Methylphenidate for Treating ADHD: A Naturalistic Clinical Study of Methylphenidate Blood Concentrations in Children and Adults With Optimized Dosage

Maria D Chermá, Martin Josefsson, Irene Rydberg, Per Woxler, Tomas Trygg, Olle Hollertz, Per A Gustafsson, Maria D Chermá, Martin Josefsson, Irene Rydberg, Per Woxler, Tomas Trygg, Olle Hollertz, Per A Gustafsson

Abstract

Background: Methylphenidate (MPH), along with behavioral and psychosocial interventions, is the first-line medication to treat attention-deficit hyperactivity disorder (ADHD) in Sweden. The dose of MPH for good symptom control differs between patients. However, studies of MPH concentration measurement in ADHD treatment are limited.

Objective: To describe blood and oral fluid (OF) concentrations of MPH after administration of medication in patients with well-adjusted MPH treatment for ADHD, and to identify the most suitable matrix for accurate MPH concentration during treatment.

Methods: Patients were recruited from Child and Adolescent Psychiatry (CAP), General Psychiatry (GP), and the Department of Dependency (DD). Blood and OF samples were collected in the morning before MPH administration as well as 1 and 6 h after administration of the prescribed morning dose of MPH.

Results: Fifty-nine patients aged between 9 and 69 years, 76 % males. The daily dose of MPH varied from 18 to 180 mg, but the median daily dose per body weight was similar, approximately 1.0 mg/kg body weight. The median MPH concentration in blood 1 and 6 h after the morning dose was 5.4 and 9.3 ng/mL, respectively. Highly variable OF-to-blood ratios for MPH were found at all time points for all three groups.

Conclusions: Weight is a reliable clinical parameter for optimal dose titration. Otherwise, MPH blood concentration might be used for individual dose optimization and for monitoring of the prescribed dose. Relying only on the outcome in OF cannot be recommended for evaluation of accurate MPH concentrations for treatment monitoring.

Conflict of interest statement

Funding

Grants from the following research funds are acknowledged: Swedish Medical Research Council (No. 2009-4740), Medical Research Council of Southeast Sweden (FORSS-12147 and FORSS-155281). The funding sources had no further role in study design, collection, analysis and interpretation of data, the writing of the report, or the decision to submit the paper for publication.

Conflict of interest

MDC, MJ, IR, PW, TT, OH and PAG declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Committee of the Medical Faculty of Linköping University, Sweden (Dnr M92-07), the Swedish Medical Products Agency and the Swedish Data Inspection Board (Dnr 1405-2007) approved the collection of patient samples. All patients gave written as well as oral informed consent before inclusion in the study.

Figures

Fig. 1
Fig. 1
Concentration–time profile of methylphenidate (MPH) blood concentrations in 50 patients before and after the morning dose (1 and 6 h) of the osmotic release oral system (OROS)-MPH
Fig. 2
Fig. 2
Frequency distribution of blood methylphenidate (MPH) concentrations in 50 patients 1 and 6 h after the morning dose of the osmotic release oral system (OROS)-MPH

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