ADHD Medication and Predictors of Treatment Outcome
Condition: Attention Deficit Disorder With Hyperactivity (ADHD)
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational [Patient Registry]

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.
    

Intervention name(s): methylphenidate medication; atomoxetine medication; lisdexamphetamine medication; guanfacine medication
Intervention type(s): Drug; Drug; Drug; Drug
Other intervention name(s): N06BA04; Concerta; Ritalin; Equasym; Medikinet; N06BA09; Strattera; N06BA12; Elvanse; C02AC02; Intuniv
Intervention MeSH terms: Guanfacine; Methylphenidate; Lisdexamfetamine Dimesylate; Atomoxetine Hydrochloride
Observational model: Cohort
Time perspective: Prospective
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
      
Biospecimen description: 
      Saliva
    
Keywords: Attention Deficit Disorder with Hyperactivity; Neuropsychiatry; Drug therapy; Pharmacogenetics; Child Psychiatry