Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial

Deakin, Julia; Rahman, Shibley; Nestor, Peter J.; Hodges, John R.; Sahakian, Barbara J.

doi:10.1007/s00213-003-1686-5

Cited by 181 publications

(50 citation statements)

References 46 publications

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“…Excessive levels of serotonin in health or deficiencies in disease both impair performance ( cf . Deakin et al , 2004). This effect is analogous to the well-established ‘inverted U-shaped’ function relating dopaminergic transmission to cognitive and motor control and regional neuronal activation (Rowe et al , 2008; Cools and D'Esposito, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…SSRIs have been tested in a small number of open-label studies of bvFTD (for review see Boxer and Boeve, 2007; Freedman, 2007) with promising results, such as improvement on the Neuropsychiatric Inventory (Swartz et al , 1997; Lebert et al , 2004; Herrmann et al , 2012;) and reduced stereotypical behaviours (Ikeda et al , 2004; Mendez et al , 2005; Ishikawa et al , 2006). However, not all SSRIs reveal consistent improvements, with paroxetine for example leading to mixed results (Moretti et al , 2003; Deakin et al , 2004). Randomized placebo controlled studies are required to further establish efficacy but such clinical studies would benefit from evidence of the engagement of residual inhibitory systems in bvFTD, in addition to the preclinical evidence.…”

Section: Introductionmentioning

confidence: 99%

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Improving response inhibition systems in frontotemporal dementia with citalopram

Hughes

Rittman

Regenthal

et al. 2015

Brain

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Disinhibition is a cardinal feature of behavioural variant frontotemporal dementia, arising from both frontal atrophy and serotonin depletion. Hughes et al. show that neurophysiological signatures of inhibition are reduced in frontotemporal dementia, and that citalopram rescues prefrontal neurophysiological deficits relative to placebo. Boosting serotoninergic transmission may facilitate management of disinhibition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improving response inhibition systems in frontotemporal dementia with citalopram

Hughes

Rittman

Regenthal

et al. 2015

Brain

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“…The Mini-Mental Status Exam (MMSE) [29] was the most frequently administered cognitive measure, with use in five of nine trials. Several studies employed a battery of cognitive tests, including the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the DRS, which were the second most frequently used measures, appearing in two trials each [19,21,23,25]. The RBANS was employed in one trial [24].…”

Section: Current Summary Of Randomized Clinical Trials In Ftdmentioning

confidence: 99%

Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

Miller

Banks

Léger

et al. 2014

Transl Neurodegener

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Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturbance. Behavioral variant FTD is characterized by an initial presentation of changes in personality, behavior and/or emotion, which are often difficult to objectively capture using traditional neuropsychological measures. The two principal language variants of FTD are Progressive Nonfluent Aphasia (PNFA) with predominant agrammatic/non-fluent impairments and Semantic Dementia (SD) with semantic impairments and visual agnosia. Selection of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change, yet specific enough to isolate signal from noise, and acceptable to regulatory agencies. Given the anticipated potential for small effect sizes, measures must be able to identify small incremental changes over time. It is also imperative that the measures provide adequate coverage of the constructs or behaviors of interest. Selected outcome measures should be suitable for repeat administration, yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor reliability. To facilitate widespread adoption as an endpoint, measures should be readily accessible. We provide several examples of potential global, composite, and individual cognitive measures, as well as behavioral measures promising for FTD trials. Development and application of appropriate trial outcomes is critically important to success in advancing new treatments for FTD patients.

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“…In AD, exercise and cognitive therapies have been associated in slowed progression of the disease, but this has not been proved as yet in FTD. Treatment of depression with a selective serotonin reuptake inhibitor, such as paroxetine, sertraline, or citalopram, is frequently helpful, although one study of paroxetine was positive,88 and another negative 89. Trazodone may be helpful for sleep, as well as for “frontal” behavioral aberrations 90.…”

Section: Treatment Of Ftd and Ppamentioning

confidence: 99%

Frontotemporal dementia and primary progressive aphasia, a review

Kirshner¹

2014

NDT

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Frontotemporal dementias are neurodegenerative diseases in which symptoms of frontal and/or temporal lobe disease are the first signs of the illness, and as the diseases progress, they resemble a focal left hemisphere process such as stroke or traumatic brain injury, even more than a neurodegenerative disease. Over time, some patients develop a more generalized dementia. Four clinical subtypes characterize the predominant presentations of this illness: behavioral or frontal variant FTD, progressive nonfluent aphasia, semantic dementia, and logopenic primary progressive aphasia. These clinical variants correlate with regional patterns of atrophy on brain imaging studies such as MRI and PET scanning, as well as with biochemical and molecular genetic variants of the disorder. The treatment is as yet only symptomatic, but advances in molecular genetics promise new therapies.

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Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial

Cited by 181 publications

References 46 publications

Improving response inhibition systems in frontotemporal dementia with citalopram

Improving response inhibition systems in frontotemporal dementia with citalopram

Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

Frontotemporal dementia and primary progressive aphasia, a review

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