A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder

Springer Science and Business Media LLC - Tập 1 - Trang 1-7 - 2007
Gabrielle A Carlson1, David Dunn2, Douglas Kelsey3, Dustin Ruff3, Susan Ball3, Lisa Ahrbecker3, Albert J Allen3
1Department of Child and Adolescent Psychiatry, Stony Brook School of Medicine, Stony Brook, USA
2Department of Psychiatry, Indiana University School of Medicine, Indianapolis, USA
3Lilly Research Laboratories, Eli Lilly and Company Indianapolis USA

Tóm tắt

This study examined augmenting atomoxetine with extended-release methylphenidate in children whose attention-deficit/hyperactivity disorder (ADHD) previously failed to respond adequately to stimulant medication. Children with ADHD and prior stimulant treatment (N = 25) received atomoxetine (1.2 mg/kg/day) plus placebo. After 4 weeks, patients who were responders (n = 4) were continued on atomoxetine/placebo while remaining patients were randomly assigned to either methylphenidate (ATX/MPH) (1.1 mg/kg/day) or placebo augmentation (ATX/PB) for another 6 weeks. Patients and sites were blind to timing of active augmentation. Safety measures included vital signs, weight, and adverse events. Efficacy was assessed by ADHD rating scales. Categorical increases in vital signs occurred for 5 patients (3 patients in ATX/MPH, 2 patients in ATX/PBO). Sixteen percent discontinued the study due to AE, but no difference between augmentation groups. Atomoxetine treatment was efficacious on outcome measures (P ≤ .001), but methylphenidate did not enhance response. Methylphenidate appears to be safely combined with atomoxetine, but conclusions limited by small sample. With atomoxetine treatment, 43% of patients achieved normalization on ADHD ratings.

Tài liệu tham khảo

Biederman J, Spencer T, Wilens T: Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2004, 7 (1): 77-97. 10.1017/S1461145703003973. Faraone SV, Biederman J: Neurobiology of Attention-Deficit Hyperactivity Disorder. Biol Psychiatry. 1998, 44: 951-958. 10.1016/S0006-3223(98)00240-6. Bhatara V, Feil M, Hoagwood K, Vitiello B, Zima B: National trends in concomitant psychotropic medication with stimulants in pediatric visits: Practice versus knowledge. J Attent Disord. 2004, 7 (4): 217-226. 10.1177/108705470400700404. Safer DJ, Zito JM, dosReis S: Concomitant psychotropic medications for youths. Am J Psychiatry. 2003, 160: 438-449. 10.1176/appi.ajp.160.3.438. Carlson GA, Rapport MD, Kelly K, Grayson P, Pataki CS: Methylphenidate and desipramine in hospitalized children with comorbid behavior and mood disorders: separate and combined effects on behavior and mood. J Child Adolesc Psychopharmacol. 1995, 5: 191-204. Pataki CS, Carlson GA, Kelly KL, Rapport MD, Biancaniello TM: Side effects of methylphenidate and desipramine alone and in combination in children. J Am Acad Child Adolesc Psychiatry. 1993, 32: 1065-72. 10.1097/00004583-199309000-00028. Brown TE: Atomoxetine and stimulants in combination for treatment of attention deficit hyperactivity disorder: Four case reports. J Child Adolesc Psychopharmacol. 2004, 14 (1): 129-136. 10.1089/104454604773840571. Spencer T, Biederman J, Wilens T, Harding M, O'Donnell D, Griffin S: Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle: A literature review. J Am Acad Child Adolesc Psychiatry. 1996, 35: 409-432. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R: ADHD Rating Scale-IV: Checklists, Norms, and Clinical Impressions. 1998, New The Guildford Press WMA. Declaration of Helsinki: Ethical principles for medical research involving human subjects. World Medical Association. First adopted in 1964; most recent revision in 2000. 2000, [http://www.healthscience.net/resources/declaration-of-helsinki/] Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N: Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997, 36: 980-988. 10.1097/00004583-199707000-00021. Guy W: ECDEU assessment manual for psychopharmacology, revised. 1976, Bethesda, MD: US Department of Health, Education, and Welfare Conners CK, Barkley RA: Rating scales and checklists for child psychopharmacology. Psychopharmacol Bull. 1985, 21: 809-843. Kelsey DK, Sumner CR, Casat CD, Coury DL, Quintana H, Saylor KE, Sutton VK, Gonzales J, Malcolm SK, Schuh KJ, Allen AJ: Once daily atomoxetine treatment for children with attention deficit hyperactivity disorder, including an assessment of evening and morning behavior: A double-blind, placebo controlled trial. Pediatrics. 2004, 114: e1-e8. 10.1542/peds.114.1.e1. National High Blood Pressure Education Program Working Group: Update on the 1987 task force report on high blood pressure in children and adolescents: A working group report from the national high blood pressure education program. Pediatrics. 1996, 98: 649-658. Kelly RP, Yeo KP, Teng CH, Smith BP, Lowe S, Soon D, Read HA, Wise SD: Hemodynamic effects of acute administration of atomoxetine and methylphenidate. J Clin Pharmacol. 2005, 45: 851-855. 10.1177/0091270005276737. Quintana H, Cherlin E, Duesenberg D, Bangs M, Ramsey J, Feldman P, Allen AJ, Kelsey D: Transitioning from methylphenidate or amphetamine to atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder – a preliminary tolerability and efficacy study. Clin Ther. 2007, 29 (6): 1168-1177. 10.1016/j.clinthera.2007.06.017. Newcorn J: Atomoxetine and psychostimulants for ADHD: Is there differential response?. 2004, Oral presentation given at the American Academy Child and Adolescent Psychiatry national conference, Washington, DC