Methylphenidate effects in the young brain: friend or foe?

Abstract

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH) is a first-line stimulant drug available worldwide for its treatment. Despite the proven therapeutic efficacy, concerns have been raised regarding the possible consequences of chronic MPH exposure during childhood and adolescence. Disturbances in the neurodevelopment at these crucial stages are major concerns given the unknown future life consequences. This review is focused on the long-term adverse effects of MPH to the brain biochemistry. Reports conducted with young and/or adolescent animals and studies with humans are reviewed in the context of long-term consequences after early life-exposure. MPH pharmacokinetics is also reviewed as there are differences among laboratory animals and humans that may be relevant to extrapolate the findings. Studies reveal that exposure to MPH in laboratory animals during young and/or adolescent ages can impact the brain, but the outcomes are dependent on MPH dose, treatment period, and animal's age. Importantly, the female sex is largely overlooked in both animal and human studies. Unfortunately, human reports that evaluate adults following adolescent or child exposure to MPH are very scarce. In general, human data indicates that MPH is generally safe, although it can promote several brain changes in early ages. Even so, there is a lack of long course patient evaluation to clearly establish whether MPH-induced changes are friendly or foe to the brain and more human studies are needed to assess the adult brain changes that arise from early MPH treatment.

Unraveling Individual Differences In The HIV-1 Transgenic Rat: Therapeutic Efficacy Of Methylphenidate

“…The natural heterogeneity in the HIV-1 transgene was assessed in ovariectomized female Fischer (F344/N; Harlan Laboratories Inc., Indianapolis, IN) rats (HIV-1 Tg, n = 19; control, n = 20) by examining the potential therapeutic efficacy of MPH. Given the prevalence of HIV-1 seropositive women worldwide, accounting for approximately 51% of all HIV-1 seropositive individuals 42 , and the underrepresentation of the female sex in clinical and preclinical assessments of MPH 43 , female animals were evaluated in the present study. All animals were pair- or group-housed throughout the duration of the experiment.…”

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

“…It is well-known that MPH is one of the first-line drugs for the treatment of ADHD but despite its relatively high effect sizes in ADHD children (0.8-1.0 for hyperactivity and 0.6-0.8 for attention deficit) 68 , its acute and chronic effects are still unclear and of continuous concern 69,70 . However, no conclusive evidence supporting or dismissing short-and long-term negative effects of MPH has been reported up to this date.…”

Attention-Deficit and Hyperactivity Disorder: A Disorder or a Fraud?

“…A drug such as methylphenidate® is widely misused by children and adolescents who do not meet the full diagnostic criteria for ADHD (Akay et al, 2006;Dafny & Yang, 2006;Gonçalves, Baptista, & Silva, 2014;Loureiro-Vieira, Costa, de Lourdes Bastos, Carvalho, & Capela, 2017). 90% of these 4.5 million kids do not have an abnormal DA metabolism (Kagan, 2009).…”