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Eur Neuropsychopharmacol. 2018 Jan;28(1):185-194. doi: 10.1016/j.euroneuro.2017.11.003. Epub 2017 Nov 23.

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

Author information

1
Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, Germany. Electronic address: Ulrich.Hegerl@medizin.uni-leipzig.de.
2
Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, Germany.
3
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
4
University Psychiatric Center KU Leuven, Leuven, Belgium.
5
Departamento de Psiquiatria, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; ISPUP, Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.
6
Department of Psychiatry, Hospital Santiago Apostol, Vitoria, Spain; Centro de Investigación Biomédica en Red de Salud Mental. CIBERSAM, Madrid, Spain.
7
Centro de Investigación Biomédica en Red de Salud Mental. CIBERSAM, Madrid, Spain; Department of Psychiatry, Hospital del Mar, Barcelona, Spain.
8
Centro de Investigación Biomédica en Red de Salud Mental. CIBERSAM, Madrid, Spain; Department of Psychiatry, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain.
9
Department of Psychiatry and Psychotherapy, University of Bochum, Bochum, Germany.
10
Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
11
Centro de Investigación Biomédica en Red de Salud Mental. CIBERSAM, Madrid, Spain; Department of Psychiatry, Universidad Autonoma de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.

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 (20-40mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20-40mg 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).

KEYWORDS:

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

PMID:
29174864
DOI:
10.1016/j.euroneuro.2017.11.003
[Indexed for MEDLINE]

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