ADHD Medication and Predictors of Treatment Outcome

NCT ID: NCT02136147

Last Updated: 2023-10-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 632 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2022-06-30

Brief Summary

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.

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.

Conditions

Attention Deficit Disorder With Hyperactivity (ADHD)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

methylphenidate medication

Intervention Type: DRUG

atomoxetine medication

Intervention Type: DRUG

lisdexamphetamine medication

Intervention Type: DRUG

guanfacine medication

Intervention Type: DRUG

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.

lisdexamphetamine medication

Intervention Type: DRUG

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.

atomoxetine medication

Intervention Type: DRUG

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.

methylphenidate medication

Intervention Type: DRUG

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.

guanfacine medication

Intervention Type: DRUG

Interventions

methylphenidate medication

Intervention Type: DRUG

atomoxetine medication

Intervention Type: DRUG

lisdexamphetamine medication

Intervention Type: DRUG

guanfacine medication

Intervention Type: DRUG

Other Intervention Names

N06BA04; Concerta; Ritalin; Equasym; Medikinet; N06BA09; Strattera; N06BA12; Elvanse; C02AC02; Intuniv

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Linda Halldner Henriksson

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Division for Child and Adolescent Psychiatry in Stockholm

Stockholm, Stockholm County, Sweden

Countries

Sweden

References

Lilja MM, Lichtenstein P, Serlachius E, Bhagia J, Malmberg K, Malm C, Lenhard F, Halldner L. Can response to ADHD medication be predicted? Eur Child Adolesc Psychiatry. 2025 Aug;34(8):2431-2442. doi: 10.1007/s00787-025-02650-8. Epub 2025 Jan 29.

Reference Type: DERIVED

PMID: 39875602 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35249540 (View on PubMed)

Other Identifiers

LS 1110-1339

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SLS-309701

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ADAPT

Identifier Type: -

Identifier Source: org_study_id