Disparate regulatory status of methylphenidate for adults with ADHD across Europe

Chappuy, Mathieu; Boulanger, Antoine; Nourredine, Mikaïl; Fourneret, Pierre; Rolland, Benjamin

doi:10.1016/s2215-0366(19)30482-1

Cited by 8 publications

(3 citation statements)

References 4 publications

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“…In addition, these two distinct profiles of subjects converge with another study on the databases of the French Health Insurance, which showed that patterns of use in adults are characterized by high quantities dispensed, high number of prescribers and pharmacies visited, and high number of concomitant dispensings of other psychoactive medications, whereas patterns of use in children are consistent with guidelines [16]. Interestingly, a third of the subjects of this cohort of incident users were adults, although prescription of methylphenidate for initiating a treatment of ADHD in adults is off‐label in France, as in several other countries [46]. Similarly, only a minority of adults was previously prescribed modafinil, although methylphenidate is indicated for the second‐line treatment of narcolepsy when modafinil lacked efficacy.…”

Section: Discussionmentioning

confidence: 97%

Doctor shopping for methylphenidate as a proxy for misuse and potential abuse in the 67 million inhabitants in France

Soeiro

Frauger

Pradel

et al. 2020

Fundamemntal Clinical Pharma

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Doctor shopping enables subjects to receive more than the prescribed dose out of any medical management, which suggests a search for high doses and makes doctor shopping a relevant proxy for misuse and potential abuse. Therefore, this study aimed to identify and characterize profiles of subjects with doctor‐shopping behavior for methylphenidate in the entire French population. This study is a cross‐sectional study of doctor‐shopping behavior for methylphenidate in France, in 2016, using the Système national des données de santé, and accounting for overlapping prescriptions. Subjects who obtained >840 mg by doctor shopping were defined as subjects with heavy doctor‐shopping behavior, and subjects who obtained >0 mg and ≤840 mg by doctor shopping were defined as subjects with light doctor‐shopping behavior. A total of 63 739 subjects were included, and received 339.6 kg of methylphenidate. Among them, 216 (0.3%) subjects had heavy doctor‐shopping behavior, and 313 (0.5%) subjects had light doctor‐shopping behavior. Compared with subjects with light doctor‐shopping behavior, subjects with heavy doctor‐shopping behavior were older (64% of 30‐ to 49‐year‐old subjects vs. 77% of ≤17‐year‐old subjects; P < 0.001), received more concomitant dispensings of antipsychotics (37% vs. 26%; P = 0.008) and opioid maintenance treatments (50% vs. 6%; P < 0.001), and had more prescribers (4 [IQR = 2‐5] vs. 2 [IQR = 2–3]; P < 0.001). In the French context where prescription and dispensing of methylphenidate are highly regulated and methylphenidate is much less used than in other countries, these results are a warning signal to avoid trivializing methylphenidate in adults.

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Section: Discussionmentioning

confidence: 97%

Doctor shopping for methylphenidate as a proxy for misuse and potential abuse in the 67 million inhabitants in France

Soeiro

Frauger

Pradel

et al. 2020

Fundamemntal Clinical Pharma

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“…MPH is the first-line treatment for ADHD in children and adolescents according to the NICE and the German guidelines ( Banaschewski et al, 2018 ; Cortese et al, 2018 ). Safety and efficacy have also been demonstrated in adults with ADHD ( Castells et al, 2011 ; Cortese et al, 2018 ; Solmi et al, 2020 ), however, despite evidence based guidelines, only half of the European countries have approved the use of MPH for the management of adult ADHD ( Chappuy et al, 2020 ). In AD, MPH has been used as a treatment for apathy ( Ruthirakuhan et al, 2018 ; Kishi et al, 2020 ; Mintzer et al, 2021 ), and although it was shown to be a safe and efficacious medication, this use is still off-label.…”

Section: Methylphenidate In Attention-deficit Hyperactivity Disorder ...mentioning

confidence: 99%

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

et al. 2023

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder with the majority of patients classified as sporadic AD (sAD), in which etiopathogenesis remains unresolved. Though sAD is argued to be a polygenic disorder, apolipoprotein E (APOE) ε4, was found three decades ago to pose the strongest genetic risk for sAD. Currently, the only clinically approved disease-modifying drugs for AD are aducanumab (Aduhelm) and lecanemab (Leqembi). All other AD treatment options are purely symptomatic with modest benefits. Similarly, attention-deficit hyperactivity disorder (ADHD), is one of the most common neurodevelopmental mental disorders in children and adolescents, acknowledged to persist in adulthood in over 60% of the patients. Moreover, for ADHD whose etiopathogenesis is not completely understood, a large proportion of patients respond well to treatment (first-line psychostimulants, e.g., methylphenidate/MPH), however, no disease-modifying therapy exists. Interestingly, cognitive impairments, executive, and memory deficits seem to be common in ADHD, but also in early stages of mild cognitive impairment (MCI), and dementia, including sAD. Therefore, one of many hypotheses is that ADHD and sAD might have similar origins or that they intercalate with one another, as shown recently that ADHD may be considered a risk factor for sAD. Intriguingly, several overlaps have been shown between the two disorders, e.g., inflammatory activation, oxidative stress, glucose and insulin pathways, wingless-INT/mammalian target of rapamycin (Wnt/mTOR) signaling, and altered lipid metabolism. Indeed, Wnt/mTOR activities were found to be modified by MPH in several ADHD studies. Wnt/mTOR was also found to play a role in sAD and in animal models of the disorder. Moreover, MPH treatment in the MCI phase was shown to be successful for apathy including some improvement in cognition, according to a recent meta-analysis. In several AD animal models, ADHD-like behavioral phenotypes have been observed indicating a possible interconnection between ADHD and AD. In this concept paper, we will discuss the various evidence in human and animal models supporting the hypothesis in which ADHD might increase the risk for sAD, with common involvement of the Wnt/mTOR-pathway leading to lifespan alteration at the neuronal levels.

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“…Firstly the case selection for the study of long-acting methylphenidate indicated for adult patients with ADHD. From the very beginning, about two decades ago, this topic has been heavily debated and contested by various stakeholders [2,3]. Briefly summarized, the clinical evidence that methylphenidate may work in adult patients with ADHD has never been very convincing, for various reasons.…”

mentioning

confidence: 99%

Missing trials in drug regulatory dossiers may have good reasons, but should be predefined and transparent

Leufkens

2022

Journal of Clinical Epidemiology

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Disparate regulatory status of methylphenidate for adults with ADHD across Europe

Cited by 8 publications

References 4 publications

Doctor shopping for methylphenidate as a proxy for misuse and potential abuse in the 67 million inhabitants in France

Doctor shopping for methylphenidate as a proxy for misuse and potential abuse in the 67 million inhabitants in France

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

Missing trials in drug regulatory dossiers may have good reasons, but should be predefined and transparent

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