抗抑郁药对长期抑郁老年患者疗效较好

洛杉矶——美国老年精神病学会(AAGP)2013年会上公布的一项meta分析显示，抗抑郁药对长期患有至少中度重性抑郁障碍的老年患者疗效较好。另外，研究者表示，由于病程长的患者复发风险较高，加之抗抑郁药预防复发的作用已被确认，因此应考虑使用抗抑郁药治疗这些患者。

这项meta由加州大学旧金山分校的精神病学教授J. Craig Nelson博士及其同事进行，纳入7项具有完整信息的研究，涉及2,283例患者(平均71.4岁)，平均重性抑郁障碍病程为11.8年，平均基线汉密尔顿抑郁量表(HDRS)评分为21.5。约2/3(64.6%)的患者为女性，3/4(73.9%)患有复发性抑郁。

结果显示，安慰剂组观察到病程与疗效之间呈显著线性关联，但药物组未观察到此关联(z评分分别为–3.81和–0.92)，药物组基线抑郁严重程度与疗效显著相关，但安慰剂组未观察到此关联(z评分分别为3.40和–0.40)。

多因素分析显示，疗效的最强烈独立预测因素为病程，其次为抑郁严重程度。此外，还观察到抑郁严重程度与病程之间有交互作用。在抑郁病程＜10年且HDRS评分＜21的患者中，药物治疗组和安慰剂组的有效率分别为46.3%和41.5%，需治数为21；在抑郁病程＞10年且HDRS评分≥21的患者中，药物组和安慰剂组的有效率分别为58%和31.4%，需治数为4。

值得注意的是，虽然根据病程和严重程度能够识别药物疗效较佳的患者，但根据这两者也能够识别安慰剂疗效较佳的患者，即抑郁病程较短且疾病严重程度较轻的患者的安慰剂疗效较好，在40%~50%的此类患者中观察到此类疗效。不过，研究者表示，安慰剂组此类患者的较好疗效并不是单纯因为安慰剂，还因为对患者进行了随访观察，一般第1个月每周观察1次，此后可能每隔1周观察1次。研究者指出，临床管理是一个重要的治疗部分。

鉴于许多研究在进行药物治疗的同时还进行广泛临床管理，因此无法得出以下结论，即在不进行此类管理的情况下单凭药物治疗能否改善患者病情。需注意的是，有50%抑郁病程短且具有迟发性抑郁的患者经安慰剂和临床管理治疗后无效，这些患者将需要进一步治疗。

Nelson博士与多家药企和机构存在联系。

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By: SHARON WORCESTER, Internal Medicine News Digital Network

LOS ANGELES – Antidepressant medications have a robust effect in older patients with a long duration of major depressive disorder that is at least moderately severe, according to findings from a meta-analysis of data from seven trials.

Since patients with a long duration of disease are also at increased risk for recurrence, and since the efficacy of antidepressant medications for relapse prevention is well established, antidepressant treatment should be considered in these patients, Dr. J. Craig Nelson said at the annual meeting of the American Association for Geriatric Psychiatry.
 
Several prior studies have demonstrated that all classes of antidepressants generally are better than placebo for the treatment of depression in older adults, and that they have similar effectiveness, but the effects are modest, said Dr. Nelson, a professor of psychiatry at the University of California, San Francisco.

For example, in a 2008 meta-analysis of data from 10 studies that included adults aged 60 years and older with major depressive disorder, the response rates in the antidepressant and placebo groups were 44.4% vs. 34.7%, respectively (odds ratio, 1.40), and the remission rates were 34.6% vs. 26.5%, respectively (OR, 1.27), he said (Am. J. Geriatr. Psychiatry 2008;16:558-67).

The findings raised the question of whether moderators associated with a more robust response could be identified, he said, noting that several open studies have suggested that those with high levels of anxiety have lower responses to drug treatment, and several other moderators, such as disease severity and recurrent depression, appear to predict worse outcomes.

To look more closely at such moderators, Dr. Nelson and his colleagues revisited the 10 studies included in their 2008 meta-analysis, and obtained trial-level data from 8 of the studies for which complete information was available. They found no difference in outcomes between anxious and nonanxious depressed patients treated with antidepressants (Int. J. Geriatr. Psychiatry 2009;24:539-44).

The investigators decided to take an even closer look at possible moderators of response by performing a meta-analysis using patient-level data from seven of those trials for which complete information was available. These trials included 2,283 patients (mean age, 71.4 years), a mean duration of major depressive disorder of 11.8 years, and a mean baseline Hamilton Depression Rating Scale (HDRS) score of 21.5. About two-thirds (64.6%) were women, and nearly three-fourths (73.9%) had recurrent depression.

The findings, which were pending publication in the American Journal of Psychiatry at the time of Dr. Nelson’s presentation, showed significant linearity for the relationship between duration of illness and response in the placebo group, but not in the drug group (z scores, –3.81 and –0.92, respectively), and baseline depression severity was significantly associated with response in the drug group but not in the placebo group (z scores, 3.40 and –0.40, respectively).

On multivariate analysis, the strongest independent predictor of response was duration of illness, followed by severity of depression. An interaction between severity and duration also was noted.

"It turned out that among patients with longer duration of depression, severity did have a more significant relationship with drug-placebo difference. Among patients with a long duration of depression, patients with severity of at least moderate intensity – a Hamilton score of 21 or greater – showed the greatest drug effects," Dr. Nelson said.

Among patients with depression duration of less than 10 years and an HDRS score of less than 21, the response rates were 46.3% and 41.5% in the drug treatment vs. placebo groups, respectively, with a number needed to treat of 21; among patients with depression duration greater than 10 years and an HDRS score of 21 or greater, the response rates were 58% and 31.4% in the groups, respectively, with a number needed to treat of 4.

Of note, while disease duration and severity appear to identify patients who are more drug responsive, they also identify patients who have a pretty good response to placebo, he added.

That is, patients with a shorter duration of depression and less severe disease tend to have a good placebo response. Such a response is seen in 40%-50% of such patients.

"But of course, this is not just placebo. These are patients who are being seen, usually, on a weekly basis for the first month and then maybe every other week for the remainder of the trial," he explained, noting that the clinical management remains an important aspect of care.

Given that many trials include extensive clinical management along with drug treatment, it cannot be concluded that drug treatment without such management would lead to improvement, he said.

"So is it a mistake to give these patients an antidepressant? I think the mistake is not that you give an antidepressant; the mistake may be [thinking that is] all you need to do," he said. He added: "If clinical management is really accounting for most of the change, you can’t just give an antidepressant and walk away, and not do the clinical management."

A caveat, however, is that the about 50% of patients with short-duration and late-onset depression who do not respond to placebo with clinical management will need further treatment, he said.

Dr. Nelson disclosed that he has received honoraria from Korea Otsuka International Asia Arab Co. and has served as a paid consultant or advisory board member for Bristol-Myers Squibb, Cenestra Health, and other companies. He also has received research support from the National Institute of Mental Health and the Health Resources and Services Administration.