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Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate

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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.

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Acknowledgments

This work was supported by CHRU Montpellier, INSERM, Assistance Publique—Hôpitaux de Paris, and RTRS Santé Mentale (Fondation Fondamental). We thank Hélène Boudon and Arti Jetshan, fellows in pharmacy, Université Montpellier 1, Montpellier, F-34000, France, for their contribution in experiments.

Conflict of interest

Dr. G. Fond, Dr. A. Macgregor, Pr. M. Leboyer, Pr. R. Tamouza, Dr. N. Hamdani, Dr. A. Meary, and Dr. J. F. Dubremetz declare no conflict of interests in connection with the present study.

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Authors and Affiliations

  1. 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, Nora Hamdani, Alexandre Meary & Marion Leboyer

  2. INSERM U1061, Service Universitaire de Psychiatrie Adulte, Hôpital La Colombière, CHRU de Montpellier, 39 Avenue Charles Flahault, 34000, Montpellier, France

    Alexandra Macgregor

  3. Jean Dausset Department and INSERM UMRS 940, Hôpital Saint Louis, 75000, Paris, France

    Ryad Tamouza

  4. UMR 5235 CNRS, Université de Montpellier 2, Place Eugène Bataillon, 34000, Montpellier, France

    Jean-Francois Dubremetz

Authors
  1. Guillaume Fond
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  2. Alexandra Macgregor
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  3. Ryad Tamouza
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  4. Nora Hamdani
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  5. Alexandre Meary
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  6. Marion Leboyer
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  7. Jean-Francois Dubremetz
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Corresponding author

Correspondence to Guillaume Fond.

Additional information

M. Leboyer and J.-F. Dubremetz equally contributed to this work and are both last authors.

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Fond, G., Macgregor, A., Tamouza, R. et al. Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate. Eur Arch Psychiatry Clin Neurosci 264, 179–183 (2014). https://doi.org/10.1007/s00406-013-0413-4

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  • DOI: https://doi.org/10.1007/s00406-013-0413-4

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