抗抑郁药联合认知行为疗法对老年焦虑效果好

加州拉霍亚——美国焦虑与抑郁学会(ADAA)2013年会上公布的一项研究显示，选择性5-羟色胺再摄取抑制剂(SSRI)艾司西酞普兰联合认知行为疗法(CBT)对老年广泛性焦虑障碍(GAD)的效果较好。

这项随机对照研究在匹兹堡大学、华盛顿大学和加州大学圣地亚哥分校(UCSD)进行，纳入73例老年GAD患者，观察指标包括汉密尔顿焦虑量表和宾州忧虑问卷。

所有患者在一开始时接受艾司西酞普兰治疗，12周后，从汉密尔顿焦虑量表评分降低的情况来看，单用该药治疗的效果较好。不过，宾州忧虑问卷测定的忧虑评分未出现显著降低。12周后，患者被随机分成两组，一组继续使用艾司西酞普兰并同时接受CBT，另一组继续使用艾司西酞普兰但不接受CBT。汉密尔顿焦虑量表评分无显著降低，但接受CBT的患者的宾州忧虑问卷评分显著降低。在一个为期28周的维持期内，患者被进一步随机分组，一组减停药物过渡至安慰剂，另一组继续使用艾司西酞普兰。在接受增强CBT并持续使用艾司西酞普兰且再次接受进一步增强CBT的患者中，无1例出现复发。在未接受CBT但持续使用艾司西酞普兰的患者中观察到的预后相似。该研究结果表明，虽然CBT通常在作为单纯治疗时的效果不佳，但其具有一定的增强作用和预防复发的作用，这使得许多老年患者在停止药物治疗后仍可维持较好的精神状态。

研究者表示，苯二氮卓类药物和夜间镇静剂(如唑吡坦和艾司佐匹克隆)尤其可干扰对GAD的治疗。这些药物的副作用包括患者“时不时会忘记你说的话”，他们可在治疗期间睡着或处于半睡半醒状态。这些副作用在所有年龄组均可见到，但老年患者更易于发生苯二氮卓类和其他镇静剂的认知和镇静反应。老年患者较难安全治疗，因为伴随衰老出现的药代动力学改变可导致药物浓度更高及更多变。在大剂量用药(所用剂量高于FDA批准的剂量范围)、使用具有非线性药代动力学的药物或可抑制代谢的药物时需加以注意。此外，药效动力学的改变可导致对某一药物的敏感性(包括耐药性)增加。多重用药也是需注意的问题，如安非他酮合用帕罗西汀或氟西汀可发生相互作用，有时可将安非他酮的浓度推至毒性范围。使用多种抗胆碱能类药物或镇静剂可导致风险累积，也是一种不好的多重用药。

研究者声明从罗氏、Lundbeck公司和强生公司获得资金支持。

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By: DOUG BRUNK, Internal Medicine News Digital Network

LA JOLLA, CALIF. – When older adults with generalized anxiety disorder ask Julie Wetherell, Ph.D., for a nonmedication approach to deal with their symptoms, she faces a certain quandary.

"One of the most striking things to me as a psychotherapist working with older adults is how relatively ineffective psychotherapy is for anxiety in later life, as compared to psychotherapy for geriatric depression or psychotherapy for anxiety in younger or middle-aged people," Dr. Wetherell, of the psychiatry department at the University of California, San Diego (UCSD), said at the annual meeting of the Anxiety and Depression Association of America.
 
"When older people come to me with depression and they say, ‘I want a nonmedication approach,’ I say, ‘Fine. I have 10 or 12 interventions I can try and I’m confident they will work.’ But when someone comes to me and their primary problem is anxiety, I feel anxious, because I don’t have that level of confidence."

Data from a meta-analysis of 89 studies comparing psychotherapy with medication for depression found no significant difference between the two approaches (Am. J. Psych. 2006;163:1493-1501). However, a meta-analysis of 32 studies comparing psychotherapy with medication for anxiety found that patients treated with medication fared significantly better on clinician-rated outcome measures (P less than .001) (Am J. Geriatr. Psych. 2007;15:639-51). "The difference is not in the medications," said Dr. Wetherell, who was not involved with either study. "The odd man out is the psychotherapy for older adults with anxiety. Cognitive-behavioral therapy for generalized anxiety in older adults is better than nothing, but it’s not much better than nothing. We’re really not getting the results we would like to see with CBT for older people with GAD [generalized anxiety disorder]."

In a study soon to be published in the American Journal of Psychiatry, Dr. Wetherell and Dr. Eric Lenze conducted a randomized controlled trial that combined the selective serotonin reuptake inhibitor (SSRI) escitalopram with CBT in 73 older adults with GAD.

"We proposed a model by which older adults with GAD would first be treated with an SSRI to help with acute levels of distress and somatization," explained Dr. Lenze, a geriatric psychiatrist affiliated with the psychiatry department at Washington University in St. Louis, who specializes in anxiety disorders. "Then, after those benefits are realized with medication, [we would] continue the medication but add a course of CBT to address some of the underlying pathological worry that doesn’t seem particularly responsive to medication, and to improve coping skills as well."

Measures for the trial, which was carried out at the University of Pittsburgh, Washington University, and UCSD, included the Hamilton Anxiety Rating Scale and the Penn State Worry Questionnaire. All study participants started out with escitalopram and did well after 12 weeks in terms of reductions in the Hamilton Anxiety Rating Scale with the drug alone, "which is not surprising," Dr. Lenze said. "We did not see a whole lot of reduction in worry pathology as measured by the Penn State Worry Questionnaire."

At 12 weeks, patients remained on escitalopram and were then randomized to individual CBT or continued medication without CBT. "There was not a whole lot more reduction in the Hamilton Anxiety Rating Scale, but those who received CBT had a significant reduction in the Penn State Worry Questionnaire," Dr. Lenze said. The researchers further randomized individuals in a 28-week maintenance phase to either receive a taper down to placebo or to remain on escitalopram. None of the patients who received augmenting CBT and stayed on escitalopram and received further booster sessions of CBT relapsed.
 
"They had the best outcome as a group," Dr. Lenze said. "The group that didn’t receive CBT but stayed on medication had a nearly equal outcome." The findings suggest that while CBT often "doesn’t work well as a monotherapy, it seems to have some augmentation benefits and also some relapse prevention benefits, such that many older adults can get off medication and remain well."

In his opinion, benzodiazepines and nighttime sedatives such as zolpidem and eszopiclone particularly interfere with therapy for GAD. Side effects from these medications can include patients "forgetting what you said from session to session," Dr. Lenze said. "They may fall asleep during therapy or be in some phase between sleeping and waking. These side effects are true for all ages, but older adults are more susceptible to the cognitive and sedative effects of benzodiazepines and other sedatives."

Elderly patients are more difficult to treat safely, he added, because pharmacokinetic changes that occur with aging result in higher and more variable drug concentrations. "Watch out for megadoses of medications, which sometimes practitioners still use – doses well above the FDA-approved range – as well as drugs with nonlinear pharmacokinetics or drugs that inhibit metabolism, such a paroxetine or fluoxetine."

In addition, pharmacodynamic changes might result in increased sensitivity to a given drug, including treatment resistance. "Another problem is polypharmacy, such as someone who takes bupropion with paroxetine or fluoxetine, Dr. Lenze said. "Those two drugs interact, sometimes pushing the levels of bupropion to toxic ranges. The other bad kind of polypharmacy is taking multiple anticholinergics or sedatives that provide cumulative risk."

Dr. Wetherell said she had no relevant financial conflicts to disclose.

Dr. Lenze disclosed that he has received grant support from Roche, Lundbeck, and Johnson & Johnson.