Investigating the effects of methylphenidate on adult ADHD and mood disorders using EEG and MRI

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

This study is testing if the medication methylphenidate can help adults with ADHD and mood disorders improve their attention and brain activity compared to those without these conditions.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: University Hospital, Strasbourg, France (other)
• Locations: 1 site (Strasbourg)
• Trial ID: NCT05832489 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to explore the effects of methylphenidate on adults with Attention Deficit Hyperactivity Disorder (ADHD) and those with ADHD associated with mood disorders. It employs a randomized, controlled, double-blind, cross-over design involving three groups: adults with pure ADHD, adults with ADHD and mood disorders, and healthy controls. Participants will undergo neuropsychological assessments and imaging sessions using MRI and EEG to evaluate attentional symptoms and brain activity before and after treatment with methylphenidate or placebo. The study seeks to clarify the impact of methylphenidate on cognitive functions in these populations.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 60 diagnosed with ADHD, either with or without associated mood disorders.

Not a fit: Patients with ADHD who do not have any mood disorders or those outside the age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for adults with ADHD and co-occurring mood disorders.

How similar studies have performed: Previous studies have shown promising results in using pharmacological interventions for ADHD, but this specific approach combining EEG and MRI with methylphenidate is relatively novel.

Eligibility criteria

Inclusion criteria common to all groups:

* 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)

Inclusion criteria for Group A: ADHD patients without associated mood disorder (ADHD-P)

* 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

Inclusion criteria for Group B: Patients with attention deficit disorder due to/accentuated by mood disorders (ADHD-MD)

* 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

Inclusion criteria for Group C: healthy subjects control

\- Subject with no psychiatric or neurological history

Exclusion criteria common to all groups

* Subjects with contraindication to methylphenidate :

  * hypersensitivity to the active substance,
  * glaucoma,
  * pheochromocytoma,
  * treatment with other indirect sympathomimetics or alpha sympathomimetics (oral and/or nasal routes), irreversible MAOIs
  * Hyperthyroidism or thyrotoxicosis,
  * Pre-existing cardiovascular disorders including severe hypertension, heart failure, occlusive arterial disease, angina pectoris, congenital heart disease with hemodynamic impact, cardiomyopathy, myocardial infarction, arrhythmias and potentially life-threatening ductopathies (disorders caused by ion channel dysfunction),
  * Pre-existing cerebrovascular disorders, brain aneurysms, vascular abnormalities including vasculitis or stroke,
  * wheat allergy (other than celiac disease)
* Diagnosis or history of severe depression, anorexia nervosa or anorexic disorder, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic or borderline personality disorder.
* Diagnosis or history of episodic and severe (type 1) (and poorly controlled) bipolar (affective) disorder.
* Subjectis with contraindication to performing an MRI: presence of non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump, vascular clip or stent, heart valve or ventricular shunt
* History that may affect brain anatomy or be related to an abnormality (neonatal suffering, neurosurgical operation, comitiality, stroke, head injury with unconsciousness of more than 15 minutes and mental retardation)
* History that may affect brain function (general anaesthesia or ECT within 3 months prior to inclusion)
* Substance Use Disorder as per DSM-5 criteria (except tobacco)
* Pregnant women or, in women of childbearing age and ability (non-sterile), lack of effective contraception
* Breastfeeding women
* Severe or unstable somatic pathology.
* Subject deprived of liberty, or in care under restraint
* Subject under safeguard of justice
* Incompetent subject (subject to a legal protection measure: curatorship, guardianship, future protection mandate, family habilitation)
* Impossibility to give informed information about the subject (subject in an emergency situation, difficulties in understanding the subject, ...)
* Subject in exclusion period defined by another protocol in progress

Exclusion criteria for Group A: ADHD patients without associated mood disorder (ADHD-P)

* Current Mood Disorder
* History of bipolar disorder in a first-degree relative
* Taking unauthorized psychotropic drugs: all antidepressants, antipsychotics, sedative antihistamines, regular hypnotics, benzodiazepines in unstable doses.

Exclusion criteria for Group B: Patients with attention deficit disorder due to/accentuated by mood disorders (ADHD-MD)

* Acute phase of mood disorder defined by scores a depression score in the QIDS-16SC ≥ 6 and a mania score in the YRMS ≥ 6. NB: for ISQ item 10 (concentration/decision making, score decision making only).
* Use of unauthorized psychotropic drugs including antipsychotics, sedative antihistamines, high-dose IRSNa (\>150mg/d venlafaxine and \>60mg/d duloxetine), MAOIs, tricyclic antidepressants, benzodiazepines in unstable doses.

Where this trial is running

Strasbourg

• Service de Psychiatrie 2, Hôpitaux Universitaires de Strasbourg — Strasbourg, France (RECRUITING)

Study contacts

• Principal investigator: Sébastien WEIBEL, MD — Hôpitaux Universitaires de Strasbourg
• Study coordinator: Sébastien WEIBEL, MD

Conditions: Adult ADHD, Adult-onset ADHD With Mood Disorder, Sustained attention, fMRI, EEG, Pharmacoimaging, Methylphenidate