Abstract
Considering the high clinical and forensic relevance of pharmaco-adherence during lisdexamphetamine (LDX) treatment for attention-deficit/hyperactivity disorder (ADHD), the aim here was to evaluate hair analysis as a tool for monitoring compliance in patients currently undergoing long term treatment with LDX, by detecting possible interruptions of medication intake or changes in dosage. For this purpose, a total of 24 patients from an outpatient clinic for ADHD were recruited. Hair and urine samples were taken after three consecutive therapy sessions over a 7-month period and analyzed for amphetamine (AMP) enantiomers and other drugs, using chiral and achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). Participants also provided information on the condition of their hair, the consumption of illegal psychotropic substances and the regularity of taking LDX. Two participants withdrew from the study early. Urine analyses were positive for D-AMP in all urine samples and therapy sessions, except in two patients who did not take LDX on a daily basis. D-AMP was detected in all hair samples; however, no correlation was found between prescribed dose/day and D-AMP concentrations in proximal hair segments. Qualitative interpretation of hair analysis showed that 18 of the 22 study completers were compliant concerning the intake of LDX without additional consumption of illegal D,L-AMP. Analysis of urine taken during the therapy sessions showed no correlation between D-AMP concentrations and prescribed dosage, with or without normalization for creatinine. In conclusion, chiral LC-MS/MS hair analysis might represent a non-invasive way to confirm LDX use within the approximate period covered by the hair segment tested, but it does not allow for quantitative therapeutic drug monitoring because of interindividual variability of concentrations in hair. Drug concentrations in hair at different stages of long-term treatment should thus be interpreted with caution by clinicians and forensic experts alike when making assessments of treatment adherence.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobiological disorder predominantly manifesting itself in childhood and persisting into adulthood in an estimated twothirds of cases [1]
We found that individuals undergoing long-term treatment with Elvanse1 were positive for D-AMP in all urine samples and therapy sessions, except for two patients who did not take LDX on a daily basis
D-AMP was detected in all hair samples of participants taking prescribed LDX in dosages between 20 and 320 mg on a daily basis, adding further evidence to the feasibility of chiral liquid chromatography (LC)-MS/MS analysis to confirm LDX use within the approximate period covered by the hair segment tested
Summary
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobiological disorder predominantly manifesting itself in childhood and persisting into adulthood in an estimated twothirds of cases [1]. Adherence is commonly defined as a combination of persistence (i.e., whether an individual continues to refill prescriptions in line with the recommended duration of therapy) and compliance (whether an individual takes doses according to the issued prescription) [2, 3]. Adler and Nierenberg found that among children and adults, 13% to 64% discontinued their treatment [4]. Stimulants like methylphenidate (MPH) and amphetamine (AMP) are the most commonly prescribed pharmacological treatments for ADHD [5]. In Switzerland LDX (Elvanse1) is approved as a treatment for ADHD in children from 6 years of age, adolescents and—since 2014— for adults up to 55 years of age who show insufficient response to MPH treatment, serving as a second-line treatment [9]
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