Institute for Safe Medication Practices, Alexandria, Virginia2Department of Epidemiology and Biostatistics, The George Washington University Milken Institute School of Public Health, Washington, DC.
Department of Psychiatry, Cambridge Hospital, Harvard Medical School, Cambridge, Massachusetts.
JAMA Intern Med. 2014 Dec;174(12):1930-3. doi: 10.1001/jamainternmed.2014.5262.
Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia.
To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System.
Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs.
We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3 receptor (n = 37; PRR = 8.6, P < .001).
Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings.
在病例系列和回顾性患者调查中，与使用多巴胺受体激动剂药物相关的严重冲动控制障碍，包括病理性赌博、性欲亢进和强迫性购物，已有报道。这些药物用于治疗帕金森病、不宁腿综合征和高催乳素血症。
分析美国食品和药物管理局（FDA）收到的关于这些冲动控制障碍的严重药物不良事件报告，并评估这些病例报告与 6 种 FDA 批准的多巴胺受体激动剂药物之间的关系。
设计、设置和参与者：我们对 2003 年至 2012 年从 FDA 不良事件报告系统中提取的 270 万例国内外严重不良药物事件报告进行了回顾性不成比例分析。
如果报告中包含 MedDRA（监管活动医学词典）中的 10 个首选术语之一来描述异常行为，则选择病例。我们使用比例报告比（PRR）来比较研究药物的目标事件与所有严重事件的比例与所有其他药物的相似比例。
我们从美国和其他 21 个国家/地区确定了 1580 例冲动控制障碍事件：710 例为多巴胺受体激动剂药物，870 例为其他药物。多巴胺受体激动剂药物与这些冲动控制障碍有强烈的信号关联（n=710；PRR=277.6，P<.001）。与多巴胺激动剂普拉克索（n=410；PRR=455.9，P<.001）和罗匹尼罗（n=188；PRR=152.5，P<.001）的关联最强，对多巴胺 D3 受体有优先亲和力。阿立哌唑（一种被归类为 D3 受体部分激动剂的抗精神病药物）也出现了信号（n=37；PRR=8.6，P<.001）。
我们的发现证实并扩展了证据，表明多巴胺受体激动剂药物与这些特定的冲动控制障碍有关。目前，FDA 批准的多巴胺受体激动剂药物均无作为处方信息一部分的盒装警告。我们的数据以及先前研究的数据表明，需要更突出的警告。
