Relationship Between Clozapine and Non-Hematological Malignant Tumors: A Pharmacovigilance Analysis Using the FDA Adverse Event Reporting System Database

Clozapine shows higher efficacy against treatment-resistant schizophrenia than other antipsychotics. This study aimed to investigate whether clozapine is associated with the risk of non-hematological malignant tumors, utilizing the US Food and Drug Administration (FDA) Adverse Event Report System (FAERS) database.

The records from the first quarter of 2004 to the third quarter of 2012 were used for disproportionality analysis, and patients who developed non-hematological malignant tumors were identified by the Standardized Medical Dictionary for Regulatory Activities Queries (SMQ).

Of the 3,641,281 patients with 12,401,586 reports of adverse drug events, 151,904 reports belonged to non-hematological malignant tumors (SMQ). We identified 1668 reports of non-hematological malignant tumors (SMQ) in clozapine users, and the reporting odds ratio (ROR) was calculated to be 1.28 (95% confidence interval (CI): 1.22–1.34). ROR (95% CI) for the relationship between clozapine and the risk of testis cancer was calculated as 10.94 (6.99–17.12), 9.87 (7.42–13.15) for gastrointestinal carcinoma, 7.48 (5.57–10.05) for metastatic lung cancer, 6.71 (4.52–9.97) for throat cancer, 6.12 (4.56–8.21) for metastases to the spine, 5.97 (5.30–6.72) for lung malignant neoplasm, 5.07 (3.69–6.95) for esophageal carcinoma, 1.88 (1.43–2.47) for colon cancer, and 1.65 (1.24–2.21) for metastases to the liver. Colon cancer, esophageal carcinoma, and throat cancer were predominantly reported in males, and metastases to the spine and liver were in females.

This study detected signals indicating a relationship between clozapine and certain non-hematological malignant tumors, utilizing the FAERS database. Despite the database relying on spontaneous reporting, the current results justify further investigation.