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Journal of Neurology
Published in: Journal of Neurology 12/2021

01-12-2021 | Amyotrophic Lateral Sclerosis | Review

A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis

Authors: Emily Beswick, Emily Park, Charis Wong, Arpan R. Mehta, Rachel Dakin, Siddharthan Chandran, Judith Newton, Alan Carson, Sharon Abrahams, Suvankar Pal

Published in: Journal of Neurology | Issue 12/2021

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Abstract

Background

Up to 50% of people with amyotrophic lateral sclerosis (ALS) experience cognitive dysfunction, whilst depression and anxiety are reported in up to 44% and 33%, respectively. These symptoms impact on quality of life, and are associated with a poorer prognosis. Historically, outcomes in clinical trials have focused on the effect of candidate drugs on physical functioning.

Methods

We reviewed the past 25 years of clinical trials of investigative medicinal products in people with ALS, since the licensing of riluzole, and extracted data on frequency and type of assessment for neuropsychiatric symptoms and cognitive impairment. Trial registry databases, including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed, were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 31/10/2019. No language restrictions were applied. Outcome measures, exclusion criteria and assessment tool used were extracted.

Results

216 trials, investigating 26,326 people with ALS, were reviewed. 35% assessed neuropsychiatric symptoms, and 22% assessed cognition, as Exclusion Criteria or Outcome Measures. 3% (n = 6) of trials assessed neuropsychiatric symptoms as a Secondary Outcome Measure, and 4% (n = 8) assessed cognition as Outcome Measures; only one trial included assessments for both cognition and neuropsychiatric symptoms as Outcome Measures. Three ALS-specific assessments were used in six trials.

Conclusions

Trials for people with ALS have neglected the importance of neuropsychiatric symptoms and cognitive impairment. Evaluation of these extra-motor features is essential to understanding the impact of candidate drugs on all symptoms of ALS.

PROPSERO registration

CRD42020175612.
Appendix
Available only for authorised users
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Metadata
Title
A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis
Authors
Emily Beswick
Emily Park
Charis Wong
Arpan R. Mehta
Rachel Dakin
Siddharthan Chandran
Judith Newton
Alan Carson
Sharon Abrahams
Suvankar Pal
Publication date
01-12-2021
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 12/2021
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-020-10203-z

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