Associations Between Venous Thromboembolism and Antipsychotics: A Study of the WHO Database of Adverse Drug Reactions

• Published in: Drug safety 2008-01, Vol.31 (8), p.685-694
• Main Authors: Hägg, Staffan, Bate, Andrew, Stahl, Malin, Spigset, Olav
• Format: Article
• Language: English
• Subjects: Adult; Adverse Drug Reaction Reporting Systems - statistics & numerical data; Antipsychotic Agents - adverse effects; Antipsychotics; Bayes Theorem; Benzodiazepines - adverse effects; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clopenthixol - adverse effects; Databases, Factual; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Safety and Pharmacovigilance; Drug toxicity and drugs side effects treatment; Female; Humans; Imidazoles - adverse effects; Indoles - adverse effects; Male; Medical sciences; MEDICIN; MEDICINE; Medicine & Public Health; Middle Aged; Original Research Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Time Factors; Toxicity: blood; Venous Thromboembolism - chemically induced; World Health Organization; Young Adult
• ISSN: 0114-5916; 1179-1942; 1179-1942
• DOI: 10.2165/00002018-200831080-00005

Background: Concern has been raised about the occurrence of venous thromboembolism (VTE) during treatment with antipsychotics. However, to date, clozapine is the only antipsychotic agent for which recurring evidence supports an association with VTE. Therefore, the aim of this study was to investigate the association between antipsychotic drugs, including clozapine and VTE. Study design and methods: Data mining of the WHO database of adverse drug reactions (ADRs) using Bayesian statistics is in routine use for early alerting to possible ADRs. An information component measure was used to investigate the association between antipsychotic drugs and VTE reactions in the database. Results: A total of 754 suspected cases of VTE related to treatment with antipsychotics had been reported. After excluding cases related to clozapine, 379 cases remained. A robust association was found for the second-generation antipsychotics group but not for the high-potency, first-generation antipsychotics group or the low-potency first-generation antipsychotics group. The individual compounds with statistically significant associations were olanzapine, sertindole and zuclopenthixol. A time-dependent analysis showed that the associations were positive for these drugs in 2002, 2001 and 2003, respectively. Case analyses were undertaken after excluding ten suspected duplicate reports. Of the remaining 369 cases, 91 cases were associated with olanzapine, 9 with zuclopenthixol and 6 with sertindole. Conclusions: VTE was more often reported with the antipsychotic drugs olanzapine, sertindole and zuclopenthixol than with other drugs in the WHO database. Further studies are warranted to explain this disproportional reporting. Since the associations found were based on incomplete clinical data, the results should be considered as preliminary and interpreted cautiously.