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Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder

A randomized, double-blind, placebo-controlled study in stimulant-naïve Swedish children and adolescents

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Abstract

Objective

The primary objective of this study was to assess the impact of atomoxetine in combination with psychoeducation, compared with placebo and psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant-naïve pediatric patients with attention deficit/hyperactivity disorder (ADHD). HRQL results will be presented elsewhere. Here, psychoeducation as well as efficacy and safety of the treatment are described.

Patients and methods

A total of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients received four sessions of psychoeducation. Atomoxetine was dosed up to approximately 1.2 mg/kg day (≤70 kg) or 80 mg/day (>70 kg). Improvement of ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical global impression (CGI) rating scales. Safety was assessed based on adverse events (AEs).

Results

The study population was predominantly male (80.8%) and diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean) change from baseline to endpoint in total ADHD-RS score was −19.0 for atomoxetine patients and −6.3 for placebo patients, resulting in an effect size (ES) of 1.3 at endpoint. Treatment response (reduction in ADHD-RS score of ≥25 or ≥40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was −1.8 in the atomoxetine group compared with −0.3 in the placebo group. The difference between treatments in CGI-Improvement at endpoint was −1.4 in favor of atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in line with the current label.

Conclusions

Atomoxetine combined with psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms improvement. The large ES might be a result of including stimulant-naïve patients only, but also may indicate a positive interaction between atomoxetine treatment and psychoeducation, possibly by increased compliance.

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Abbreviations

ADHD:

Attention deficit/hyperactivity disorder

ADHD-RS:

Attention deficit/hyperactivity disorder rating scale

AE:

Adverse event

ANCOVA:

Analysis of covariance

ANOVA:

Analysis of variance

CD:

Conduct disorder

CGI-I:

Clinical global impression-improvement

CGI-S:

Clinical global impression-severity

DSM-IV:

Diagnostic and statistical manual of mental disorders, 4th edition

ES:

Effect size

K-SADS-PL:

Kiddie schedule for affective disorders and schizophrenia for school-age children-present and lifetime version

LOCF:

Last observation carried forward

MMRM:

Mixed-model repeated measures

ODD:

Oppositional defiant disorder

HRQL:

Health-related quality of life

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Acknowledgments

This research was funded by Eli Lilly Sweden AB. Hamid Bakhshi, former team leader CNS Eli Lilly Sweden AB, for support, encouragement and technical expertise. Ansgar Dressler and Dr. Birgit von Janowsky, Trilogy Writing & Consulting GmbH, Frankfurt, Germany for their help with preparation of this manuscript. Agneta Hellström, currently Director, ADHD-Center, Stockholm Habilitation Services, for managing the study parental educational program, and for educating the supervisors of the study sites. Åsa Nylen, former Clinical Research Associate (CRA) and in charge of the study operations, currently Medical liason CNS, Eli Lilly Sweden AB. Alexander Schacht, Eli Lilly Deutschland GmbH, for statistical help during the preparation of the manuscript. The following investigators participated in the study: Bernt Danielsson, M.D. (Mölnlycke), Lennart Eriksson, M.D. (örebro), Peter Gottfarb, M.D. (Huddinge), Christina Högström, M.D. (Lund), Mats Johnson, M.D. (Göteborg), Eva Norén, M.D. (Uppsala), Tatjana Olofsson, M.D. (UmeÅ), Aivar Päären, M.D. (örebro), Mats Reimer, M.D. (Mölnlycke). Authors Per A Gustafsson, M.D., Ph.D., Bruno Hägglöf, M.D., Ph.D., Björn Kadesjö, M.D., Ph.D., and Gunilla Thernlund, M.D., Ph.D., were also investigators.

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Svanborg, P., Thernlund, G., Gustafsson, P.A. et al. Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry 18, 240–249 (2009). https://doi.org/10.1007/s00787-008-0725-5

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