title: Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate.
abstract: Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ≈2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients.
authors.affiliation: Fondation FondaMental Fondation de Coopération Scientifique en Santé Mentale, Eq Psychiatrie Génétique, INSERM U955, DHU Pepsy, Pôle de Psychiatrie du Groupe des Hôpitaux Universitaires de Mondor, Université Paris Est-Créteil, 94000, Créteil, France, guillaume.fond@gmail.com.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Fond
authors.forename: Alexandra
authors.initials: A
authors.lastname: Macgregor
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: Nora
authors.initials: N
authors.lastname: Hamdani
authors.forename: Alexandre
authors.initials: A
authors.lastname: Meary
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Dubremetz
mesh_terms: D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy*; D014123:Toxoplasmosis; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000981:Antiprotozoal Agents; D014150:Antipsychotic Agents; D014635:Valproic Acid