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

Abstract

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, 1-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.