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


OBJECTIVE
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.
Deakin
J B
JB
Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Box 189, CB2 2QQ Cambridge, England, UK.
Rahman
S
S
Nestor
P J
PJ
Hodges
J R
JR
Sahakian
B J
BJ
D000368:Aged; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003704:Dementia / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005625:Frontal Lobe; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000187:drug effects; D012309:Risk-Taking; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D013997:Time Factors; D014796:Visual Perception / Q000187:drug effects
D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors