軀體癥狀在焦慮抑郁障礙治療中的地位和意義

1、軀體癥狀在焦慮抑郁障礙診療中的地位和意義,上海同濟(jì)大學(xué)附屬同濟(jì)醫(yī)院上海交通大學(xué)附屬精神衛(wèi)生中心陸,討論要點(diǎn),焦慮抑郁障礙診療中易被忽略的軀體癥狀軀體癥狀對(duì)臨床治愈的影響為什么達(dá)到臨床治愈很重要？雙重機(jī)制抗抑郁藥的優(yōu)勢(shì),EPI研究顯示：綜合醫(yī)院抑郁/焦慮障礙患者的識(shí)別率不到15%,*EPI Study data on file,N=8426,2007年在中國五城市綜合醫(yī)院門診就診者中抑郁／焦慮障的礙患病率調(diào)查，共計(jì)15家醫(yī)院；

2、4個(gè)科室包括神經(jīng)內(nèi)科、消化內(nèi)科、心血管內(nèi)科、婦科；例數(shù)總計(jì)8487例。,69%主訴軀體癥狀,一個(gè)國際性研究中，1146名求助于通科醫(yī)生的抑郁患者，69%在首次求醫(yī)時(shí)主訴僅僅是軀體癥狀1,1. Simon GE, et al. N Engl J Med. 1999;341:1329-1335.2. Kirmayer LJ, et al. Am J Psychiatry. 1993;150:734-741.,其它,首次去綜合醫(yī)院求醫(yī)的

3、抑郁癥患者69%為軀體癥狀,EPI研究顯示：綜合醫(yī)院被診斷抑郁/焦慮障礙患者的就診主訴,N=2456,*EPI Study,7%,內(nèi)科醫(yī)師對(duì)以軀體為主訴的抑郁/焦慮病人的識(shí)別率低,*Diagnosis of depression/anxiety presenting only with somatic complaints and attributions (n=9).?Diagnosis of depression/anxiety

4、presenting with at least 1 psychosocial symptom or problem (n=13).Kirmayer LJ, et al. Am J Psychiatry. 1993;150:734-741.,軀體化主訴*,社會(huì)心理主訴?,22%,77%,小結(jié)： 軀體癥狀在抑郁癥患者中非常普遍且經(jīng)常被忽略,抑郁/焦慮障礙的患者在綜合醫(yī)院非常多見由于去綜合醫(yī)院求醫(yī)的抑郁/焦慮障礙患者以

5、軀體癥狀為主訴掩蓋了心理問題，所以內(nèi)科醫(yī)生對(duì)其識(shí)別率很低因此，關(guān)注多種軀體癥狀的患者是否存在抑郁/焦慮非常重要,討論要點(diǎn),抑郁/焦慮診療中易被忽略的軀體癥狀軀體癥狀對(duì)臨床治愈的影響為什么達(dá)到臨床治愈很重要？雙重機(jī)制抗抑郁藥的優(yōu)勢(shì),抑郁癥是一種高復(fù)發(fā)的慢性疾病,*.連續(xù)8周沒有或者極少癥狀（精神病狀態(tài)評(píng)估少于1或2）則定義為康復(fù)?符合重癥抑郁障礙、輕度抑郁障礙、躁狂、輕躁狂、分裂情感障礙－躁狂或分裂情感障礙－抑郁的研究標(biāo)準(zhǔn)則被定

6、義為復(fù)發(fā)1.Mueller TI, et al. Am J Psychiatry. 1999;156:1000-1006.2.Keller MB, et al. JAMA. 1983;250:3299-3304.,康復(fù)后15年內(nèi),* 85% 的患者經(jīng)歷過1次復(fù)發(fā)1,2?,復(fù)發(fā)的累積可能性1,康復(fù)后時(shí)間 （年）,,,,,,,0,0.2,0.4,0.6,0.8,1.0,,,,,,,,,,1,7,9,11,13,15,5,3,,,

7、N=380,Kupfer DJ. J Clin Psychiatry. 1991;52(Suppl 5):28-34.,抑郁癥的病程癥狀和功能損傷的長期臨床治愈（完全緩解）是治療的目標(biāo)1,,抑郁癥狀的嚴(yán)重程度,,臨床治愈癥狀最少或無癥狀 (HAM-D?7)，至少3個(gè)月,痊愈癥狀最少或無癥狀 至少6個(gè)月,正常人群HAM-D?7,治療,近70%的抑郁癥患者未達(dá)到臨床治愈,STAR*D 中至重度抑郁的有效性研究“臨床現(xiàn)實(shí)”中

8、的患者樣本西酞普蘭20-60 mg/d x 12 周 QIDS-SR 評(píng)定結(jié)局,Trivedi MH et al. Am J Psychiatry 2006; 163:28-40,臨床治愈=33%,有效=14%,無效=53%,N=2,876,STAR*D Level 1,殘留癥狀有多常見?,,心境,患者比例,Nierenberg AA, Keefe BR, Leslie VC, et al. J Clin Psychiatry. 1

9、999(Apr);60(4):221-225,50,40,30,20,10,0,抑郁癥狀,自殺意念,N=108 對(duì)氟西汀治療有效的患者,,,,,,,,,,,,,,,,,,,改善,,,,,,,睡眠,精神運(yùn)動(dòng),疲乏,自罪,注意,體重,興趣,,,殘留,,軀體癥狀是妨礙獲得臨床治愈的主要障礙之一,抑郁癥的殘留癥狀中，94%是軀體癥狀,Adapted from Paykel ES, et al. Psychol Med. 1995; 25(6):

10、 1171-1180,,With Physical Symptoms,,Without Physical Symptoms,用HAM-D17第13項(xiàng)(軀體癥狀/全身癥狀)來評(píng)估軀體癥狀,抑郁癥殘留癥狀增加復(fù)發(fā)的風(fēng)險(xiǎn),*Residual symptoms: Longitudinal Follow-up Evaluation Psychiatric Status Rating (LIFE PSR) Scales. Judd LL, et

11、al. J Affect Disord. 1998;50:97-108.,殘留癥狀*,無殘留癥狀,13.4,34.2,無經(jīng)歷復(fù)發(fā)的患者 (10-y; %),小結(jié),抑郁癥是一種高復(fù)發(fā)的慢性疾病2/3抑郁癥患者有殘留癥狀，且主要是軀體癥狀抑郁癥患者有殘留癥狀導(dǎo)致相當(dāng)一部分患者無法達(dá)到臨床治愈，增加了復(fù)發(fā)的風(fēng)險(xiǎn),討論要點(diǎn),抑郁/焦慮診療中易被忽略的軀體癥狀軀體癥狀對(duì)臨床治愈的影響為什么達(dá)到臨床治愈很重要？雙重機(jī)制抗抑郁藥的優(yōu)勢(shì),達(dá)到

12、臨床治愈非常重要,,,,,,,,,,,,,1. Sobocki P, et al. Int J Clin Pract. 2006;60:791-798.2. Keller MB. JAMA. 2003;289:3152-3160.3. Weissman MM, et al. JAMA. 2006;295:1389-1398.,4. Bromberger JT, et al. J Nerv Ment Dis. 1994;182:40-

13、44.5.Judd LL, et al. J Affect Disord. 1997;45:5-17.,,職業(yè)功能1,2,軀體功能1,2,婚姻功能4,以后復(fù)發(fā)的可能性1,2,自殺危險(xiǎn)5,治愈(或未達(dá)治愈)能影響,,子女的心理健康3,,社會(huì)功能1,2,指南注明臨床治愈作為治療目標(biāo),美國衛(wèi)生保健政策和研究機(jī)構(gòu) (1993)1美國精神病學(xué)會(huì)(APA) (2000)2英國精神藥理學(xué)會(huì)(2000)3加拿大精神病學(xué)會(huì)和加拿大心境和焦慮障

14、礙治療網(wǎng)絡(luò)CPA/CANMAT (2001)4,1. Depression Guideline Panel. Depression in Primary Care: Volume 2.Clinical Practice Guideline. AHCPR publication no. 93-0551. 1993.2. APA. Practice Guidelines for the Treatment of Patients Wit

15、h Major Depression. 2nd ed. 2000.3. Anderson IM, et al. J Psychopharmacol. 2000;14:3-20. 4. Reesal RT, Lam RW. Can J Psychiatry. 2001;46(suppl 1):21S-28S.,討論要點(diǎn),抑郁/焦慮診療中易被忽略的軀體癥狀軀體癥狀對(duì)臨床治愈的影響為什么達(dá)到臨床治愈很重要？雙重機(jī)制抗抑郁藥的優(yōu)勢(shì),抑

16、郁與焦慮是常見的精神障礙共病類型,瑞典一般人群調(diào)查研究顯示(n=3001)，抑郁焦慮共病可表現(xiàn)為：在臨床顯著抑郁（PHQ-9?10分）和臨床顯著焦慮（GAD-7 ?8分）的患者中，約50%患者同時(shí)存在臨床顯著抑郁焦慮。抑郁癥與廣泛性焦慮的患者中28.2%患者同時(shí)存在抑郁癥和廣泛性焦慮。,Robert Johansson1,et al. Depression, anxiety and their comorbidity in the

17、Swedish general population: point prevalence and the effect on health-related quality of life. PeerJ. 2013 Jul 9;1:e98.,抑郁癥: 系統(tǒng)性疾病,Adapted from:DSM-IV-TR?. Washington, DC: American Psychiatric Association; 2000. K

18、roenke K, et al. Arch Fam Med. 1994;3:774-779.,軀體癥狀頭痛疲勞睡眠障礙頭暈疼痛胸痛關(guān)節(jié)/淋巴結(jié)痛背/腹痛消化道主訴不適性功能障礙月經(jīng)紊亂,情緒癥狀情緒抑郁愉快感缺失絕望自我評(píng)價(jià)低記憶損傷注意力集中困難焦慮憤怒/情緒不穩(wěn),內(nèi)心,抑郁癥患者可能出現(xiàn)的多種焦慮癥狀*,*依照HAMD抑郁量表中的焦慮/軀體化亞量表評(píng)估項(xiàng),HAMILTON M. A rating

19、 scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62.,抑郁和焦慮共患關(guān)系的示意圖,(A) 臨床顯著抑郁和臨床顯著焦慮及兩者的共??；(B)抑郁癥、廣泛性焦慮及兩者的共病。注：由于不同疾病單元受訪者樣本不同，因此患病率并不能直接疊加比較,Robert Johansson1,et al. Depression, anxiety and their

20、 comorbidity in the Swedish general population: point prevalence and the effect on health-related quality of life. PeerJ. 2013 Jul 9;1:e98.,抑郁焦慮共病的多種危害,疾病嚴(yán)重程度增加，慢性化比例增高。即使患者恢復(fù)后，原有抑郁焦慮共病也會(huì)增加再發(fā)的可能性。加重患者的社會(huì)功能（包括工作能力、心

21、理社會(huì)功能）和生活質(zhì)量損害。醫(yī)療住院率增加：抑郁與焦慮合并存在時(shí)住院風(fēng)險(xiǎn)增大2.5倍，特別是與驚恐障礙共?。∣R=3.2）。自殺風(fēng)險(xiǎn)增加：抑郁焦慮共病患者較抑郁或焦慮單獨(dú)患病者的自殺企圖率增高70%，較單純驚恐障礙患者風(fēng)險(xiǎn)增大4倍。,Robert M. A. Hirschfeld. The Comorbidity of Major Depression and Anxiety Disorders: Recognition and M

22、anagement in Primary Care. Primary Care Companion J Clin Psychiatry 2001;3:244–254.,DSM-5抑郁障礙中增加了“焦慮嚴(yán)重程度”維度,Depressive Disorders (155)The following specifiers apply to Depressive Disorders where indicated:^Specify: Wit

23、h anxious distress (specify current severity: mild, moderate, moderate-severe, severe); 【合并焦慮困擾（確定當(dāng)前嚴(yán)重度：輕度、中度、中重度、嚴(yán)重）】With mixed features; With melancholic features; With atypical features; With mood congruent psycho

24、tic features; With mood-incongruent psychotic features; With catatonia (use additional code 293.89 [F06.1]); With péripartum onset; With seasonal pattern,DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS FIF

25、TH EDIT ION. DSM-V. American Psychiatric Association. 2013.,抑郁癥病因與5-HT和NE兩個(gè)神經(jīng)遞質(zhì)相關(guān),28,SSRIs治療后改善軀體癥狀的療效指數(shù)較低,ARTIST = A Randomized Trial Investigating SSRI Treatment,積極體驗(yàn),抑郁情緒,Data from: Greco T, et al. J Gen Intern Med. 2

26、004;19(8):813-818,抑郁/焦慮與單胺神經(jīng)遞質(zhì)假說,5-HT,DA,NE,1964 Schildkraut et al,1969 Carlsson et al,1975 Radrup et al,Schilkraut JJ, et al. J Psychiatr Res 1964;33:257-66Carlsson A, et al. Eur J Pharmacol 1969;5(4):357-66Randrup A,

27、 Braestrup C. Psychopharmacology (Berl) 1977.16;53(3):309-14.,焦慮/抑郁患者存在多種神經(jīng)遞質(zhì)系統(tǒng)功能異常,影像學(xué)研究顯示：與對(duì)照者(n=593)相比，焦慮障礙患者(n=504，包括OCD、GAD、PD、恐怖癥或PTSD)的DA、5-HT和GABA系統(tǒng)都存在異常1。NE、促皮質(zhì)激素釋放激素等神經(jīng)肽、膽囊收縮素和神經(jīng)肽Y也與焦慮有關(guān)2。,Nikolaus S, et al.

28、Cortical GABA, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders--results from in vivo imaging studies. Rev Neurosci. 2010;21(2):119-39.Toth M. Use of Mice with Targeted Gen

29、etic Inactivation in the Serotonergic System for the Study of Anxiety. Serotonin Receptors in Neurobiology. Boca Raton (FL): CRC Press; 2007. Chapter 9. Frontiers in Neuroscience.,,SNRI增強(qiáng)NE對(duì)疼痛抑制的作用,,Θ,Θ,Θ,Θ,下行NE投射通道,,疼痛信

30、號(hào),SNRI增強(qiáng)NE,,胃痛,背痛,肌肉關(guān)節(jié)痛,疼痛信號(hào)被抑制,為什么SSRI效果不好,5-HT功能異常與杏仁核應(yīng)激調(diào)控異常有關(guān),杏仁核依賴于5-HT調(diào)節(jié)對(duì)于外部應(yīng)激的反應(yīng)，相關(guān)信使系統(tǒng)包括SGK-1、ERK1/2和GSK3通路。GSK3也參與5-HT不足時(shí)的行為學(xué)反應(yīng)1。動(dòng)物實(shí)驗(yàn)中，5-HT不足造成杏仁核的應(yīng)激調(diào)控異常，表現(xiàn)出焦慮樣行為和行為去抑制1。,Sachs BD, et al. The effects of brai

31、n serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress. Int J Neuropsychopharmacol. 2013 Oct;16(9):2081-94.Stahl's Essential Psychopharmacology Online. Chapte

32、r 14. Revised and Updated Edition 4th Edition,以杏仁核為中心的環(huán)路,杏仁核是產(chǎn)生焦慮的重要結(jié)構(gòu)基礎(chǔ),焦慮恐懼癥狀和以杏仁核為中心的環(huán)路的功能障礙有關(guān)。階段性害怕和焦慮均由杏仁核介導(dǎo)，傳出信號(hào)到下丘腦和腦干引起臨床癥狀。,Asan E, et al. Serotonergic innervation of the amygdala: targets, receptors, and impli

33、cations for stress and anxiety. Histochem Cell Biol. 2013 Jun;139(6):785-813. Michael Davis, et al. Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety. Neuropsychopharmacology