David Baumeister1,2, Simone Ciufolini1,3, Valeria Mondelli4,5. 1. Department of Psychological Medicine, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Cutcombe Road, SE5 9RT, London, UK. 2. Department of Psychology London, King's College, Institute of Psychiatry, Psychology and Neuroscience, London, UK. 3. National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley, NHS Foundation Trust and King's College London, London, UK. 4. Department of Psychological Medicine, King's College London, Institute of Psychiatry, Psychology and Neuroscience, Cutcombe Road, SE5 9RT, London, UK. valeria.mondelli@kcl.ac.uk. 5. National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley, NHS Foundation Trust and King's College London, London, UK. valeria.mondelli@kcl.ac.uk.
Abstract
RATIONALE: 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. OBJECTIVE: 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. RESULTS: 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. CONCLUSIONS: 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.
RATIONALE: 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. OBJECTIVE: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Michael Maes; Gunter Kenis; Marta Kubera; Mark De Baets; Harry Steinbusch; Eugene Bosmans Journal: Int Immunopharmacol Date: 2005-03 Impact factor: 4.932
Authors: Jari-Pekka Klemettilä; Olli Kampman; Niko Seppälä; Merja Viikki; Mari Hämäläinen; Eeva Moilanen; Esa Leinonen Journal: Psychiatry Res Date: 2014-05-09 Impact factor: 3.222
Authors: Annamaria Cattaneo; Massimo Gennarelli; Rudolf Uher; Gerome Breen; Anne Farmer; Katherine J Aitchison; Ian W Craig; Christoph Anacker; Patricia A Zunsztain; Peter McGuffin; Carmine M Pariante Journal: Neuropsychopharmacology Date: 2012-09-19 Impact factor: 7.853
Authors: Mary de Groot; David Marrero; Lisa Mele; Todd Doyle; Frank Schwartz; Kieren J Mather; Ronald Goldberg; David W Price; Yong Ma; William C Knowler Journal: Psychosom Med Date: 2018 Feb/Mar Impact factor: 4.312