A multi-centre, randomised, double-blind, placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study)

Ulrich Hegerl, Roland Mergl, Christian Sander, Jens Dietzel, Istvan Bitter, Koen Demyttenaere, Ricardo Gusmão, Ana Gonzalez Pinto Arrillaga, Iñaki Zorrilla, Adriana García Alocén, Victor Perez Sola, Eduard Vieta, Georg Juckel, Ulrich S. Zimmermann, Michael Bauer, Pascal Sienaert, Sónia Quintão, Marc Andreas Edel, Csilla Bolyos, Jose Luis Ayuso-MateosPilar López-García, Michael Kluge

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).

Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Clinical trial
  • Mania
  • Methylphenidate
  • Placebo
  • Short-term effects

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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  • Cite this

    Hegerl, U., Mergl, R., Sander, C., Dietzel, J., Bitter, I., Demyttenaere, K., Gusmão, R., Arrillaga, A. G. P., Zorrilla, I., Alocén, A. G., Sola, V. P., Vieta, E., Juckel, G., Zimmermann, U. S., Bauer, M., Sienaert, P., Quintão, S., Edel, M. A., Bolyos, C., ... Kluge, M. (2018). A multi-centre, randomised, double-blind, placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study). European Neuropsychopharmacology, 28(1), 185-194. https://doi.org/10.1016/j.euroneuro.2017.11.003