Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Clin Psychiatry. 2019 Jul 30;80(4):19f12999. doi: 10.4088/JCP.19f12999.
The risk of bone fracture is increased in the elderly, in persons with depression, and in those who receive antidepressant drugs. Plausible mechanisms explain these risks. It is not clear whether the risk in depression is related to the disorder alone or to its treatment with antidepressant drugs as well; this is because observational studies of the fracture risk associated with antidepressant exposure may adjust analyses for confounding variables but cannot eliminate residual confounding by inadequately measured, unmeasured, and unknown confounds. A recent observational study examined hip fracture in the context of depression and antidepressant treatment using a resourceful method to address confounding by indication. The authors studied the risk of fracture not only in the year after antidepressant initiation but also in the year before antidepressant initiation. They found a significantly increased risk of fracture in all of 10 time windows during the 2 years; the highest risks, in fact, lay in the weeks to months before antidepressant initiation. These findings suggest that unremitted depression and persistence of depression-related mechanisms in remitted depression may together drive the risk of hip fracture in observational studies of antidepressant-treated patients; however, there is evidence from other sources to suggest that a contribution from antidepressant-related mechanisms cannot be ruled out. An additional message is that investigators need to use resourceful methods to address confounding by indication, as is now being done in several fields of research. Finally, readers who evaluate the findings of studies that relate exposures to outcomes must consider how the investigators addressed confounding and must draw conclusions based not merely on the findings but also on issues related to research design.
老年人、抑郁症患者以及接受抗抑郁药物治疗的人群骨折风险增加。这些风险可以用一些合理的机制来解释。目前尚不清楚抑郁症相关的风险是仅与疾病本身有关，还是与抗抑郁药物治疗有关；这是因为观察性研究对抗抑郁药物暴露与骨折风险的相关性进行分析时，虽然可以调整混杂因素，但仍可能存在未测量或未知的混杂因素。最近的一项观察性研究使用了一种资源丰富的方法，根据适应证调整分析，考察了抑郁症和抗抑郁药物治疗与髋部骨折之间的关系。作者不仅研究了抗抑郁药物治疗开始后一年的骨折风险，还研究了开始前一年的骨折风险。他们发现，在两年内的 10 个时间窗口中，骨折风险均显著增加；实际上，风险最高的时期是在开始使用抗抑郁药物前的几周至几个月内。这些发现表明，未缓解的抑郁症和缓解后抑郁症相关机制的持续存在，可能共同导致接受抗抑郁药物治疗的患者在观察性研究中出现髋部骨折的风险；但是，其他来源的证据表明，不能排除抗抑郁药物相关机制的作用。此外，研究人员需要使用资源丰富的方法来解决适应证偏倚问题，这在许多研究领域已经在进行。最后，评估与暴露相关的研究结果的读者必须考虑研究人员如何处理混杂因素，并不仅基于研究结果，还要基于与研究设计相关的问题得出结论。
