朱哲生 1 葉慶輝 2 前言 WHO 1998 ( m a j o r depressive disorder) 21 ( DSM-IV-TR ) 2005 WHO Global Burden of Disease, GBD D i s a b i l i t y Adjusted Life Years, DALYs 2 0 3 0 1 高雄榮民總醫院精神部住院醫師 2 國軍左營總醫院家庭醫學科主任 depressive disorder, psychotic depressive (depressive disorder) 流行病學 7% 2008 6 5 10.4% 2026 20% 1997 2000 226 家庭醫學與基層醫療第二十五卷第六期
12.9% 21.7% 6.2% 6.8% 15.5% 2003 ( G e r i a t r i c Depression Scales, GDS) 3 9. 2 % 29.5%(GDS ) 75% 危險因子及自殺議題 2008 17.9 WHO ( WHO 13 6.5-13 6.5 ) 65 36.5 75% 老人憂鬱性疾患評估及鑑別診斷 (psychotic depression) B12 家庭醫學與基層醫療第二十五卷第六期 227
25~50% (8~44%) (1~40%) (40%) (20~40%) (17~31%) 憂鬱性疾患 The 10th International Classifications of Disease, ICD-10 ICD-10 ( I C D - 1 0 F32 F33 F34.1 F38.1) 1994 ( T h e Diagnostic and Statistical Manual of Mental Disorders, DSM-IV) 2 0 0 0 D S M - I V- T R ( T e x t Revision of the DSM-IV) DSM-IV-TR DSM-IV-TR D S M - I V- T R (d y s t h y m i a) (single episode) (recurrent) (mild) (moderate) 表一 : 可能導致憂鬱性疾患的藥物及內科疾病 藥物 心血管藥物 beta-blocker, clonidine, digitalis, hydralazine methyldopa, reserpine, thiazide diuretic 化療藥物 6-azauridine, asparaginase, azathioprine, bleomycin, cisplatin, cyclophosphamide, doxorubicin, vinblastine, vincristine 抗精神病藥物 fluphenazine, haloperidol 安定及抗焦慮藥物 barbiturates, benzodiazepines, chloral hydrate, ethanol 抗帕金森氏病藥物類固醇非類固醇抗發炎藥物 疾病 癌病 ( 特別是胰臟癌 ) 神經系統疾病老化性及血管性失智症 帕金森氏病 阿茲海默氏病 多發性硬化症 心血管疾病心肌梗塞 心臟衰竭 心肌病變 代謝性疾病糖尿病 葉酸及維他命 B12 不足 電解質不平衡 內分泌疾病甲狀腺功能亢進或低下 Addison 氏病 Cushing 氏症 腦下垂體低下症 病毒感染病毒性肝炎 HIV 感染 病毒性肺炎 流行性感冒 風濕性免疫疾病紅斑性狼瘡 類風濕性關節炎 本圖修改自 Depression in Later Life: A Diagnostic and Therapeutic Challenge, Am Fam Physician 2004;69:2375-82. 228 家庭醫學與基層醫療第二十五卷第六期
( s e v e r e w i t h o u t psychotic features) (severe with psychotic features) (major depressive episode) ( 5%) ( ) (1) ( ) (2) (3) ( 4 ) (mood disorder) (1) ( ) (2) 2 (3) 2 ( 4 ) (5) ( ) (1) ( ) (2) (3) 2001 ICF ( I n t e r n a t i o n a l C l a s s i f i c a t i o n o f Functioning, Disability, and Health) ICF ICF 評估工具 家庭醫學與基層醫療第二十五卷第六期 229
( T a i w a n G e r i a t r i c Depression Scales, TGDS-30 ) [ / ] G D S - 1 5 10 4 1 (1) Hamilton 1960 (Hamilton Depression Rating Scale, HAMD) (2)Beck 1967 (Beck Depression Inventory) (BDI-II) (3) ( C e n t e r f o r Epidemiological Studies Depression Scale, CES-D) 病因 ( ) ( b r a i n a t r o p h y a n d w h i t e m a t t e r hyperintensities) 治療 65%~75% 40% 2 6~12 6 藥物治療 selective serotonin-reuptake inhibitors: S S R I t r i c y c l e antidepressants, TCA 70%~75% TCA 230 家庭醫學與基層醫療第二十五卷第六期
SNRI(serotonin-norepinephrine reuptake inhibitor), venlafaxine (efexor); NDRI(norepinephrine-dopamine reuptake i n h i b i t o r ), b u p r o p i o n ; N a S S A ( n o r a d r e n e r g i c a n d s p e c i f i c s e r o t o n e r g i c a n t i d e p r e s s a n t s ), m i r t a z a p i n e ( R e m e r o n ) venlafaxine mirtazapine 2009 Lancet 表二抗憂鬱劑選擇及使用劑量 e s c i t a l o p r a m sertraline mirtazapine venlafaxine 2 0 0 9 C A N M AT ( C a n a d i a n N e t w o r k f o r M o o d a n d A n x i e t y Treatments) 第一線治療 * 抗憂鬱劑作用機轉劑量 ( daily) 副作用 ( 詳述如表三 ) bupropion[wellbutrin] citalopram[celexa] fluoxetine[prozac] sertraline[zoloft] fluvoxamine[luvox] paroxetine[seroxat] venlafaxine[efexor] duloxetine[cymbalta] escitalopram[lexapro] 第二線治療 amitriptyline, clomipramine and others selegiline transdermal[emsam] trazodone[desyrel]# NDRI SNRI SNRI 抑制突觸前 serotonin and norepinephrine 回 收 ( 主要機轉 ) Irreversible MAO-B inhibitor SARI 150-300 mg 20-60 mg 20-80 mg 50-200 mg 100-300 mg 20-50 mg 75-375 mg 60-120 mg 10-20 mg Various 6-12 mg transdermal 150-300 mg 癲癇 (dose-dependent) S S R I S N R I 併用 M A O I 使用時會引起 serotonin syndrome 危險 口乾 便秘 小便困難 視力模糊 體重 增加 嗜睡 心搏過速 血壓降低等 併用提升血清素藥物如 TCAs s 等 會引起 serotonin syndrome 危險 嗜睡及姿勢性低血壓 * 第一線藥物在 CANMAT 所作的 systemic review 文章中定義為有 level 1 或 level 2 證據加上臨床運用的支持 ; 第二線藥物為 level 3 證據加上臨床運用支持 (level 1: 至少兩篇 RCTs 文章證據 ;level 2: 至少一篇 RCT 文章 ;level 3: 非隨機取樣 case series 回顧性文章證據支持 ) * 患者對於第一線治療藥物的耐受性和副作用小, 接受度也較高, 因此使用上優於第二線藥物如 TCA MAOI, 但研究也指出 第一線和第二線藥物對於患者的療效大致相同 #trazodone 在治療劑量下 sedative effect( 鎮定效果 ) 很強, 因此放在第二線治療 資料來源 :Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy 家庭醫學與基層醫療第二十五卷第六期 231
表三第二代抗憂鬱劑藥物常見副作用嗜睡失眠頭痛口乾視力模糊解尿困難腸胃不適噁心便秘性功能障礙 citalopram b * * b * * a b * 10-30% escitalopram a a * a * * a b a 10-30% fluoxetine b b * b * * a b * >30% fluvoxamine c b c b * a a c b >30% paroxetine b b b b a a a b b >30% sertraline b b c b a a a c a >30% bupropion * b * b a * a b b <10% duloxetine a b a b a a a c b 10-30% selegiline a b b a a * a * * <10% trazodoe c a a b a a b * a ( 未註明 ) a=9% or lower, b=10-29%, c=30-49%, d=50% or higher, *=usually 5% or less 資料來源 :Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy 2 0 0 6 (major depression in old age) 978 ( 11%) 9 (1) ( 2 ) (start low, go slow) (3) BZD ( ) 心理治療 232 家庭醫學與基層醫療第二十五卷第六期
電痙攣療法 (ECT, electroconvulsive therapy) ECT ECT 結語 參考資料 1. Cipriani A, Furukawa TA, Salanti G et al: Comparative efficacy and acceptability of 12 new-generation antidepressants: amultipletreatmentsmeta-analysis. Lancet 2009; 373: 746-58. 2. 2004 14 81-93 3. A l e x o p o u l o s G S, K a t z I R, R e y n o l d s C F, Carpenter D, Docherty JP: The expert consensus guideline series. Pharmacotherapy of depressive disorders in older patients. Postgrad Med 2001. Accessed April 21. 4. Carota A, Berney A, Aybek S et al: A prospective study of predictors of post stroke depression Neurology 2005; 64:428-33. 5. Birrer RB, Vemuri SP: Depression in Later Life: A Diagnostic and Therapeutic Challenge, Am Fam Physician 2004; 69:2375-82. 6. Ryan J, Carriere I, Ritchiek, et al: Late-life depression and mortality: influence of gender and antidepressant use, The Bri J Psychiatry. 2008; 192: 12-8. 7. Charney DS, Reynolds CF III, Lewis L, et al: Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Arch Gen Psychiatry 2003; 60:664-72. 8. Reynolds CF 3rd, Dew MA, Pollock BG, et al: Maintenance Treatment of Major Depression in Old Age N Engl J Med 2006; 354:1130-8. 9. Fitch K, Molnar FJ, Power B, Wilkins D, Man- San-Hing M: Antidepressant use in older people Family physicians knowledge, attitudes, and practices Can Fam Physician 2005; 51:80-81. 10. Givens JL, Datto CJ, Ruckdeschel K et al: Older Patients Aversion to Antidepressants. A Qualitative Study. J Gen Intern Med 2006; 21:146-51. 家庭醫學與基層醫療第二十五卷第六期 233