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

Abstract

Background: 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.

Objective: 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.

Methods: 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 ADHD-RS-IV.es 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 ADHD-RS-IV.es score and CGI-S final score of 1 or 2 maintained for the previous 3 months.

Results: 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 ADHD-RS-IV.es 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.

Conclusion: 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; Methylphenidate; Neuropsychological variables; Predictive factors; Spanish sample; Treatment.

Fig. (1)

Proportion of ADHD patients with Altered Neuropsychological Tests. Considering that the presence of a 1SD away from the average value of the healthy population in any of the test to evaluate the Executive Function (EF) of ADHD patients, we found that a most patients showed no alteration in the different neuropsychological tests. These data suggest that not all children with ADHD suffer from neuropsychological dysfunction. Note : WISC= Wechsler Intelligence Scale (IQ: intelligence quotient, T-IQ : Total IQ, V-IQ: Verbal IQ, M-IQ: Manipulative IQ, VC: Verbal Comprehension, PR: Perceptual Reasoning, WM: Working Memory, PS: Perceptual Reasoning) CPT-II: Conners’ Continuous Performance Test II (CE: Commission Errors, OE: Omission Errors, Hit RT: Reaction Time,). STROOP: Stroop COLOR WORD Test (I= interference).

Fig. (2)

Number of Proportion Altered Neuropsychological Tests in ADHD patients. Neuropsychological Tests evaluated are detailed and described in Fig. (1). We consider “altered test”, according to 1SD cut-off rule (Biederman et al., 1993). In our sample, 48.3% of ADHD patients had no neuropsychological impairment, and only 23% had impairment in one neuropsychological test, and 14.5% had two-test impairment.

Fig. (3)

Treatment response (%) reached at end-point (last follow-up visit) according to number of altered neuropshychological tests. We observed a gradual decline in the response rate, as the number of altered tests increased. The response rate (CGI) in patients with normal executive function (EF) evaluation was 76.4%, while the response rate for patients with 1 or 2 altered tests was 73.1% and 62.7% respectively. Note : NR: “no-response” PR= “partial response” CR = “complete response”.