精 神 科 實 證 期 刊 閱 讀 報 告 EBM-style Journal Reading 報告人：R1 陳佳儒 Email: 144406@cch.org.tw 指導臨床教師：莫庚翰醫師/廖以誠醫師 日期：11/19/2009 地點：鹿東分院二樓會議室

Clinical Scenario （臨床情境） 19歲男性，診斷為Psychotic disorder, NOS, suspect schizophrenia. 入院後主線用藥為paliperidone 9mg/day，個案自訴被害想法及幻聽有減少。但四周後精神症狀開始惡化，自言自語並出現怪異行為。故劑量增加為12mg/day，但改善不顯著。 與家屬討論後更換主線用藥為olanzapine 15mg/day，並轉往國泰醫院汐止分院繼續治療。

Clinical Uncertainty → PICO 問題 For first-episode psychosis, which antipsychotics would significantly reduce the severity of psychotic symptoms?

Type of Question: Treatment 臨床個案的PICO Patient / Problem First-episode psychosis Intervention Antipsychotics Comparison Placebo Outcome Improvement of PANSS score Type of Question: Treatment

Search Terms & Strategy: （搜尋關鍵字與策略） 資料庫：Pubmed 搜尋日期： 11/01/2009 搜尋關鍵字與隅策略： #1 (Schizophrenia AND first episode patient) AND ((clinical[Title/Abstract] AND trial[Title/Abstract]) OR clinical trials[MeSH Terms] OR clinical trial[Publication Type] OR random*[Title/Abstract] OR random allocation[MeSH Terms] OR therapeutic use[MeSH Subheading])

Best available evidence: （挑選可獲得之最佳研究證據） Citation/s: Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission: An open randomized clinical trial (EUFEST) Schizophrenia Research, Volume 115, Issue 2, Pages 97-103 , Sep 2009 Lead author's name : H. Boter, J. Peuskens, J. Libiger, W. Fleischhacker, M. Davidson, S. Galderisi, R. Kahn

The Study: （研究效度）- 1 A total of 50 centers participated in 13 European countries and Israel. Eligible patients were 18–40 years of age and met DSM-IV criteria for schizophrenia, schizophreniform, or schizoaffective disorder confirmed by the Mini International Neuropsychiatric Interview Plus. Patients were excluded if: more than 2 years had passed since the onset of positive symptoms any antipsychotic had been used exceeding 2 weeks in the previous year or 6 weeks lifetime patients had a known intolerance to one of the study drugs patients met any of the contraindications for any of the study drugs as mentioned in the (local) package insert texts.

The Study: （研究效度）- 2 Patients were randomized by a dedicated web based online system to: haloperidol 1–4 mg/d, amisulpride 200– 800 mg/d, olanzapine 5–20 mg/d, quetiapine 200–750 mg/d, or ziprasidone 40–160 mg/d. All study medications were administered orally within the dose ranges at the treating physician's discretion. The use of mood stabilizers, benzodiazepines, antidepressants, and anticholinergics was allowed and documented.

The Study: （研究效度）- 3 The following formula was used to calculate response rates: ((PANSS baseline −30)−(PANSS follow-up−30))×100/ (PANSSbaseline−30) Remission was defined as a score of mild or less(≤3) on eight predefined PANSS items —each maintained for at least 6 months: delusions (P1), conceptual disorganization (P2), hallucinatory behavior (P3), blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerisms/ posturing (G5), and unusual thought content(G9)

The Study: （研究效度）- 2 (multicenter, open randomized clinical trial) Level of Evidence: 1b (multicenter, open randomized clinical trial)

The Study: （研究效度）- 3 本篇文獻的PICO (T) Patient / Problem Patients of first episode schizophrenia and schizophreniform disorder Intervention Atypical antipsychotics Comparison Haloperidol Outcome Response and remission on PANSS score Time 12 months

The Evidence: （研究重要結果）- 1 Of the 498 patients enrolled, 200 (40%) were female, 162 (33%) were antipsychotic naïve, 198 (40%) had schizophreniform disorder, 35 (7%) had schizoaffective disorder, and 265 (53%) had schizophrenia. Higher proportions of patients on haloperidol or amisulpride used anticholinergic drugs (overall p<0.0001), and higher proportions of patients on olanzapine used antidepressants (overall p<0.0001)

The Evidence: （研究重要結果）- 2 Patients with ≥50% response within 12 months: 36 (37%) for haloperidol 70 (67%) for amisulpride 70 (67%) for olanzapine 47 (46%) for quetiapine 44 (56%) for ziprasidone.

The Evidence: （研究重要結果）- 3 The number of patients who remitted within 12 months 18 (17%) for haloperidol 42 (40%) for amisulpride 43 (41%) for olanzapine 25 (24%) for quetiapine 23 (28%) for ziprasidone.

Comment & Discussion: -1 Patients on a low dose of haloperidol were less likely to respond or remit within 12 months when compared with patients on amisulpride, olanzapine, or ziprasidone. The most important predictor of ≥50% response and remission was the use of amisulpride and olanzapine.

Comment & Discussion: -2 Psychiatrists with negative expectations about haloperidol could have discontinued treatment with haloperidol sooner. For remission, we assumed that non-remitters continued to be non-remitters at missing observations For response, missing observations were substituted by the LOCF method.

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 For first episode schizophrenia, Patients on amisulpride, olanzapine, and ziprasidone showed higher response and remission rates when compared with patients on low doses of haloperidol. 證據等級1b, 建議等級A

References: Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomized clinical trial. Lancet 371, 1085–1097. Remission in schizophrenia: proposed criteria and rationale for consensus. Am. J. Psychiatry 162, 441–449..

Kill or Update By（下次更新日期）: 結 論 （標題 Title） For first episode schizophrenia, amisupride and olanzapine revealed the most response and remission rate Kill or Update By（下次更新日期）: May. 15, 2010

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