Antimalarial drugs and the prevalence of mental and neurological manifestations: A systematic review and meta-analysis [version 1; peer review: 1 approved, 1 approved with reservations]

Abstract: Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans. Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques. Results: Of the 2,349 records identified in the initial search, 51 human studies met the eligibility criteria. The median pooled prevalence range of mental and neurological manifestations associated with antimalarial drugs ranged from 0.7% (dapsone) to 48.3% (minocycline) across all studies, while it ranged from 0.6% (pyrimethamine) to 42.7% (amodiaquine) during treatment of acute malaria, and 0.7% (primaquine/dapsone) to 55.0% (sulfadoxine) during prophylaxis. Pooled prevalence of mental and neurological manifestations across all studies was associated with an increased number of antimalarial drugs (prevalence ratio= 5.51 (95%CI, 1.05-29.04); P=0.045) in a meta-regression analysis. Headaches (15%) and dizziness (14%) were the most common mental and neurological manifestations across all studies. Of individual antimalarial drugs still on the market, mental and neurological manifestations were most common with the use of sulphadoxine (55%) for prophylaxis studies and amodiaquine (42.7%) for acute malaria studies. Mefloquine affected more domains of mental and neurological manifestations than any other antimalarial drug. Conclusions: Antimalarial drugs, particularly those used for prophylaxis, may be associated with mental and neurological manifestations, and the number of antimalarial 1 1 2,3 3,4 3 1,5 1 2 3 4 5 Reviewer Status Invited Reviewers version 2 published 02 Jun 2017 version 1 published 20 Feb 2017 1 2 report report report André Silva-Pinto, São João Hospital Center (CHSJ), Porto, Portugal 1 Melissa Gladstone , Liverpool School of Tropical Medicine, Liverpool, UK Institute of Translational Medicine, University of Liverpool, Liverpool, UK 2 First published: 20 Feb 2017, 2:13 ( https://doi.org/10.12688/wellcomeopenres.10658.1) Latest published: 02 Jun 2017, 2:13 ( https://doi.org/10.12688/wellcomeopenres.10658.2) v1 Page 1 of 20 Wellcome Open Research 2017, 2:13 Last updated: 23 NOV 2019 mental and neurological manifestations, and the number of antimalarial drugs taken determines the association. Mental and neurological manifestations should be assessed following the use of antimalarial drugs