RATIONALE: Patients with frontal variant frontotemporal dementia (fvFTD) present with disinhibition, impulsiveness, apathy, altered appetite and stereotypic behaviors. A non-randomized clinical trial found improvement in these symptoms after treatment with a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy using a double-blind, placebo-controlled experimental design. METHODS:Ten subjects meeting the consensus criteria for FTD were entered into a double-blind, placebo-controlled crossover trial. Doses of paroxetine were progressively increased to 40 mg daily. The same regimen was used for placebo capsules. Subjects were assessed with a battery of cognitive tests in the sixth week of paroxetine and placebo treatment. At each assessment, caregivers were interviewed using the Neuropsychiatric Inventory and asked to complete the Cambridge Behavioral Inventory. RESULTS: There were no significant differences on the Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine caused a decrease in accuracy on the paired associates learning task, reversal learning and a delayed pattern recognition task. There were no changes on the decision-making task, in spatial span, spatial recognition, spatial working memory, digit span and verbal fluency. CONCLUSIONS: This study finds no evidence for the efficacy of paroxetine in the treatment of fvFTD. The results suggest that a chronic course of paroxetine may selectively impair paired associates learning, reversal learning and delayed pattern recognition. This pattern of deficits closely resembles that seen after tryptophan depletion. Results are discussed with respect to current theories on serotonergic modulation of orbitofrontal/ventromedial prefrontal cortex.
RCT Entities:
RATIONALE: Patients with frontal variant frontotemporal dementia (fvFTD) present with disinhibition, impulsiveness, apathy, altered appetite and stereotypic behaviors. A non-randomized clinical trial found improvement in these symptoms after treatment with a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy using a double-blind, placebo-controlled experimental design. METHODS: Ten subjects meeting the consensus criteria for FTD were entered into a double-blind, placebo-controlled crossover trial. Doses of paroxetine were progressively increased to 40 mg daily. The same regimen was used for placebo capsules. Subjects were assessed with a battery of cognitive tests in the sixth week of paroxetine and placebo treatment. At each assessment, caregivers were interviewed using the Neuropsychiatric Inventory and asked to complete the Cambridge Behavioral Inventory. RESULTS: There were no significant differences on the Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine caused a decrease in accuracy on the paired associates learning task, reversal learning and a delayed pattern recognition task. There were no changes on the decision-making task, in spatial span, spatial recognition, spatial working memory, digit span and verbal fluency. CONCLUSIONS: This study finds no evidence for the efficacy of paroxetine in the treatment of fvFTD. The results suggest that a chronic course of paroxetine may selectively impair paired associates learning, reversal learning and delayed pattern recognition. This pattern of deficits closely resembles that seen after tryptophan depletion. Results are discussed with respect to current theories on serotonergic modulation of orbitofrontal/ventromedial prefrontal cortex.
Authors: J S Rubinsztein; R D Rogers; W J Riedel; M A Mehta; T W Robbins; B J Sahakian Journal: Psychopharmacology (Berl) Date: 2001-03 Impact factor: 4.530
Authors: Adam L Boxer; Michael Gold; Edward Huey; William T Hu; Howard Rosen; Joel Kramer; Fen-Biao Gao; Edward A Burton; Tiffany Chow; Aimee Kao; Blair R Leavitt; Bruce Lamb; Megan Grether; David Knopman; Nigel J Cairns; Ian R Mackenzie; Laura Mitic; Erik D Roberson; Daniel Van Kammen; Marc Cantillon; Kathleen Zahs; George Jackson; Stephen Salloway; John Morris; Gary Tong; Howard Feldman; Howard Fillit; Susan Dickinson; Zaven S Khachaturian; Margaret Sutherland; Susan Abushakra; Joseph Lewcock; Robert Farese; Robert O Kenet; Frank Laferla; Steve Perrin; Steve Whitaker; Lawrence Honig; Marsel M Mesulam; Brad Boeve; Murray Grossman; Bruce L Miller; Jeffrey L Cummings Journal: Alzheimers Dement Date: 2012-10-10 Impact factor: 21.566