olanzapine and Pituitary-Neoplasms

One of the possible long-term consequences of antipsychotic-induced hyperprolactinemia is the development of pituitary tumors - prolactinomas. So far, two pharmacovigilance studies of spontaneous adverse event report databases have suggested an increased risk, whereas a longitudinal study carried out with risperidone showed no evidence of increased risk of tumors with mass effect. Besides, information on amisulpride and paliperidone is lacking. Thus, in this study, we aimed to analyze the European pharmacovigilance database (EudraVigilance) to shed light on this issue. We searched for all suspected spontaneous cases of pituitary tumors associated with antipsychotics in EudraVigilance up to 23 March 2017. To assess the association between pituitary tumor cases and each antipsychotic, we calculated the proportional reporting ratios. Among 4 964 866 events of all types recorded in EudraVigilance, we found 292 cases of pituitary tumors associated with antipsychotics. All atypical antipsychotics except clozapine fulfilled the criteria to generate a safety signal. The highest proportional reporting ratio values were found for amisulpride 51.57 (36.3-73.2), risperidone 21.83 (18.4-25.8), and paliperidone 19.95 (14.7-27.1). Sulpiride and haloperidol showed a higher risk among typical antipsychotics 12.4 (5.89-26.1) and 7.0 (4.35-11.3). Notably, we found that a mass effect was present in 16% of the cases. Besides, 18 cases occurred in patients aged below 18 years. Our analysis of the data in EudraVigilance confirms the safety signal detected by previous studies. Interestingly, for the first time, we show that the association seems to be the strongest for amisulpride and that a mass effect was present in around 16% of the cases.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Child; Databases, Factual; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Pharmacovigilance; Pituitary Neoplasms; Pregnancy; Quetiapine Fumarate; Retrospective Studies; Risperidone; Sulpiride; Young Adult

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Middle Aged; Olanzapine; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Psychotic Disorders; Remission, Spontaneous; Sulpiride; Thyrotropin-Releasing Hormone

Topics: Adenoma; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bromocriptine; Dopamine Antagonists; Female; Hormone Antagonists; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Pituitary Neoplasms; Quinolones; Risperidone; Schizophrenia; Serotonin Antagonists; Trifluoperazine

To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs.. Retrospective pharmacovigilance study.. United States Food and Drug Administration's Adverse Event Reporting System (AERS) database.. 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.. 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.. 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.

Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Amenorrhea; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Clozapine; Dibenzothiazepines; Female; Galactorrhea; Gynecomastia; Haloperidol; Humans; Hyperprolactinemia; Male; Olanzapine; Piperazines; Pituitary Neoplasms; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Sex Factors; Thiazoles; United States; United States Food and Drug Administration

Treatment-resistant schizophrenia presents a particular problem in patients who, for whatever reason, cannot be treated with clozapine. Pharmacological strategies for the further management of such individuals usually involve the coadministration of two or more antipsychotic drugs, leading to an increased potential for adverse effects. Hyperprolactinaemia (elevation of serum prolactin levels) is a common side-effect of antipsychotics and one that it is especially important to minimize in patients with primary pituitary pathology. We present a patient with treatment resistant schizophrenia and a prolactin-secreting microadenoma of the pituitary who was intolerant of clozapine therapy. She was prescribed a combination of olanzapine and quetiapine and experienced almost complete resolution of her psychosis, with no elevation of serum prolactin levels. We suggest that this may be a strategy worthy of consideration in patients for whom conventional treatment methods have failed, particularly those who are sensitive to the prolactinogenic effects of many antipsychotic medications.

Topics: Adenoma; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Olanzapine; Pituitary Neoplasms; Prolactin; Quetiapine Fumarate; Schizophrenia