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Frontotemporal Dementia: Recommendations for Therapeutic Studies, Designs, and Approaches

Published online by Cambridge University Press:  02 December 2014

Morris Freedman
Morris Freedman*
Affiliation:
The Division of Neurology and Rotman Research Institute, Baycrest
*
Division of Neurology, Baycrest, Brain Health Complex, Rm. 656, 3560 Bathurst Street, Toronto, Ontario, M6A 2E1, Canada.
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Abstract

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Frontotemporal dementia (FTD) is one of three neurobehavioural syndromes produced by frontotemporal lobar degeneration. Despite the importance of FTD as a cause of dementia, especially in younger age groups, and a rationale for therapies targeting serotonergic and dopaminergic systems, there have been no large scale treatment trials in FTD. Moreover, there is no consensus on standards to facilitate comparison across therapeutic trials. This paper reviews the literature on therapeutic trials in FTD and outlines general recommendations for standards related to the development of future treatment studies in this disorder. Drugs tested in FTD include trazodone, galantamine, idazoxan, lithium plus fluoxetine, lithium plus paroxetine, SSRIs, l-deprenyl, moclobemide, methylphenidate, piracetam, rivastigmine, donepezil, olanzapine, risperidone, amantadine, guanfacine, allopurinol, and bromocriptine. Improvement has been reported in FTD for all drugs except piracetam, guanfacine and galantamine, although there was improvement on galantamine in primary progressive aphasia. Whereas improvement has been reported for paroxetine and other SSRIs, as well as idazoxan and methylphenidate, paroxetine and idazoxan have also been reported to cause a decline in function, and a marginally significant decline has been reported for methylphenidate. In addition, patients with Pick's disease, which is part of the spectrum of frontotemporal lobar degeneration, showed improvement on calcium EDTA. Six studies are double-blind placebo-controlled trials: two reports of cases using idazoxan and group trials using trazodone, paroxetine, galantamine and methylphenidate. It is recommended that experts in FTD arrive at a consensus to define standards for all clinical trials in FTD. These should include standards for diagnostic criteria, tests of severity, experimental design, and outcome measures.

Résumé:

RÉSUMÉ:

La démence fronto-temporale (DFT) est l'un des trois syndromes neurocomportementaux résultant de la dégénérescence lobaire fronto-temporale. Malgré l'importance de la DFT comme cause de démence, surtout chez les gens moins âgés, et le fait que les systèmes sérotoninergique et dopaminergique soient une cible logique pour le développement de médicaments, aucun essai clinique de grande envergure n'a été effectué dans la DFT. De plus, il n'existe pas de consensus sur des standards qui faciliteraient la comparaison entre les essais cliniques. Cet article revoit la littérature sur les essais cliniques portant sur la DFT et formule des recommandations générales sur les standards à utiliser à l'avenir pour élaborer des essais cliniques pour cette maladie. Les médicaments qui ont été étudiés dans la DFT sont le trazodone, la galantamine, l'idazoxan, le lithium associé à la fluoxétine, le lithium associé à la paroxétine, les IRSSs, le 1-déprényl, le moclobémide, le méthylphénidate, le piracétam, la rivastigmine, le donépézil, l'olanzapine, la rispéridone, l'amantadine, la guanfacine, l'allopurinol et la bromocriptine. Une amélioration a été rapportée avec l'utilisation de tous ces médicaments dans la DFT sauf avec le piracétam, la guanfacine et la galantamine, bien qu'on ait observé une amélioration sous galantamine dans l'aphasie progressive primitive. Bien qu'une amélioration ait été rapportée sous paroxétine et d'autres IRSSs ainsi que sous idazoxan et sous méthylphénidate, un déclin fonctionnel causé par la paroxétine et l'idazoxan a également été rapporté et un déclin à peine significatif a également été rapporté avec le méthylphénidate. De plus, les patients atteints de la maladie de Pick, une maladie qui fait partie des dégénérescences lobaires fronto-temporales, se sont améliorés sous EDTA calcique. Six des études sont des essais en double insu contre placebo : deux comptes rendus de patients sous idazoxan et des essais cliniques avec le trazodone, la paroxétine, la galantamine et le méthylphénidate. Nous recommandons que les experts dans le domaine de la DFT établissent un consensus sur la définition de standards pour tous les essais cliniques sur la DFT, soit des standards sur les critères diagnostiques, les tests pour évaluer la sévérité, le plan des études et les critères d'évaluation des résultats.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue S1 , March 2007 , pp. S118 - S124
Copyright
Copyright © The Canadian Journal of Neurological 2007

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