Association between single dose and longer-term clinical response to stimulants in ADHD: a systematic review of randomized controlled trials.: Single dose and long-term ADHD treatment response

Abstract

Objectives: stimulants, such as methylphenidate (MPH) and amphetamines, represent the first-line pharmacological option for Attention-deficit/hyperactivity disorder (ADHD). Randomized controlled trials (RCTs) have demonstrated beneficial effects at a group level but could not identify characteristics consistently associated with varying individual response. Thus, more individualized approaches are needed. Experimental studies have suggested that the neurobiological response to a single dose is indicative of longer-term response. It is unclear whether this also applies to clinical measures.

Methods: we carried out a systematic review of RCTs testing the association between the clinical response to a single dose of stimulants and longer-term improvement. Potentially suitable single-dose RCTs were identified from the MED-ADHD dataset, the European ADHD Guidelines Group (EAGG) RCT Dataset (https://med-adhd.org/), as updated on the 01/02/2024. Quality assessment was carried out using the Cochrane Risk of Bias (RoB) 2.0 tool.

Results: 63 single-dose RCTs (94% testing MPH, 85% in children) were identified. Among these, only one RCT tested the association between acute and longer-term clinical response. This showed that the clinical improvement after a single dose of MPH was significantly associated with symptom improvement after four-week MPH treatment in 46 children (89% males) with ADHD. The risk of bias was rated as moderate. A further RCT used near-infrared spectroscopy (NIRS), thus did not meet inclusion criteria, and reported an association between brain changes under a single dose and longer-term clinical response in 22 children (82% males) with ADHD. The remaining RCTs only reported single dose effects on neuropsychological, neuroimaging or neurophysiological measures.

Conclusion: this systematic review highlighted an important gap in the current knowledge. Investigating how acute and long-term response may be related can foster our understanding of stimulant mechanism of action and help develop stratification approaches for more tailored treatment strategies. Future studies need to investigate potential age and sex-related differences.

More information

Identifiers

ORCID for Valeria Parlatini: orcid.org/0000-0002-4754-2494

ORCID for Alessio Bellato: orcid.org/0000-0001-5330-6773

ORCID for Sulagna Roy: orcid.org/0009-0005-6824-7266

ORCID for Samuele Cortese: orcid.org/0000-0001-5877-8075

Catalogue record

Export record