ADHD Medication and Predictors of Treatment Outcome (ADAPT)

Naturalistic Study of ADHD Medication and Predictors of Treatment Outcome

ADHD medication of children and adolescents is becoming increasingly common. Clinical experience and scientific studies have proven that approximately 30% of children/adolescents with ADHD do not benefit from this treatment. However, there is insufficient knowledge about who these children are. All children and adolescents, who start treatment with ADHD medication at public Child and Adolescent Psychiatry units in Stockholm, on Gotland, an in Västerbotten, will be asked to participate in the study. The investigators intend to monitor the patients´clinical symptoms and possible side-effects after treatment start. The investigators will collect background information and saliva samples from the patient and his/her parents to be able to study if there are any genetic (hereditary) or other markers that can predict positive or negative outcomes of the ADHD medication. With this information, the investigators aim at, to a greater extent, be able to individualize treatment choices for children and adolescents with ADHD without unnecessary, costly and possibly unfavorable treatment attempts.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Disorder With Hyperactivity (ADHD)
• Intervention / Treatment: Drug: methylphenidate medication; Drug: atomoxetine medication; Drug: lisdexamphetamine medication; Drug: guanfacine medication

Detailed Description

The specific aims for the ADAPT study are:

1. Investigate if certain gene polymorphisms are associated with poor effect of ADHD drugs (non-responders).
2. Investigate if other biologically, phenotypic or psychosocial factors are associated with poor effect of ADHD drugs (non-responders).
3. Investigate if the frequency of side-effects of ADHD drugs differs between children with different genotypes.
4. Investigate if the frequency of side-effects of ADHD drugs differs between children with different phenotypic and/or psychosocial factors

Method:

This study has a naturalistic design. The aim is to map all new treatments with ADHD drugs at all 13 public BUP units in Stockholm County, one BUP unit on Gotland, and three BUP units in Västerbotten Region. The participation means that medication is initiated as planned in normal clinical practice by the child´s ordinary physician, and beyond this only means a somewhat denser and more structured follow-up. In addition, the investigators will ask for saliva samples from the patient and his/her parents. The investigators aim at including at least 1000 individuals in total in the study.

Part of the data will be collected via the national Quality Register for ADHD Treatment Follow-up (BUSA), which has approved security procedures approved by the Swedish Data Inspection Board.

Case report forms are computerized and separate from the database registry for collected study data. The database and detailed variable lists are constructed in collaboration with professional database managers.

Standard Operation Procedures are designed in collaboration by project coordinator, study nurse and principal investigator, and may be revised after pilot phase.

Collected samples will be stored at KI biobank.

Data analysis:

1. To judge if the patient is a responder to ADHD drugs the SNAP-IV rating of ADHD symptoms (before and after medication start) is used. The patients who at 3 months have an at least 40% reduction in SNAP-IV score are reckoned "responders" and those who at the same time point have a less than 20% change in SNAP-IV score are reckoned "non-responders". Differences between the groups will be analyzed with logistic regression, with responder status as depending variable, and genotype and the other risk markers (biological, phenotypic, and psychosocial markers) as independent variables after correction for symptoms at baseline. Even a 50% drop-out rate will (i.e. 1000 out of estimated 2000 eligible individuals) give a 98% power to identify a 49% increase in non-responder proportion for a specific genotype.
2. Concomitantly, the outcome in side-effects, heart rate, blood pressure, weight (z-score) and length (z-score) will be analyzed with linear regression with the same independent variables.
3. The analyses are performed separately for each ADHD drug.
4. There are significantly more boys than girls (about 4:1) with ADHD. Given the sex difference in prevalence it is obvious to also include sex as a covariate in our analyses of treatment outcome.
5. Missing data will be treated according to the principles of complete case and multiple imputation.

• Study Type: Observational
• Enrollment (Actual): 632

Contacts and Locations

Study Locations

• Sweden
  • Stockholm County
    • Stockholm, Stockholm County, Sweden
      • Division for Child and Adolescent Psychiatry in Stockholm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All children/adolescents starting ADHD medication at the public child and adolescent psychiatry services in Stockholm and on Gotland

Description

Inclusion Criteria:

• Clinical diagnosis of ADHD
• Starting medication against ADHD symptoms with atomoxetine, methylphenidate, lisdexamphetamine, or guanfacine

Exclusion Criteria: Any medication against ADHD the last 3 months

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with ADHD medication; Identified responders and non-responders in children/adolescents starting medication for treatment of ADHD in public child and adolescent psychiatric services in Stockholm, on Gotland, and in Västerbotten.	Drug: methylphenidate medication; Other Names: Concerta; Ritalin; Medikinet; N06BA04; Equasym; Drug: atomoxetine medication; Other Names: Strattera; N06BA09; Drug: lisdexamphetamine medication; Other Names: N06BA12; Elvanse; Drug: guanfacine medication; Other Names: Intuniv; C02AC02
Lisdexamphetamine medication; Identified responders and non-responders in children/adolescents starting medication with lisdexamphetamine in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: lisdexamphetamine medication; Other Names: N06BA12; Elvanse
Atomoxetine medication; Identified responders and non-responders in children/adolescents starting medication with atomoxetine in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: atomoxetine medication; Other Names: Strattera; N06BA09
Methylphenidate medication; Identified responders and non-responders in children/adolescents starting medication with methylphenidate in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: methylphenidate medication; Other Names: Concerta; Ritalin; Medikinet; N06BA04; Equasym
Guanfacine medication; Identified responders and non-responders in children/adolescents starting medication with guanfacine in public child and adolescent psychiatric services in Stockholm and on Gotland.	Drug: guanfacine medication; Other Names: Intuniv; C02AC02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in SNAP-IV Teacher and Parent rating scale (Swanson, Nolan and Pelham ADHD Rating Scale)	ADHD symptoms	at 3 months follow-up
change in P-SEC (Pediatric Side Effects Checklist)	Side-effect measure	at 3 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in C-GAS (Children´s global assessment scale)	global functioning measure	at 12 months follow-up
change in CGI-S (Clinical Global Impression- of Severity)	disease severity	at 12 months follow-up
change in SNAP-IV Teacher and Parent rating scale	ADHD symptoms	at 1 month follow-up
change in SNAP-IV Teacher and Parent rating scale	ADHD symptoms	at 6 months follow-up
change in SNAP-IV Teacher and Parent rating scale	ADHD symptoms	at 12 months follow-up
change in P-SEC (Pediatric Side Effects Checklist)	side effect measure	at 1 month follow-up
change in P-SEC (Pediatric Side Effects Checklist)	side effect measure	at 6 months follow-up
change in P-SEC (Pediatric Side Effects Checklist)	side effect measure	at 12 months follow-up
change in Spence Children's Anxiety Scale (SCAS)	symptoms of anxiety	at 1 month follow-up
change in Spence Children's Anxiety Scale (SCAS)	symptoms of anxiety	at 3 months follow-up
change in Spence Children's Anxiety Scale (SCAS)	symptoms of anxiety	at 6 months follow-up
change in Spence Children's Anxiety Scale (SCAS)	symptoms of anxiety	at 12 months follow-up
change in heart rate		at 1 month follow-up
change in heart rate		at 3 months follow-up
change in heart rate		at 6 months follow-up
change in heart rate		at 12 months follow-up
change in systolic blood pressure		at 1 month follow-up
change in systolic blood pressure		at 3 months follow-up
change in systolic blood pressure		at 6 months follow-up
change in systolic blood pressure		at 12 months follow-up
change in diastolic blood pressure		at 1 month follow-up
change in diastolic blood pressure		at 3 months follow-up
change in diastolic blood pressure		at 6 months follow-up
change in diastolic blood pressure		at 12 months follow-up
change in weight z-score		at 1 month follow-up
change in weight z-score		at 3 months follow-up
change in weight z-score		at 6 months follow-up
change in weight z-score		at 12 months follow-up
change in height z-score		at 6 months follow-up
change in height z-score		at 12 months follow-up
change in Autism Spectrum Screening Questionnaire (ASSQ) score	symptoms of autism	at 3 months follow-up
change in Autism Spectrum Screening Questionnaire (ASSQ) score	symptoms of autism	at 1 months follow-up
change in Autism Spectrum Screening Questionnaire (ASSQ) score	symptoms of autism	at 6 months follow-up
change in Autism Spectrum Screening Questionnaire (ASSQ) score	symptoms of autism	at 12 months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in self-harm frequency	change in self-harm frequency behavior as noted in the quality register BUSA	at 12 months follow-up
change in suicide attempt frequency	change in suicide attempt frequency as reported in quality register BUSA	at 12 months follow-up

Collaborators and Investigators

• Sponsor: Karolinska Institutet

Publications and helpful links

General Publications

• Lilja MM, Sandblom E, Lichtenstein P, Serlachius E, Hellner C, Bhagia J, Halldner L. The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort. J Neurodev Disord. 2022 Mar 6;14(1):17. doi: 10.1186/s11689-022-09424-2.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: April 30, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimated): May 12, 2014

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Drug therapy; Pharmacogenetics; Child Psychiatry; Neuropsychiatry; Attention Deficit Disorder with Hyperactivity
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Adrenergic Uptake Inhibitors; Methylphenidate; Lisdexamfetamine Dimesylate; Atomoxetine Hydrochloride; Guanfacine
• Other Study ID Numbers: ADAPT; LS 1110-1339 (Other Grant/Funding Number: ALF/PPG); SLS-309701 (Other Grant/Funding Number: Stiftelsen Söderström-Königska sjukhemmet)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED