Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate

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

Abstract

Background: Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the 'vigilance regulation model of mania' which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania.

Methods/design: A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression-Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-'Vigilance Algorithm Leipzig' (VIGALL).

Discussion: A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives.

Trial registration: ClinicalTrials.gov NCT01541605.

Figures

Figure 1
Figure 1
The vigilance regulation model of mania: Unstable vigilance induces a pathogenic circle with vigilance stabilisation syndrome leading to full-blown mania. Figure taken from: Hegerl U., et al. Are psychostimulants a treatment option in mania? Pharmacopsychiatry 2009; 42:169-174. Reproduced with kind permission of Georg Thieme Verlag KG”.

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