Switching patterns of immediate-release forms of generic mixed amphetamine salts products among privately and publicly insured individuals aged 15-64 years in the United States, 2013-2019.

PURPOSE: Immediate-release forms of generic mixed amphetamine salts (MAS) have been the subject of passive surveillance reports signaling lack of effectiveness. We examined switching patterns that might suggest whether long-term users of specific MAS are more likely to switch away or switch back after use of the MAS of interest in the FDA's Sentinel Distributed Database. METHODS: We required at least 60-day continuous supply of selected MAS grouped by Abbreviated New Drug Application (ANDA) to describe patterns of switching away from and to generics approved under the ANDAs of interest among individuals ages 15-64 years with attention deficit hyperactivity disorder or narcolepsy during 2013-2019. RESULTS: We observed the greatest number of treatment episodes for ANDA 040422 (n = 525 771), followed by ANDA 202424 (n = 181 693), ANDA 040439 (n = 62 363), ANDA 040440 (n = 21 143), and ANDA 040480 (n = 8792). Of those with switches away from their original ANDA, episodes initiated on generic products under ANDA 040422 (48.6%) and ANDA 202424 (43.0%) were most likely to switch back, while those initiated on generic product under ANDA 040480 were least likely (24.1%). Of those episodes with switches to a generic under an ANDA of interest, about one-third (range 27.1% to 37.0%) switched back to the same product. These switches back had a median time to switch of about 30 days. CONCLUSIONS: These descriptive analyses, although subject to limitations, did not suggest increased switching away or switching back after use of the generics of interest. Continued post-marketing surveillance is warranted.

Trends in stimulant dispensing by age, sex, state of residence, and prescriber specialty - United States, 2014-2019.

BACKGROUND: Stimulant medications are commonly prescribed for the treatment of attention-deficit/hyperactivity disorder; however, they also have high potential for diversion and misuse. We estimated national stimulant dispensing trends from 2014 to 2019 and differences in dispensing by age, sex, state, prescriber specialty, payor type, patient copay, and stimulant type. METHODS: We calculated rates of stimulant dispensing using IQVIA National Prescription Audit (NPA) New to Brand, NPA Regional, and NPA Extended Insights data, which provide dispensing estimates from approximately 49,900 pharmacies representing 92 % of prescriptions dispensed in the United States. Average annual percent change (AAPC) from 2014 to 2019 was analyzed using Joinpoint regression. RESULTS: From 2014 to 2019, the national annual rate of stimulant dispensing increased significantly from 5.6 to 6.1 prescriptions per 100 persons. Rates differed by prescription stimulant type, with increases occurring among both amphetamine-type stimulants and long-acting stimulants. Rates among females (AAPC = 3.6 %; P = 0.001) and adults aged 20-39 years (AAPC=6.7 %; P = 0.002), 40-59 years (AAPC=9.7 %; P < 0.001), and ≥60 years (AAPC = 6.9 %; P = 0.001) increased significantly during the study period. Stimulant dispensing rates varied substantially across states, ranging from 1.0 per 100 in Hawaii to 13.6 per 100 in Alabama. CONCLUSIONS: National stimulant dispensing rates increased from 2014 to 2019, driven by notable increases among females and adults aged ≥20 years. These trends should be considered when prescribing stimulants given growing concerns over prescription stimulant diversion, misuse, and related health harms.

Psychosis with Methylphenidate or Amphetamine in Patients with ADHD.

BACKGROUND: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. METHODS: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases. RESULTS: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09). CONCLUSIONS: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).

Is adjunctive pharmacotherapy in attention-deficit/hyperactivity disorder cost-effective in Canada: a cost-effectiveness assessment of guanfacine extended-release as an adjunctive therapy to a long-acting stimulant for the treatment of ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada. METHOD: A Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles. RESULTS: Over a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11,845/QALY. Probabilistic sensitivity analysis (PSA) of GXR + stimulant showed that it remains a cost-effective strategy in 100 % of the simulations from both perspectives in numerous PSA and one-way sensitivity analyses, relative to a willingness to pay threshold of $50,000/QALY. CONCLUSIONS: This economic evaluation demonstrates that GXR + stimulant is cost-effective compared to stimulant alone in the treatment of children and adolescents with ADHD in Canada.

ADHD medication use, adherence, persistence and cost among Texas Medicaid children.

OBJECTIVES: (1) Describe ADHD medication use, adherence and persistence. (2) Determine factors (e.g., medication type, demographics, concomitant medication use) associated with ADHD medication adherence and persistence. (3) Compare ADHD medication costs. METHODS: Continuously enrolled Texas Medicaid children (3-18 years) with ≥ 2 ADHD prescription claims (July 2002-December 2008) were included. Prescription claims were grouped by medication type (i.e., immediate-release, extended-release, prodrug, non-stimulant); medication class (i.e., stimulant, non-stimulant); and duration of action (i.e., long-acting, short-acting). Adherence, using medication possession ratio, was measured continuously and dichotomously (80% cut-off). Persistence was days of continuous therapy without a 30-day gap and medication costs were reimbursement amount paid to dispensing pharmacies. RESULTS: The study sample (n = 62,789) was primarily 6-12 years (61.7%) and male (69.2%). The majority of the subjects were prescribed extended-release agents (70.3%), stimulant agents (86.4%), and long-acting agents (84.5%). Adherence and persistence (adherence mean ± SD; adherence dichotomous; persistence mean ± SD) varied among medication type and was highest for non-stimulants (52.5 ± 30.9; 25.8%; 153.3 ± 124.3), followed by extended-release stimulants (52.1 ± 30.2; 24.1%; 143.7 ± 120.8), prodrug stimulants (47.6 ± 30.9; 21.1%; 113.3 ± 100.5) and immediate-release stimulants (37.2 ± 27.1; 9.8%; 95.4 ± 92.6). Logistic regression showed immediate-release stimulant users were 67% less adherent than non-stimulant users (p < 0.0001) and linear regression showed immediate-release, extended-release and long-acting users (p < 0.0001) were significantly less persistent than non-stimulant users. Females, increase in total number of medications, and comorbid medications were associated with better adherence and persistence. Non-stimulant agents ($4.04 ± $2.15) had the highest mean medication cost per patient per day and immediate-release stimulants had the lowest ($1.24 ± $0.97). CONCLUSIONS: ADHD medication adherence and persistence was suboptimal. Although there was no difference in adherence between long-acting stimulant and non-stimulant users, non-stimulant users were more persistent compared to stimulant users. This study was limited due to the use of retrospective prescription claims data, which cannot capture actual patient use patterns, ICD-9 diagnoses, family history and support, or side effect profiles. Because ADHD can be effectively treated with pharmacotherapy, providers should be proactive in identifying patients with poor adherence and intervene to address barriers to medication adherence and persistence.

Stimulant adherence and academic performance in urban youth with attention-deficit/hyperactivity disorder.

OBJECTIVE: This analysis assessed whether stimulant adherence was associated with improvement in academic grade point average (GPA) among children diagnosed with and treated for attention-deficit/hyperactivity disorder (ADHD). METHOD: Medicaid claims were merged with academic records from Philadelphia public schools of Medicaid-eligible children in first through eighth grades who were diagnosed with ADHD and who had filled one or more stimulant prescription. Students diagnosed with mental retardation, autism, or speech, hearing, visual, or language impairments were excluded. Marking periods were scored for GPA (range: 0-4.0) based on English, mathematics, social studies, and science grades and for stimulant adherence (medication possession ratio ≥ 0.70). Random and fixed-effects models estimated the effects of stimulant adherence on GPA, between all adherent and nonadherent marking periods in aggregate and within individual student's marking periods, respectively. RESULTS: A total of 3,543 students contributed 29,992 marking periods, of which 18.6% were adherent. Mean GPA was significantly higher during stimulant-adherent (2.18) than stimulant-nonadherent (1.99) marking periods in aggregate (p < .0001). The regression coefficient representing within-student association between stimulant adherence and GPA over time was 0.108 (p < .0001), indicating that adherence was associated with a 0.108 increase in GPA. In stratified analyses, analogous coefficients were 0.106 for boys, 0.111 for girls, 0.078 for elementary students, and 0.118 for middle school students (all p < .0001). The association was stronger among students with (0.139) than without (0.088) comorbid disruptive behavior disorders (both p < .0001). CONCLUSIONS: Stimulant adherence, although found to be low among urban elementary and middle school students diagnosed with ADHD, was associated with a marginal improvement in GPA.

[Methylphenidate of retard forms in children and adolescents with ADHD - an overview]. / Methylphenidat-Retard-Präparate bei Kindern und Jugendlichen mit ADHs - eine Ubersicht.

As yet, stimulants remain the preferred means of treating attention-deficit/hyperactivity disorder (ADHD) pharmacologically. They are indicated when measures based on behavioural therapy or psychoeducation alone are not sufficient. How-ever, the period of effectiveness of immediate release stimulants is often not satisfactory. A variety of retarded forms of methylphenidate have now been developed and approved for the German market. This paper presents an overview of clinical studies on effectiveness, period of effectiveness and the profile of side effects of different forms stimulants available in Germany. In clinical practice, the new retard products represent effective alternatives. There is an advantage in administering this drug in a once-daily single dose. At the same time, the side effects that are caused by an extended period of effectiveness have to be studied in detail. A more precise adaptation to the daily obligations and needs of children and adolescents is needed. Possibly, a combination with unretareded MPH might lead to a better effect/side-effect profile.

The consequences of attention-deficit/hyperactivity disorder in adults.

Until recently, attention-deficit/hyperactivity disorder (ADHD) was a diagnosis reserved for children and adolescents as it was believed to dissipate before adulthood. New evidence, however, supports the persistence of ADHD beyond adolescence, and it is now recognized as a chronic neurobehavioral disorder in adults. Adults with ADHD have difficulties with school, work, family interactions, and social activities. Although treatments are available for adult ADHD, many patients never receive an accurate diagnosis that would afford them appropriate therapeutic intervention. If left untreated, adult ADHD can cause significant personal, social, and economic burdens that can have a negative impact on overall quality of life. This article discusses how ADHD presents in adults and the effects of the disorder on educational, occupational, interpersonal, and social functioning. Currently available treatments for ADHD in adults are also reviewed.