title: Pilot Phase II study of mazindol in children with attention deficit/hyperactivity disorder.
abstract: OBJECTIVE
  Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its pharmacokinetics, short-term efficacy, and safety.
  
  
  METHODS
  A total of 24 children (aged 9-12 years) with ADHD (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text-revision criteria) received a daily dose of 1 mg for 7 days and were followed for 3 additional weeks. Pharmacokinetic samples were collected after the first administration. ADHD symptoms were assessed using the ADHD Rating Scale (RS)-IV, Conners' Parent Rating Scale - Revised: Long (CPRS-R:L) at screening, baseline, and the end of the study. The Clinical Global Impression - Severity (CGI-S) scale was assessed at baseline, and the CGI - Improvement (CGI-I) scale was assessed at subsequent visits.
  
  
  RESULTS
  Twenty-one subjects (aged 10±1 years) were analyzed. Pharmacokinetic data were described by a one-compartment model with first-order absorption, elimination, and lag time. The typical apparent clearance and apparent volume of distribution were 27.9 L/h and 234 L, and increased with fat-free mass and age, respectively. The mean change in score in ADHD RS-IV after 1 week of mazindol was -24.1 (P<0.0001), greater than a 90% improvement from baseline. Reduction of CPRS-R:L and CGI-S scores were -52.1 (P<0.0001) and -2.5 (P<0.01), respectively. Adverse events were mild to moderate, decreased appetite and upper abdominal pain being the most common.
  
  
  CONCLUSIONS
  This preliminary study shows that mazindol might be an effective, well-tolerated, and long-acting (more than 8 hours) agent for the treatment of ADHD in children.
authors.affiliation: Pediatric Sleep Disorders Center, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Child and Adolescent Psychiatric Department, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Konofal
authors.affiliation: Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; INSERM, Infection, Antimicrobiens, Modélisation, Evolution (IAME), UMR1137, Paris, France ; Department of Biostatistiques, Hôpital Bichat, APHP, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Laouénan
authors.affiliation: Pediatric Sleep Disorders Center, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Child and Adolescent Psychiatric Department, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.affiliation: Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Florentia
authors.initials: F
authors.lastname: Kaguelidou
authors.affiliation: Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
authors.forename: Lila
authors.initials: L
authors.lastname: Benadjaoud
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Paris, France ; INSERM, Infection, Antimicrobiens, Modélisation, Evolution (IAME), UMR1137, Paris, France ; Department of Biostatistiques, Hôpital Bichat, APHP, Paris, France.
authors.forename: France
authors.initials: F
authors.lastname: Mentré
authors.affiliation: Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France ; Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008454:Mazindol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010865:Pilot Projects; D012449:Safety
chemical_list: D008454:Mazindol
keywords: ADHD; efficacy; mazindol; pediatrics; pharmacokinetics; safety