Genotoxic and carcinogenic effects of antipsychotics and antidepressants.
This review provides a compendium of the results of genotoxicity and carcinogenicity assays performed on marketed antipsychotics and antidepressants. Of the 104 drugs examined, 47 (45.2%) do not have retrievable data. The remaining 57 (54.8%) have at least one and often more than one genotoxicity and/or carcinogenicity test result. Of these 57 drugs, 33 (57.9%) have at least one positive finding: 24 tested positive in at least one genotoxicity assay, 14 in at least one carcinogenicity assay, and 5 gave a positive response in both. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 25 drugs have both genotoxicity and carcinogenicity data: 8 of them (32.0%) were neither genotoxic nor carcinogenic, 8 (32.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 4 (16.0%) tested positive in at least one genotoxicity assay but were non-carcinogenic, and 5 (20.0%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 16 (15.4%) of the 104 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior to the present regulatory climate.
Brambilla
Giovanni
G
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedettio XV 2, I-16132 Genoa, Italy. Antonietta.Martelli@unige.it
Mattioli
Francesca
F
Martelli
Antonietta
A
D000818:Animals; D000928:Antidepressive Agents / Q000633:toxicity*; D014150:Antipsychotic Agents / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002869:Chromosome Aberrations / Q000139:chemically induced*; D003257:Consumer Product Safety; D006801:Humans; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000139:chemically induced*; D018570:Risk Assessment
D000928:Antidepressive Agents; D014150:Antipsychotic Agents