双相障碍与过早死亡高度相关

《美国医学会杂志-精神病学》7月17日在线发表了一项涉及近660万成人的瑞典全国性队列研究结果：女性和男性双相障碍患者过早死亡风险均高于无病者[JAMA Psychiatry 2013 July 17 (doi: 10.1001/jamapsychiatry.2013.1394)]。

斯坦福大学加州分校的Casey Crump博士及其同事报告称，校正年龄、婚姻状况、受教育水平、就业及收入状况后， 在6,618例双相障碍成人患者中，无论女性[校正后危险比(AHR)，2.34]还是男性(AHR，2.03)，其全因死亡率均比无病者增加1倍以上，死亡年龄分别提前9.0年和8.5年。

多种原因导致双相障碍患者过早死亡，包括心血管疾病、糖尿病、慢性阻塞性肺病(COPD)、流感或肺炎、意外伤害以及自杀。卒中和癌症(尤其是结肠癌)还是女性患者过早死亡的原因。自杀是双相障碍患者特殊风险因素，女性和男性患者自杀风险分别增加9倍和7倍(AHR分别为10.37 和8.09)，但非自然死亡并不能完全解释预期寿命差异。

双相障碍患者最主要的死因是流感或肺炎(女性和男性患者风险分别增加2.7和3.4倍)、糖尿病(风险分别增加2.6和1.6倍)以及COPD(风险分别增加1.9和1.6倍)。

研究者还利用另一个模型评估了物质使用障碍的潜在中介效应，结果发现该效应为中度。

对各种疾病与过早死亡的相关性分析显示，与无病者相比，慢性疾病与双相障碍患者过早死亡的相关程度最小(AHR，2.38  vs. 1.40)，表明早期诊断和治疗可能使这些患者的高死亡风险有所降低。

研究者认为：“应当对双相障碍患者采取更为全面的初级预防保健措施，以降低其早期死亡风险。”生活方式因素、病理生理机制、遗传因素以及某些双相障碍治疗药物等多重潜在机制导致了上述差异。

该研究显示，应用卡马西平、利培酮或丙戊酸或单用奥氮平可使双相障碍患者死亡率中度增加，而与单独使用锂盐相比，使用阿立哌唑、喹硫平或拉莫三嗪可使死亡率中度下降。但与既往研究结果一致的是，不使用上述药物的患者全因死亡率更高，自杀风险是用药者的2倍。

这项研究的受试者为截止2003年1月1日在瑞典至少生活2年的3,918例女性和2,700例男性患者，年龄≥20岁。随访时间为7年，评估患者的共病和死亡情况。这些患者是在最初2年通过任何诊断方法确诊以及通过双相障碍维持治疗常用特殊药物应用情况确认的患者。

研究者指出，这项研究首次利用完整的全国性人口诊断数据分析双相障碍与死亡率的相关性，进一步加深了人们对双相障碍患者过早死亡因素的了解，但尚不清楚这些结果能否外推至医疗体系不同的其他国家。

研究者推测，双相障碍患者与其他人群在健康方面的实质性差异，或许在那些没有全民医疗保险覆盖的其他国家更为明显。

该研究由国立药物滥用研究所和瑞典隆德医学训练与研究协议项目基金资助。研究者报告无利益冲突。

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By: SHARON WORCESTER, Internal Medicine News Digital Network

Women and men with bipolar disorder were more likely to die prematurely than were those without bipolar disorder, according to results from a Swedish national cohort study involving nearly 6.6 million adults.

After adjustment for age, marital status, educational level, employment status, and income, all-cause mortality among the 6,618 adults with bipolar disorder in the cohort was increased twofold for both women (adjusted hazard ratio, 2.34) and men (AHR, 2.03), who died an average of 9.0 and 8.5 years earlier, respectively, did than those without bipolar disorder, according to Dr. Casey Crump of Stanford (Calif.) University, and his colleagues.

Those with bipolar disorder died prematurely from various causes, including cardiovascular disease, diabetes, chronic obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional injuries, and suicide. Among women, stroke and cancer (particularly colon cancer) were also among the causes of premature death. Suicide was a particular risk for both women and men, who had 10-fold and 8-fold increases in risk, respectively (AHRs, 10.37 and 8.09), but the life expectancy differences were not fully explained by unnatural deaths, the investigators reported July 17 online in JAMA Psychiatry.

The most significant causes of death were influenza or pneumonia (3.7- and 4.4-fold increased risk for women and men, respectively), diabetes (3.6- and 2.6-fold increased risk, respectively), and COPD (2.9- and 2.6-fold increased risk).

In a separate model, the potential mediating effect of substance use disorders also was evaluated, and the effect was found to be modest, the investigators noted.

The associations between the various conditions and premature death were weakest for chronic diseases in those with a prior diagnosis, compared with those without a prior diagnosis (AHRs, 1.40 vs. 2.38), suggesting that earlier medical diagnosis and treatment might attenuate the increased mortality risk among affected individuals, they said (JAMA Psychiatry 2013 July 17 [doi: 10.1001/jamapsychiatry.2013.1394]).

"More complete provision of primary, preventive medical care among bipolar disorder patients is needed to reduce early mortality in this vulnerable population," they said, noting that multiple underlying mechanisms, including lifestyle factors, pathophysiologic mechanisms, genetic factors, and certain treatments for bipolar disorder, contribute to the disparities.

"The current study found evidence of modestly increased mortality among bipolar disorder patients who used carbamazepine, risperidone, or valproic acid or who solely used olanzapine, whereas users of aripiprazole, quetiapine, or lamotrigine had modestly reduced mortality compared with those who solely used lithium," they said.

However, consistent with prior research, those who used none of these medications had even higher rates of all-cause mortality – and twice the suicide risk – of those who used medication.

Study participants were 3,918 women and 2,700 men aged 20 years or older who lived in Sweden for at least 2 years as of Jan. 1, 2003. They were followed up to assess for physical comorbidities and mortality for 7 years. Bipolar disorder in the cohort was identified by any diagnosis during the preceding 2 years, and by the use of specific medications commonly used for bipolar disorder maintenance treatment.

The findings of this study, which is among the first to examine the association between bipolar disorder and mortality using complete diagnoses for a national population, adds to the increasing knowledge about factors that contribute to premature mortality in patients with bipolar disorder, but it is unclear to what extent the findings can be generalized to other health care systems, the investigators said.

"The substantial health disparities we found between bipolar disorder patients and the rest of the Swedish population may be even larger in other countries without universal health care," they noted.

This study was supported by a grant from the National Institute on Drug Abuse and an Agreement on Medical Training and Research (Lund, Sweden) project grant. The authors reported having no disclosures.