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Atypical antipsychotics and pituitary tumors: a pharmacovigilance study.
Pharmacotherapy. 2006 Jun; 26(6):748-58.P

Abstract

STUDY OBJECTIVE

To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs.

DESIGN

Retrospective pharmacovigilance study.

DATA SOURCE

United States Food and Drug Administration's Adverse Event Reporting System (AERS) database.

INTERVENTION

We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D2-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D2 receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol.

MEASUREMENTS AND MAIN RESULTS

To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed:expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (>10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D2 receptors.

CONCLUSION

Treatment with potent D2-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies.

Authors+Show Affiliations

Office of Pharmacoepidemiology and Statistical Sciences, Immediate Office, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA. szarfman@cder.fda.govNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16716128

Citation

Szarfman, Ana, et al. "Atypical Antipsychotics and Pituitary Tumors: a Pharmacovigilance Study." Pharmacotherapy, vol. 26, no. 6, 2006, pp. 748-58.
Szarfman A, Tonning JM, Levine JG, et al. Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy. 2006;26(6):748-58.
Szarfman, A., Tonning, J. M., Levine, J. G., & Doraiswamy, P. M. (2006). Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy, 26(6), 748-58.
Szarfman A, et al. Atypical Antipsychotics and Pituitary Tumors: a Pharmacovigilance Study. Pharmacotherapy. 2006;26(6):748-58. PubMed PMID: 16716128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. AU - Szarfman,Ana, AU - Tonning,Joseph M, AU - Levine,Jonathan G, AU - Doraiswamy,P Murali, PY - 2006/5/24/pubmed PY - 2006/12/9/medline PY - 2006/5/24/entrez SP - 748 EP - 58 JF - Pharmacotherapy JO - Pharmacotherapy VL - 26 IS - 6 N2 - STUDY OBJECTIVE: To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs. DESIGN: Retrospective pharmacovigilance study. DATA SOURCE: United States Food and Drug Administration's Adverse Event Reporting System (AERS) database. INTERVENTION: We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D2-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D2 receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol. MEASUREMENTS AND MAIN RESULTS: To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed:expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (>10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D2 receptors. CONCLUSION: Treatment with potent D2-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies. SN - 0277-0008 UR - https://www.unboundmedicine.com/medline/citation/16716128/Atypical_antipsychotics_and_pituitary_tumors:_a_pharmacovigilance_study_ L2 - https://doi.org/10.1592/phco.26.6.748 DB - PRIME DP - Unbound Medicine ER -