精神科 實 證 期 刊 閱 讀 報 告 EBM-style Journal Reading 指導臨床教師： Dr. 周少華, Dr. 廖以誠 日期：2009/5/19 地點：十樓精神科會議室

Clinical Scenario （臨床情境） 50歲蔡女性，因難以控制的schizophrenia的positive symptoms(不停大喊、嚴重被害妄想)，自鹿東轉來彰基精神科病房治療 在鹿東期間使用Haloperidol治療一個多月，但症狀仍持續難以改善 轉來之後停掉Haloperidol，改用上second-generation antipsychotic (SGA)--Zotepine ，這藥對治療positive symptoms的效果會比first-generation antipsychotic (FGA)--Haloperidol好嗎？

Clinical Uncertainty → PICO 問題 In a schizophrenic patient with severe positive symptoms, is the efficacy of Zotepine better than Haloperidol?

Type of Question: Therapy 臨床個案的PICO Patient / Problem Schizophrenic patient with severe positive symptoms Intervention SGA (Zotepine) Comparison FGA (Haloperidol) Outcome PANSS Type of Question: Therapy

Search Terms & Strategy: （搜尋關鍵字與策略） 資料庫： pubmed 搜尋日期： 2009/5/21 搜尋關鍵字與隅策略： #4 Select 8 document(s)   8 #3 Search #1 OR #2   165 #2 Search (generation AND antipsychotic AND schizophreni*) AND systematic[sb]   83 #1 Search (generation AND antipsychotic AND schizophreni*) AND (randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND controlled[Title/Abstract] AND trial[Title/Abstract]))   87

Best available evidence: （挑選可獲得之最佳研究證據） Citation/s: Second-generation Versus First-generation Antipsychotic Drugs for Schizophrenia: A Meta-analysis Lancet 2009; 373: 31–41 Lead author's name : Stefan Leucht, Caroline Corves, Dieter Arbter, Rolf R Engel, Chunbo Li, John M Davis

The Study: （研究效度）- 1 This study compared nine second-generation antipsychotic drugs SGA with first-generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. It included 150 double-blind, mostly short-term, studies, with 21533 participants. Open studies were excluded because they systematically favoured second-generation drugs. Level of Evidence: 1a

The Study: （研究效度）- 3 本篇文獻的PICO (T) Patient / Problem Schizophrenia or related disorders (schizoaffective, schizophreniform, or delusional disorder) Intervention Nine kinds of SGA (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, and zotepine) Comparison FGA (大部分是Haloperidol, 95/159) Outcome PANSS or BPRS scores Time <12 weeks: 121 (81%) 12 weeks – 6 months: 17 (11%) > 6 months: 12 (8%)

The Evidence: （研究重要結果）- 1 Four of these drugs were better than FGA for overall efficacy, with small to medium effect sizes (amisulpride −0·31 [95% CI −0·44 to −0·19, p<0·0001], clozapine −0·52 [−0·75 to −0·29, p<0·0001], olanzapine −0·28 [−0·38 to −0·18, p<0·0001], and risperidone −0·13 [−0·22 to −0·05, p=0·002]) The other SGA were not more efficacious than FGA, even for negative symptoms.

The Evidence: （研究重要結果）- 2 Overall Efficacy Four SGA— amisulpride, clozapine, olanzapine, and risperidone—were more efficacious than FGA

The Evidence: （研究重要結果）- 3 Positive Symptoms

The Evidence: （研究重要結果）- 4

The Evidence: （研究重要結果）-5 Extrapyramidal Side-Effects – SGA vs The Evidence: （研究重要結果）-5 Extrapyramidal Side-Effects – SGA vs. Haloperidol All SGA were associated with much fewer extrapyramidal side-effects than haloperidol

The Evidence: （研究重要結果）- 6 Sedation – SGA vs. Haloperidol Clozapine, quetiapine, and zotepine were significantly more sedating than was haloperidol, whereas aripiprazole was significantly less sedating

Comment & Discussion: -1 本篇研究所得結論為Zotepine對於overall symptoms、positive symptoms和negative symptoms等方面的治療成效，並沒有比Haloperidol來得優異 但Zotepine在sedation方面的副作用則較Haloperidol來得強，但EPS的副作用則較少 若此位病人從Haloperidol換成Zotepine後，在治療positive symptoms方面可能不會有明顯改善，但會有較少的EPS，較多的鎮靜作用，因此病人可能會較嗜睡

Comment & Discussion: -2 本篇研究是採meta-analysis，是總結159篇研究的結論，因原始各研究設計的不同，導致其整合起來的結論中可能存有許多變異因子 此篇研究沒有驗證所取得的各研究資料的證據強度，因此其收錄的研究不論其取樣規模的大小，都等同視之，所以可能會影響到最終結果的差異性

Comment & Discussion: -3 在另一篇CUtLASS (Arch Gen Psychiatry. 2006 Oct;63(10):1079-87)中得到的結論，也是發現到若從FGA換成SGA，在治療schizophrenia的病人，並沒有得到特別好的效果

Clinical bottom line 臨床決策底線 回到臨床個案情境 Clinical bottom line 臨床決策底線 To treatment schizophrenic patient with severe positive symptoms, Zotepine is not superior than Haloperidol, but has less EPS and more sedation 證據等級1a, 建議等級A

References: Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis Lancet. 2009 Jan 3;373(9657):31-41. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29(1):15-31. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry. 2006 Oct;63(10):1079-87

Kill or Update By（下次更新日期）: 結 論 （標題 Title） To treat schizophrenic patient with severe positive symptoms, the efficacy of Zotepine is not better than Haloperidol Kill or Update By（下次更新日期）: May. 20, 2010