Neuropsychiatric Effects of Antimalarial Treatments

Antimalarial drugs, essential in reducing global malaria burden, carry a spectrum of neuropsychiatric effects ranging from mild insomnia and vivid dreams to severe agitation, psychosis and cerebellar ataxia. Quinoline compounds, notably mefloquine and chloroquine, have been most closely associated with adverse mood changes, anxiety and, in rare cases, psychotic episodes or seizures. Proposed mechanisms include disruption of calcium homeostasis in neurons, induction of oxidative stress and perturbation of cholinergic neurotransmission. Artemisinin derivatives and partner drugs generally exhibit lower central nervous system penetration but can, at high doses or in susceptible individuals, precipitate sleep disturbances and transient cognitive slowing. Tetracycline-class agents such as doxycycline are infrequently implicated in neuropsychiatric manifestations, though isolated reports describe headache, dizziness and mood alteration. Risk factors include female sex, low body weight, high cumulative dose and pre-existing psychiatric history. Delayed syndromes, such as post-malaria neurological syndrome and autoimmune encephalitis, underscore immune-mediated contributions to late-onset neuropsychiatric complications. Clinicians must balance efficacy against potential central nervous system toxicity, applying careful screening, dose adjustment and monitoring strategies to mitigate risk while preserving the lifesaving benefits of antimalarial therapies.

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Neuropsychiatric Effects of Antimalarial Treatments publication trend

The graph below shows the total number of articles in neuropsychiatric effects of antimalarial treatments across all publications each year (not limited to Nature Index journals).

Technical terms

Mefloquine: A quinoline antimalarial known for its long half-life and association with central nervous system side effects.

Oxidative stress: A cellular state characterised by excess reactive oxygen species leading to neuronal injury.

Cholinesterases: Enzymes (acetylcholinesterase and butyrylcholinesterase) that hydrolyse acetylcholine and are targets for drug binding.

Post-malaria neurological syndrome (PMNS): A delayed onset of neurological and psychiatric symptoms occurring after apparent recovery from malaria.

Autoimmune encephalitis: Inflammation of brain tissue resulting from an aberrant immune response against neural antigens.

References

1. An In Silico and In Vitro Assessment of the Neurotoxicity of Mefloquine. Biomedicines (2024).
2. Anti-septin complex positive autoimmune encephalitis after severe falciparum malaria: a case report. Malaria Journal (2024).
3. Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives. Malaria Journal (2016).
4. The acute neurotoxicity of mefloquine may be mediated through a disruption of calcium homeostasis and ER function in vitro. Malaria Journal (2003).
5. Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature. Malaria Journal (2020).