Understanding and Managing Depression and its Physical Symptoms

1. 憂鬱症與身體症狀 振興醫院精神醫學部 游佩琳醫師

3. 終生盛行率： 5-11% • 美國每年有一千萬到一千五百萬人 • 症狀可以長達數年 • 單次發作後 有 50 % 以上的復發率、多次發作後 復發率更高 • 嚴重性與心絞痛和冠狀動脈疾病相當 • 若未治療，則有高自殺身亡率

4. 憂鬱症的分類 • 重鬱症(MAJOR DEPRESSION) • 輕鬱症(DYSTHYMIC DISORDER) • 混合焦慮與憂鬱症( MIXED ANXIETY AND DEPRESSIVE DISORDER) • 適應障礙症( ADJUSTMENT DISORDER) • 雙極性情感性疾病憂鬱期( BIPOLAR DISORDER, DEPRESSIVE TYPE) • 次發性憂鬱症（其他精神疾病、人格違常、身體疾病或藥物使用）

5. Affect Behavior Cognition Drive 情緒 行為 認知功能 生理驅力 憂鬱症的診斷

6. 美國精神醫學會「精神疾病診斷及統計手冊第四版」美國精神醫學會「精神疾病診斷及統計手冊第四版」 • 1.幾乎每天都是憂鬱的心情。 • 2.對日常生活中大部份的事物都失去興趣；或從事各種活動時，感覺不出快樂的心情。 • 3.在未刻意改變飲食習慣下，體重改變超過5％。 • 4.幾乎每天都失眠或嗜睡。 • 5.思考行動變得躁動不安或遲緩呆滯。 • 6.每天都覺得疲累不堪或失去能量。 • 7.覺得活著沒有價值或心中充滿過多的罪惡感。 • 8.思考及專注能力下降，猶豫不決無法做決定。 • 9.一再地想起死亡和自殺的主題，甚至嘗試自殺的舉動。

7. 憂鬱症的病因 • 真正病因：未知 • 生物病因 -基因遺傳 -單胺神經介質假說 -神經內分泌失調 • 性格病因 • 社會心理壓力病因

8. Serotonin Anxiety Irritability Energy Interest Impulse Mood, Emotion,Cognitive function Sex Appetite Aggression Motivation Drive Dopamine Physiological / behavioral roles of NE, 5-HT and DA Norepinephrine

9. Relation of Depression and Somatic symptoms

10. Common Somatic Manifestations • Pain---headache, backache, visceral or abdominal • Soreness • Fatigue • Dizziness • Shortness of breath • Others

11. Overall Assessment • Medical syndromes • Non-somatoform disorders --Depressive disorders --Anxiety disorders --Psychosis • Somatoform disorders

12. Functional Somatic Syndromes • Several related syndromes characterized by a collection of somatic symptoms, suffering and disability rather than by an identifiable tissue abnormality • Highly prevalent • Ill-defined pathological mechanisms • Considerably disability and functional impairment

13. Examples of FSS • GI---Irritable bowel syndrome • Rheumatology---Fibromyalgia • Neurology---Tension headache • CV---Atypical or non-cardiac chest pain • Infection---Chronic fatigue syndrome • CM---Hyperventilation syndrome’ • Dentistry---TM joint • ENT---Globus syndrome

14. Depression and Anxiety • 45-95% of primary care patients with depression present with only somatic symptoms • Medically unexplained symptoms should increase the suspicion of these disorders • FSS are more frequently associated with anxiety and depression than with well-defined medical diseases Simon et al. N Engl J Med 1999; 341:1329-1335

15. International Study of the Relation between Somatic Symptoms and Depression • Patients from non-Western culture and lower socioeconomic status are less willing or less able to express emotional distress • A somatic presentation of depression was related to characteristics of physicians and health care systems, and cultural differences Simon, G.E. et al (1999) The New England Journal of Medicine

16. A somatic presentation was more common at centers where patient slacked an ongoing relationship with a primary care physician • Half of the depressed patients reported multiple unexplained somatic symptoms • 11% denied psychological symptoms of depression on direct questioning

17. Somatization • Patients with psychiatric illness but present with somatic symptoms • The association between depression and medically unexplained somatic symptoms (the influence of psychological distress on the perception or reporting of somatic symptoms) • The denial of psychological distress and the substitution of somatic symptoms

18. BSRS-5 > 10 points • 全身疲累 • 頭痛 • 疼痛 • 頭不舒服 • 失眠 • 暈眩

19. 心病? 裝病? 身心病?

20. Mood disorders affect the course of medical illnesses • A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. mood disorders medical illnesses BIOL PSYCHIATRY 2005;58:175–189

21. Prevalence of depression in medically ill • Wide variation of the prevalence • Major depression (by diagnostic interview) • 4.8%-9.2% in medical outpatients • 8%-15% in medical inpatients • 1.5%-50% in cancer patients (mean 24%) (McDaniel et al. 1995) • 8-60% in different populations (by questionnaire) (Meakin et al.) • 30% had psychiatric morbidity (using GHQ) 12% had major depressive disorder (Clarke et al. 1991) • Major depression rates range from 4.8% to 13.5% Minor depression rates range from 3.4% to 6.4% (Lobo and Campos 1997)

22. Prevalence of Depression in Chronic Diseases NHDS, NAMCS, NHAMCS Sutor B, et al. Mayo Clin Proc. 1998;73(4):329-337; Jiang et al, CNS Drugs, 2002

23. What kinds of chronic medical illnesses increased prevalence of depression ? • various forms of vascular disease - cardiovascular - cerebrovascular - peripheral vascular • diabetes mellitus • Arthritis X 3 risk X 2~3 risk  40~60% risk J Am Geriatr Soc 2004;52:86–92.

24. Relationship between the depressive Ss/ Dis. and the physical illness • Depressive dis. is a reaction to the physical illness and its treatment • Depression which precedes the onset of physical illness • Depressive dis. precedes the onset of the physical symptoms • Depressive dis. itself is induced by physical condition

25. Factors associated with emotional disturbances • Nature of physical disease • Measuring the illness: diagnosis, anatomical location, course, severity, loss of function or self-esteem • Nature of treatment • Patient factors: biological and psychological vulnerability, personality, supporting system, other life stressors • Social consequences of the illness

26. 其實你不懂我的心 心病與心臟病曾經被認為是互不相關的事，特別是有一些患者在主訴胸悶以及心悸時，其症狀與一般心臟病所呈現的略有不同，醫生多半告訴病人是因為緊張、焦慮以及壓力的關係，那是心病的表徵而非心臟病。所以醫生會為患者開一些緩和情緒以及抗焦慮的藥物，病人可能得到相當程度的改善，但常復發。　隨著醫學的進一步研究發現，心病與心臟病並不一定是完全不相關的，近年來許多研究報告發現，可以得到的答案是—憂鬱症與冠心病，可能互為因果關係。 根據一項新的研究顯示，在罹患心臟病病人中具有嚴重憂鬱與焦慮症狀者，只有三分之一獲得必要的治療。顯示一般的心臟科醫師常會忽略這個大問題。

27. Depression as a predictor for coronary heart disease • Anda 等人在一項前瞻性研究中，針對 2,832 位沒有心血管疾病者，追蹤 12.4 年，初步資料發現 2,832 個案中，11.1% 有憂鬱症狀，10.8% 有中度無望感，2.9% 有重度無望感，在研究期間，有 6.7% 死亡，9.7% 因心血管疾病住院。 • 這些個案與沒有症狀者比較的結果，發生缺血性心臟病者，不管是否致死，其相對危險性均很高，致死性心肌梗塞相對危險率分別為 1.4、1.6、2.1，非致死性心肌梗塞相對危險率分別為 1.6、1.3、1.9，不論吸菸與否 (吸菸是心臟血管疾病之危險因子)，與沒有憂鬱症者比較，高出 50% 有產生心血管疾病的危險。 • 這是 1993 年的報告，也是第一個流行病學研究結果，顯示憂鬱症與心血管疾病相關。憂鬱症是好發缺血性心臟病的獨立危險因子，與抽菸、高膽固醇、家庭史等同為獨立危險因子。 Anda R, Williamson D, Jones D: Depressed affect, hopelessness and the risk of ischemic heart disease in a cohort of US adults. Epidemiology 1993;4:285-294.

28. Depression in MI patients • 30-40% had depressive syndromes in the 1st week after MIs, 15-30% had MD (by DSM-III-R) • Such disorders persist in a similar percentage for up to 3-6 months (vs. 3% in general population) • Absence of social support as a risk factor for MI (Tranella 1994; Garcia 1994)

29. Depression and outcome of MI • Depression increase the risks of vascular-related deaths in H/T patients (Wells 1995) • Post-MI patients with MD had a risk of mortality in the 6 months 3 times higher than in non-depressed post-MI patients (Frasure-Smith et al. 1993) • Presence of depression constitute a factor predictive of mortality following dx of MI (Carney et al. 1988, Schleifer et al. 1989, Freedland et al. 1992)

30. Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet 2003; 362: 604-09 • Background：Studies that have shown clinical depression to be a risk factor for cardiac events after coronary artery bypass graft (CABG) surgery have had small sample sizes, short follow-up, and have not had adequate power to assess mortality. We sought to assess whether depression is associated with an increased risk of mortality. • Methods：We assessed 817 patients undergoing CABG at Duke University Medical Center between May, 1989, and May, 2001. Patients completed the Center for Epidemiological Studies-Depression (CES-D) scale before surgery, 6 months after CABG, and were followed-up for up to 12 years. • Findings： • In 817 patients there were 122 deaths (15%) in a mean follow-up of 5·2 years. 310 patients (38%) met the criterion for depression (CES-D 16): 213 (26%) for mild depression (CES-D 16-26) and 97 (12%) for moderate to severe depression (CES-D 27). • Survival analyses, controlling for age, sex, number of grafts, diabetes, smoking, LVEF, and previous MI, showed that patients with moderate to severe depression at baseline (adjusted hazard ratio [HR] 2·4, [95% CI 1·4-4·0]; p=0·001) and mild or moderate to severe depression that persisted from baseline to 6 months (adjusted HR 2·2, [1·2-4·2]; p=0·015) had higher rates of death than did those with no depression. • Patients with moderate to severe depression at baseline had higher rates (HR:2.2-2.4) of death than did those with no depression. • Despite advances in surgical and medical management of patients after CABG, depression is an important independent predictor of death after CABG and should be carefully monitored and treated if necessary.

31. Post-stroke depression (PSD) • Rates of PTD have ranged from 18 to 61 % (House 1987) • 50% developing depression during the acute post-stroke period • 30% among outpatient stroke patients (Strarkstein and Robison 1989)

32. Depression and vascular disease • Elderly H/T subjects with severe depression sxs (CES-D >=15) were 2.3-2.7 times more likely to suffer from stroke than non-depressed H/T patients (Simonsick et al. 1995) • Depressive symptoms were associated with increased risk of stroke mortality (Everson et al. 1998) • Increase propensity for platelets to aggregate and high levels of cholesterol and high density lipoproteins (Musselman et al. 1996) • Aged 60  with H/T depressive elderly had more than twice the risk of heart failure as non-depressed patients (Musselman et al. 1996)

33. Depression is a risk factor for noncompliance with medical treatment Arch Intern Med 2000;160:2101-2107

34. Increased mortality may relate to decreased adherence to treatment recommendations or possibly to direct effects of the depressed state on autonomic tone, platelet aggregation, or immune and inflammatory responses. • the prognosis of depression is worsened by the presence of significant medical comorbidity.

35. Watch out for a clinically occult medical illness when: • Severe new-onset depression, including melancholia and psychotic depression • New-onset depression in an older adult • New-onset or recurrent depression that is not readily understood in the context of the patient's psychosocial stressors and circumstances • Depression that has not responded to treatment attempts • Depression with significant coexisting cognitive impairment, anxiety, substance use disorder, or other comorbid psychopathology

36. Differential Diagnosis

37. 廣泛性焦慮症 • 什麼都想、什麼都擔心、什麼都不奇怪 • 擔心、害怕、注意力不集中 • 肌肉張力增加、颤抖頭痛 • 冒汗、心悸、呼吸困難、胃痛、腹瀉、失眠

38. 恐慌症 • 公司大老闆症候群? • 突然嚴重焦慮發作、胸悶心悸、呼吸困難、手腳發麻、瀕死的感覺 • 擁擠或密閉空間、一直擔心再次發作 • 心臟科、急診的常客

39. Treatment

40. 憂鬱症的治療 • 藥物治療 • 電痙治療 (ECT) • 心理治療 • 其他(照光 etc)

41. 憂鬱症的藥物治療 • TCA (Tricyclic antidepressants) • MAOI/RIMA (Monoamine oxidase inhibitors) • SSRI (Selective serotonin reuptake inhibitors) • SNRI (Selective noradrenergic reuptake inhibitors) • NaSSA (Noradrenergic and specific serotonergic antidepressant) • NDRI (Norepinephrine and dopamine reuptake inhibitors)

42. Cardiovascular Effects with TCA Orthostatic hypotension α-blockade Dizziness and Syncope PR prolongation Conduction block QT prolongation VT VF Class IA antiarrythmia Increased heart rate Vagolytic effect Decreased HRV Contraindicated in structural heart disease

43. MAOI/RIMA • Classical MAO inhibitors---irreversible and nonselective phenelzine (Nardil) tranylcypromine (Parnate) isocarboxazid (Marplan) • Reversable inhibitors of MAO A moclobemide (Aurorix) • Selective inhibitors of MAO B deprenyl (Selegiline; Eldepryl)

44. MAOI • Irreversible inhibition of MAO A and B • Hypertensive crisis after tyramine-containing food • MAO B used in the prevention of neurodegenerative processes, such as those in Parkinson’s disease

45. RIMA • Atypical depression • Second-line treatment for anxiety disorders, such as panic disorder or social phobia • RIMASSRI washout for 2 weeks • SSRIRIMA washout for one week (except fluoxetine, whose metabolic product has a longer half-life, hence washout time being two weeks)

46. 血清素再回收抑制劑 (SSRI) • Fluoxetine (Prozac) • Sertraline (Zoloft) • Fluvoxamine (Luvox) • Citalopram (Cipram) • Paroxetine (Seraxet)

47. SSRI • Fewer side effects • Safety even in high dose/overdose • Side effects related to serotonin receptor subtypes 5HT2A, 5HT2C, 5HT3, 5HT4 • Indications other than major depression OCD, Panic disorder, Bulimia, Social phobia, PTSD, PMS

48. SSRI的限制 • 對重度到極重度憂鬱症個案, 療效似乎較dual mechanisms antidepressants來得差 • SSRI discontinuation syndrome • Serotonin syndrome • Drug interactions

49. Rationale for Agents with Dual Reuptake Inhibition Serotonin-related symptoms Norepinephrine-related symptoms Impulse • Appetite Aggression Anxiety • Irritability Mood • Emotion Motivation • Zest Energy • Social drive Anxiety • Irritability Mood • Emotion Stahl S. J Clin Psychiatry 1999; 60: 213-214. Healy D et al. J Psychopharmacol 1997; 11(Suppl): S25-S31. EFEXOR XR

50. NaSSA • Mirtazapine (Remeron) • Alpha 2 antagonism, therefore increases 5HT and NE • Only 5HT1A receptors are stimulated because 5HT2A, 5HT2C and 5HT3 receptors are blocked. • Sedation and weight gain due to H1 receptor blockage