Safety and Efficacy of Mexidol® for ADHD in Children Aged 6-12 (MEGA)

A Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Trial in Three Parallel Groups to Evaluate the Effectiveness and Safety of Mexidol® Film-coated Tablets, 125 mg (LLC 'NPK PHARMASOFT', Russia) in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Children Aged 6-12 Years With Various Dosing Regimens (MEGA).

The primary objective of this study was to evaluate the efficacy and safety of Mexidol® film-coated tablets (125 mg) compared to a placebo in children aged 6 to 12 years with Attention Deficit Hyperactivity Disorder (ADHD). This multicenter, prospective, double-blind, randomized trial included 333 children who met the diagnostic criteria established by the International Classification of Diseases (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Participants received either Mexidol or placebo for 42 days, and various efficacy and safety parameters were assessed.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD); Anxiety Disorders and Symptoms
• Intervention / Treatment: Drug: Placebo; Drug: Mexidol + Placebo; Drug: Mexidol

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Kazan, Russian Federation, 420012
    • Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" Ministry of Health of the Russian Federation
  • Krasnodar, Russian Federation, 350007
    • State Budgetary Healthcare Institution "Specialized Clinical Psychiatric Hospital №1" of the Ministry of Health of the Krasnodar Territory
  • Krasnodar, Russian Federation, 350051
    • Limited Liability Company "Center for Professional Therapy"
  • Moscow, Russian Federation, 117997
    • Federal State Autonomous Educational Institution of Higher Education "Russian National Research Medical University named after N.I. Pirogov" Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 129344
    • State Budgetary Healthcare Institution of the City of Moscow "Scientific and Practical Center for Child Psychoneurology of the Moscow Department of Healthcare"
  • Nizhny Novgorod, Russian Federation, 603006
    • Limited Liability Company "NizhMedClinic"
  • Orenburg, Russian Federation, 460015
    • State Budgetary Healthcare Institution "Orenburg Regional Clinical Psychiatric Hospital №1"
  • Saint Petersburg, Russian Federation, 192148
    • Limited Liability Company "Medical Technologies"
  • Saratov, Russian Federation, 410005
    • Limited Liability Company "DNA Research Center"
  • Tver, Russian Federation, 170100
    • Federal State Budgetary Educational Institution of Higher Education "Tver State Medical University" Ministry of Health of the Russian Federation
  • Tyumen, Russian Federation, 625000
    • Federal State Budgetary Educational Institution of Higher Education "Tyumen State Medical University" Ministry of Health of the Russian Federation
  • Ulyanovsk, Russian Federation, 432026
    • State Healthcare Institution "Central Clinical Medical-Sanitary Unit named after Honored Doctor of Russia V.A. Egorov"
  • Yekaterinburg, Russian Federation, 620144
    • Limited Liability Company "European Medical Center 'UGMK-Health'"
  • Ural Region
    • Yekaterinburg, Ural Region, Russian Federation, 620075
      • State Autonomous Healthcare Institution of the Sverdlovsk Region "Multispecialty Clinical Medical Center 'Bonum'

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written informed consent for participation in the study from the patient's parents.
2. Patients - boys and girls aged 6 to 12 years, inclusive, at the time of signing the informed consent.
3. The child is raised by a father and/or mother.
4. The child is attending general education preschool or school institutions.

5. Diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) established in accordance with ICD-10 and DSM-5 criteria by a psychiatrist or neurologist, specifically:

   - According to DSM-5:

   1. Six or more symptoms of inattention persisting for at least 6 months and/or
   2. Six or more symptoms of hyperactivity and impulsivity persisting for at least 6 months

   3. Symptoms are present in at least two areas of functioning (in preschool or school and at home).

      - And/or according to ICD-10:

   4. Presence of at least 6 symptoms of inattention
   5. Presence of at least 3 symptoms of hyperactivity
   6. Presence of at least 1 symptom of impulsivity
   7. Persisting for at least 6 months.
6. Moderate severity of ADHD as determined by the Clinical Global Impression - Severity Scale for ADHD (CGI-ADHD-S), not requiring hospitalization for treatment.
7. No more than two comorbid disorders that do not require additional pharmacotherapy, in the investigator's opinion, during the study period.

Exclusion Criteria:

Individuals who exhibit at least one of the following characteristics were not included in the study:

1. Increased sensitivity to the active substance of the investigational drug (ethylmethylhydroxypyridine succinate) and/or other components of the drug.
2. Liver dysfunction: ALT and/or AST ≥2.5 times the upper limit of normal (ULN) based on screening lab results.
3. Kidney dysfunction: serum creatinine ≥1.5 times ULN based on screening lab results.
4. Intracranial pathology (including but not limited to: intracranial hemorrhage, tumors, infections, history of head trauma, excluding concussion).
5. Co-occurring autism spectrum disorders, Asperger syndrome.
6. Intellectual disability of any degree.
7. Other mental disorders, except for behavioral disorders (ICD-10 code F91).
8. Inability to discontinue psychotropic medications used for the treatment of ADHD.
9. Other somatic and/or neurological disorders requiring treatment with medications that may affect the efficacy of the investigational drug (including but not limited to: epilepsy, depression).
10. Use of nootropic, vasoactive medications, neuroprotectors, antioxidants, or metabolic agents within 7 days or 5 half-lives (whichever is longer) prior to randomization.
11. Presence of any oncological disease in the medical history within 5 years prior to the screening visit.
12. Participation in any other clinical study of drugs and/or medical devices within 3 months prior to the screening visit and/or 5 half-lives, whichever is longer.
13. Inability or unwillingness to comply with protocol requirements, including for physical, mental, or social reasons, in the opinion of the investigator.
14. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Main (Mexidol) + Control (Placebo); Participants received Mexidol 125 mg 1 tablet orally once a day and Mexidol Placebo matching Mexidol 125 mg 1 tablet orally once a day for 42 days.	Drug: Mexidol + Placebo; Combination of Mexidol and Placebo
Active Comparator: Main (Mexidol); Participants received Mexidol 125 mg 1 tablet orally twice a day for 42 days.	Drug: Mexidol; 125 mg tablets
Placebo Comparator: Control (Placebo); Participants received Mexidol Placebo matching Mexidol 125 mg 1 tablet orally twice a day for 42 days.	Drug: Placebo; Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Average Change in the Total Score Across the "Inattention" and "Hyperactivity/Impulsivity" Subscales of the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) After 6 Weeks of Therapy Compared to the Baseline Level.	The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder and oppositional defiant disorder symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores are calculated by summing the scores on the subset and dividing by the number of items in the subset. The main criterion for the treatment efficacy was the mean change in the total score on the "inattention" and "hyperactivity/impulsivity" subscales after 6 weeks of therapy. A conclusion of superiority of Mexidol over placebo can be made if the upper limit of the 95% confidence interval for the difference in mean changes is negative. 55 point scale: min value 0, max value 54, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change in the the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Inattention"	The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 28 point scale: min value 0, max value 27, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)
Average Change in the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Hyperactivity/Impulsivity"	The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 28 point scale: min value 0, max value 27, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)
Average Change in the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Oppositional Defiant Disorder"	The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 25 point scale: min value 0, max value 24, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)
Average Change in the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Connors Index"	The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 31 point scale: min value 0, max value 30, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)
Average Change in the Spence Children's Anxiety Scale - Parent Version (SCAS-Parent) Score	The Spence Children's Anxiety Scale - Parent Version (SCAS-Parent) is a 39-item parent report measure designed to assess anxiety symptoms in children. Built upon contemporary diagnostic frameworks, the SCAS-Parent evaluates six distinct domains of anxiety that align with clinical diagnostic categories. Each question on the test addresses the frequency of certain anxiety symptoms, measured on a 0-3 scale from "never", "sometimes", "often", to "always". SCAS-Parent scores consist of a total raw score (range from 0 to 114) and six sub-scale scores, with higher scores indicating greater severity of anxiety symptoms. 124 point scale: min value 0, max value 123, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)
Average Change in the Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Score	The Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) is an 18-question inventory used to aid in the diagnosis of attention deficit hyperactivity disorder (ADHD) in children. Each question measures the frequency of the behavior on a 0-3 scale from "rarely or never", "sometimes", "often", to "very often". The questionnaire is intended to be filled out by parents and teachers. Higher scores indicate greater severity of ADHD symptoms. 55 point scale: min value 0, max value 54, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)
Assessment Using the Clinical Global Impressions for Attention Deficit Hyperactivity Disorder Severity (CGI-ADHD-S) Scale	The Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) is a clinician-rated scale used to assess the severity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms. This tool is part of the Clinical Global Impressions (CGI) scales. It typically consists of a single item that rates the severity of ADHD on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). 7 point scale: min value 1, max value 7, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)
Assessment Using the Clinical Global Impressions Scale for Improvement (CGI-I)	The Clinical Global Impressions (CGI) Scale is a standardized assessment tool used to rate the severity of illness, change over time, and efficacy of medication. It consists of 3 subscales. The subscale Clinical Global Impression-Improvement (CGI-I) is a 7-point scale that assesses how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention, and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. 7 point scale: min value 1, max value 7, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (before treatment)
Assessment Using the Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS), Days	The Pediatric Migraine Disability Assessment questionnaire (PedMIDAS) is used to assess the impact of headaches on school performance (three questions), activities at home (one question on homework or chores), and social and/or sports functions (two questions). The PedMIDAS is scored by summing the answers across the six questions. The frequency and severity are not scored but can be used for clinical reference. PedMIDAS score range from 0 to 10 indicates little to none disability grade, score range from 11 to 30 indicates mild disability grade, score range from 31 to 50 indicates moderate disability grade and score range greater than 50 indicates severe disability grade. Min value 0, max value 240, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day1 = Randomization Visit)
Assessment Using the Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS), Headache Severity	The Pediatric Migraine Disability Assessment questionnaire (PedMIDAS) is used to assess the impact of headaches on school performance (three questions), activities at home (one question on homework or chores), and social and/or sports functions (two questions). The PedMIDAS is scored by summing the answers across the six questions. The frequency and severity are not scored but can be used for clinical reference. PedMIDAS score range from 0 to 10 indicates little to none disability grade, score range from 11 to 30 indicates mild disability grade, score range from 31 to 50 indicates moderate disability grade and score range greater than 50 indicates severe disability grade. Min value 0, max value 240, higher scores mean a worse outcome.	Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day1 = Randomization Visit)

Collaborators and Investigators

• Sponsor: Pharmasoft
• Investigators: Principal Investigator: Polina S. Nikiforova, MD, State Autonomous Healthcare Institution of the Sverdlovsk Region "Multispecialty Clinical Medical Center 'Bonum'; Principal Investigator: Nikolay N. Zavadenko, Dr.Med.Sci, Prof., Federal State Autonomous Educational Institution of Higher Education "Russian National Research Medical University named after N.I. Pirogov" Ministry of Health of the Russian Federation; Principal Investigator: Olga V. Khaletskaya, Dr.Med.Sci, Prof., Limited Liability Company "NizhMedClinic"; Principal Investigator: Elena V. Levitina, Dr.Med.Sci, Prof., Federal State Budgetary Educational Institution of Higher Education "Tyumen State Medical University" Ministry of Health of the Russian Federation,; Principal Investigator: Irina N. Vakula, MD, Limited Liability Company "Center for Professional Therapy"; Principal Investigator: Olga S. Panina, Cand.Med.Sci, MD, Limited Liability Company "DNA Research Center"; Principal Investigator: Dina D. Gainetdinova, Dr.Med.Sci, Prof., Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" Ministry of Health of the Russian Federation; Principal Investigator: Anna N. Platonova, Cand.Med.Sci, MD, State Budgetary Healthcare Institution of the City of Moscow "Scientific and Practical Center for Child Psychoneurology of the Moscow Department of Healthcare"; Principal Investigator: Yuliya O. Boychevskaya, MD, State Budgetary Healthcare Institution "Specialized Clinical Psychiatric Hospital №1" of the Ministry of Health of the Krasnodar Territory; Principal Investigator: Natalya E. Maksimova, Cand.Med.Sci, MD, Federal State Budgetary Educational Institution of Higher Education "Tver State Medical University" Ministry of Health of the Russian Federation; Principal Investigator: Elena M. Kryukova, MD, State Budgetary Healthcare Institution "Orenburg Regional Clinical Psychiatric Hospital №1"; Principal Investigator: Elmira S. Sagutdinova, Cand.Med.Sci, MD, Limited Liability Company "European Medical Center 'UGMK-Health'"; Principal Investigator: Anna S. Nezabudkina, MD, Limited Liability Company "Medical Technologies"; Principal Investigator: Viktor V. Mashin, Dr.Med.Sci, Prof., State Healthcare Institution "Central Clinical Medical-Sanitary Unit named after Honored Doctor of Russia V.A. Egorov"

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2019
• Primary Completion (Actual): July 13, 2020
• Study Completion (Actual): July 13, 2020

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): March 3, 2025

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: ADHD; anxiety; inattention; oppositional defiant disorder; hyperactivity; Neurodevelopmental disorders; Impulsive behavior; Mexidol; Hyperactive behavior
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Dyskinesias; Anxiety Disorders; Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Psychotropic Drugs; Antioxidants; Protective Agents; Emoxypine succinate
• Other Study ID Numbers: MexidolMEGA2020; PHS-ADHD-002-MEX-TAB (Other Identifier: Pharmasoft)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No