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社交焦虑障碍的药物治疗

Pharmacotherapy for social anxiety disorder (SAnD).

作者信息

Williams Taryn, Hattingh Coenraad J, Kariuki Catherine M, Tromp Sean A, van Balkom Anton J, Ipser Jonathan C, Stein Dan J

机构信息

Department of Psychiatry and Mental Health, University of Cape Town, Education Centre, Valkenberg Hospital, Private Bage X1, Observatory, Cape Town, South Africa, 7925.

出版信息

Cochrane Database Syst Rev. 2017 Oct 19;10(10):CD001206. doi: 10.1002/14651858.CD001206.pub3.

Abstract

BACKGROUND

Recognition is growing that social anxiety disorder (SAnD) is a chronic and disabling disorder, and data from early trials demonstrate that medication may be effective in its treatment. This systematic review is an update of an earlier review of pharmacotherapy of SAnD.

OBJECTIVES

To assess the effects of pharmacotherapy for social anxiety disorder in adults and identify which factors (methodological or clinical) predict response to treatment.

SEARCH METHODS

We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR-Studies and CCMDCTR-References) to 17 August 2015. The CCMDCTR contains reports of relevant RCTs from MEDLINE (1950-), Embase (1974-), PsycINFO (1967-) and CENTRAL (all years). We scanned the reference lists of articles for additional studies. We updated the search in August 2017 and placed additional studies in Awaiting Classification, these will be incorporated in the next version of the review, as appropriate.

SELECTION CRITERIA

We restricted studies to randomised controlled trials (RCTs) of pharmacotherapy versus placebo in the treatment of SAnD in adults.

DATA COLLECTION AND ANALYSIS

Two authors (TW and JI) assessed trials for eligibility and inclusion for this review update. We extracted descriptive, methodological and outcome information from each trial, contacting investigators for missing information where necessary. We calculated summary statistics for continuous and dichotomous variables (if provided) and undertook subgroup and sensitivity analyses.

MAIN RESULTS

We included 66 RCTs in the review (> 24 weeks; 11,597 participants; age range 18 to 70 years) and 63 in the meta-analysis. For the primary outcome of treatment response, we found very low-quality evidence of treatment response for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (number of studies (k) = 24, risk ratio (RR) 1.65; 95% confidence interval (CI) 1.48 to 1.85, N = 4984). On this outcome there was also evidence of benefit for monoamine oxidase inhibitors (MAOIs) (k = 4, RR 2.36; 95% CI 1.48 to 3.75, N = 235), reversible inhibitors of monoamine oxidase A (RIMAs) (k = 8, RR 1.83; 95% CI 1.32 to 2.55, N = 1270), and the benzodiazepines (k = 2, RR 4.03; 95% CI 2.45 to 6.65, N = 132), although the evidence was low quality. We also found clinical response for the anticonvulsants with gamma-amino butyric acid (GABA) analogues (k = 3, RR 1.60; 95% CI 1.16 to 2.20, N = 532; moderate-quality evidence). The SSRIs were the only medication proving effective in reducing relapse based on moderate-quality evidence. We assessed tolerability of SSRIs and the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine on the basis of treatment withdrawal; this was higher for medication than placebo (SSRIs: k = 24, RR 2.59; 95% CI 1.97 to 3.39, N = 5131, low-quality evidence; venlafaxine: k = 4, RR 3.23; 95% CI 2.15 to 4.86, N = 1213, moderate-quality evidence), but there were low absolute rates of withdrawal for both these medications classes compared to placebo. We did not find evidence of a benefit for the rest of the medications compared to placebo.For the secondary outcome of SAnD symptom severity, there was benefit for the SSRIs, the SNRI venlafaxine, MAOIs, RIMAs, benzodiazepines, the antipsychotic olanzapine, and the noradrenergic and specific serotonergic antidepressant (NaSSA) atomoxetine in the reduction of SAnD symptoms, but most of the evidence was of very low quality. Treatment with SSRIs and RIMAs was also associated with a reduction in depression symptoms. The SSRIs were the only medication class that demonstrated evidence of reduction in disability across a number of domains.We observed a response to long-term treatment with medication for the SSRIs (low-quality evidence), for the MAOIs (very low-quality evidence) and for the RIMAs (moderate-quality evidence).

AUTHORS' CONCLUSIONS: We found evidence of treatment efficacy for the SSRIs, but it is based on very low- to moderate-quality evidence. Tolerability of SSRIs was lower than placebo, but absolute withdrawal rates were low.While a small number of trials did report treatment efficacy for benzodiazepines, anticonvulsants, MAOIs, and RIMAs, readers should consider this finding in the context of potential for abuse or unfavourable side effects.

摘要

背景

越来越多的人认识到社交焦虑障碍(SAnD)是一种慢性致残性疾病,早期试验数据表明药物治疗可能对其有效。本系统评价是对早期社交焦虑障碍药物治疗综述的更新。

目的

评估药物治疗对成人社交焦虑障碍的疗效,并确定哪些因素(方法学或临床因素)可预测治疗反应。

检索方法

我们检索了Cochrane常见精神障碍对照试验注册库(CCMDCTR-研究和CCMDCTR-参考文献)至2015年8月17日。CCMDCTR包含来自MEDLINE(1950年起)、Embase(1974年起)、PsycINFO(1967年起)和CENTRAL(所有年份)的相关随机对照试验报告。我们查阅了文章的参考文献列表以寻找其他研究。我们在2017年8月更新了检索,并将其他研究置于“等待分类”中,这些研究将在综述的下一版本中酌情纳入。

选择标准

我们将研究限制为药物治疗与安慰剂对比治疗成人社交焦虑障碍的随机对照试验(RCT)。

数据收集与分析

两位作者(TW和JI)评估试验是否符合本次综述更新的纳入标准。我们从每项试验中提取描述性、方法学和结果信息,必要时联系研究者获取缺失信息。我们计算了连续变量和二分变量的汇总统计量(如提供),并进行了亚组分析和敏感性分析。

主要结果

我们在综述中纳入了66项RCT(>24周;11597名参与者;年龄范围18至70岁),在荟萃分析中纳入了63项。对于治疗反应的主要结局,我们发现与安慰剂相比,选择性5-羟色胺再摄取抑制剂(SSRI)治疗反应的证据质量极低(研究数量(k)=24,风险比(RR)1.65;95%置信区间(CI)1.48至1.85,N = 4984)。关于这一结局,也有证据表明单胺氧化酶抑制剂(MAOI)(k = 4,RR 2.36;95%CI 1.48至3.75,N = 235)、单胺氧化酶A可逆抑制剂(RIMA)(k = 8,RR 1.83;95%CI 1.32至2.55,N = 1270)和苯二氮卓类药物(k = 2,RR 4.03;95%CI 2.45至6.65,N = 132)有益,尽管证据质量较低。我们还发现γ-氨基丁酸(GABA)类似物的抗惊厥药有临床反应(k = 3,RR 1.60;95%CI 1.16至2.20,N = 532;中等质量证据)。基于中等质量证据,SSRI是唯一被证明对减少复发有效的药物。我们根据治疗停药情况评估了SSRI以及5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)文拉法辛的耐受性;药物治疗的耐受性高于安慰剂(SSRI:k = 24,RR 2.59;95%CI 1.97至3.39,N = 5131,低质量证据;文拉法辛:k = 4,RR 3.23;95%CI 2.15至4.86,N = 1213,中等质量证据),但与安慰剂相比,这两类药物的绝对停药率都较低。与安慰剂相比,我们未发现其他药物有益的证据。对于社交焦虑障碍症状严重程度的次要结局,SSRI、SNRI文拉法辛、MAOI、RIMA、苯二氮卓类药物、抗精神病药物奥氮平以及去甲肾上腺素能和特异性5-羟色胺能抗抑郁药(NaSSA)阿托西汀在减轻社交焦虑障碍症状方面有益,但大多数证据质量极低。SSRI和RIMA治疗也与抑郁症状减轻相关。SSRI是唯一一类在多个领域显示出有减少残疾证据的药物。我们观察到SSRI(低质量证据)、MAOI(极低质量证据)和RIMA(中等质量证据)长期药物治疗有反应。

作者结论

我们发现了SSRI治疗有效的证据,但基于极低至中等质量的证据。SSRI的耐受性低于安慰剂,但绝对停药率较低。虽然少数试验确实报告了苯二氮卓类药物、抗惊厥药、MAOI和RIMA的治疗疗效,但读者应在存在滥用可能性或不良副作用的背景下考虑这一发现。

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