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.

SUBJECTS AND 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.

CONCLUSION:

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: Eric Konofal, Wei Zhao, Cédric Laouénan, Michel Lecendreux, Florentia Kaguelidou, Lila Benadjaoud, France Mentré, Evelyne Jacqz-Aigrain
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 8 Pg. 2321-32 ( 2014) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 25525331 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mazindol

Topics

• Adolescent
• Attention Deficit Disorder with Hyperactivity (drug therapy)
• Child
• Drug Administration Schedule
• Female
• Humans
• Male
• Mazindol (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Pilot Projects
• Safety