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Original Research

Antipsychotic Medication and Oxidative Cell Stress: A Systematic Review

Peter Lepping, MD, MRCPsych, MSc; John Delieu, PhD; Richard Mellor, MB, ChB, MRCPsych; John H. H. Williams, PhD; Peter R. Hudson, PhD; and Claire Hunter-Lavin, PhD

Published: June 29, 2010

Article Abstract

Objective: To look at (1) the association between antipsychotics and cell stress, (2) whether first-generation antipsychotics may show different effects than second-generation antipsychotics, and (3) whether recommendations can be made regarding medication.

Data Sources: We conducted a systematic review of 5 databases for all articles published until December 31, 2007: PubMed, Ovid MEDLINE, EMBASE, PsycINFO, and EBM Reviews. Under specific headings (eg, “heat shock proteins” and “oxidative stress”), a systematic search of these databases included such terms as HSP70 and homocysteine, and specific search strings were constructed. No limits were placed on the year or language of publication. References from pertinent articles or books were retrieved.

Study Selection: We included 42 articles of human studies from 2,387 references originally retrieved. We included only articles that (1) were quantitative; (2) referred only to human tissue, in vivo, or in vitro; (3) stated what tissue was examined; (4) identified what metabolites were measured; and (5) had references.

Data Extraction: All articles were assessed by 2 authors, which ensured that the inclusion criteria were met. The selected studies were too heterogeneous to be combined for any useful meta-analysis. Three authors, therefore, independently interpreted the data, using specified criteria to judge whether each study showed a beneficial, detrimental, or no effect on the markers measured.

Data Synthesis: The analysis revealed no conclusive association with direct or indirect markers of oxidative cell stress and antipsychotics. For every reviewed antipsychotic, we revealed differing research results showing a beneficial, detrimental, or no effect. This was true for in vivo as well as in vitro studies.

Conclusions: It remains unclear whether antipsychotics increase or reduce cell stress. Claims of neuroprotective properties of antipsychotics seem premature.

J Clin Psychiatry

Submitted: April 7, 2009; accepted September 16, 2009.

Online ahead of print: June 29, 2010 (doi:10.4088/JCP.09r05268yel).

Corresponding author: Peter Lepping, MD, Wrexham Academic Unit, Croesnewydd Rd, Wrexham, LL13 7TY, Wales, UK (

Volume: 71

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