Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study

Javier Quintero1, Francisco López-Muñoz2, Cecilio Alamo2, Mercedes Loro3, Natalia García-Campos4
1Department of Psychiatry, Infanta Leonor Hospital, Madrid, Spain
2Department of Pharmacology, Faculty of Medicine, University of Alcalá, Madrid, Spain
3Department of Child and Adolescent Psychiatry, Doctor Quintero Clinic, Madrid, Spain
4Department of Psychology, Doctor Quintero Clinic, Madrid, Spain

Tóm tắt

Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

Tài liệu tham khảo

Adler LA, Spencer TJ, Milton DR, Moore RJ, Michelson D (2005) Long-term, open-label study of the safety and efficacy of atomoxetine in adults with attention-deficit/hyperactivity disorder: an interim analysis. J Clin Psychiatry 66:294–299 Aguglia E (2000) Reboxetine in the maintenance therapy of depressive disorder in the elderly: a long-term open study. Int J Geriatr Psychiatry 15:784–793 Alamo C, López-Muñoz F, Rubio G, García-García P, Pardo A (2007) Combined treatment with reboxetine in depressed patients with no response to venlafaxine: a 6-week follow-up study. Acta Neuropsychiatr 19:291–296 Banaschewski T, Roessner V, Dittmann RW, Santosh PJ, Rothenberger A (2004) Non-stimulant medications in the treatment of ADHD. Eur Child Adolesc Psychiatry 13(Suppl 1):102–116 Barkley RA (1977) A review of stimulant drug research with hyperactive children. J Child Psychol Psychiatry 18:137–165 Berzewski H, Van Moffaert M, Gagiano CA (1997) Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive episodes. Eur Neuropsychopharmacol 7(1):37–47 Biederman J, Spencer T (1999) Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry 46:1234–1242 Biederman J, Gastfriend DR, Jellinek MS (1986) Desipramine in the treatment of children with attention deficit disorder. J Clin Psychopharmacol 6:359–363 Biederman J, Newcorn J, Sprich S (1991) Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 148:564–577 Biederman J, Faraone S, Milberger S, Guite J, Mick E, Chen L, Mennin D, Marrs A, Ouellette C, Moore P, Spencer T, Norman D, Wilens T, Kraus I, Perrin J (1996) A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders. Arch Gen Psychiatry 53:437–446 Biederman J, Spencer T, Wilens T (2004) Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol 7:77–97 Buitelaar JK, Danckaerts M, Gillberg C, Zuddas A, Becker K, Bouvard M, Fagan J, Gadoros J, Harpin V, Hazell P, Johnson M, Lerman-Sagie T, Soutullo CA, Wolanczyk T, Zeiner P, Fouche DS, Krikke-Workel J, Zhang S, Michelson D, Atomoxetine International Study Group (2004) A prospective, multicenter, open-label assessment of atomoxetine in non-North American children and adolescents with ADHD. Eur Child Adolesc Psychiatry 13:249–257 Cantwell DP (1996) Attention deficit disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 35:978–987 Castellanos FX (1997) Toward a pathophysiology of attention-deficit/hyperactivity disorder. Clin Pediatrics (Phil) 36:381–393 Daviss WB, Bentivoglio P, Racusin R, Brown KM, Bostic JQ, Wiley L (2001) Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression. J Am Acad Child Adolesc Psychiatry 40:307–314 Ding YS, Lin KS, Logan J (2006) PET imaging of norepinephrine transporters. Curr Pharm Design 12:3831–3845 DuPaul GJ, Power TJ, Anastopoulos AD, Reid R (1998) ADHD Rating Scale-IV: checklists, norms, and clinical interpretation. Guilford, New York Elia J, Borcherding BG, Rapoport JL, Keysor CS (1991) Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders? Psychiatry Res 36:141–155 Faraone SV, Sergeant JA, Gillberg C, Biederman J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2:104–113 MTA Cooperative Group (1999) A 14-month randomized clinical trial of treatment strategies for ADHD. Arch Gen Psychiatry 56:1073–1086 Hajos M, Fleishaker JC, Filipiak-Reisner JK, Brown MT, Wong EH (2004) The selective norepinephrine reuptake inhibitor antidepressant reboxetine: pharmacological and clinical profile. CNS Drugs Rev 10:23–44 Hansen C, Weiss D, Last CG (1999) ADHD boys in young adulthood: psychosocial adjustment. J Am Acad Child Adolesc Psychiatry 38:165–171 Kasper SF, Resinger E (2001) Efficacy of noradrenergic-selective agents in the treatment of neuropsychiatric diseases. CNS Spectrums 6:710–713 Kasper S, el Giamal N, Hilger E (2000) Reboxetine: the first selective noradrenaline re-uptake inhibitor. Exp Opin Pharmacother 1:771–782 Kratochvil CJ, Vaughan BS, Harrington MJ, Burke WJ (2003) Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder. Exp Opin Pharmacother 4:1165–1174 López-Muñoz F, Rubio G, Alamo C, García-García P, Pardo A (2006) Reboxetine addition in patients with mirtazapine-resistant depression: a case series. Clin Neuropharmacol 29:192–196 López-Muñoz F, Alamo C, Rubio G, García-García P, Pardo A (2007) Reboxetine combination in treatment-resistant depression to selective serotonin reuptake inhibitors. Pharmacopsychiatry 40:14–19 López-Muñoz F, Alamo C, Quintero-Gutiérrez FJ, García-García P (2008) A bibliometric study of international scientific productivity in attention-deficit hyperactivity disorder covering the period 1980–2005. Eur Child Adolesc Psychiatry 17:381–391 Maidment ID (2003) The use of antidepressants to treat attention deficit hyperactivity disorder in adults. J Psychopharmacol 17:332–336 Mannuzza S, Klein RG (2000) Long-term prognosis in attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin North Am 9:711–726 Massana J, Moller HJ, Burrows GD, Montenegro RM (1999) Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder. Int Clin Psychopharmacol 14:73–80 Michelson D, Faries D, Wernicke J, Kelsey D, Kendrick K, Sallee FR, Spencer T (2001) Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 108(5):E83 Michelson D, Allen AJ, Busner J, Casat C, Dunn D, Kratochvil C, Newcorn J, Sallee R, Sangal B, Saylor K, West S, Kelsey D, Wernicke J, Trapp NJ, Harder D (2002) Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 159:1896–1901 Miller A (1999) Appropriateness of psychostimulant prescription to children: theoretical and empirical perspectives. Can J Psychiatry 44:1017–1024 Mozes T, Meiri G, Ben-Amity G, Sabbagh M, Weizman A (2005) Reboxetine as an optional treatment for hyperkinetic conduct disorder: a prospective open-label trial. J Child Adolesc Psychopharmacol 15:259–269 Otka JE, Mercadante MT, Scahill L, Leckman JF (2001) Reboxetine as a potentially effective treatment for attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 11:203–204 Page ME, Lucki I (2002) Effects of acute and chronic reboxetine treatment on stress-induced monoamine efflux in the rat frontal cortex. Neuropsychopharmacology 27:237–247 Pliszka SR (2001) New developments in psychopharmacology of attention deficit hyperactivity disorder. Exp Opin Invest Drugs 10:1797–1807 Pliszka SR (2003) Psychiatric comorbidities in children with attention deficit hyperactivity disorder: implications for management. Paediatr Drugs 5:741–750 Pliszka SR, McCracken JT, Maas JW (1996) Catecholamines in attention-deficit hyperactivity disorder: current perspectives. J Am Acad Child Adolesc Psychiatry 35:264–272 Ratner S, Laor N, Bronstein Y, Weizman A, Toren P (2005) Six-week open-label reboxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 44:428–433 Rubio G, San L, López-Muñoz F, Alamo C (2004) Reboxetine adjunct for partial or nonresponders to antidepressant treatment. J Affect Disord 81:67–72 Servera M, Cardo E (2007) ADHD rating scale-IV en una muestra escolar española: datos normativos y consistencia interna para maestros, padres y madres. Rev Neurol 45:393–399 Simpson D, Plosker GL (2004) Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder. Drugs 64:205–222 Spencer T, Wilens T, Biederman J, Faraone SV, Ablon JS, Lapey K (1995) A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry 52:434–443 Spencer T, Biederman J, Wilens T, Harding M, O’Donnell D, Griffin S (1996) Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry 35:409–432 Spencer T, Biederman J, Wilens T, Prince J, Hatch M, Jones J, Harding M, Faraone SV, Seidman L (1998) Effectiveness and tolerability of atomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatr 155:693–695 Spencer T, Biederman J, Coffey B, Geller D, Crawford M, Bearman SK, Tarazi R, Faraone SA (2002) A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 59:649–656 Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke EJ, Jensen PS, Cantwell DP (1998) Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 351(9100):429–433 Tanum L (2000) Reboxetine: tolerability and safety profile in patients with major depression. Acta Psychiatr Scand 101(402):37–40 Tehrani-Doost M, Moallemi S, Shahrivar Z (2008) An open-label trial of reboxetine in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 18:179–184 Toren P, Ratner S, Laor N, Lerer-Amisar D, Weizman A (2005) A possible antienuretic effect of reboxetine in children and adolescents with attention deficit/hyperactivity disorder: case series. Neuropsychobiology 51:239–242 Toren P, Ratner S, Weizman A, Lask M, Ben-Amitay G, Laor N (2007) Reboxetine maintenance treatment in children with attention-deficit/hyperactivity disorder: a long-term follow-up open study. J Child Adolesc Psychopharmacol 17:803–811 Ulloa RE, Arroyo E, Ávila JM, Cárdenas JA, Cruz E, Gómez D, Higuera F, Rivera FR, Santos G, Velásquez V, Peña F (2005) Algoritmo del tratamiento para el trastorno por déficit de atención con hiperactividad en niños y adolescentes. Salud Ment 28:1–10 Valentini V, Frau R, Di Chiara G (2004) Noradrenaline transporter blockers raise extracellular dopamine in medial prefrontal but not parietal and occipital cortex: differences with mianserin and clozapine. J Neurochem 88:917–927 Versiani M, Mehilane L, Gaszner P, Arnaud-Castiglioni R (1999) Reboxetine, a unique selective NRI, prevent relapse and recurrence in long-term treatment of major depressive disorder. J Clin Psychiatry 60:400–406 Weiss M, Weiss G (2006) Attention deficit hyperactivity disorder. In: Lewis M (ed) Child and adolescent psychiatry. Williams & Williams, Baltimore, pp 645–670 Wender PH, Reimherr FW (1990) Bupropion treatment of attention-deficit hyperactivity disorder in adults. Am J Psychiatry 147:1018–1020 Wilens T (2006) Mechanism of action of agents used in attention-deficit/hyperactivity disorder. J Clin Psychiatry 67(Suppl 8):32–37 Wilens TE, Spencer TJ (2000) The stimulants revisited. Child Adolesc Psychiatr Clin North Am 9:573–603 Wilens TE, Biederman J, Prince J, Spencer TJ, Faraone SV, Warburton R, Schleifer D, Harding M, Linehan C, Geller D (1996) Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder. Am J Psychiatry 153:1147–1153 Wilens TE, Spencer TJ, Biederman J, Girard K, Doyle R, Prince J, Polisner D, Solhkhah R, Comeau S, Monuteaux MC, Parekh A (2001) A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry 158:282–288 Wong EH, Sonders MS, Amara SG, Tinholt PM, Piercey MF, Hoffmann WP, Hyslop DK, Franklin S, Porsolt RD, Bonsignori A, Carfagna N, McArthur RA (2000) Reboxetine: a pharmacologically potent, selective, and specific norepinephrine reuptake inhibitor. Biol Psychiatry 47:818–829 Zhang S, Faries DE, Vowles M, Michelson D (2005) ADHD rating scale IV: psychometric properties from a multinational study as a clinician-administered instrument. Int J Meth Psychiatr Res 14:186–201 Zhou J (2004) Norepinephrine transporter inhibitors and their therapeutic potential. Drugs Future 29:1235–1244