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

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Abstract

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.

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Acknowledgements

Funding was provided by a Wellcome Trust programme grant (019407) to Prof. T.W. Robbins, Prof. B.J. Everitt, Dr. A.C. Roberts and Prof. B.J. Sahakian and carried out within a MRC Center for Behavioural and Clinical Neuroscience. J.B.D. was funded by Merck Sharp and Dohme, a James Baird Award from the University of Cambridge School of Clinical Medicine and an Oon Khye Beng studentship. S.R. was funded by the MRC and the James Baird Fund. John Hodges funding was provided by a MRC program grant. The authors would like to thank Dr. S. Bozeat for help with collecting the data, Dr. M. Aitken for statistical advice and Prof. Robbins for his comments on the results.

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Authors and Affiliations

  1. Department of Psychiatry, University of Cambridge, Addenbrooke’s Hospital, Box 189, CB2 2QQ, Cambridge, England, UK

    J. B. Deakin, S. Rahman & B. J. Sahakian

  2. Department of Neurology, University of Cambridge, Addenbrooke’s Hospital, CB2 2QQ, Cambridge, England, UK

    P. J. Nestor & J. R. Hodges

Authors
  1. J. B. Deakin
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  2. S. Rahman
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  3. P. J. Nestor
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  4. J. R. Hodges
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  5. B. J. Sahakian
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Corresponding author

Correspondence to B. J. Sahakian.

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Deakin, J.B., Rahman, S., Nestor, P.J. et al. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology 172, 400–408 (2004). https://doi.org/10.1007/s00213-003-1686-5

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  • DOI: https://doi.org/10.1007/s00213-003-1686-5

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