Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE)

The aim of the ADDUCE project is to investigate any adverse effects of methylphenidate (trade name ritalin) on growth, neurological system, psychiatric states and cardiovascular system over a two year period in children and adults.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD)

Detailed Description

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children, affecting approximately 5% children in Europe. Methylphenidate (MPH, trade name ritalin) is the most-commonly prescribed medication for ADHD children; it is also increasingly used in ADHD adults. In 2007, the European Commission requested a referral to the Committee for Medicinal Products for Human Use (CHMP) under Article 31 of Directive 2001/83/EC, as amended, for MPH because of safety concerns. The CHMP concluded that study of the long-term effects of MPH on growth, sexual development, neurological system, psychiatric states and cardiovascular system is needed. In response to the CHMP s concerns, the ADDUCE (Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects) research team has been formed by a consortium of experts in the fields of ADHD, drug safety, neuro-psychopharmacology and cardiovascular research.

The ADDUCE project aims to investigate the long-term adverse effects of MPH on growth, neurological system, psychiatric states and cardiovascular system in children and adults.

Furthermore the ADDUCE team will develop research tools for the evaluation of adverse effects of MPH on cognition and motivation.

• Study Type: Observational
• Enrollment (Actual): 1398

Contacts and Locations

Study Locations

• Germany
  • Stadtkreis
    • Mannheim, Stadtkreis, Germany
      • Zentralinstitut fuer Seelische Gesundheit
• Hungary
  • Budapest, Hungary
    • Vadaskert Child and Adolescent Psychiatry Hospital and Outpatient Clinic
• Italy
  • Sardegna
    • Cagliari, Sardegna, Italy
      • Università degli Studi di Cagliari
• United Kingdom
  • Tayside
    • Dundee, Tayside, United Kingdom, DD1 9SY
      • University of Dundee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Attention Deficit Disorder clinic

Description

Inclusion Criteria:

ADHD-treated group:

• Clinical diagnosis of ADHD
• Aged between 5 and 17 years.
• Not previously treated with methylphenidate
• Agreement between clinician, patient and their family to commence on methylphenidate (baseline measures will be taken before first prescription of methylphenidate is issued).
• Any co-medication other than dexamfetamine or atomoxetine will be allowed.
• All psychiatric and physical illness comorbidities will be allowed

ADHD-unmedicated controls:

• Clinical diagnosis of ADHD not previously treated with medication.
• Aged between 5 and 17 years.
• Agreement between clinician, patient and their family not to treat with methylphenidate.
• Any medication other than dexamfetamine or atomoxetine will be allowed.
• All comorbidities will be allowed.

Non-ADHD controls:

• Child who does not have ADHD.
• Aged between 5 and 17 years.
• Mean total clinician rated Swanson Nolan and Pelham IV Rating scale (SNAP IV) score (ADHD items) < 1.5
• Parent rated Strengths and Difficulties Questionnaire (SDQ) Hyperactivity Score within normal range for country (e.g. < 6 for UK)
• Any current medication other than dexamfetamine or atomoxetine will be allowed.
• Must never have taken methylphenidate
• Any other mental health or physical illness diagnoses will be allowed.

Exclusion Criteria:

All Groups:

• Current or past treatment with dexamfetamine or atomoxetine.

Un-medicated ADHD controls:

• Previous or current treatment with methylphenidate.

Non-ADHD controls:

• Previous or current treatment with methylphenidate.
• Clinician rated SNAP score ≥ 1.5. Parent rated SDQ Hyperactivity Score in Borderline or Abnormal range.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
ADHD medicated; Children aged 5-17 years with clinical diagnosis of ADHD and not previously treated with methylphenidate who have an agreement with their physician to begin treatment with methylphenidate.
ADHD unmedicated controls; Children aged between 5-17 years with clinical diagnosis and not previously treated with methylphenidate who have an agreement with their physician NOT to treat with methylphenidate
Non-ADHD controls; Any child, including siblings of a child in either the ADHD-medicated or ADHD-unmedicated control group, who is 5-17 years old. These children must have a low rating (<1.5) on the clinician-rated Swanson Nolan and Pelham IV Rating scale (SNAP IV) and not be medicated with with either dexamfetamine or atomoxetine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The height velocity standard deviation score	Child's height velocity-mean height velocity for sex and age / Standard deviation of height velocity for sex and age.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in growth	Proportion height < 2nd centile, 0.4th centile (according to best available country specific norms); Weight (z-scores according to best available country specific norms); Proportion weight < 2nd centile, 0.4th centile (according to best available country specific norms); BMI (z-scores according to best available country specific norms); Proportion BMI < 2nd centile, 0.4th centile (according to best available country specific norms); Pubertal stage (Tanner stage); Bone age (selected sample from Italian cohort)	2 years
Changes to the cardiovascular system	Heart rate; Proportion heart rate > 120 bpm; Diastolic blood pressure; Proportion diastolic blood pressure > 90 mm/hg; Systolic blood pressure; Proportion systolic blood pressure > 95th centile	2 years
Effects on Psychiatric state	SNAP-IV mean scores; Clinical Global Impressions score(CGI; severity, improvement); Children's Global Assessment Scale score (CGAS); Strengths and Difficulties questionnaire (SDQ); Mood and Feelings Scale (parent and child ratings); Developmental and Wellbeing Assessment; DAWBA Rapidly changing mood section (proportion > cut off); DAWBA tics section (proportion > cut off); Columbia - Suicide Severity Rating Scale; Psychosis-like symptoms; Substance Use Questionnaire	2 years
Changes in neurological state	Child's Sleep Habits Questionnaire (CSHQ; total score and subscale scores, proportion > cut offs); Abnormal Involuntary Movement Scale (AIMS; total score, Q8 score)	2 years

Collaborators and Investigators

• Sponsor: NHS Tayside
• Collaborators: Zentralinstitut für Seelische Gesundheit Mannheim; Universita degli Studi di Cagliari; Vadaskert Child and Adolescent Psychiatric Hospital
• Investigators: Principal Investigator: David Coghill, ', University of Dundee

Publications and helpful links

General Publications

• Inglis SK, Carucci S, Garas P, Hage A, Banaschewski T, Buitelaar JK, Dittmann RW, Falissard B, Hollis C, Kovshoff H, Liddle E, McCarthy S, Nagy P, Neubert A, Rosenthal E, Sonuga-Barke E, Wong I, Zuddas A, Coghill DC; ADDUCE Consortium. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. BMJ Open. 2016 Apr 26;6(4):e010433. doi: 10.1136/bmjopen-2015-010433.

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): April 1, 2016

Study Registration Dates

• First Submitted: November 9, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (ESTIMATE): November 11, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 21, 2016
• Last Update Submitted That Met QC Criteria: September 20, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: methylphenidate; ritalin; Attention Deficit Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: 2011PW02