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 metaanalytic 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 drugs taken determines the
association. Mental and neurological manifestations should be assessed following the use
of antimalarial drugs.