治疗目标是消除抑郁症状,改善日常功能及生活质量,[58]Hofmann SG, Curtiss J, Carpenter JK, et al. Effect of treatments for depression on quality of life: a meta-analysis. Cogn Behav Ther. 2017 Jun;46(4):265-86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663193/http://www.ncbi.nlm.nih.gov/pubmed/28440699?tool=bestpractice.com 提高工作能力,[59]Lee Y, Rosenblat JD, Lee J, et al. Efficacy of antidepressants on measures of workplace functioning in major depressive disorder: a systematic review. J Affect Disord. 2018 Feb;227:406-15.http://www.ncbi.nlm.nih.gov/pubmed/29154157?tool=bestpractice.com 减少自杀行为,最大限度地减少治疗不良反应,以及防止复发。[60]Barbui C, Butler R, Cipriani A, et al. Depression in adults. BMJ Clinical Evid, Issue 16, 2006.http://www.clinicalevidence.com/ceweb/conditions/meh/1003/1003.jsp 治疗形式包括抗抑郁药物、其他药物治疗、心理治疗、支持性干预,以及及电休克治疗(ECT)。对于接受门诊治疗的抑郁症患者,协作性慢病照护模式可以带来显著获益,该模式包括患者培训、组织支持、社区资源和其他多学科干预。[61]Woltmann E, Grogan-Kaylor A, Perron B, et al. Comparative effectiveness of collaborative chronic care models for mental health conditions across primary, specialty, and behavioral health care settings: systematic review and meta-analysis. Am J Psychiatry. 2012 Aug;169(8):790-804.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2012.11111616http://www.ncbi.nlm.nih.gov/pubmed/22772364?tool=bestpractice.com[62]Richards DA, Hill JJ, Gask L, et al. Clinical effectiveness of collaborative care for depression in UK primary care (CADET): cluster randomised controlled trial. BMJ. 2013 Aug 19;347:f4913.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746956/http://www.ncbi.nlm.nih.gov/pubmed/23959152?tool=bestpractice.com [
]In adults with depression and anxiety problems, what are the benefits and harms of collaborative care compared with usual care?https://cochranelibrary.com/cca/doi/10.1002/cca.495/full显示答案协同诊疗似乎对仅患抑郁症的患者和抑郁症共患慢性身体疾病的患者都有效。[63]Panagioti M, Bower P, Kontopantelis E, et al. Association between chronic physical conditions and the effectiveness of collaborative care for depression: an individual participant data meta-analysis. JAMA Psychiatry. 2016 Sep 1;73(9):978-89.http://www.ncbi.nlm.nih.gov/pubmed/27602561?tool=bestpractice.com 有效部署协作性照护模式尚未解决的问题包括服务提供者的教育、财务问题和联络沟通。[64]Overbeck G, Davidsen AS, Kousgaard MB. Enablers and barriers to implementing collaborative care for anxiety and depression: a systematic qualitative review. Implement Sci. 2016 Dec 28;11(1):165.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192575/http://www.ncbi.nlm.nih.gov/pubmed/28031028?tool=bestpractice.com利用基于互联网和移动方式的干预措施也被证明可以减缓抑郁症状。[65]Josephine K, Josefine L, Philipp D, et al. Internet- and mobile-based depression interventions for people with diagnosed depression: a systematic review and meta-analysis. J Affect Disord. 2017 Dec 1;223:28-40.http://www.ncbi.nlm.nih.gov/pubmed/28715726?tool=bestpractice.com[66]Păsărelu CR, Andersson G, Bergman Nordgren L, et al. Internet-delivered transdiagnostic and tailored cognitive behavioral therapy for anxiety and depression: a systematic review and meta-analysis of randomized controlled trials. Cogn Behav Ther. 2017 Jan;46(1):1-28. http://www.ncbi.nlm.nih.gov/pubmed/27712544?tool=bestpractice.com
重度抑郁
严重抑郁症患者包括精神病、自杀、白内障或严重的精神运动迟缓,阻碍日常生活活动,或产生严重躁动。这些患者会有以下风险的增高:自杀,冲动和潜在自我毁灭的行为,因自我照料差或僵住不动而导致的躯体并发症。
须转诊至主任医生、住院、持续观察、镇静和/或接受 ECT 治疗以保证患者安全,直到确定性抗抑郁治疗起效。一旦风险得到稳定,此类患者采用的药物和非药物治疗方案将在 "中度抑郁症" 一节(见下)中进行讨论。
如果患者存在以下情况时,应转诊至专科咨询,考虑住院:
自杀风险管理
自杀风险评估至关重要,特别是在治疗初期,该风险可能会增加。常规询问患者自杀观念,并勿使其接近致命手段或装备(尤其是枪支)能够降低自杀风险。[67]Mann JJ, Apter A, Bertolote J, et al. Suicide prevention strategies: a systematic review. JAMA. 2005 Oct 26;294(16):2064-74.http://www.ncbi.nlm.nih.gov/pubmed/16249421?tool=bestpractice.com 由受过训练的精神科医生密切的电话随访可能有助于减少此前有过自杀企图者再次自杀身亡的风险。[68]Vaiva G, Vaiva G, Ducrocq F, et al. Effect of telephone contact on further suicide attempts in patients discharged from an emergency department: randomised controlled study. BMJ. 2006 May 27;332(7552):1241-5.http://www.ncbi.nlm.nih.gov/pubmed/16735333?tool=bestpractice.com
药物治疗
处方抗抑郁药的一般性原则在下述关于 "中度抑郁症" 一节中予以描述。单纯抗抑郁药可能无法有效解决精神症状,如妄想或幻觉;[69]Wijkstra J, Lijmer J, Burger H, et al. Pharmacological treatment for psychotic depression. Cochrane Database Syst Rev. 2015 Jul 30;(7):CD004044.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004044.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26225902?tool=bestpractice.com 因此,在若干情况下,临床医生在重症病例中,在抗抑郁药物中添加抗精神病药物的门槛应该更低。
电休克疗法 (Electroconvulsive therapy,ECT)
尽管大多数转为 ECT治疗的患者都已尝试过其他抗抑郁药物治疗,但在某些严重抑郁症患者中, ECT 可被考虑为一线治疗。在治疗早期可用于治疗精神性疾病,自杀或紧张性抑郁障碍,治疗后期可用于难治性抑郁或者无法耐受抗抑郁治疗的患者。对重度抑郁的老年患者,ECT 通常是首选治疗;ECT 具有疗效,[70]Geduldig ET, Kellner CH. Electroconvulsive therapy in the elderly: new findings in geriatric depression. Curr Psychiatry Rep. 2016 Apr;18(4):40.http://www.ncbi.nlm.nih.gov/pubmed/26909702?tool=bestpractice.com 并可避免可能由于药物不耐受,以及与并存机体疾病治疗相关的药物相互作用所产生的并发症。
患者和临床医生必须充分了解潜在风险,以便患者能够达成知情同意。ECT 的死亡率估计约为每 100,000次治疗2例死亡,[71]Watts BV, Groft A, Bagian JP. An examination of mortality and other adverse events related to electroconvulsive therapy using a national adverse event report system. J ECT. 2011 Jun;27(2):105-8.http://www.ncbi.nlm.nih.gov/pubmed/20966769?tool=bestpractice.com[72]Tørring N, Sanghani SN, Petrides G, et al. The mortality rate of electroconvulsive therapy: a systematic review and pooled analysis. Acta Psychiatr Scand. 2017 May;135(5):388-97.http://www.ncbi.nlm.nih.gov/pubmed/28332236?tool=bestpractice.com这意味着这种治疗方法是全麻情况下进行的安全性更高的手术之一。冠心病患者的死亡风险可能升高,因为从理论上来讲,在诱发癫痫发作时,此类患者缺血的风险升高。一项系统评价显示,大多数患者在治疗期间和治疗不久之后报告出现认知方面的不良反应,其中最常见的是记忆减退(可为顺行性和逆行性遗忘)。[73]Rose D, Fleischmann P, Wykes T, et al. Patients' perspectives on electroconvulsive therapy: systematic review. BMJ. 2003 Jun 21;326(7403):1363.http://www.ncbi.nlm.nih.gov/pubmed/12816822?tool=bestpractice.com 客观评估显示,这种损害的持续时间似乎不长,[74]Semkovska M, McLoughlin DM. Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biol Psychiatry. 2010 Sep 15;68(6):568-77.http://www.ncbi.nlm.nih.gov/pubmed/20673880?tool=bestpractice.com 尽管很大一部分患者诉 ECT 治疗后出现持续性记忆丢失。[73]Rose D, Fleischmann P, Wykes T, et al. Patients' perspectives on electroconvulsive therapy: systematic review. BMJ. 2003 Jun 21;326(7403):1363.http://www.ncbi.nlm.nih.gov/pubmed/12816822?tool=bestpractice.com必须权衡这种治疗方法的潜在风险与疗效证据,特别是对重度抑郁患者。
支持性治疗
心理治疗
中度抑郁症
中度抑郁症患者有严重的症状,、明显的障碍,但没有精神病症状, 没有自杀念想,没有严重的精神运动迟缓或躁动。此类患者十分痛苦,如果不能顺利完成正常的生活任务,他们就将会发现这样做无比困难。
抗抑郁药物在这些患者中是有必要应用的,[75]Gibbons RD, Hur K, Brown CH, et al. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012 Jun;69(6):572-9.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371295/http://www.ncbi.nlm.nih.gov/pubmed/22393205?tool=bestpractice.com[76]Vöhringer PA, Ghaemi SN. Solving the antidepressant efficacy question: effect sizes in major depressive disorder. Clin Ther. 2011 Dec;33(12):B49-61.http://www.clinicaltherapeutics.com/article/S0149-2918%2811%2900770-3/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/22136980?tool=bestpractice.com[77]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-66.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/29477251?tool=bestpractice.com 但可能不足以改善患者的结局。中度至重度抑郁症患者可从抗抑郁药物治疗和心理治疗的结合中得到最大获益。[78]Oestergaard S, Møldrup C. Optimal duration of combined psychotherapy and pharmacotherapy for patients with moderate and severe depression: a meta-analysis. J Affect Disord. 2011 Jun;131(1-3):24-36.http://www.ncbi.nlm.nih.gov/pubmed/20950863?tool=bestpractice.com抑郁症状:中等质量证据显示,联合药物治疗和心理治疗较两者单用更能改善抑郁患者的症状。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 在治疗开始阶段,密切的随访和最少化的支持或教育干预,可以提高患者对药物的依从性。它们还可以降低自残或自杀的风险,这些风险可以在恢复的最早期阶段出现,此时能量水平和觉醒有所增加,但情绪依然低落。
抗抑郁药物治疗的一般原则
抗抑郁药物的选择取决于不同制剂相对疗效以外的其他因素; 各个抗抑郁药物之间在安全性或疗效方面没有一致的差异,[79]Gartlehner G, Hansen RA, Morgan LC, et al. Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis. Ann Intern Med. 2011 Dec 6;155(11):772-85.http://annals.org/article.aspx?articleid=1033198http://www.ncbi.nlm.nih.gov/pubmed/22147715?tool=bestpractice.com 尽管在一项大型荟萃分析中揭示了药物之间在功效和可接受性方面存在的一些头对头差异,但可被认为是治疗选择中需要考虑的众多因素之一。[77]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-66.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32802-7/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/29477251?tool=bestpractice.com 根据对15项急性期重度抑郁症对照试验取得的个体患者数据进行的一项不同的荟萃分析显示,米氮平可能是比SSRIs更快速有效的抗抑郁药。[80]Thase ME, Nierenberg AA, Vrijland P, et al. Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression. Int Clin Psychopharmacol. 2010 Jul;25(4):189-98.http://www.ncbi.nlm.nih.gov/pubmed/20531012?tool=bestpractice.com [
]Is there randomized controlled trial evidence to support the use of mirtazapine in people with depression?https://cochranelibrary.com/cca/doi/10.1002/cca.810/full显示答案
药物选择应该基于患者的偏好、耐受性,以及其既往用药有效性证据。如果某种抗抑郁药对患者的家庭成员有效,一些临床医生可能会在考虑使用此抗抑郁药治疗该患者时降低用药门槛。其中一个理由是,见证了特定药物对某位家庭成员有效后,患者可能更容易接受用该药物治疗,而且对恢复的期望也会更高。然而,这不是一种循证的方法; 药物基因组学的进展(检查可遗传的遗传因素对个体患者的治疗效果和药物耐受性的影响)可能会最终对这个问题予以澄清,但药物基因组学分析尚未推荐用于常规使用。[81]Peterson K, Dieperink E, Anderson J, et al. Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder. Psychopharmacology (Berl). 2017 Jun;234(11):1649-61.http://www.ncbi.nlm.nih.gov/pubmed/28456840?tool=bestpractice.com
虽然抗抑郁反应的最终结果是自杀意念的显著减少,[75]Gibbons RD, Hur K, Brown CH, et al. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012 Jun;69(6):572-9.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371295/http://www.ncbi.nlm.nih.gov/pubmed/22393205?tool=bestpractice.com[82]Rucci P, Frank E, Scocco P, et al. Treatment-emergent suicidal ideation during 4 months of acute management of unipolar major depression with SSRI pharmacotherapy or interpersonal psychotherapy in a randomized clinical trial. Depress Anxiety. 2011 Apr;28(4):303-9.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079416/http://www.ncbi.nlm.nih.gov/pubmed/21308882?tool=bestpractice.com 但有部分证据表明,在治疗的起初数周,自杀行为将增加,特别是在青少年和年轻成人中,以及在药物起始剂量相对较高的患者中。[83]Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA. 2004 Jul 21;292(3):338-43.https://jamanetwork.com/journals/jama/fullarticle/199120http://www.ncbi.nlm.nih.gov/pubmed/15265848?tool=bestpractice.com[84]Miller M, Swanson SA, Azrael D, et al. Antidepressant dose, age, and the risk of deliberate self-harm. JAMA Intern Med. 2014 Jun;174(6):899-909.http://archinte.jamanetwork.com/article.aspx?articleid=1863925http://www.ncbi.nlm.nih.gov/pubmed/24782035?tool=bestpractice.com 一些证据表明,青少年和年轻成人特别容易经历自杀和自残意念的增加。[85]Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomized controlled trials submitted to the MHRA's safety review. BMJ. 2005 Feb 19;330(7488):385.http://www.ncbi.nlm.nih.gov/pubmed/15718537?tool=bestpractice.com[86]Saperia J, Ashby D, Gunnell D. Suicidal behaviour and SSRIs: updated meta-analysis. BMJ. 2006 Jun 17;332(7555):1453.http://www.ncbi.nlm.nih.gov/pubmed/16777898?tool=bestpractice.com 一项大型 meta 分析结果表明,在 25 岁以下的成人患者中,自杀念头出现和恶化的风险在治疗的第 3-6 周(而不是第 1-2 周)可能增加,此结果比其他研究得出的结果更晚。[87]Näslund J, Hieronymus F, Lisinski A,et al. Effects of selective serotonin reuptake inhibitors on rating-scale-assessed suicidality in adults with depression. Br J Psychiatry. 2018 Mar;212(3):148-54.http://www.ncbi.nlm.nih.gov/pubmed/29436321?tool=bestpractice.com
在开始治疗后的 1 至 2 周内对患者进行随访,然后在接下来的12周内每月对患者进行随访。如果您更倾向于系统性评估,可利用患者健康问卷 9(PHQ-9)来评估症状严重程度的变化。在2至4周后出现部分反应的患者中,将抗抑郁药物剂量滴定至最大耐受剂量。患者很可能在治疗的前1至2周内开始出现反应;然而,成功的抗抑郁治疗到所有症状的缓解时间点可能需要6至8周。症状评分减少达 50% 提示患者对药物反应良好,减少 25% 到 50% 之间可能提示需要调整治疗。
根据已知的目标剂量范围确定抗抑郁药物剂量。在少数患者中,药物基因组学检测可能表明根据基因型采用最小或最大剂量。总的来说,没有证据支持常规给予增加超过既定剂量范围的剂量。[88]Dold M, Bartova L, Rupprecht R, et al. Dose escalation of antidepressants in unipolar depression: a meta-analysis of double-blind, randomized controlled trials. Psychother Psychosom. 2017 Sep 14;86(5):283-91.http://www.ncbi.nlm.nih.gov/pubmed/28903107?tool=bestpractice.com
如果对一线治疗的反应不足,可以考虑改用替代抗抑郁药物。[89]McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006 Sep;163(9):1531-41.http://ajp.psychiatryonline.org/doi/full/10.1176/ajp.2006.163.9.1531http://www.ncbi.nlm.nih.gov/pubmed/16946177?tool=bestpractice.com[90]Schlaepfer TE, Agren H, Monteleone P, et al. The hidden third: improving outcome in treatment-resistant depression. J Psychopharmacol. 2012 May;26(5):587-602.http://www.ncbi.nlm.nih.gov/pubmed/22236505?tool=bestpractice.com 到4项不同的试验性用药结束时,60% 至70% 的患者可能会对治疗做出反应。如果在治疗的前2周内没有出现症状改善,则可能需要更换药物;[91]Kemp DE, Ganocy SJ, Brecher M, et al. Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression. J Affect Disord. 2011 Apr;130(1-2):171-9.http://www.ncbi.nlm.nih.gov/pubmed/21071096?tool=bestpractice.com[92]Lam RW. Onset, time course and trajectories of improvement with antidepressants. Eur Neuropsychopharmacol. 2012;22(suppl 3):S492-8.http://www.ncbi.nlm.nih.gov/pubmed/22959114?tool=bestpractice.com 然而,要知道早期反应可能是,但不一定是持续反应的可靠指标。[93]Wagner S, Engel A, Engelmann J, et al. Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with major depressive disorder: systematic review and meta-analysis. J Psychiatr Res. 2017 Nov;94:96-106.http://www.ncbi.nlm.nih.gov/pubmed/28697423?tool=bestpractice.com[94]Olgiati P, Serretti A, Souery D, et al. Early improvement and response to antidepressant medications in adults with major depressive disorder. Meta-analysis and study of a sample with treatment-resistant depression. J Affect Disord. 2018 Feb;227:777-86.http://www.ncbi.nlm.nih.gov/pubmed/29254066?tool=bestpractice.com 如果至少在整个6到8周内有一些改善,则继续治疗,但如果处方药物提供的是不充分的获益,则不要无限期的继续使用。 值得一提的是,在使用氟西汀治疗的患者中,如果一开始症状没有改善,一项研究表明随着时间延长,得到肯定疗效的可能性下降。[95]Posternak MA, Baer L, Nierenberg AA, et al. Response rates to fluoxetine in subjects who initially show no improvement. J Clin Psychiatry. 2011 Jul;72(7):949-54.http://www.ncbi.nlm.nih.gov/pubmed/21672502?tool=bestpractice.com
症状缓解后的治疗时间取决于病程。有证据表明,当抗抑郁药物持续6个月以上时,复发的风险会降低。[96]Baldessarini RJ, Lau WK, Sim J, et al. Duration of initial antidepressant treatment and subsequent relapse of major depression. J Clin Psychopharmacol. 2015 Feb;35(1):75-6.http://www.ncbi.nlm.nih.gov/pubmed/25502491?tool=bestpractice.com[97]Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003 Feb 22;361(9358):653-61.http://www.ncbi.nlm.nih.gov/pubmed/12606176?tool=bestpractice.com[98]El-Mallakh RS, Briscoe B. Studies of long-term use of antidepressants: how should the data from them be interpreted? CNS Drugs. 2012 Feb 1;26(2):97-109.http://www.ncbi.nlm.nih.gov/pubmed/22296314?tool=bestpractice.com复发:高质量证据显示,使用处方抗抑郁药维持治疗较安慰剂更能降低在 1 到 3 年内患者的复发率。系统评价或者受试者>200名的随机对照临床试验(RCT)。 在缓解后9至12个月内继续进行成功的抗抑郁治疗。[97]Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003 Feb 22;361(9358):653-61.http://www.ncbi.nlm.nih.gov/pubmed/12606176?tool=bestpractice.com[98]El-Mallakh RS, Briscoe B. Studies of long-term use of antidepressants: how should the data from them be interpreted? CNS Drugs. 2012 Feb 1;26(2):97-109.http://www.ncbi.nlm.nih.gov/pubmed/22296314?tool=bestpractice.com复发:高质量证据显示,使用处方抗抑郁药维持治疗较安慰剂更能降低在 1 到 3 年内患者的复发率。系统评价或者受试者>200名的随机对照临床试验(RCT)。 如果患者有多次发作和复发、治疗反应不充分或药物滥用等复杂问题,可能会导致复发,则需无限期的继续进行维持治疗。[99]Bauer M, Severus E, Köhler S, et al; World Federation of Societies of Biological Psychiatry Task Force on Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 2: maintenance treatment of major depressive disorder - update 2015. World J Biol Psychiatry. 2015 Feb;16(2):76-95.http://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/Bauer_et_al_2015.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25677972?tool=bestpractice.com
心理治疗和其他非药物治疗
各种形式的心理治疗已被证明在减少抑郁症状方面既有效又可兼顾成本。[100]Health Quality Ontario. Psychotherapy for major depressive disorder and generalized anxiety disorder: a health technology assessment. Ont Health Technol Assess Ser. 2017 Nov 13;17(15):1-167.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709536/http://www.ncbi.nlm.nih.gov/pubmed/29213344?tool=bestpractice.com[101]Karyotaki E, Smit Y, de Beurs DP, et al. The long-term efficacy of acute-phase psychotherapy for depression: a meta-analysis of randomized trials. Depress Anxiety. 2016 May;33(5):370-83.http://www.ncbi.nlm.nih.gov/pubmed/27000501?tool=bestpractice.com
除了药物治疗策略,认知行为疗法(CBT)与药理安慰剂比较,在不同的严重程度均显示了更优的疗效。[102]Furukawa TA, Weitz ES, Tanaka S, et al. Initial severity of depression and efficacy of cognitive-behavioural therapy: individual-participant data meta-analysis of pill-placebo-controlled trials. Br J Psychiatry. 2017 Mar;210(3):190-6.http://www.ncbi.nlm.nih.gov/pubmed/28104735?tool=bestpractice.com 在一些研究中,CBT 的治疗效果与抗抑郁药的治疗效果相当。[103]Gartlehner G, Wagner G, Matyas N, et al. Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews. BMJ Open. 2017 Jun 14;7(6):e014912.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623437/http://www.ncbi.nlm.nih.gov/pubmed/28615268?tool=bestpractice.com 分阶段治疗试验表明在持续治疗期内使用 CBT 可能会特别有益;CBT 至少可减低复发/再发风险,并且或许优于抗抑郁药持续治疗。[104]Kuyken W, Hayes R, Barrett B, et al. Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial. Lancet. 2015 Jul 4;386(9988):63-73.http://www.sciencedirect.com/science/article/pii/S0140673614622224http://www.ncbi.nlm.nih.gov/pubmed/25907157?tool=bestpractice.com[105]Guidi J, Tomba E, Fava GA. The sequential integration of pharmacotherapy and psychotherapy in the treatment of major depressive disorder: a meta-analysis of the sequential model and a critical review of the literature. Am J Psychiatry. 2016 Feb 1;173(2):128-37.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2015.15040476http://www.ncbi.nlm.nih.gov/pubmed/26481173?tool=bestpractice.com[106]Bockting CLH, Klein NS, Elgersma HJ, et al. Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial. Lancet Psychiatry. 2018 May;5(5):401-10.http://www.ncbi.nlm.nih.gov/pubmed/29625762?tool=bestpractice.com 大量临床试验的结果表明,正念 CBT 对预防复发尤其有效。[107]Kuyken W, Warren FC, Taylor RS, et al. Efficacy of mindfulness-based cognitive therapy in prevention of depressive relapse: an individual patient data meta-analysis from randomized trials. JAMA Psychiatry. 2016 Jun 1;73(6):565-74.http://www.ncbi.nlm.nih.gov/pubmed/27119968?tool=bestpractice.com 辅助性 CBT 也被发现能改善初级医疗机构中的抑郁症治疗结局。[108]Wiles N, Thomas L, Abel A, et al. Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial. Health Technol Assess. 2014 May;18(31):1-167.https://www.ncbi.nlm.nih.gov/books/NBK261983/http://www.ncbi.nlm.nih.gov/pubmed/24824481?tool=bestpractice.com
治疗师常常联合使用认知行为疗法 (CBT)抑郁症状:中等质量证据表明,对于门诊或社区的老年患者,认知治疗较没有治疗更能改善抑郁症状。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 和人际心理治疗 (interpersonal psychotherapy, IPT)[109]Cuijpers P, Geraedts AS, van Oppen P, et al. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry. 2011 Jun;168(6):581-92.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2010.10101411http://www.ncbi.nlm.nih.gov/pubmed/21362740?tool=bestpractice.com治疗成功:高质量的证据表明,人际心理治疗单独使用或与药物治疗联用可有效减轻抑郁。[109]Cuijpers P, Geraedts AS, van Oppen P, et al. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry. 2011 Jun;168(6):581-92.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2010.10101411http://www.ncbi.nlm.nih.gov/pubmed/21362740?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。或者问题解决治疗 (problem-solving therapy, PST)。[110]Bell AC, D'Zurilla TJ. Problem-solving therapy for depression: a meta-analysis. Clin Psychol Rev. 2009 Jun;29(4):348-53.http://www.ncbi.nlm.nih.gov/pubmed/19299058?tool=bestpractice.com[111]Kirkham JG, Choi N, Seitz DP. Meta-analysis of problem solving therapy for the treatment of major depressive disorder in older adults. Int J Geriatr Psychiatry. 2016 May;31(5):526-35.http://www.ncbi.nlm.nih.gov/pubmed/26437368?tool=bestpractice.comIPT 可能改善人际方面的功能,而 CBT 似乎拥有持续的效果,能降低治疗结束后的后续风险。[112]Hollon SD, DeRubeis RJ, Shelton RC, et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry. 2005 Apr;62(4):417-22.http://www.ncbi.nlm.nih.gov/pubmed/15809409?tool=bestpractice.com IPT 仅在患者拥有心理方面的内省能力并能够进行长期治疗时有效。[113]De Mello MF, De Jesus Mari J, Bacaltchuk J, et al. A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci. 2005 Apr;255(2):75-82.http://www.ncbi.nlm.nih.gov/pubmed/15812600?tool=bestpractice.com 进行 CBT 和 IPT 的频率应由治疗者决定,大致的起效时间在 12 周。PST 着重训练当前情境下解决问题的态度和技巧。[110]Bell AC, D'Zurilla TJ. Problem-solving therapy for depression: a meta-analysis. Clin Psychol Rev. 2009 Jun;29(4):348-53.http://www.ncbi.nlm.nih.gov/pubmed/19299058?tool=bestpractice.com[114]Cuijpers P, van Straten A, Warmerdam L. Problem solving therapies for depression: a meta-analysis. Eur Psychiatry. 2007 Jan;22(1):9-15.http://www.ncbi.nlm.nih.gov/pubmed/17194572?tool=bestpractice.com
阅读疗法是一种自助阅读计划,可能对某些患者有长期益处。[115]Gualano MR, Bert F, Martorana M, et al. The long-term effects of bibliotherapy in depression treatment: systematic review of randomized clinical trials. Clin Psychol Rev. 2017 Dec;58:49-58.http://www.ncbi.nlm.nih.gov/pubmed/28993103?tool=bestpractice.com
行为激活治疗是 CBT 的一种替代方法,这种方法较少强调大脑,而更多强调行为。它能有效促进功能恢复,还有一个优点是无需医生级别的治疗师即可应用。一项随机对照试验发现,对于成人抑郁症来说,它的效力不亚于CBT。[116]Richards DA, Ekers D, McMillan D, et al. Cost and outcome of behavioural activation versus cognitive behavioural therapy for depression (COBRA): a randomised, controlled, non-inferiority trial. Lancet. 2016 Aug 27;388(10047):871-80.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007415/http://www.ncbi.nlm.nih.gov/pubmed/27461440?tool=bestpractice.com
对于那些对抗抑郁药无效或不能耐受的患者,可选择 ECT 治疗;抑郁症状:中等质量的证据显示,对于中重度抑郁患者,治疗 1-6 周期间,ECT 较模拟治疗或抗抑郁药更能改善症状。但 ECT 相比模拟治疗,更易在治疗后立即出现认知功能受损。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 严重抑郁症患者的反应率优于中度或 轻度抑郁症患者。
轻度抑郁症
轻度抑郁症的患者具有严重程度为低至中度的症状,部分损害,无精神病症状,无自杀意念,并且没有精神运动迟缓或躁动。
患者治疗效果相当,无论是采用 CBT 治疗抑郁症状:中等质量证据表明,对于门诊或社区的老年患者,认知治疗较没有治疗更能改善抑郁症状。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 亦或是采用抗抑郁药物治疗。[117]Gartlehner G, Gaynes BN, Amick HR, et al. Comparative benefits and harms of antidepressant, psychological, complementary, and exercise treatments for major depression: an evidence report for a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016 Mar 1;164(5):331-41.http://www.ncbi.nlm.nih.gov/pubmed/26857743?tool=bestpractice.com抑郁症状:低质量证据显示,服用处方抗抑郁药 [三环类抗抑郁药(包括小剂量三环类抗抑郁药)、SSRI 类、MAOI 类或文拉法辛] 较安慰剂对所有程度的抑郁都更有效。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 对这个群体而言,联合心理治疗和药物治疗并未被证实具有短期获益,但长程的心理治疗与抗抑郁药维持在不管是急性期还是持续期治疗均是有效的方法。[78]Oestergaard S, Møldrup C. Optimal duration of combined psychotherapy and pharmacotherapy for patients with moderate and severe depression: a meta-analysis. J Affect Disord. 2011 Jun;131(1-3):24-36.http://www.ncbi.nlm.nih.gov/pubmed/20950863?tool=bestpractice.com
初始的治疗选择应当以患者偏好为导向,包括:
抗抑郁药物治疗
心理治疗[118]Cuijpers P, van Straten A, van Schaik A, et al. Psychological treatment of depression in primary care: a meta-analysis. Br J Gen Pract. 2009 Feb;59(559):e51-60.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629842http://www.ncbi.nlm.nih.gov/pubmed/19192368?tool=bestpractice.com[119]Cuijpers P, van Straten A, Andersson G, et al. Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. J Consult Clin Psychol. 2008 Dec;76(6):909-22.http://www.ncbi.nlm.nih.gov/pubmed/19045960?tool=bestpractice.com[120]Cuijpers P, van Straten A, Warmerdam L, et al. Psychological treatment of depression: a meta-analytic database of randomized studies. BMC Psychiatry. 2008 May 16;8:36.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408566http://www.ncbi.nlm.nih.gov/pubmed/18485191?tool=bestpractice.com
支持性干预包括:自助手册、瑜伽、放松训练、光照治疗、运动、太极、音乐治疗,以及针灸。[121]Aalbers S, Fusar-Poli L, Freeman RE, et al. Music therapy for depression. Cochrane Database Syst Rev. 2017 Nov 16;(11):CD004517.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004517.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29144545?tool=bestpractice.com[122]Even C, Schröder CM, Friedman S, et al. Efficacy of light therapy in nonseasonal depression: a systematic review. J Affect Disord. 2008 May;108(1-2):11-23.http://www.ncbi.nlm.nih.gov/pubmed/17950467?tool=bestpractice.com[123]Penders TM, Stanciu CN, Schoemann AM, et al. Bright light therapy as augmentation of pharmacotherapy for treatment of depression: a systematic review and meta-analysis. Prim Care Companion CNS Disord. 2016 Oct 20;18(5).http://www.ncbi.nlm.nih.gov/pubmed/27835725?tool=bestpractice.com[124]Morgan, AJ, Jorm AF. Self-help interventions for depressive disorders and depressive symptoms: a systematic review. Ann Gen Psychiatry. 2008 Aug 19;7:13.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542367http://www.ncbi.nlm.nih.gov/pubmed/18710579?tool=bestpractice.com[125]Sun YL, Chen SB, Gao Y, et al. Acupuncture versus western medicine for depression in China: a systematic review. Chin J Evid Based Med. 2008;8:340-5.[126]Herring MP, Puetz TW, O'Connor PJ, et al. Effect of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Jan 23;172(2):101-11.http://archinte.jamanetwork.com/article.aspx?articleid=1108677http://www.ncbi.nlm.nih.gov/pubmed/22271118?tool=bestpractice.com[127]Chi I, Jordan-Marsh M, Guo M, et al. Tai chi and reduction of depressive symptoms for older adults: a meta-analysis of randomized trials. Geriatr Gerontol Int. 2013 Jan;13(1):3-12.http://www.ncbi.nlm.nih.gov/pubmed/22680972?tool=bestpractice.com[128]Bridle C, Spanjers K, Patel S, et al. Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2012 Sep;201(3):180-5.http://bjp.rcpsych.org/content/201/3/180.full.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22945926?tool=bestpractice.com[129]Belvederi Murri M, Amore M, Menchetti M, et al; Safety and Efficacy of Exercise for Depression in Seniors (SEEDS) Study Group. Physical exercise for late-life major depression. Br J Psychiatry. 2015 Sep;207(3):235-42.http://bjp.rcpsych.org/content/207/3/235.longhttp://www.ncbi.nlm.nih.gov/pubmed/26206864?tool=bestpractice.com[130]Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016 Jan;73(1):56-63.http://www.ncbi.nlm.nih.gov/pubmed/26580307?tool=bestpractice.com[131]Trivedi MH, Greer TL, Church TS, et al. Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison. J Clin Psychiatry. 2011 May;72(5):677-84.http://www.ncbi.nlm.nih.gov/pubmed/21658349?tool=bestpractice.com[132]Cooney GM, Dwan K, Greig CA, et al. Exercise for depression. Cochrane Database Syst Rev. 2013 Sep 12;(9):CD004366.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004366.pub6/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24026850?tool=bestpractice.com[133]Sukhato K, Lotrakul M, Dellow A, et al. Efficacy of home-based non-pharmacological interventions for treating depression: a systematic review and network meta-analysis of randomised controlled trials. BMJ Open. 2017 Jul 12;7(7):e014499.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734422/http://www.ncbi.nlm.nih.gov/pubmed/28706086?tool=bestpractice.com[134]Catalan-Matamoros D, Gomez-Conesa A, Stubbs B, et al. Exercise improves depressive symptoms in older adults: an umbrella review of systematic reviews and meta-analyses. Psychiatry Res. 2016 Oct 30;244:202-9.http://www.ncbi.nlm.nih.gov/pubmed/27494042?tool=bestpractice.com[135]Smith CA, Armour M, Lee MS, et al. Acupuncture for depression. Cochrane Database Syst Rev. 2018 Mar 4;(3):CD004046.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004046.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29502347?tool=bestpractice.com [
]What are the effects of exercise for improving symptoms in adults with depression?https://cochranelibrary.com/cca/doi/10.1002/cca.355/full显示答案 和
基于计算机的心理治疗(Computer-based treatment):CBT[136]Spek V, Nyklícek I, Smits N, et al. Internet-based cognitive behavioural therapy for subthreshold depression in people over 50 years old: a randomized controlled clinical trial. Psychol Med. 2007 Dec;37(12):1797-806.http://www.ncbi.nlm.nih.gov/pubmed/17466110?tool=bestpractice.com[137]Kaltenthaler E, Parry G, Beverley C, et al. Computerised cognitive-behavioural therapy for depression: systematic review. Br J Psychiatry. 2008 Sep;193(3):181-4.https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/computerised-cognitivebehavioural-therapy-for-depression-systematic-review/CB1DC3F5CE548A93B1049382AE958B01http://www.ncbi.nlm.nih.gov/pubmed/18757972?tool=bestpractice.com[138]Alvarez LM, Sotres JF, Leon SO, et al. Computer program in the treatment for major depression and cognitive impairment in university students. Comp Human Behav. 2008 May;24(3):816-26.[139]Charova E, Dorstyn D, Tully P, et al. Web-based interventions for comorbid depression and chronic illness: a systematic review. J Telemed Telecare. 2015 Jun;21(4):189-201.http://www.ncbi.nlm.nih.gov/pubmed/insert id?tool=bestpractice.com[140]Karyotaki E, Riper H, Twisk J, et al. Efficacy of self-guided internet-based cognitive behavioral therapy in the treatment of depressive symptoms: a meta-analysis of individual participant data. JAMA Psychiatry. 2017 Apr 1;74(4):351-9.https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2604310http://www.ncbi.nlm.nih.gov/pubmed/28241179?tool=bestpractice.com[141]Zhou T, Li X, Pei Y, et al. Internet-based cognitive behavioural therapy for subthreshold depression: a systematic review and meta-analysis. BMC Psychiatry. 2016 Oct 21;16(1):356.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073460/http://www.ncbi.nlm.nih.gov/pubmed/27769266?tool=bestpractice.com PST,[142]Warmerdam L, van Straten A, Twisk J, et al. Internet-based treatment for adults with depressive symptoms: randomized controlled trial. J Med Internet Res. 2008 Nov 20;10(4):e44.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629364http://www.ncbi.nlm.nih.gov/pubmed/19033149?tool=bestpractice.com[143]van Straten A, Cuijpers P, Smits N. Effectiveness of a web-based self-help intervention for symptoms of depression, anxiety, and stress: randomized controlled trial. J Med Internet Res. 2008 Mar 25;10(1):e7.http://www.ncbi.nlm.nih.gov/pubmed/18364344?tool=bestpractice.com 以及压力管理。[144]Billings DW, Cook RF, Hendrickson A, Dove DC. A web-based approach to managing stress and mood disorders in the workforce. J Occup Environ Med. 2008 Aug;50(8):960-8.http://www.ncbi.nlm.nih.gov/pubmed/18695455?tool=bestpractice.com
抗抑郁药物治疗
抗抑郁药物可能对于某些患者更为适用,因为它可能比非药物治疗产生更为迅速的反应。最常处方的抗抑郁药,SSRI 类和 SNRI 类,反应率相似,单一用药可作为轻中度抑郁的一线治疗。[145]Gartlehner G, Gaynes BN, Hansen RA, et al. Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. Ann Intern Med. 2008 Nov 18;149(10):734-50.http://www.annals.org/content/149/10/734.longhttp://www.ncbi.nlm.nih.gov/pubmed/19017592?tool=bestpractice.com 并没有一致的证据表明传统抗抑郁药效果优于其他治疗。[146]Gartlehner G, Thaler K, Hill S, et al. How should primary care doctors select which antidepressants to administer? Curr Psychiatry Rep. 20122 Aug;14(4):360-9.http://www.ncbi.nlm.nih.gov/pubmed/22648236?tool=bestpractice.com
药物选择应该基于患者的偏好、耐受性,以及其既往用药有效性证据。如果某种抗抑郁药对患者的家庭成员有效,一些临床医生可能会在考虑使用此抗抑郁药治疗该患者时降低用药门槛。其中一个理由是,见证了特定药物对某位家庭成员有效后,患者可能更容易接受用该药物治疗,而且对恢复的期望也会更高。然而,这不是一种循证的方法;药物基因组学的进展(检查可遗传的遗传因素对个体患者的治疗效果和耐受性的影响)可能最终会将i此问题澄清。[81]Peterson K, Dieperink E, Anderson J, et al. Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder. Psychopharmacology (Berl). 2017 Jun;234(11):1649-61.http://www.ncbi.nlm.nih.gov/pubmed/28456840?tool=bestpractice.com
在开始治疗后的 1 至 2 周内对患者进行随访,然后在接下来的12周内每月对患者进行随访。使用 PHQ-9 来监测某时段内的症状。对于服用抗抑郁药后出现部分缓解的患者,可在 2 到 4 周后调整剂量至最大耐受剂量。 在缓解后9至12个月内继续给予取得成功的抗抑郁治疗。[97]Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003 Feb 22;361(9358):653-61.http://www.ncbi.nlm.nih.gov/pubmed/12606176?tool=bestpractice.com[98]El-Mallakh RS, Briscoe B. Studies of long-term use of antidepressants: how should the data from them be interpreted? CNS Drugs. 2012 Feb 1;26(2):97-109.http://www.ncbi.nlm.nih.gov/pubmed/22296314?tool=bestpractice.com复发:高质量证据显示,使用处方抗抑郁药维持治疗较安慰剂更能降低在 1 到 3 年内患者的复发率。系统评价或者受试者>200名的随机对照临床试验(RCT)。 然而,,一些医生建议无限期治疗频繁复发,但对抗抑郁治疗成功产生反应的患者。
心理治疗
心理治疗也被认为是针对轻、中度抑郁的一线治疗。心理治疗似乎能对抑郁症患者的生活质量产生积极影响,其对抑郁症状严重程度的降低效果无法评估。[147]Kolovos S, Kleiboer A, Cuijpers P. Effect of psychotherapy for depression on quality of life: meta-analysis. Br J Psychiatry. 2016 Dec;209(6):460-8.http://bjp.rcpsych.org/content/209/6/460.longhttp://www.ncbi.nlm.nih.gov/pubmed/27539296?tool=bestpractice.com 经心理疗法治疗的轻度抑郁进展为重度抑郁的可能性较低。[148]Cuijpers P, Koole SL, van Dijke A, et al. Psychotherapy for subclinical depression: meta-analysis. Br J Psychiatry. 2014 Oct;205(4):268-74.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180844/http://www.ncbi.nlm.nih.gov/pubmed/25274315?tool=bestpractice.com 在某些病例中,仅靠心理教育就能达到疾病缓解。[149]Casañas R, Catalán R, del Val JL, et al. Effectiveness of a psycho-educational group program for major depression in primary care: a randomized controlled trial. BMC Psychiatry. 2012 Dec 18;12:230.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551665/pdf/1471-244X-12-230.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23249399?tool=bestpractice.com
治疗师常常联合使用认知行为疗法 (CBT)抑郁症状:中等质量证据表明,对于门诊或社区的老年患者,认知治疗较没有治疗更能改善抑郁症状。受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 以及 IPT[109]Cuijpers P, Geraedts AS, van Oppen P, et al. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry. 2011 Jun;168(6):581-92.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2010.10101411http://www.ncbi.nlm.nih.gov/pubmed/21362740?tool=bestpractice.com治疗成功:高质量的证据表明,人际心理治疗单独使用或与药物治疗联用可有效减轻抑郁。[109]Cuijpers P, Geraedts AS, van Oppen P, et al. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry. 2011 Jun;168(6):581-92.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2010.10101411http://www.ncbi.nlm.nih.gov/pubmed/21362740?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 或 PST。[110]Bell AC, D'Zurilla TJ. Problem-solving therapy for depression: a meta-analysis. Clin Psychol Rev. 2009 Jun;29(4):348-53.http://www.ncbi.nlm.nih.gov/pubmed/19299058?tool=bestpractice.com[111]Kirkham JG, Choi N, Seitz DP. Meta-analysis of problem solving therapy for the treatment of major depressive disorder in older adults. Int J Geriatr Psychiatry. 2016 May;31(5):526-35.http://www.ncbi.nlm.nih.gov/pubmed/26437368?tool=bestpractice.com IPT 可以改善人际方面的功能,而 CBT 则拥有持续的效果,能降低治疗结束后的后续风险。[112]Hollon SD, DeRubeis RJ, Shelton RC, et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry. 2005 Apr;62(4):417-22.http://www.ncbi.nlm.nih.gov/pubmed/15809409?tool=bestpractice.com IPT 仅在患者拥有心理方面的内省能力并能够进行长期治疗时有效。[113]De Mello MF, De Jesus Mari J, Bacaltchuk J, et al. A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci. 2005 Apr;255(2):75-82.http://www.ncbi.nlm.nih.gov/pubmed/15812600?tool=bestpractice.com 进行 CBT 和 IPT 的频率应由治疗者决定,大致的起效时间在 12 周。作为一种针对重性抑郁的治疗方法,限时心理动力学疗法已得到了经验性的支持。[150]Driessen E, Cuijpers P, de Maat SC, et al. The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis. Clin Psychol Rev. 2010 Feb;30(1):25-36.http://www.ncbi.nlm.nih.gov/pubmed/19766369?tool=bestpractice.com
支持性干预
自助书籍很普及,阅读治疗被证明治疗效能优于无治疗。[151]den Boer PC, Wiersma D, Van den Bosch RJ. Why is self-help neglected in the treatment of emotional disorders? A meta-analysis. Psychol Med. 2004 Aug;34(6):959-71.http://www.ncbi.nlm.nih.gov/pubmed/15554567?tool=bestpractice.com
瑜伽可能对抑郁症产生有益的影响,但在干预、报告和可行性方面存在显著差异。[152]Pilkington K, Kirkwood G, Rampes H, et al. Yoga for depression: the research evidence. J Affect Disord. 2005 Dec;89(1-3):13-24.http://www.ncbi.nlm.nih.gov/pubmed/16185770?tool=bestpractice.com[153]Krogh J, Nordentoft M, Sterne JA, et al. The effect of exercise in clinically depressed adults: systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2011 Apr;72(4):529-38.http://www.ncbi.nlm.nih.gov/pubmed/21034688?tool=bestpractice.com抑郁症状:低质量证据显示,高耗能运动可能对 12 周时的疗效改善更有效。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。
其他支持性干预措施包括放松训练、光照治疗、运动、太极、音乐治疗和针灸。[121]Aalbers S, Fusar-Poli L, Freeman RE, et al. Music therapy for depression. Cochrane Database Syst Rev. 2017 Nov 16;(11):CD004517.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004517.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29144545?tool=bestpractice.com[122]Even C, Schröder CM, Friedman S, et al. Efficacy of light therapy in nonseasonal depression: a systematic review. J Affect Disord. 2008 May;108(1-2):11-23.http://www.ncbi.nlm.nih.gov/pubmed/17950467?tool=bestpractice.com[123]Penders TM, Stanciu CN, Schoemann AM, et al. Bright light therapy as augmentation of pharmacotherapy for treatment of depression: a systematic review and meta-analysis. Prim Care Companion CNS Disord. 2016 Oct 20;18(5).http://www.ncbi.nlm.nih.gov/pubmed/27835725?tool=bestpractice.com[124]Morgan, AJ, Jorm AF. Self-help interventions for depressive disorders and depressive symptoms: a systematic review. Ann Gen Psychiatry. 2008 Aug 19;7:13.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542367http://www.ncbi.nlm.nih.gov/pubmed/18710579?tool=bestpractice.com[125]Sun YL, Chen SB, Gao Y, et al. Acupuncture versus western medicine for depression in China: a systematic review. Chin J Evid Based Med. 2008;8:340-5.[126]Herring MP, Puetz TW, O'Connor PJ, et al. Effect of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Jan 23;172(2):101-11.http://archinte.jamanetwork.com/article.aspx?articleid=1108677http://www.ncbi.nlm.nih.gov/pubmed/22271118?tool=bestpractice.com[127]Chi I, Jordan-Marsh M, Guo M, et al. Tai chi and reduction of depressive symptoms for older adults: a meta-analysis of randomized trials. Geriatr Gerontol Int. 2013 Jan;13(1):3-12.http://www.ncbi.nlm.nih.gov/pubmed/22680972?tool=bestpractice.com[128]Bridle C, Spanjers K, Patel S, et al. Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2012 Sep;201(3):180-5.http://bjp.rcpsych.org/content/201/3/180.full.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/22945926?tool=bestpractice.com[129]Belvederi Murri M, Amore M, Menchetti M, et al; Safety and Efficacy of Exercise for Depression in Seniors (SEEDS) Study Group. Physical exercise for late-life major depression. Br J Psychiatry. 2015 Sep;207(3):235-42.http://bjp.rcpsych.org/content/207/3/235.longhttp://www.ncbi.nlm.nih.gov/pubmed/26206864?tool=bestpractice.com[130]Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016 Jan;73(1):56-63.http://www.ncbi.nlm.nih.gov/pubmed/26580307?tool=bestpractice.com[131]Trivedi MH, Greer TL, Church TS, et al. Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison. J Clin Psychiatry. 2011 May;72(5):677-84.http://www.ncbi.nlm.nih.gov/pubmed/21658349?tool=bestpractice.com[132]Cooney GM, Dwan K, Greig CA, et al. Exercise for depression. Cochrane Database Syst Rev. 2013 Sep 12;(9):CD004366.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004366.pub6/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24026850?tool=bestpractice.com[133]Sukhato K, Lotrakul M, Dellow A, et al. Efficacy of home-based non-pharmacological interventions for treating depression: a systematic review and network meta-analysis of randomised controlled trials. BMJ Open. 2017 Jul 12;7(7):e014499.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734422/http://www.ncbi.nlm.nih.gov/pubmed/28706086?tool=bestpractice.com[134]Catalan-Matamoros D, Gomez-Conesa A, Stubbs B, et al. Exercise improves depressive symptoms in older adults: an umbrella review of systematic reviews and meta-analyses. Psychiatry Res. 2016 Oct 30;244:202-9.http://www.ncbi.nlm.nih.gov/pubmed/27494042?tool=bestpractice.com[135]Smith CA, Armour M, Lee MS, et al. Acupuncture for depression. Cochrane Database Syst Rev. 2018 Mar 4;(3):CD004046.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004046.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29502347?tool=bestpractice.com [
]What are the effects of exercise for improving symptoms in adults with depression?https://cochranelibrary.com/cca/doi/10.1002/cca.355/full显示答案 在未缓解患者中,高强度运动联合持续性 SSRI 类药物治疗组与低强度运动联合SSRI组相比,观察到更高的缓解率。[131]Trivedi MH, Greer TL, Church TS, et al. Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison. J Clin Psychiatry. 2011 May;72(5):677-84.http://www.ncbi.nlm.nih.gov/pubmed/21658349?tool=bestpractice.com 相反,停止运动可能会加重抑郁症状。[154]Morgan JA, Olagunju AT, Corrigan F, et al. Does ceasing exercise induce depressive symptoms? A systematic review of experimental trials including immunological and neurogenic markers. J Affect Disord. 2018 Jul;234:180-92.http://www.ncbi.nlm.nih.gov/pubmed/29529552?tool=bestpractice.com[155]Morres ID, Hatzigeorgiadis A, Stathi A, et al. Aerobic exercise for adult patients with major depressive disorder in mental health services: a systematic review and meta-analysis. Depress Anxiety. 2019 Jan;36(1):39-53.https://onlinelibrary.wiley.com/doi/full/10.1002/da.22842http://www.ncbi.nlm.nih.gov/pubmed/30334597?tool=bestpractice.com [
]What are the effects of exercise for improving symptoms in adults with depression?https://cochranelibrary.com/cca/doi/10.1002/cca.355/full显示答案
圣约翰草提取物是一种被认为可以有效治疗轻中度抑郁的草药。[156]Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000448.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/18843608?tool=bestpractice.com[157]Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John's wort for major depressive disorder. Syst Rev. 2016 Sep 2;5(1):148.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010734/http://www.ncbi.nlm.nih.gov/pubmed/27589952?tool=bestpractice.com治疗成功:低质量证据显示,圣约翰草较安慰剂在治疗重性抑郁方面更有效。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。 如果一线、二线治疗都无效的话,可被用作一种备选的治疗(单用)。[158]Schulz V. Safety of St. John's Wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13:199-204.http://www.ncbi.nlm.nih.gov/pubmed/16428030?tool=bestpractice.com[159]Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27.http://www.ncbi.nlm.nih.gov/pubmed/19028540?tool=bestpractice.com 圣约翰草有非常好的安全性,但多项报道也指出临床显著的药物间相互作用可能,在处方该药前应纳入考虑范畴。[158]Schulz V. Safety of St. John's Wort extract compared to synthetic antidepressants. Phytomedicine. 2006;13:199-204.http://www.ncbi.nlm.nih.gov/pubmed/16428030?tool=bestpractice.com[159]Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27.http://www.ncbi.nlm.nih.gov/pubmed/19028540?tool=bestpractice.com
基于电脑的治疗
有证据支持基于计算机的 CBT 的效力,[136]Spek V, Nyklícek I, Smits N, et al. Internet-based cognitive behavioural therapy for subthreshold depression in people over 50 years old: a randomized controlled clinical trial. Psychol Med. 2007 Dec;37(12):1797-806.http://www.ncbi.nlm.nih.gov/pubmed/17466110?tool=bestpractice.com[137]Kaltenthaler E, Parry G, Beverley C, et al. Computerised cognitive-behavioural therapy for depression: systematic review. Br J Psychiatry. 2008 Sep;193(3):181-4.https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/computerised-cognitivebehavioural-therapy-for-depression-systematic-review/CB1DC3F5CE548A93B1049382AE958B01http://www.ncbi.nlm.nih.gov/pubmed/18757972?tool=bestpractice.com[138]Alvarez LM, Sotres JF, Leon SO, et al. Computer program in the treatment for major depression and cognitive impairment in university students. Comp Human Behav. 2008 May;24(3):816-26.[139]Charova E, Dorstyn D, Tully P, et al. Web-based interventions for comorbid depression and chronic illness: a systematic review. J Telemed Telecare. 2015 Jun;21(4):189-201.http://www.ncbi.nlm.nih.gov/pubmed/insert id?tool=bestpractice.com[140]Karyotaki E, Riper H, Twisk J, et al. Efficacy of self-guided internet-based cognitive behavioral therapy in the treatment of depressive symptoms: a meta-analysis of individual participant data. JAMA Psychiatry. 2017 Apr 1;74(4):351-9.https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2604310http://www.ncbi.nlm.nih.gov/pubmed/28241179?tool=bestpractice.com[141]Zhou T, Li X, Pei Y, et al. Internet-based cognitive behavioural therapy for subthreshold depression: a systematic review and meta-analysis. BMC Psychiatry. 2016 Oct 21;16(1):356.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073460/http://www.ncbi.nlm.nih.gov/pubmed/27769266?tool=bestpractice.com PST,[142]Warmerdam L, van Straten A, Twisk J, et al. Internet-based treatment for adults with depressive symptoms: randomized controlled trial. J Med Internet Res. 2008 Nov 20;10(4):e44.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629364http://www.ncbi.nlm.nih.gov/pubmed/19033149?tool=bestpractice.com[143]van Straten A, Cuijpers P, Smits N. Effectiveness of a web-based self-help intervention for symptoms of depression, anxiety, and stress: randomized controlled trial. J Med Internet Res. 2008 Mar 25;10(1):e7.http://www.ncbi.nlm.nih.gov/pubmed/18364344?tool=bestpractice.com 以及压力管理。[144]Billings DW, Cook RF, Hendrickson A, Dove DC. A web-based approach to managing stress and mood disorders in the workforce. J Occup Environ Med. 2008 Aug;50(8):960-8.http://www.ncbi.nlm.nih.gov/pubmed/18695455?tool=bestpractice.com 但是,往往退出率很高。
治疗抵抗性/难治性抑郁症
大多数抑郁症患者对第一次抗抑郁药物试验反应不足, 但其中很大一部分患者会对第二种抗抑郁药物做出反应。[90]Schlaepfer TE, Agren H, Monteleone P, et al. The hidden third: improving outcome in treatment-resistant depression. J Psychopharmacol. 2012 May;26(5):587-602.http://www.ncbi.nlm.nih.gov/pubmed/22236505?tool=bestpractice.com 普遍的共识是,对于两种给予足够剂量和维持时间(最好为两种具有不同作用机制的抗抑郁药)的抗抑郁药试验性用药没有反应的抑郁症,需要考虑治疗抵抗性或难治性抑郁症。[160]Berlim MT, Turecki G. What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials. Eur Neuropsychopharmacol. 2007 Nov;17(11):696-707.http://www.ncbi.nlm.nih.gov/pubmed/17521891?tool=bestpractice.com
尽管目前有已经发布的针对治疗抵抗性抑郁症的处理流程,但在临床中,因为患者个体差异,其处理流程常被改变或打破。例如,药物副反应、并存疾病或经济条件,以及社会心理因素,例如情绪脆弱性、行为模式和生活环境等,都可能影响治疗。以个体患者为中心的临床试验可能是可行的,但并不经常采用。[161]Kronish IM, Hampsey M, Falzon L, et al. Personalized (N-of-1) trials for depression: a systematic review. J Clin Psychopharmacol. 2018 Jun;38(3):218-25.http://www.ncbi.nlm.nih.gov/pubmed/29596148?tool=bestpractice.com
重新评估
抗抑郁药物治疗
考虑到重度抑郁症仍然是最突出的临床问题,抗抑郁药物类别中应对治疗抵抗性/难治性抑郁症的替代选择包括使用第三类(或第四类或第五类)SSRI、SNRI或非典型药物的单药疗法。联合抗抑郁治疗(即 SSRI 或 SNRI 加安非他酮或米氮平)可作为最好的利用其不良反应的一种手段(例如,将米氮平加入SNRI以促进睡眠,或安非他酮加入SSRI以试图改善性行为功能);然而,证据并未始终如一地支持联合抗抑郁药在减轻抑郁症方面的协同作用。[162]Rush AJ, Trivedi MH, Stewart JW, et al. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry. 2011 Jul;168(7):689-701.http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2011.10111645http://www.ncbi.nlm.nih.gov/pubmed/21536692?tool=bestpractice.com[163]Dold M, Kasper S. Evidence-based pharmacotherapy of treatment-resistant unipolar depression. Int J Psychiatry Clin Pract. 2017 Mar;21(1):13-23.http://www.ncbi.nlm.nih.gov/pubmed/27848269?tool=bestpractice.com[164]Henssler J, Bschor T, Baethge C. Combining antidepressants in acute treatment of depression: a meta-analysis of 38 studies including 4511 patients. Can J Psychiatry. 2016 Jan;61(1):29-43.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756602/http://www.ncbi.nlm.nih.gov/pubmed/27582451?tool=bestpractice.com[165]Kessler D, Burns A, Tallon D, et al. Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT. Health Technol Assess. 2018 Nov;22(63):1-136.https://www.ncbi.nlm.nih.gov/books/NBK533904/http://www.ncbi.nlm.nih.gov/pubmed/30468145?tool=bestpractice.com 有一些证据表明,一种或数种抗抑郁药物治疗失败并不妨碍以后的成功治疗。[89]McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry. 2006 Sep;163(9):1531-41.http://ajp.psychiatryonline.org/doi/full/10.1176/ajp.2006.163.9.1531http://www.ncbi.nlm.nih.gov/pubmed/16946177?tool=bestpractice.com[90]Schlaepfer TE, Agren H, Monteleone P, et al. The hidden third: improving outcome in treatment-resistant depression. J Psychopharmacol. 2012 May;26(5):587-602.http://www.ncbi.nlm.nih.gov/pubmed/22236505?tool=bestpractice.com 到4项不同的试验性用药结束时,60% 至70% 的患者可能会对治疗做出反应。虽然一般的经验法则是给予抗抑郁药至少 6至8周,但如果前2周没有任何改善,那么在此时切换治疗方案可能是恰当的。[91]Kemp DE, Ganocy SJ, Brecher M, et al. Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression. J Affect Disord. 2011 Apr;130(1-2):171-9.http://www.ncbi.nlm.nih.gov/pubmed/21071096?tool=bestpractice.com
如果没有其它方法可以治疗,并且患者能够耐受当前抗抑郁药的洗脱期,单胺氧化酶抑制剂(MAOI)(例如,异卡波肼、苯乙肼、司来吉兰、反苯环丙胺)可以是具有独特疗效的,即使它与更严重的不良反应相关,但仅在其他治疗选择无效时进行推荐。[166]Shulman KI, Herrmann N, Walker SE. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs. 2013 Oct;27(10):789-97.http://www.ncbi.nlm.nih.gov/pubmed/23934742?tool=bestpractice.com 洗脱期取决于患者目前服用的抗抑郁药物的半衰期,时间范围为 1 至 5周。在没有咨询精神科医生的情况下,切勿使用 MAOI。
一些研究表明,抗抑郁药物与其他类别的药物联合优于仅仅是不同抗抑郁药物的联合。[167]Strawbridge R, Carter B, Marwood L, et al. Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis. Br J Psychiatry. 2019 Jan;214(1):42-51.https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/augmentation-therapies-for-treatmentresistant-depression-systematic-review-and-metaanalysis/0FEA123FDECE5FB2E838517DC22F8C57/core-readerhttp://www.ncbi.nlm.nih.gov/pubmed/30457075?tool=bestpractice.com 对于对常规抗抑郁药无反应的患者,锂强化治疗仍然是最好的循证治疗方法;然而,理想情况下,它应由精神科医生启动,因为其治疗指数狭窄,并且存在由于过量给药和药物 - 药物相互作用而产生意外毒性的风险。尽管这些限制使锂盐难以成为一线治疗,来自芬兰的一项队列研究产生的证据表明,锂盐单药治疗不仅能有效预防重度抑郁患者再入院,而且单独使用比联用其他抗抑郁药效果也更为满意。[168]Tiihonen J, Tanskanen A, Hoti F, et al. Pharmacological treatments and risk of readmission to hospital for unipolar depression in Finland: a nationwide cohort study. Lancet Psychiatry. 2017 Jul;4(7):547-53.http://www.ncbi.nlm.nih.gov/pubmed/28578901?tool=bestpractice.com 在抗抑郁药物中添加非典型抗精神病药物历来存在争议;[169]Spielmans GI, Berman MI, Linardatos E, et al. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med. 2013;10(3):e1001403.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595214/pdf/pmed.1001403.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23554581?tool=bestpractice.com[170]Philip NS, Carpenter LL, Tyrka AR, et al. Augmentation of antidepressants with atypical antipsychotics: a review of the current literature. J Psychiatr Pract. 2008 Jan;14(1):34-44.http://www.ncbi.nlm.nih.gov/pubmed/18212601?tool=bestpractice.com 然而,采用某些药物强化正变得越来越常用,且可能会改善治疗结局。[171]Tohen M, Case M, Trivedi MH, et al. Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies. J Clin Psychiatry. 2010 Apr;71(4):451-62.http://www.ncbi.nlm.nih.gov/pubmed/20361905?tool=bestpractice.com[172]Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017 Jul 11;318(2):132-45.http://www.ncbi.nlm.nih.gov/pubmed/28697253?tool=bestpractice.com 第二代抗精神病药物与抗抑郁药物联合应用已被证实有效,并且该类用药正在普及。[173]Edwards SJ, Hamilton V, Nherera L, et al. Lithium or an atypical antipsychotic drug in the management of treatment-resistant depression: a systematic review and economic evaluation. Health Technol Assess. 2013 Nov;17(54):1-190.http://www.ncbi.nlm.nih.gov/pubmed/24284258?tool=bestpractice.com [
]What are the effects of exercise for improving symptoms in adults with depression?https://cochranelibrary.com/cca/doi/10.1002/cca.355/full显示答案 市场上已有的奥氮平/氟西汀合剂被认为优于氟西汀单药和奥氮平单药治疗,能够让对于一种抗抑郁药治疗无效的患者能够早期得到改善。[171]Tohen M, Case M, Trivedi MH, et al. Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies. J Clin Psychiatry. 2010 Apr;71(4):451-62.http://www.ncbi.nlm.nih.gov/pubmed/20361905?tool=bestpractice.com阿立哌唑已被美国食品药品监督管理局(FDA)批准用于抗抑郁强化治疗,且已发现在患有治疗抵抗性抑郁症的美国退伍军人中,使用这种药物强化的效果略优于换用其他抗抑郁药。[172]Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017 Jul 11;318(2):132-45.http://www.ncbi.nlm.nih.gov/pubmed/28697253?tool=bestpractice.com 依匹哌唑,为一种新型的 5-羟色胺-多巴胺活性调节剂,已被 FDA 批准作为重性抑郁障碍的辅助治疗,[174]Thase ME, Hobart M, Augustine C, et al. EPA-0808 - efficacy and safety of adjunctive brexpiprazole (opc-34712) in major depressive disorder (MDD): a phase iii, randomized, placebo-controlled study. Eur Psychiatry. 2014;29(suppl 1):1. 尽管其疗效证据仅来自相对少量的研究。[175]Yoon S, Jeon SW, Ko YH, et al. Adjunctive brexpiprazole as a novel effective strategy for treating major depressive disorder: a systematic review and meta-analysis. J Clin Psychopharmacol. 2017 Feb;37(1):46-53.http://www.ncbi.nlm.nih.gov/pubmed/27941419?tool=bestpractice.com体重增加和静坐不能是最常报告的不良反应,而且该药对血糖和血脂也略有影响。[176]Citrome L. Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2015 Sep;69(9):978-97.http://www.ncbi.nlm.nih.gov/pubmed/26250067?tool=bestpractice.com 尽管在临床试验数据的荟萃分析中显示有部分获益,但对于没有精神疾病的患者来说,使用这些药物的获益与风险孰轻孰重仍不明确。[169]Spielmans GI, Berman MI, Linardatos E, et al. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med. 2013;10(3):e1001403.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595214/pdf/pmed.1001403.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23554581?tool=bestpractice.com 专科医生使用的其他强化策略包括甲状腺激素、莫达非尼、氯胺酮和吲哚洛尔。[177]Hollinghurst S, Carroll FE, Abel A, et al. Cost-effectiveness of cognitive-behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: economic evaluation of the CoBalT Trial. Br J Psychiatry. 2014 Jan;204(1):69-76.http://www.ncbi.nlm.nih.gov/pubmed/24262818?tool=bestpractice.com[178]Ijaz S, Davies P, Williams CJ, et al. Psychological therapies for treatment-resistant depression in adults. Cochrane Database Syst Rev. 2018 May 14;(5):CD010558.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010558.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29761488?tool=bestpractice.com[179]Kleeblatt J, Betzler F, Kilarski LL, et al. Efficacy of off-label augmentation in unipolar depression: a systematic review of the evidence. Eur Neuropsychopharmacol. 2017 May;27(5):423-41.http://www.ncbi.nlm.nih.gov/pubmed/28318897?tool=bestpractice.com
非药理学方法
复发
反复发作的抑郁症应给予先前诱导缓解的相同抗抑郁药治疗,前提是在使用此类药物进行充分的维持治疗时,未出现复发。考虑对第三次发作抑郁症的患者进行至少3至5年或终身的维持治疗。[98]El-Mallakh RS, Briscoe B. Studies of long-term use of antidepressants: how should the data from them be interpreted? CNS Drugs. 2012 Feb 1;26(2):97-109.http://www.ncbi.nlm.nih.gov/pubmed/22296314?tool=bestpractice.com 第一次复发的患者及存在再次发作危险因素的患者(包括双相情感障碍家族史,一年内复发,青少年起病,严重抑郁或尝试自杀,起病症状突然),进行长期维持治疗也能获益。一般通过抑郁症状的类型和严重程度来选择治疗,在很多时候也依靠试验性的治疗和失败的经验。对于反复发作的患者,如果心理治疗可解决患者常常认为他们的恢复仅仅只是对于痛苦暂时缓解的绝望,并且如果它能教育患者如何应对、以及也许能预防复发,则心理治疗将可能很有针对性。
妊娠
与妊娠同时发生的抑郁会造成重大临床难题。一方面,母体药物误用或者忽视健康问题或自杀的可能性增加,导致胎儿面临潜在伤害。另一方面,抗抑郁药均可通过胎盘屏障,可能对胎儿造成医源性伤害。 幸运的是,在妊娠期间使用抗抑郁药的安全性研究表明,在大部分情况下,抗抑郁药对胎儿造成的风险(如有)已降至最低。[180]Chaudron LH. Complex challenges in treating depression during pregnancy. Am J Psychiatry. 2013 Jan;170(1):12-20.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2012.12040440http://www.ncbi.nlm.nih.gov/pubmed/23288385?tool=bestpractice.com[181]Lassen D, Ennis ZN, Damkier P, et al. First-trimester pregnancy exposure to venlafaxine or duloxetine and risk of major congenital malformations: a systematic review. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):32-6.http://onlinelibrary.wiley.com/doi/10.1111/bcpt.12497/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26435496?tool=bestpractice.com 不幸的是,几乎没有对照性试验证据。[182]McAllister-Williams RH, Baldwin DS, Cantwell R, et al. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol. 2017 May;31(5):519-52.http://www.ncbi.nlm.nih.gov/pubmed/28440103?tool=bestpractice.com 缺乏支持在充分知情情况下所作决策的一致性数据。[183]Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med. 2006 Feb 9;354(6):579-87.http://www.ncbi.nlm.nih.gov/pubmed/16467545?tool=bestpractice.com[184]Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. 2013 Apr;70(4):436-43.http://www.ncbi.nlm.nih.gov/pubmed/23446732?tool=bestpractice.com[185]Furu K, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ. 2015 Apr 17;350:h1798.http://www.bmj.com/content/350/bmj.h1798.longhttp://www.ncbi.nlm.nih.gov/pubmed/25888213?tool=bestpractice.com[186]Huybrechts KF, Palmsten K, Avorn J, et al. Antidepressant use in pregnancy and the risk of cardiac defects. N Engl J Med. 2014 Jun 19;370(25):2397-407.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062924/http://www.ncbi.nlm.nih.gov/pubmed/24941178?tool=bestpractice.com[187]McDonagh MS, Matthews A, Phillipi C, et al. Depression drug treatment outcomes in pregnancy and the postpartum period: a systematic review and meta-analysis. Obstet Gynecol. 2014 Sep;124(3):526-34.http://www.ncbi.nlm.nih.gov/pubmed/25004304?tool=bestpractice.com[188]Bérard A, Zhao JP, Sheehy O. Sertraline use during pregnancy and the risk of major malformations. Am J Obstet Gynecol. 2015 Jun;212(6):795.e1-795.e12.https://www.ajog.org/article/S0002-9378(15)00090-3/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25637841?tool=bestpractice.com[189]Huybrechts KF, Bateman BT, Palmsten K, et al. Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA. 2015 Jun 2;313(21):2142-51.http://jamanetwork.com/journals/jama/fullarticle/2300602http://www.ncbi.nlm.nih.gov/pubmed/26034955?tool=bestpractice.com
抗抑郁药物的风险可能延伸至出生时和出生后。一项系统评价和 meta 分析的结果发现,母体使用 SSRI(不是未使用 SSRI 的抑郁症患者)与早产风险增加有关。[190]Eke AC, Saccone G, Berghella V. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG. 2016 Nov;123(12):1900-7.http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14144/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27239775?tool=bestpractice.com 另一项系统评价和荟萃分析发现,与未患抑郁症的女性相比,未接受治疗的抑郁症妊娠患者的早产和婴儿低出生体重风险更高,这表明未治疗的抑郁症本身可能是早产的一个危险因素。[191]Jarde A, Morais M, Kingston D, et al. Neonatal outcomes in women with untreated antenatal depression compared with women without depression: a systematic review and meta-analysis. JAMA Psychiatry. 2016 Aug 1;73(8):826-37.https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2526241http://www.ncbi.nlm.nih.gov/pubmed/27276520?tool=bestpractice.com出生前宫内暴露于抗抑郁药的新生儿中,在出生后有很大比例会出现短暂易激惹及其他提示抗抑郁药停药综合征的症状。[192]Sanz EJ, De-las-Cuevas C, Kiuru A, et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 2005 Feb 5-11;365(9458):482-7.http://www.ncbi.nlm.nih.gov/pubmed/15705457?tool=bestpractice.com
抑郁症、抗抑郁药治疗和自闭症谱系障碍 (autism spectrum disorders, ASD) 之间关系的证据不一致,一些研究表明,母体在妊娠期使用抗抑郁药会导致孩子患 ASD 的风险略微增加;另一些研究表明,产前精神障碍且未使用抗抑郁药母亲的孩子患 ASD 的风险会增加。[193]Rai D, Lee BK, Dalman C, et al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ. 2017 Jul 19;358:j2811.http://www.bmj.com/content/358/bmj.j2811.longhttp://www.ncbi.nlm.nih.gov/pubmed/28724519?tool=bestpractice.com[194]Kaplan YC, Keskin-Arslan E, Acar S, et al. Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta-analysis of cohort studies. Br J Clin Pharmacol. 2017 Dec;83(12):2798-806.http://www.ncbi.nlm.nih.gov/pubmed/28734011?tool=bestpractice.com[195]Brown HK, Hussain-Shamsy N, Lunsky Y, et al. The association between antenatal exposure to selective serotonin reuptake inhibitors and autism: a systematic review and meta-analysis. J Clin Psychiatry. 2017 Jan;78(1):e48-58.http://www.ncbi.nlm.nih.gov/pubmed/28129495?tool=bestpractice.com
非常明确的是停用抗抑郁药的女性很可能会在妊娠期间出现抑郁复发。[196]Cohen LS, Altshuler LL, Harlow BL, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006 Feb 1;295(5):499-507.https://jamanetwork.com/journals/jama/fullarticle/202291http://www.ncbi.nlm.nih.gov/pubmed/16449615?tool=bestpractice.com 抑郁症本身可能对胎儿发育产生不良影响(例如引起胎动增多和胎心率不规则)、增加婴儿的皮质醇水平、影响婴儿性情以及童年晚期和青春期行为。[197]Gentile S. Untreated depression during pregnancy: short- and long-term effects in offspring. A systematic review. Neuroscience. 2017 Feb 7;342:154-66.http://www.ncbi.nlm.nih.gov/pubmed/26343292?tool=bestpractice.com
可能源自所有这些缺乏说服力和/或矛盾数据的最佳建议是:临床医生与患者认真讨论妊娠期间继续接受抗抑郁药治疗的风险,防范停止或避免使用抗抑郁药以及胎儿暴露于产前抑郁的有害影响所产生的风险。尽管缺乏一致性证据证明抗抑郁药对胎儿和婴儿健康和发育的危害,但必须保持谨慎。有关抗抑郁药物和其他药物潜在危害的最新信息,可参见各类资源。UK Teratology Information Service
对于怀孕期间患有重度抑郁症的孕妇来说,ECT 可能是首选的治疗方法,因为它不会使胎儿暴露于任何已知的风险。[198]Pompili M, Dominici G, Giordano G, et al. Electroconvulsive treatment during pregnancy: a systematic review. Expert Rev of Neurother. 2014 Dec;14(12):1377-90.http://www.ncbi.nlm.nih.gov/pubmed/25346216?tool=bestpractice.com[199]Anderson EL, Reti IM. ECT in pregnancy: a review of the literature from 1941 to 2007. Psychosom Med. 2009 Feb;71(2):235-42.http://www.ncbi.nlm.nih.gov/pubmed/19073751?tool=bestpractice.com 对于中度至重度发作,几乎没有一致性对照试验证据表明抗抑郁药应在怀孕期间禁忌使用;母体未经治疗的抑郁症对她健康的潜在有害影响产生的对胎儿的风险,显然超过了抗抑郁药物对胎儿的任何可测得的风险。[180]Chaudron LH. Complex challenges in treating depression during pregnancy. Am J Psychiatry. 2013 Jan;170(1):12-20.http://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2012.12040440http://www.ncbi.nlm.nih.gov/pubmed/23288385?tool=bestpractice.com[181]Lassen D, Ennis ZN, Damkier P, et al. First-trimester pregnancy exposure to venlafaxine or duloxetine and risk of major congenital malformations: a systematic review. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):32-6.http://onlinelibrary.wiley.com/doi/10.1111/bcpt.12497/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26435496?tool=bestpractice.com[182]McAllister-Williams RH, Baldwin DS, Cantwell R, et al. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol. 2017 May;31(5):519-52.http://www.ncbi.nlm.nih.gov/pubmed/28440103?tool=bestpractice.com 应像对待任何其他患者一样治疗妊娠期轻度抑郁症,或许给予药物治疗的阈值略高于非怀孕患者。从风险/获益平衡分析,可能倾向于非药物疗法,特别是由于许多患者可能对妊娠期间使用药物有所顾忌。CBT 与妊娠期重度抑郁症的中等治疗效果相关。人际心理治疗(IPT)似乎也具有疗效,但其疗效程度不如 CBT。[200]van Ravesteyn LM, Lambregtse-van den Berg MP, Hoogendijk WJ, et al. Interventions to treat mental disorders during pregnancy: a systematic review and multiple treatment meta-analysis. PLoS One. 2017 Mar 30;12(3):e0173397.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373816/http://www.ncbi.nlm.nih.gov/pubmed/28358808?tool=bestpractice.com
有证据支持使用咨询性干预措施,如CBT和人际心理治疗,以预防由于家族史、紧张的生活环境以及怀孕和分娩产生的母婴并发症,而导致抑郁风险相对较高的患者在妊娠和产后罹患抑郁症。[201]US Preventive Services Task Force, Curry SJ, Krist AH, et al. Interventions to prevent perinatal depression: US Preventive Services Task Force recommendation statement. JAMA. 2019 Feb 12;321(6):580-7.https://jamanetwork.com/journals/jama/fullarticle/2724195http://www.ncbi.nlm.nih.gov/pubmed/30747971?tool=bestpractice.com
产后抑郁症
对于有产后抑郁危险因素的女性进行筛查,以预防或立即治疗产后抑郁症。联合研究得出的证据表明,CBT 可能对预防和治疗产后抑郁症状均有疗效。[202]Lee EW, Denison FC, Hor K, et al. Web-based interventions for prevention and treatment of perinatal mood disorders: a systematic review. BMC Pregnancy Childbirth. 2016 Feb 29;16:38.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770541/http://www.ncbi.nlm.nih.gov/pubmed/26928898?tool=bestpractice.com 长期治疗可能能进一步提高其对母亲和孩子的心理治疗效果。需谨慎应用药物治疗。很多母乳喂养的女性会因为担心婴儿暴露而拒绝服药。临床医生在患者妊娠和哺乳期间开具精神类药物的门槛应该更高。尽管统计学数据显示胎儿和新生儿药物暴露的风险很小,但由于药物可能对胎儿或新生儿产生长期影响,因此基本的风险获益公式有所变化。随着抑郁症严重程度的增加,该公式可能倾向于药物治疗。对于曾有重性抑郁严重发作的女性患者,必须权衡胎儿或婴儿暴露于药物的轻度风险以及母亲抑郁、自我忽略或婴儿忽略或自杀行为带来的风险二者之间的关系。
有关抗抑郁药和其他药物对母乳喂养婴儿造成的潜在危害最新信息,可参见各种资源。TOXNET: LactMed
如需更详细信息,请参阅产后抑郁的单独主题。
围绝经期女性
尽管女性即将来临的更年期症状可能伴随抑郁症表现,但与激素状态相比,该类人群中抑郁症的风险,与之前所患的抑郁症更为密切相关,治疗与其他患者相同。[203]Maki PM, Kornstein SG, Joffe H, et al; Board of Trustees for The North American Menopause Society (NAMS) and the Women and Mood Disorders Task Force of the National Network of Depression Centers. Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause. 2018 Oct;25(10):1069-85.http://www.ncbi.nlm.nih.gov/pubmed/30179986?tool=bestpractice.com
季节性情感障碍
季节性情感障碍 (Seasonal affective disorder, SAD) 是重性抑郁的一个亚型,伴随季节的变化而出现。SAD 在北纬地区更常见,亮光或蓝光疗法(优先与 CBT 联用)[204]Rohan KJ, Meyerhoff J, Ho SY, et al. Outcomes one and two winters following cognitive-behavioral therapy or light therapy for seasonal affective disorder. Am J Psychiatry. 2016 Mar 1;173(3):244-51.http://www.ncbi.nlm.nih.gov/pubmed/26539881?tool=bestpractice.com 以及抗抑郁药物的辅助治疗。
如需更详细信息,请参阅有关季节性情感障碍这一单独主题的内容。
共病
抗抑郁药可以有效地减少抑郁症和酒精依赖患者的抑郁和酒精使用。[205]Agabio R, Trogu E, Pani PP. Antidepressants for the treatment of people with co-occurring depression and alcohol dependence. Cochrane Database Syst Rev. 2018 Apr 24;(4):CD008581.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008581.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/CD008581?tool=bestpractice.com 在服用阿片类激动剂治疗的抑郁症患者中,抗抑郁药物的使用没有得到很好的支持。[206]Hassan AN, Howe AS, Samokhvalov AV, et al. Management of mood and anxiety disorders in patients receiving opioid agonist therapy: review and meta-analysis. Am J Addict. 2017 Sep;26(6):551-63. http://www.ncbi.nlm.nih.gov/pubmed/28675762?tool=bestpractice.com 关于使用抗抑郁药物治疗抑郁症合并痴呆的现有证据很少,这表明它们的潜在价值在许多情况下可能会被潜在的不良反应所抵消。[207]Dudas R, Malouf R, McCleery J, et al. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2018 Aug 31;(8):CD003944. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003944.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/CD003944?tool=bestpractice.com 抑郁症和 HIV 感染患者使用抗抑郁药物的证据质量也很低, 但更倾向使用。[208]Eshun-Wilson I, Siegfried N, Akena DH, et al. Antidepressants for depression in adults with HIV infection. Cochrane Database Syst Rev. 2018 Jan 22;(1):CD008525. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008525.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/CD008525?tool=bestpractice.com 对于抑郁症合并癌症,是否支持抗抑郁药物治疗尚无定论。[209]Li M, Kennedy EB, Byrne N, et al. Management of depression in patients with cancer: a clinical practice guideline. J Oncol Pract. 2016 Aug;12(8):747-56.http://ascopubs.org/doi/full/10.1200/JOP.2016.011072?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&http://www.ncbi.nlm.nih.gov/pubmed/27382000?tool=bestpractice.com[210]Ostuzzi G, Matcham F, Dauchy S, et al. Antidepressants for the treatment of depression in people with cancer. Cochrane Database Syst Rev. 2018 Apr 23;(4):CD011006.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011006.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/CD011006?tool=bestpractice.com