Clinical and Neuropsychological Predictors of Methylphenidate Response in Children and Adolescents with ADHD: A Naturalistic Follow-up Study in a Spanish Sample

María Vallejo-Valdivielso1, 3, *, Pilar de Castro-Manglano2, 3, Azucena Díez-Suárez1, 3, Juan J. Marín-Méndez4, Cesar A. Soutullo1, 2, 3
1 Child & Adolescent Psychiatry Unit, Department of Psychiatry & Medical Psychology, University of Navarra Clinic, Pamplona, Navarra, Spain
2 Child & Adolescent Psychiatry Unit, Department of Psychiatry & Medical Psychology, University of Navarra Clinic, Madrid, Spain
3 IDISNA (Health Research Institute of Navarra - Instituto de Investigación Sanitaria de Navarra), Navarra, Spain
4 Pharmamodelling Inc, Navarra, Spain

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Creative Commons License
© 2019 Vallejo-Valdivielso et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: ( This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Child & Adolescent Psychiatry Unit, Department of Psychiatry & Medical Psychology, University of Navarra Clinic, Ave. Pío XII 36, 31008, Pamplona, Navarra, Spain; Tel: 0034645686345; Fax: 0034948296500; E-mail:



Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD.


To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD.


We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview. We collected and CGI-S scores at baseline and at follow up, and neuropsychological testing (WISC-IV, Continuous Performance Test (CPT-II) & Stroop). Clinical response was defined as >30% reduction from baseline of total score and CGI-S final score of 1 or 2 maintained for the previous 3 months.


We included 518 children and adolescents with ADHD, mean (SD) age of patients was 11.4 (3.3) years old; 79% male; 51.7% had no comorbidities; and 75.31% had clinical response to a mean MPH dose of 1.2 mg/kg/day. Lower scores, absence of comorbidities (oppositional-defiant symptoms, depressive symptoms and alcohol/cannabis use), fewer altered neuropsychological tests, higher total IQ and low commission errors in CPT-II, were significantly associated with a complete clinical response to methylphenidate treatment.


Oppositional-defiant symptoms, depressive symptoms, and a higher number of impaired neuropsychological tests are associated with worse clinical response to methylphenidate. Other stimulants or non-stimulants treatment may be considered when these clinical and neuropsychological variables converged in the first clinical interview.

Keywords: ADHD, Predictive factors, Neuropsychological variables, Methylphenidate, Treatment, Spanish sample.