神經(jīng)系統(tǒng)疾病伴發(fā)抑郁焦慮障礙的診斷治療專家共識

1、會計(jì)學(xué)1神經(jīng)系統(tǒng)疾病伴發(fā)抑郁焦慮障礙的診斷神經(jīng)系統(tǒng)疾病伴發(fā)抑郁焦慮障礙的診斷治療專家共識治療專家共識流行病學(xué)流行病學(xué)1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression i

2、n neurological disorders: an update. Curr Opin Psychiatry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5 Pohjasvaara T, Leppavuori A，Siira I，et al. Frequency and clinical determinan

3、ts of poststroke depression. Stroke，1998，29:2311-2317.6 Hackett ML, Yapa C, Parag V, et al. Frequency of depression after stroke：A systematic review of observational studies. Stroke，2005，36:1330-1340.1 Holtzer R, Scarmeas N, Wegesin DJ, et al. J Am Geriatr Soc，2005，53:2083-2089.2 Modrego PJ, Ferrnde

4、z J. Arch Neurol，2004，61:1290-1293.3. Potter GG, Steffens DC. Contribution of depression ,Neurologist，2007，13: 105117. 1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinic

5、al Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Ring HA, Serra

6、-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry，2002，72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons disease：. Neurology, 2002，58(Suppl 1):S63S70.7. Ehrt U，Aarsland D. Psychiatric aspects of Parkinsons disease. Curr Opin Psychiatry，2005，18: 335-341

7、.1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry

8、，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder:JAMA 2003，289:30953105.6. Janssens AC, Buljev

9、ac D, van Doorn PA. Prediction of anxiety and distress following diagnosis . Mult Scler，2006 ，12:794-801.7. Siegert RJ，Abernethy DA. Depression in multiple sclerosis: a review. J Neurol Neurosurg Psychiatry，2005，76;469-475.1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorder

10、s. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinson

11、s disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Lambert M, Robertson M. Depression in epilepsy: etiology, phenomenology and treatment. Epilepsia，1999，40(suppl 10):S21S47.6. Gaitatzis A，Trimble MR，Sander JW. The psychiatric comorbidity of epilepsy. Acta Neuro

12、logica Scandinavica，2004，110:207-220.1 Radat F，Swendsen J. Psychiatric comorbidity in migraine: a review. Cephalalgia，2005，25:165-178.2 Wang SJ，Juang KD，F(xiàn)uh JL，et al. Psychiatric comorbidity and suicide risk in adolescents with chronic daily headache. Neurology, 2007，68:14681473.神經(jīng)系統(tǒng)疾病伴發(fā)抑郁焦慮障礙的特點(diǎn)神經(jīng)系

13、統(tǒng)疾病伴發(fā)抑郁焦慮障礙的特點(diǎn)海馬海馬杏仁核杏仁核扣帶回扣帶回 皮質(zhì)皮質(zhì)前額葉前額葉皮質(zhì)皮質(zhì)38 Female Outpatients With Recurrent Depression in Remission*Significant inverse relationship between total hippocampal volume and the length of time depression went untreated.Sheline YI, et al. Am J Psychiatry. 2003;160:1516-1518.海馬總體積海馬總體積( mm3)未治療的抑郁未治

14、療的抑郁R2=0.28 P=0.0006*01,0002,0003,0004,0003,0003,5004,0004,5005,0005,5006,000R2=0.28P=0.0006*目前主要神經(jīng)生物學(xué)假設(shè)目前主要神經(jīng)生物學(xué)假設(shè)/發(fā)現(xiàn)發(fā)現(xiàn)-3（形態(tài)學(xué)）（形態(tài)學(xué)） 抑郁癥與細(xì)胞凋亡抑郁癥與細(xì)胞凋亡BDNF=brain-derived neurotrophic factor.1. Sapolsky RM. Arch Gen Psychiatry. 2000;57:925-935.2. Duman RS, et al. Biol Psychiatry. 2000;48:732-739.應(yīng)激應(yīng)激2糖

15、皮質(zhì)激素糖皮質(zhì)激素BDNF正常存活和生長正常存活和生長神經(jīng)元的萎縮神經(jīng)元的萎縮/死亡死亡樹突分支樹突分支1目前主要神經(jīng)生物學(xué)假設(shè)目前主要神經(jīng)生物學(xué)假設(shè)/發(fā)現(xiàn)發(fā)現(xiàn)-4（形態(tài)學(xué)）（形態(tài)學(xué)）治療能預(yù)防或逆轉(zhuǎn)損傷嗎？治療能預(yù)防或逆轉(zhuǎn)損傷嗎？5-HT=serotonin; NE=norepinephrine; ECT=electroconvulsive therapy. 1. Sapolsky RM. Arch Gen Psychiatry. 2000;57:925-935.2. Duman RS, et al. Biol Psychiatry. 2000;48:732-739.應(yīng)激應(yīng)激2糖皮質(zhì)激素糖皮

16、質(zhì)激素BDNF正常存活和生長正常存活和生長神經(jīng)元萎縮神經(jīng)元萎縮/死亡死亡BDNF增加存活和生長增加存活和生長5-HT and NE，DA糖皮質(zhì)激素糖皮質(zhì)激素?藥物治療藥物治療, ECT, 心理治療心理治療2樹突分支樹突分支1下丘腦下丘腦杏仁核杏仁核藍(lán)斑藍(lán)斑ACTH細(xì)胞因子細(xì)胞因子可的松可的松骨骨脂肪組織脂肪組織腎上腺腎上腺前額葉皮前額葉皮層層軀體感覺軀體感覺/情緒情緒心血管心血管代謝代謝免疫與神經(jīng)元再激活免疫與神經(jīng)元再激活認(rèn)知認(rèn)知腎上腺素腎上腺素, NE骨質(zhì)疏松癥骨質(zhì)疏松癥OConnor,etal.QJM2000;93:323-33Miller,OCallaghan.Metabolism200

17、2:51:5-10PSD雖然常見，但由于患者常有失語、忽略或認(rèn)知損害雖然常見，但由于患者常有失語、忽略或認(rèn)知損害而不被訴說或識別而不被訴說或識別1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H

18、. Depression in neurological disorders: an update. Curr Opin Psychiatry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal gangli

19、a. J Neurol Neurosurg Psychiatry，2002，72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons disease：. Neurology, 2002，58(Suppl 1):S63S70.l皮質(zhì)下小血管病性皮質(zhì)下小血管病性VaD或或VCI患者的抑郁障患者的抑郁障礙持續(xù)時(shí)間長、難治礙持續(xù)時(shí)間長、難治. 突出表現(xiàn)：始動性差突出表現(xiàn)：始動性差、精神運(yùn)動遲緩和易伴執(zhí)行功能障礙、精神運(yùn)動遲緩和易伴執(zhí)行功能障礙lAD伴發(fā)的抑郁障礙有隨病程延長而逐漸減伴發(fā)的抑郁障礙有隨病程延長而逐漸減少的趨勢少

20、的趨勢1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiat

21、ry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry，2002，72:1221.6. Okun MS, Watts RL. D

22、epression associated with Parkinsons disease：. Neurology, 2002，58(Suppl 1):S63S70.PD患者的情感障礙與腦內(nèi)多種神經(jīng)遞質(zhì)的改變有關(guān)患者的情感障礙與腦內(nèi)多種神經(jīng)遞質(zhì)的改變有關(guān)1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars

23、 Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression in neurological disorders: an update. Curr Opin Psychiatry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Ring HA

24、, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry，2002，72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons disease：. Neurology, 2002，58(Suppl 1):S63S70.MS患者的抑郁可能與病灶部位（額葉、顳葉）及炎癥患者的抑郁可能與病灶部位（額葉、顳葉）及炎癥有關(guān)有關(guān)l抑郁可為癲癇發(fā)作和發(fā)作后表現(xiàn)，但更多見于發(fā)作間期。l顳葉癲癇和左側(cè)癇灶者容易發(fā)生抑郁。抑

25、郁與癲癇的關(guān)系是雙向的，病因多重而復(fù)雜抑郁與癲癇的關(guān)系是雙向的，病因多重而復(fù)雜1 Benedetti F, Bernasconi A，Pontiggia A. Depression and neurological disorders. Curr Opin Psychiatry，2006，19:1418.2 Tucker GJ. Neurological disorders and depression. Seminars Clinical Neuropsychiatry，2002，7:213-220. 3 Rickards H. Depression in neurological diso

26、rders: an update. Curr Opin Psychiatry，2006，19:294298. 4 Rickards H. Depression in neurological disorders: Parkinsons disease, multiple sclerosis, and stroke. J Neurol Neurosurg Psychiatry，2005，76;48-52.5. Ring HA, Serra-Mestres J. Neuropsychiatry of the basal ganglia. J Neurol Neurosurg Psychiatry，

27、2002，72:1221.6. Okun MS, Watts RL. Depression associated with Parkinsons disease：. Neurology, 2002，58(Suppl 1):S63S70.Kroenke K, et al. Arch Fam Med. 1994;3:774-779.神經(jīng)科就診抑郁焦慮患者特點(diǎn)神經(jīng)科就診抑郁焦慮患者特點(diǎn)不主動敘述情緒癥狀不主動敘述情緒癥狀多見主述為多見主述為睡眠問題睡眠問題、疲乏疲乏及不確定位置的及不確定位置的軀體疼痛軀體疼痛癥狀易與神經(jīng)系統(tǒng)原發(fā)疾病相互影響，注意鑒別癥狀易與神經(jīng)系統(tǒng)原發(fā)疾病相互影響，注意鑒別Kroe

28、nke K, et al. Arch Fam Med. 1994;3:774-779.0102030405060708090軀體癥狀的個(gè)數(shù)軀體癥狀的個(gè)數(shù)*抑郁患病率抑郁患病率(%)其他精神障礙情緒障礙（焦慮/抑郁）0 to 1(n=215)2 to 3(n=225)4 to 5(n=191)6 to 8(n=230) 9(n=139)*常見軀體癥狀常見軀體癥狀:l頭痛頭痛l頭暈頭暈l疲乏疲乏l失眠失眠l背痛背痛l四肢或關(guān)節(jié)痛四肢或關(guān)節(jié)痛l月經(jīng)紊亂月經(jīng)紊亂l消化道不適消化道不適l腹痛腹痛l胸痛胸痛l性功能障礙性功能障礙多個(gè)多個(gè)軀體癥狀軀體癥狀可能預(yù)示可能預(yù)示抑郁癥抑郁癥抑郁和焦慮狀態(tài)的識別和診斷

29、抑郁和焦慮狀態(tài)的識別和診斷*Kessler RC. Et al. JAMA. 2003; 289: 3095-3105神經(jīng)系統(tǒng)疾病伴發(fā)抑郁焦慮障礙的治療目標(biāo)神經(jīng)系統(tǒng)疾病伴發(fā)抑郁焦慮障礙的治療目標(biāo)Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl 5):28-34.抑抑郁郁癥癥狀狀的的嚴(yán)嚴(yán)重重程程度度臨床治愈臨床治愈癥狀最少或無癥狀癥狀最少或無癥狀 ( (HAM-DHAM-D 7)7)，至少至少3 3個(gè)月個(gè)月痊愈痊愈癥狀最少或無癥狀癥狀最少或無癥狀 至少至少6 6個(gè)月個(gè)月正常人群正常人群HAM-DHAM-D 7 7治治療療1. Clinical Practic

30、e Guideline No. 5: Depression in Primary Care, 2: Treatment of Major Depression; 1993. AHCPR publication 93-0551.2. American Psychiatric Association. Am J Psychiatry. 2000;157(suppl4):1-45.3. Anderson IM, et al. J Psychopharmacol. 2000;14:3-20. 4. Reesal RT, Lam RW. Can J Psychiatry. 2001;46(suppl1)

31、:21S-28S.5. DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000. 6. Rush AJ, Trivedi MH. Psychiatr Ann. 1995;25:704-705, 709.Ref: 3. Ferrier IN. Treatment of major depression: Is improvement enough ？ J Clin Psychiatry 60(Suppl 6):10-14,1999有有 效效癥狀改善，但仍有癥狀改善，但仍有殘余癥狀殘余癥狀 情緒仍然低落情緒

32、仍然低落 睡眠障礙睡眠障礙 缺乏工作能力缺乏工作能力 對各種活動失去興趣對各種活動失去興趣HAM-DHAM-D分值下降分值下降 5050臨床治愈臨床治愈徹底消除殘余癥狀徹底消除殘余癥狀 臨床癥狀消失臨床癥狀消失 與正常人沒有區(qū)別與正常人沒有區(qū)別 返回工作崗位返回工作崗位HAM-DHAM-D分值分值 7 7 Remission=Psychiatric Status Rating (PSR) 1 or 2.*Psychosocial functioning after treatment with sertraline or imipramine. P0.05 compared with the

33、remission group.Miller IW, et al. J Clin Psychiatry. 1998;59:608-619.123自評社會適應(yīng)量表自評社會適應(yīng)量表 (平均平均 標(biāo)準(zhǔn)差標(biāo)準(zhǔn)差)無療效無療效改善改善臨床治愈臨床治愈健康對照健康對照(n=299)(n=122)(n=202)(n=482)神經(jīng)科抑郁焦慮障礙的藥物治療神經(jīng)科抑郁焦慮障礙的藥物治療SRIDRINRISNRISerotonin-Noreinphrine Reuptake Inhibitor 主要阻斷去甲腎上腺素和五羥色胺的再攝取主要阻斷去甲腎上腺素和五羥色胺的再攝取作用機(jī)制作用機(jī)制 抑制抑制5-HT再攝取再攝取

34、 抑制抑制NE再攝取再攝取 溫和抑制溫和抑制DA再攝取再攝取 驚恐驚恐/ /恐怖恐怖 強(qiáng)迫和沖動強(qiáng)迫和沖動 攻擊攻擊 貪食貪食/ /厭食厭食 性欲下降性欲下降5-HT5-HT功能不足的癥狀表現(xiàn)功能不足的癥狀表現(xiàn) NENE功能不足的癥狀表現(xiàn)功能不足的癥狀表現(xiàn) SSRIs：單一抑制單一抑制5-HT再攝取再攝?。ㄈ纾悍魍　⑴亮_西汀、西酞普蘭等）（如：氟西汀、帕羅西汀、西酞普蘭等）SNRI：同時(shí)抑制同時(shí)抑制5-HT和和NE的再攝取的再攝?。ㄈ纾蝴}酸文拉法辛緩釋膠囊（如：鹽酸文拉法辛緩釋膠囊怡諾思怡諾思 ） 注意力受損注意力受損 注意力集中困難注意力集中困難 工作記憶力下降工作記憶力下降 信息處理過程

35、緩慢信息處理過程緩慢 精神運(yùn)動性遲滯精神運(yùn)動性遲滯 疲乏疲乏 抑郁情緒抑郁情緒 焦慮焦慮 易激惹易激惹 認(rèn)知功能下降認(rèn)知功能下降0 010102020303040405050606070708080 基線 基線3 月后3 月后SF-36軀體疼痛量表評分軀體疼痛量表評分伴疼痛的伴疼痛的抑郁患者比例(%)抑郁患者比例(%)輕度輕度中度中度嚴(yán)重嚴(yán)重69%59%大多數(shù)患者在大多數(shù)患者在SSRISSRI類藥物治類藥物治療療3 3個(gè)月后軀體個(gè)月后軀體疼痛癥狀并未得疼痛癥狀并未得到改善到改善*573 clinically depressed patients randomized to either flu

36、oxetine, paroxetine, or sertraline.Bair MJ, et al. Psychosom Med. 2004;66:17-22.循證醫(yī)學(xué)的證據(jù)：循證醫(yī)學(xué)的證據(jù)：治療抑郁焦慮，文拉法辛臨床治愈率更高治療抑郁焦慮，文拉法辛臨床治愈率更高NemeroffCB,etal.Eur Neuropsychopharmacol.2003;13(suppl4):S254.AbstractP.1.189.Dataonfile,WyethPharmaceuticalsInc.01020304050012345678周周臨床痊愈臨床痊愈 (HAM-D17 7), %*文拉法辛文拉法辛/

37、怡諾思怡諾思 (n=3,337)氟西汀氟西汀, 舍曲林舍曲林, 帕羅西汀帕羅西汀, 氟伏沙明氟伏沙明, 西肽普蘭西肽普蘭 (n=3,280)安慰劑安慰劑 (n=932)*P0.05 文拉法辛/怡諾思 vs. 安慰劑. P0.05 文拉法辛/怡諾思 vs. 對照藥. P0.05 對照藥 vs. 安慰劑. ITT/LOCF分析;因未用HAM-D，除外1項(xiàng)試驗(yàn)Last-observation-carried-forwardanalysis文拉法辛文拉法辛/怡諾思的臨床痊愈率為怡諾思的臨床痊愈率為41%, 對照藥為對照藥為35%, 安慰劑為安慰劑為24%。平均劑量平均劑量: 文拉法辛文拉法辛134 m

38、g/日日, 怡諾思怡諾思144 mg/日日, 氟西汀氟西汀34 mg/日日, 帕羅西汀帕羅西汀25 mg/日日, 舍曲林舍曲林127 mg/日日, 西肽普蘭西肽普蘭 38 mg/日日, 氟伏沙明氟伏沙明 175 mg/日日. 臨床治愈的百分比臨床治愈的百分比 (%) (%)Rush AJ, et al. N Engl J Med. 2006;354:1231-42.0510152025303540舍曲林（舍曲林（SSRI）安非他酮（安非他酮（NDRI）文拉法辛緩釋劑（文拉法辛緩釋劑（SNRI）主要療效指標(biāo)主要療效指標(biāo)HAM-D17 7臨床臨床治愈治愈N = 727HAM-D17治愈率治愈率17

39、.6%21.3%24.8%05101520253035404550Thase et alNemeroff et al安慰劑安慰劑SSRIs文拉法辛文拉法辛治愈治愈 (%)*與安慰劑比較有顯著差異與安慰劑比較有顯著差異與與SSRI比較有顯著差異比較有顯著差異7%差異差異10% 差異差異Br J Psychiatry. 2001;178:234-241(N=2045)Manuscript in preparation(N=7697)Guelfi et. al, Clin. Neuropharmacol, 1992*p0.05, *p0.01, *p0.001 vs placebo-20-15-10

40、-50基線基線4天天1周周2周周3周周4周周安慰劑怡諾思(n=47)(n=46)*安慰劑(n=123)怡諾思(n=115)周1012141618202224260 1 2 3 4 6 8 1216202428*HAM-A評分(焦慮）MADRS評分（抑郁）051015202530HAMDHAMD-睡眠因子睡眠因子治療前治療前治療后治療后治療前后HAMD評分變化p0.01p17)的療效及睡眠的影響.結(jié)果顯示：文拉法新在顯著改善抑郁癥患者抑郁癥狀同時(shí)，明顯改善患者的主觀睡眠。HAMD-睡眠因子和PSQI評分明顯降低。p0.01怡諾思HAM-A有效患者百分比高于氟西汀2706050403020100安

41、慰劑n=118有效患者百分比氟西汀2060mg/dn=119怡諾思75225mg/dn=122Ref: 1. Sliverstone PH, Ravindran A, Once-daily Venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. J Clin Psychiatry 60: 22-28, 19992. Hackett D, Desmet A, White C, Efficacy and tolerability of once-daily Venlafaxine X