Medical use and combination drug therapy among US adult users of central nervous system stimulants: a cross-sectional analysis
2
Citation
5
Reference
10
Related Paper
Citation Trend
Abstract:
Examine patterns of adult medical use of amphetamine and methylphenidate stimulant drugs, classified in the USA as Schedule II controlled substances with a high potential for psychological or physical dependence.Cross-sectional study.Prescription drug claims for US adults, age 19-64 years, included in a commercial insurance claims database with 9.1 million continuously enrolled adults from 1 October 2019, through 31 December 2020. Stimulant use was defined as adults filling one or more stimulant prescriptions during calendar 2020.The primary outcome was an outpatient prescription claim, service date and days' supply for central nervous system (CNS)-active drugs. Combination-2 was defined as 60 days or more of combination treatment with a Schedule II stimulant and one or more additional CNS-active drugs. Combination-3 therapy was defined as the addition of 2 or more additional CNS-active drugs. Using service date and days' supply, we examined the number of stimulant and other CNS-active drugs for each of the 366 days of 2020.Among 9 141 877 continuously enrolled adults, the study identified 276 223 individuals (3.0%) using Schedule II stimulants during 2020. They filled a median of 8 (IQR, 4-11) prescriptions for these stimulant drugs that provided 227 (IQR, 110-322) treatment days of exposure. Among this group, 125 781 (45.5%) combined use of one or more additional CNS active drugs for a median of 213 (IQR, 126-301) treatment days. Also, 66 996 (24.3%) stimulant users used two or more additional CNS-active drugs for a median of 182 (IQR, 108-276) days. Among stimulants users, 131 485 (47.6%) were exposed to an antidepressant, 85 166 (30.8%) filled prescriptions for anxiety/sedative/hypnotic medications and 54 035 (19.6%) received opioid prescriptions.A large proportion of adults using Schedule II stimulants are simultaneously exposed to one or more other CNS-active drugs, many with tolerance, withdrawal effects or potential for non-medical use. There are no approved indications and limited clinical trial testing of these multi-drug combinations, and discontinuation may be challenging.Keywords:
Stimulant
Cross-sectional study
Pharmacotherapy
An increasing debate exists about the potential of early exposure to methylphenidate to increase the risk for drug abuse. In addition, little is known about the neurobiological effects of early exposure to methylphenidate. This study was designed to investigate whether chronic treatment with methylphenidate induces behavioral sensitization to subsequent methylphenidate and D-amphetamine challenge in adolescent Wistar rats. Young Wistar rats (P25) were treated with either methylphenidate (1, 2, or 10 mg/kg, intraperitoneally) or saline for 28 days. After 14 days of washout, animals were challenged with methylphenidate 2.5 mg/kg intraperitoneally or D-amphetamine 2 mg/kg intraperitoneally (P67). Locomotor behavior was assessed using the open field test. Rats chronically treated with methylphenidate in the adolescent period showed augmented locomotor sensitization to D-amphetamine but not to methylphenidate in the adult phase. These findings suggest that early exposure do methylphenidate might increase the risk for subsequent D-amphetamine abuse. Further studies focusing on the neurobiological effects of early exposure to methylphenidate are warranted.
Behavioral sensitization
Cite
Citations (47)
Behavioral effects of stimulant drugs are influenced by non-pharmacological factors, including genetic variability and age. We examined acute and sensitized locomotor effects of methylphenidate in adolescent and early adult male Sprague Dawley (SD), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats using a drug regimen that differentiates clearly between initial and enduring differences in drug responsiveness. We probed for strain and age differences in the sensitizing effects of methylphenidate using a cocaine challenge. Methylphenidate was administered to the rats in a non-home environment. Strain differences in sensitivity to single methylphenidate injections depend on age and change with continuing drug pretreatment. While SHR rats are more sensitive to methylphenidate relative to WKY regardless of age and pretreatment day, SHR rats become more sensitive to methylphenidate than SD rats towards the end of pretreatment during early adulthood. SD rats exhibit greater sensitivity to methylphenidate relative to the WKY group during adolescence, an effect that dissipates with continued drug pretreatment during adulthood. Remarkably, only SHR rats, regardless of age, exhibit methylphenidate-induced cross-sensitization to the behavioral effects of cocaine. Our findings suggest that SHR rats are more vulnerable than other strains to methylphenidate-induced cross-sensitization to cocaine, at least when methylphenidate is administered in a non-home environment. Given that SHR rats are typically used to model features of attention deficit hyperactivity disorder, these findings may have important implications for the treatment of this disorder with methylphenidate.
Stimulant
Cite
Citations (9)
Stimulant
Cite
Citations (30)
Abstract Aim: Hyperactivity, impulsivity and poor attention are the core problems of ADHD and central stimulant medication is the preferred treatment. Many children with ADHD also display motor problems. The present study investigated the presence of motor problems in subjects who showed positive response to central stimulants on ADHD symptoms, compared with non‐responders. Method: This is a retrospective study of 73 children diagnosed ADHD, aged 5–17 years, who had been assessed with parts of the ‘Motor Function Neurological Assessment’ (MFNU) and evaluated with regard to effect of central stimulant medication. The sample was divided into two subgroups based on the responses to methylphenidate: Medicine responders and Non medicine responders. Results: Stimulant responders showed significantly more motor problems than the non‐responders on all sub‐tests and on the total problem score of the MFNU. Motor problems were present both in younger (age 5–10 years) and older (11–17 years) stimulant responders. There were no gender differences in motor performance. Conclusion: Our findings indicate that the probability of positive effect of central stimulants on core problems of ADHD is higher when motor problems are present in addition to ADHD symptoms, than when motor problems are absent.
Stimulant
Cite
Citations (25)
To examine treatment with psychostimulant medicines for attention deficit hyperactivity disorder (ADHD) in children (3–17 years) within Western Australia (WA) during 2004. Using whole‐population‐based administrative pharmacy data for 2004, age‐specific prevalence of children treated with dexamphetamine and methylphenidate was determined. Treatment with immediate‐action and sustained‐release stimulants was also examined. Average daily dose (absolute and relative to body weight) of dexamphetamine, methylphenidate and total stimulant medication was also calculated. 9,658 children from 3–17 years (23.5 per 1,000 child population) were treated with stimulant medication for ADHD during 2004. Age‐specific prevalence of treatment increased rapidly from three to eight years to peak at 14 years. The male‐to‐female ratio of stimulant treatment was 4.1. Child prevalence of treatment with dexamphetamine, methylphenidate or combined therapy was 16.4, 8.9 and 1.7 per 1,000 children, respectively. Most children were treated with immediate‐action stimulants (16.9 per 1,000 child population), with fewer using sustained‐release medicines (4.0 per 1,000 child population). The prevalence of stimulant medication use for the treatment of ADHD in WA children is 2.4%, with males accounting for the majority of treated patients. Most children were treated with dexamphetamine. Prescribing of methylphenidate, sustained‐release stimulants or combined medication therapy was less common. Age‐related trends in prescribed daily dose differed for dexamphetamine and methylphenidate.
Stimulant
Cite
Citations (25)
Stimulant
Medical record
Cite
Citations (20)
Purpose of review Public health concern regarding the nonmedical use of prescription stimulants among youth has generated the need for increased understanding of diversion, which is the illegal sharing and selling of prescription drugs. Although our understanding of nonmedical use of stimulants has increased, the same cannot be said of diversion behavior among youth. Recent findings The aim of this article is to use data from the National Monitoring of Adolescent Prescription Stimulants Study, which assessed prescription stimulant use among 10–18 years old across 10 US cities to report on prescription stimulant diversion among those who misused those medications. Findings indicate that more than one half (52%) of youth had engaged in one of the three forms of diversion (incoming only, outgoing only and both incoming and outgoing diversion). Engaging in incoming diversion only and both incoming and outgoing diversion increased with age and nonmedical use of prescription stimulants. All forms of diversion increased with marijuana use and among 16–18 years old with a friend's use of prescription stimulant. Summary Findings provide an understanding of the subtypes of diversion and risk correlates of youth prescription stimulant diverter's that has value in preventing prescription stimulant diversion.
Stimulant
Cite
Citations (21)
Abuse liability
Stimulant
Conditioned place preference
Psychological dependence
Attention deficits
Drugs of abuse
Cite
Citations (35)
It has been suggested that exposure to stimulants alters the dopamine system and thus enhances sensitivity to stimulants and possibly other drugs. Sensitization has been induced experimentally in animals, especially in rats, and has been shown to be long-lasting. In addition, cross-sensitization across different compounds has been demonstrated. The animal data have raised concern that exposure to methylphenidate in childhood may enhance the risk for later abuse of stimulants and other drugs. We review the evidence bearing on sensitization in children treated with stimulants and followed into adulthood. None of four clinic-based studies found an excess of drug abuse in children previously treated with stimulants. A school-based longitudinal study obtained a relationship between early stimulant treatment and later drug use, without controlling for dinical confounds. The single prospective-controlled study of children who received placebo or methylphenidate does not support the sensitization hypothesis.
Stimulant
Drugs of abuse
Cite
Citations (4)
Objective: To assess, in hyperactive children: 1) relative efficacy of behavior therapy, methylphenidate, and their combination; 2) effects of methylphenidate withdrawal after combined treatment; and 3) normalization effects of the combination. Method: Eighty-nine children were randomly assigned to treatment for eight weeks. Children on the combined treatments were switched to a placebo, double-blind. Ratings from parents, teachers and clinicians, and school observations were obtained. Results: Parents and teachers viewed children on behavior therapy as improved, but objective observations did not document behavioral change. In contrast, methylphenidate and the combined treatment induced significant improvement in all measures of outcome. Methylphenidate and the combination treatments were significantly superior to behavior therapy. In a few instances, the combination, which normalized behavior, was superior to methylphenidate. Children switched to placebo deteriorated significantly. Discussion: Behavior therapy delivered in school and home is not nearly as effective as methylphenidate for ADHD, but may be a useful adjunct to methylphenidate.
Adjunct
Cite
Citations (131)