Antipsychotics and Mood Stabilizers as Potential Anti-Toxoplasma Agents: A Critical Mechanistic Review of Molecular, Anti-inflammatory, and Histopathological Evidence

Saadatnia, Geita; Enshaeieh, Marjan

doi:10.22104/mmb.2026.8327.1208

Antipsychotics and Mood Stabilizers as Potential Anti-Toxoplasma Agents: A Critical Mechanistic Review of Molecular, Anti-inflammatory, and Histopathological Evidence

Articles in Press

Document Type : Review Paper

Authors

Geita Saadatnia

Marjan Enshaeieh

Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran

10.22104/mmb.2026.8327.1208

Abstract

Toxoplasma gondii is a neurotropic protozoan parasite that can establish long-term infection in the central nervous system. Chronic cerebral infection has been associated with neuroinflammation, altered neurotransmission, and increased susceptibility to neuropsychiatric disorders, particularly schizophrenia and bipolar disorder. Current anti-Toxoplasma therapies mainly target actively replicating stages and show limited efficacy against established tissue cysts, while toxicity and treatment tolerance remain important concerns. These limitations have increased interest in psychiatric drugs with reported antiparasitic and immunomodulatory properties. This critical mechanistic review evaluates evidence on selected antipsychotics and mood stabilizers, mainly valproic acid, haloperidol, and risperidone, as possible adjunctive candidates against T. gondii infection. The analysis focuses on parasite-related outcomes, including parasite burden, REP-529 copy number, and BAG1 expression, as well as host inflammatory responses, particularly TNF-α expression, microglial activation, and cytokine-associated neuroinflammation. Histopathological evidence related to cyst establishment, perivascular infiltration, glial nodules, encephalitis, and preservation of brain tissue integrity is also considered. Available findings suggest that these drugs may affect parasite persistence and infection-associated inflammation under defined experimental conditions. However, inconsistencies across in vitro assays, animal models, and limited clinical observations indicate that their therapeutic relevance remains uncertain. Further mechanistic, pharmacological, and translational studies are required before these agents can be considered for clinical application in Toxoplasmosis.

Keywords

Toxoplasma gondii

Antipsychotics

Mood stabilizers

Neuroinflammation

Subjects