مقاله انگلیسی رایگان در مورد درمان اختلال کم توجهی-بیش فعالی در بزرگسالان – الزویر 2024

Abstract

To provide an overview of treatments in the pipeline for adults with attention-deficit/hyperactivity disorder (ADHD), we searched https://clinicaltrials.gov/and and https://www.clinicaltrialsregister.eu/ from 01/01/2010–10/18/2023 for ongoing or completed phase 2 or 3 randomised controlled trials (RCTs), assessing pharmacological or non-pharmacological interventions for adults with ADHD with no current regulatory approval. We found 90 eligible RCTs. Of these, 24 (27 %) reported results with statistical analysis for primary efficacy endpoints. While several pharmacological and non-pharmacological interventions had evidence of superiority compared to the control condition from a single RCT, centanafadine (norepinephrine, dopamine, and serotonin re-uptake inhibitor) was the only treatment with evidence of efficacy on ADHD core symptoms (small effect size=0.28–0.40) replicated in at least one additional RCT, alongside reasonable tolerability. Overall, the body of ongoing RCTs in adults with ADHD is insufficient, without any intervention on the horizon to match the efficacy of stimulant treatment or atomoxetine and with better tolerability profile. Additional effective and well tolerated treatments for adults with ADHD require development and testing.

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is characterised by developmentally inappropriate and impairing inattention plus hyperactivity and/or impulsivity (Faraone et al., 2024). ADHD is the most common neurodevelopmental disorder, affecting around 5 % of school-aged children worldwide according to a re-analysis of the Global Burden of Disease (GBD) data (Cortese et al., 2023) and 8 %, with an uneven gender distribution of 10 % for males and 5 % for females, based on an umbrella review including five systematic reviews and meta-analyses (57 unique primary studies) (Ayano et al., 2023).

Impairing symptoms of ADHD persist into adulthood in up to 75 % of the cases (Sibley et al., 2016), with an estimated prevalence of ADHD in adults at around 2.5 % (Song et al., 2021). ADHD is often comorbid with other disorders, including mood, anxiety, and substance use disorders, or dysfunctions, such as emotional dysregulation and executive dysfunction (Faraone et al., 2021), as well as physical disorders, including obesity and asthma (Arrondo et al., 2022).

Treatment options proposed for ADHD include pharmacological – encompassing stimulant and non-stimulant medications – and non-pharmacological interventions (Cortese, 2020). In currently available guidelines, pharmacotherapy plays an important role in the management of ADHD in adults. For instance, the 2018 (updated in 2019) National Institute for Healthcare and Excellence (NICE) guidelines (National Institute For Health and Care Excellence (NICE), 2019) suggested that medication (stimulants as first line, followed by the non-stimulant atomoxetine) should be offered after environmental modifications (such as reducing noise or distractions) have been implemented but ADHD symptoms are still impairing. Current medications for ADHD in adults are efficacious, albeit with lower effect sizes compared to children, especially in relation to stimulants for which effects sizes have been found to be high in children and medium in adults (Cortese et al., 2018). However, there are concerns around the safety of currently available ADHD medications, including their possible cardiovascular effects (Cortese and Fava, 2024) and limited abuse potential – even though the risk-benefit profile in general favours the use of medications, as recently highlighted by the ADDUCE project, a naturalistic, longitudinal, controlled study in 27 European child and adolescent mental health centres (e.g., Buitelaar et al., 2022). Therefore, there is a need for additional efficacious and safer medications for adults with ADHD.

Results

3.1. Overview of included RCTs
We initially identified 115 potentially eligible RCTs (Table S1). However, 25 of the RCTs of pharmacological treatments tested medications already approved for adults with ADHD for core symptoms of ADHD (Table S2), which will not be discussed further in the present article. Of the remaining 90 RCTs, around 27 % (n = 24) reported results with statistical analysis for primary efficacy endpoints; in the rest (73 %, n = 66), results with statistical analysis of significance were not reported/available (ongoing trials: 38 %, completed trials: 38 %, unknown status: 14 %, terminated: 4 %, not yet recruiting: 6 %).

Completed RCTs with positive results on at least one primary outcome (n = 26) and those with negative results on every primary outcome (n = 8) are reported in Table 1 (pharmacological treatment) and Table 2 (non-pharmacological treatment). When available, Tables 1–2 report also data on tolerability, in terms of percentage of participants who dropped out due to adverse events or those who experienced adverse events defined as serious by the study authors, in line with the above-mentioned FDA classification.