Maeshima Tae, Iijima Ryosuke, Watanabe Machiko, Yui Satoru, Itagaki Fumio
Department of Clinical & Pharmaceutical Sciences, Faculty of Pharma Science, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
Department of Medical & Pharmaceutical Sciences, Faculty of Pharma Science, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
J Pharm Health Care Sci. 2021 Apr 1;7(1):13. doi: 10.1186/s40780-021-00199-7.
Since antipsychotics induce hyperprolactinemia via the dopamine D receptor, long-term administration may be a risk factor for developing breast tumors, including breast cancer. On the other hand, some antipsychotic drugs have been reported to suppress the growth of breast cancer cells in vitro. Thus, it is not clear whether the use of antipsychotics actually increases the risk of developing or exacerbating breast tumors. The purpose of this study was to clarify the effects of antipsychotic drugs on the onset and progression of breast tumors by analyzing an adverse event spontaneous reporting database and evaluating the proliferation ability of breast cancer cells.
Japanese Adverse Drug Event Report database (JADER) reports from April 2004 to April 2019 were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. Reports of females only were analyzed. Adverse events included in the analysis were hyperprolactinemia and 60 breast tumor-related preferred terms. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) were used to detect signals. Furthermore, MCF-7 cells were treated with haloperidol, risperidone, paliperidone, sulpiride, olanzapine and blonanserin, and cell proliferation was evaluated by WST-8 assay.
In the JADER analysis, the IC signals of hyperprolactinemia were detected with sulpiride (IC, 3.73; 95% CI: 1.81-5.65), risperidone (IC, 3.69; 95% CI: 1.71-5.61), and paliperidone (IC, 4.54; 95% CI: 2.96-6.12). However, the IC signal of breast tumors was not observed with any antipsychotics. In cell-based experiments, MCF-7 cells were treated with six antipsychotics at concentrations of 2 and 32 μM, and none of the drugs showed any growth-promoting effects on MCF-7 cells. On the other hand, blonanserin markedly suppressed the growth of MCF-7 cells at a concentration of 32 μM, and the effect was concentration dependent.
Analysis of the JADER using the IC did not show breast tumor signals due to antipsychotic drugs. In in vitro experiments, antipsychotics did not promote MCF-7 cell proliferation whereas blonanserin suppressed MCF-7 cell growth. Further research on the effects of blonanserin on the onset and progression of breast tumor is expected.
由于抗精神病药物通过多巴胺D受体诱导高催乳素血症，长期使用可能是发生包括乳腺癌在内的乳腺肿瘤的危险因素。另一方面，有报道称一些抗精神病药物在体外可抑制乳腺癌细胞的生长。因此，目前尚不清楚使用抗精神病药物是否真的会增加发生或加重乳腺肿瘤的风险。本研究的目的是通过分析不良事件自发报告数据库并评估乳腺癌细胞的增殖能力，来阐明抗精神病药物对乳腺肿瘤发生和进展的影响。
从药品和医疗器械局（PMDA）网站获取2004年4月至2019年4月的日本药品不良事件报告数据库（JADER）报告。仅分析女性报告。分析中纳入的不良事件包括高催乳素血症和60个与乳腺肿瘤相关的首选术语。采用报告比值比（ROR）、比例报告比（PRR）和信息成分（IC）来检测信号。此外，用氟哌啶醇、利培酮、帕利哌酮、舒必利、奥氮平和布南色林处理MCF-7细胞，并通过WST-8法评估细胞增殖。
在JADER分析中，舒必利（IC，3.73；95%CI：1.81-5.65）、利培酮（IC，3.69；95%CI：1.71-5.61）和帕利哌酮（IC，4.54；95%CI：2.96-6.12）检测到高催乳素血症的IC信号。然而，未观察到任何抗精神病药物的乳腺肿瘤IC信号。在细胞实验中，用六种抗精神病药物以2和32μM的浓度处理MCF-7细胞，没有一种药物对MCF-7细胞显示出任何促生长作用。另一方面，布南色林在32μM浓度下显著抑制MCF-7细胞的生长，并呈浓度依赖性。
使用IC对JADER进行分析未显示抗精神病药物导致乳腺肿瘤的信号。在体外实验中，抗精神病药物未促进MCF-7细胞增殖，而布南色林抑制MCF-7细胞生长。期待进一步研究布南色林对乳腺肿瘤发生和进展的影响。
