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.
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
Giovanni
G
Brambilla
Francesca
F
Mattioli
Antonietta
A
Martelli
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