness initiatives, nosotros examined the near recent trends in exposure to the other widely used group of Schedule II drugs: the CNS stimulants amphetamine and methylphenidate.
Methods
We extracted the data for this written report from the US Medical Expenditure Panel Survey (MEPS), a healthcare survey of individuals and households conducted annually since 1996 and published for research use by the Agency for Healthcare Research and Quality.15 To assess alter over v years, this written report analysed the 2013 and 2018 annual surveys. MEPS collects data from a nationally representative sample of approximately thirty 000 persons each year, and its multistage probability design supports estimates and variance of the US population. The confidentiality of personal identifying information is protected by federal police force and removed earlier survey data are released for public inquiry use.16 These deidentified public utilise information are exempt from review by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board.
Identification of medications
Population estimates of exposure to prescription drugs in MEPS brainstorm with the household survey questionnaire and are then expanded with more than detailed data collected from respondents' pharmacies.17 Each annual data release contains a prescribed medicines file with records for approximately 325 000 prescriptions and multiple fields identifying the drug prescription item. We used the following algorithm to standardise medications: if the record independent a National Drug Code (NDC), we matched it to the ingredient proper name in the National Library of Medicine RxNorm database18; for prescription records without an NDC, we used the Multum Lexicon medication proper name, which is defined as the generic name nearly ordinarily used by physicians.17 Medication names provided by respondents that were vague or described a class of drugs (eg, stimulants and antidepressants) were excluded. The outpatient medications identified by survey respondents were and so confirmed in pharmacy records, which besides provided additional item most each dispensed prescription for the survey yr.19
For this report, we identified persons reporting any employ of the following standardised generic medication names: amphetamine/dextroamphetamine, lisdexamfetamine, methylphenidate and dexmethylphenidate. Notably, lisdexamfetamine and dexmethylphenidate are newer make name drugs without generics. Amphetamine/dextroamphetamine and methylphenidate describe multiple generic products. The objective of analysing the two newer brand name products separately was to measure out any effects of marketing and promotion, as compared with generics. We excluded CNS stimulants that were not classified as Schedule II (eg, atomoxetine), or those with utilisation that was too exceptional to estimate in the MEPS information (prescription methamphetamine). The extent of each respondent's exposure was measured by calculating the number of prescriptions filled in the survey year and the total annual days' supply reported for these prescriptions. If the days' supply was missing for a prescription, we imputed the days' supply based on median days supply for that drug (eg, lisdexamfetamine) among respondents with non-missing values. For some analyses, we likewise combined the four products into these two groups: amphetamine and methylphenidate products.
This study population included all persons reporting that they were xix years of age or older as last ascertained during the survey year. Other assessed population characteristics included sexual activity, race/ethnicity, didactics and marital status. Among those reporting exposure to Schedule II CNS stimulants, we also analysed the mental health, neurological or developmental atmospheric condition for which respondents indicated one or more of the following: (1) they had the condition during the survey year; (2) they took a prescribed medication for the condition; and (3) they received medical treatment, defined as an function, outpatient, inpatient or emergency department visit. The mental wellness conditions analysed were identified by the following International Classification of Affliction, 10th Revision (ICD-10) codes: ADHD (F90), major depression (F32), feet (F40 and F41) and other neurological or mental conditions (all other ICD-10 codes in the 'F' series). The mental health condition information in the ICD-ten coding format was not available for the twelvemonth 2013, limiting this assay to the 2018 survey year data.
Statistical analysis
We estimated the exposed adult population totals, percentages and 95% CIs using the MEPS multistage probability design characteristics for the entire US population in accordance with the survey statistical methods documentation.xx Each survey observation included data on the sampling unit of measurement, the sampling stratum and the specific sample weight for each observation. Populations, variance and statistical significance inside survey years were estimated using Taylor serial linearisation. SEs and CIs were calculated based on the weighted estimates when available. A Z-test of two binomial proportions was used to compare the proportions beyond years. All analyses were performed using SAS V9.4 (SAS Institute) and were conducted from July to October 2020.
Public and patient interest
The public/patients were not involved in the blueprint, conduct or reporting of this study.
Results
Stimulant population characteristics
In 2018, an estimated 4.ane meg US adults (95% CI three.4 million to four.eight 1000000) reported that they had filled one or more prescriptions for the CNS stimulants amphetamine or methylphenidate. Population characteristics are shown in tabular array one. Employ of these prescription stimulants skewed towards the younger historic period cohorts, and the percentage reporting prescription employ was highest amongst those age 19–24 years— 3.2% (95% CI one.seven% to four.viii%)—and lowest among those age 65–85 years—0.5% (95% CI 0.3% to 0.vii%). Utilisation also varied substantially by race/ethnicity with 2.iii% (95% CI i.8% to 2.8%) of whites reporting use compared with 0.6% (95% CI 0.3% to i.0%) of blacks, a nearly fourfold difference. CNS stimulant use was also higher in those with education beyond loftier school and among those never married compared with those currently or previously married.
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Table 1
Adult demographic characteristics and population estimates, 2013 and 2018
CNS stimulant medication utilize
In 2018, US adults filled an estimated 30.2 million prescriptions (95% CI 27.9 one thousand thousand to 32.four million) for CNS stimulants. Medication detail is shown in table two. These adults filled a mean of vii.3 (95% CI 6.8 to 7.8) prescriptions during the survey year, which provided a mean of 226 (95% CI 210 to 242) days' supply. Amphetamine products were more widely used amidst adults than methylphenidate products, accounting for 78.nine% versus 21.ane% of the 2018 prescription volume.
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Table 2
Adult reported prescriptions for Schedule Two stimulants 2013 and 2018
Change in utilisation
Reported use of these CNS simulants increased during the v years from the 2013 to the 2018 annual MEPS survey. Survey-to-survey changes are shown in tabular array 3. The estimated number of adults increased from 2.3 million (95% CI ane.8 million to two.8 meg) in 2013 to 4.1 million (95% CI iii.4 million to iv.8 meg) in 2018. During that period, adult exposure increased by an estimated 1.8 million adults (t=four.35, p<0.01) or an increase of 79.eight%. Examined by sexual practice, the largest increase occurred among females, who deemed for 1.3 million of 1.8 million (72.one%) of the 5-yr growth (difference: t=5.39, p<0.01). Male person use increased by 0.5 million, a 38.nine% nominal increase that was not statistically significant (t=ane.86, p=0.063). Change in use by age was full-bodied in ii cohorts, age 25–44 years and historic period 45–64 years. Among those historic period 25–44 years, an additional 0.88 million (95% CI 0.39 meg to 1.37 million) reported stimulant use from 2013 to 2018 (t=3.55, p<0.01) or an increase of 85.2%. Amid those age 45–64 years, estimated stimulant use increased by 0.59 million (t=iii.81, p<0.01) or 100.7%. Amongst those in the youngest age cohort, historic period 19–24 years, the initial rate of utilisation in 2013 was the highest of any historic period group (3.2%), but the increases were smaller, a nominal increment of 33.four% that was not statistically pregnant (t=0.91, p=0.365). Meanwhile, the total adult US population was estimated to increase during the 5-twelvemonth period from 237.5 1000000 to 248.4 million, an increase of iv.half-dozen%.
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Tabular array 3
Changes in Schedule II CNS stimulant apply, 2013 and 2018
The growth in stimulant prescriptions was full-bodied in the amphetamine products, which were estimated to increase 119.2% from 10.9 million in 2013 to 23.8 million in 2018 (t=ten.46, p<0.01). Growth in use of methylphenidate products was slower, with an estimated 39.4% increment (t=2.27, p=0.023).
Medical weather condition
Stimulant users frequently reported taking medications for a variety of mental, neurological and developmental weather condition. The 2018 survey results are shown in table iv. Amidst those exposed to the stimulants, 77.8% (95% CI 72.6% TO 83.0%) indicated they took medication for ADHD, 26.8% (95% CI 22.2% to 31.5%) reported anxiety medication, 25.one% (95% CI 19.9% to xxx.three%) said they had taken drugs for depression and fifteen.three% (95% CI ix.eight% to 20.8%) indicated drug therapy for other mental or neurological atmospheric condition. Equally shown in table 4, similar percentages reported a medical visit for the reported status and/or indicated a medical condition, regardless of whether information technology was treated with drugs or a medical visit. Overall, forty.6% (95% CI 34.9% to 46.3%) of those reporting stimulant use indicated they were taking medication for anxiety, depression or both.
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Table iv
Adult Schedule Two stimulant users' mental, neurological atmospheric condition, 2018
Discussion
In this study, we have shown that United states of america adult exposure to prescription CNS stimulants with risk of dependence is substantial—an estimated 4.1 one thousand thousand adults in 2018—and has grown by approximately 80% over v years. The total number of prescriptions dispensed grew even faster, with an increase of approximately 96%. Medication and treatment for low, anxiety and other mental conditions were mutual. Those adults reporting stimulant employ represented a population that was younger, had higher educational attainment and was more than likely to be unmarried. While use remained more frequent in the youngest age cohort, the largest percent increases occurred in adults historic period 25 years and older.
The nearly frequently reported disorder was ADHD. These information ostend, and extend to more recent years, results of previous studies indicating increasing diagnosis and drug handling of adults for ADHD roofing time periods from 1999 to 2016.21–24 I study of adults with ADHD in a large integrated health organisation also reported high rates of comorbid depression and anxiety.21 Another study of ADHD diagnosis and treatment based on role visit data in an before v-year period (2008–2009 to 2012–2013) reported a 36.4% increase.24 Our analysis differs from these studies in that the primary focus was to assess the exposure to stimulant drugs for any medical purpose, given the varied off-label and on-label uses over many decades.
While we did not assess condom in this study, some patterns of use raise issues that warrant further investigation. Notably, given that amphetamine stimulants are reported to crusade anxiety in 10%–50% of patients and methylphenidate in 10%–xxx% (p. 323),25 we observed that anxiety was the second most frequently reported mental condition reported, bookkeeping for 31.2% of exposed adults. Combination therapy with antidepressants also warrants further investigation given that many antidepressant drugs are associated non only with adverse effects of anxiety and insomnia, just also dullness and flat affect (p. 410).iii None of the major antidepressants are FDA canonical for use in combination therapy with Schedule II stimulants.
Finally, the growing utilise of these stimulants should renew interest in updating, characterising and managing the risks of this drug form. In that location are 3 concerns warranting investigation. First, these data prove that apply of CNS stimulants is overwhelmingly in the long term, with a median of 226 days' supply. Second, the skew towards utilize in younger age groups raises the question of whether or when those prescribed stimulants for ADHD in childhood or boyhood should exist discontinued equally they grow older. 3rd, while the estimates are not comparable, the major government survey of drug use and mental health for 201826 reported that the total number of adults estimated to make non-medical use of CNS stimulants was higher that our total of adults with cocky-reported medical use. Other studies indicate widespread utilize in hopes of achieving cerebral enhancement.8
This written report as well has limitations. Although MEPS is the largest publicly available survey providing data on the US use of prescription drugs, our population estimates are derived from two random samples of pocket-sized size. A source of potential bias was that utilisation was cocky-reported and might underestimate true exposure because of possible non-medical use, poor recollection or beginning therapy office way through the survey year. Withal, most self-reported medications were confirmed in pharmacy records and additional detail about each prescription collected from pharmacy records. While a validation study of this consequence reported good understanding between cocky-reports and pharmacy records, the stimulant controlled substance drugs were not assessed in that study, and understanding could differ. During the period, the US adult population increased past 4.6%, which could contribute to increased utilise. While we could report the mental and neurological conditions such as ADHD and feet and whether medication was prescribed, we could non link these conditions to specific stimulant medications or combinations of medications. The intended medical purpose of various medications was further confounded because some widely used medications are indicated for multiple conditions (eg, paroxetine and sertraline are approved for both low and social feet disorder) and because it is uncertain whether combinations were used intentionally in off-label combinations, or unintentionally.
Conclusions
Developed reporting medical use of those stimulants with the highest take chances of misuse and dependence increased markedly in 5 years and occurred in a population oftentimes reporting multiple neurological or mental disorders. Given that the epidemic in use of prescription opioids continued for years before public wellness initiatives began to control use, agreement and managing this new resurgence in a class of drugs with a decades-long history of issues should be a public health priority. Physicians seeing patients who request prescriptions for these stimulants should assess with care the risks, benefits and medical demand.
Information availability statement
Information are available in a public, open access repository. The data for this study are publicly available for research employ from the US Agency for Healthcare Research and Quality. https://world wide web.meps.ahrq.gov/mepsweb/
Ethics statements
Ethics blessing
This study reports deidentified personal data protected past United states of america federal law and published for unrestricted public research utilise; institutional review lath approval is not required.
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Source: https://bmjopen.bmj.com/content/11/8/e048528