EEG-MRI Study of the Effect of Methylphenidate on Neural Mechanisms in Adult Patients With ADHD With or Without Mood Disorders: a Randomized Controlled Trial Versus Placebo
Attention Deficit Hyperactivity Disorder (ADHD) in adults is a common psychiatric disorder, with important consequences in terms of quality of life, mental health (associated disorders and poorer response to treatment), family life, risk of accidents; with a consequent cost for society. Adult ADHD is frequently associated with psychiatric co-morbidities, and notably associated with mood disorders (major depressive disorder or bipolar disorder) in about 50% of cases. The diagnosis of ADHD in adults is made in patients with an attentional complaint (pure ADHD or ADHD-P), but also very often in the management of a comorbid mood disorder (ADHD associated with mood disorder, or ADHD-MD). In this case, the ADHD had no impact during childhood and adolescence. Medication management is well established for ADHD-P, and medication is based on methylphenidate, which has a rapid and significant effect on attentional symptoms and impulsivity. However, in the case of ADHD-HD, there is little evidence of treatment efficacy and the mechanisms of action of methylphenidate at the brain level are poorly understood. The aim of the study is to determine the neural mechanisms of the effect of methylphenidate, using functional MRI and EEG, in ADHD-P and ADHD-HD patients, and to compare them to healthy subjects. A single dose allows us to observe effects that are then persistent with repeated doses. The aim is to determine, by means of a biomarker, whether methylphenidate treatment responds to the same mechanisms in the different groups and would be relevant in ADHD-P as in ADHD-HD. Main objective: To determine whether methylphenidate impacts differently on brain circuits associated with cognitive functions in the two clinical populations studied (adult ADHD patients and patients with post mood disorder attentional deficit) and in comparison to controls. Secondary objectives: 1. To determine the effect of methylphenidate on baseline brain flow in the two clinical populations and in controls (healthy subjects). 2. To determine whether methylphenidate has a different impact on cognitive performance in the two clinical populations studied and in comparison to controls (healthy subjects). 3. To confirm the effect of methylphenidate on the maintenance of cortical arousal. 4. To distinguish the brain networks impacted by methylphenidate (maintenance of attention or inhibition) with MRI and EEG.
• Subject (male or female) aged 18 to 60 years old
• Subject affiliated to a social protection health insurance scheme
• Subject capable of understanding the objectives and risks of the research and of providing dated and signed informed consent
• Subject having been informed of the results of the prior medical examination
• For a woman of childbearing age: negative blood pregnancy test and effective contraception throughout the study (intrauterine device, sterilization, estro-progestogen or progestogen per os, injectable or in the form of an implant or ring) and refusal to perform a pregnancy test before each MRI)
• Diagnosis of ADHD according to DSM-5 (in particular criterion B: presence of symptoms before the age of 12 years) NB: the diagnosis was not necessarily made at this age.
• Subject with or without methylphenidate treatment
• Association of ADHD symptoms with attentional disorders according to the combination of the following criteria :
• Diagnosis of Recurrent Depressive Disorder or Bipolar Disorder according to DSM-5
• Currently euthymic, i.e. a QIDS-16SC depression score \< 6 and a YRMS mania score \< 6, and clinically stabilized for at least 6 weeks prior to inclusion (stable and off-acute treatment). NB: for ISQ item 10 (concentration/decision making, score decision making only)
• DSM-5 Adult ADHD Criteria A (at least 5 symptoms of inattention and/or hyperactivity/impulsivity)
• Absence of Criterion D during childhood, adolescence and before mood disorders (i.e., no significant impact with reduced quality of social, academic or occupational functioning)
• Presence of Criterion D at present (symptoms have a significant impact with a reduction in the quality of social, academic or professional functioning)
• Subject with or without approved mood disorder treatment: Mood stabilizers (lithium, valproate, lamotrigine); antidepressants (SSRIs, IRSNa ≤60mg/j of venlafaxine and ≤60mg/j of duloxetine); benzodiazepines in stable doses for more than a month.
• Subject with or without methylphenidate treatment
⁃ \- Subject with no psychiatric or neurological history