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Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment?



Current psychotropic medications have been shown to modulate immune activation. However, the effects of individual psychotropic agents on the immune system and how these might contribute to their efficacy remain largely unclear.


This paper aims to review previous literature on the effects of antidepressants and antipsychotics on the immune system, with a systematic review of in vitro findings, and discuss the relevance of these effects for the response to treatment and future drug development.


Inflammatory markers have been associated with fluctuations in clinical status and with treatment response both in depression and psychosis. The in vitro literature on antidepressants shows that some antidepressants, such as clomipramine and fluoxetine, more consistently decrease pro-inflammatory cytokines (interleukin (IL)-6, interferon (IFN)-γ, tumour necrosis factor (TNF)-α), whilst others (mirtazapine and venlafaxine) tend to increase their levels. However, any overall conclusion is challenged by several inconsistent findings, which appear partly dependent on different methodological approaches used. The in vitro studies on antipsychotics are even less clear-cut showing pro- and anti-inflammatory activity for the same antipsychotic agent (haloperidol, clozapine, risperidone) across different studies. We also noted inconsistencies between in vivo and in vitro literature, which could partly be attributed to the interaction in vivo with various biological systems or lifestyle factors that can modulate the immune system.


Inflammatory markers seem to hold potential for developing more individualised treatment strategies in the future. In this context, further research disentangling the differential immunomodulatory effects of different drugs could be used for tailoring treatment to specific individuals, according to their immune endophenotypes.

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This work was supported by the National Institute for Health Research Mental Health Biomedical Research Centre in Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Conflict of interest

Dr. Mondelli has received research funding from Johnson & Johnson, a pharmaceutical company interested in the development of anti-inflammatory strategies for depression, but the research described in this paper is unrelated to this funding.

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Correspondence to Valeria Mondelli.

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Baumeister, D., Ciufolini, S. & Mondelli, V. Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment?. Psychopharmacology 233, 1575–1589 (2016).

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