3 Clinical Uncertainty → PICO 問題 For first-episode psychosis, which antipsychotics would significantly reduce the severity of psychotic symptoms?
4 Type of Question: Treatment 臨床個案的PICOPatient / ProblemFirst-episode psychosisInterventionAntipsychoticsComparisonPlaceboOutcomeImprovement of PANSS scoreType of Question: Treatment
5 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])
6 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 , Sep 2009Lead author's name :H. Boter, J. Peuskens, J. Libiger, W. Fleischhacker, M. Davidson, S. Galderisi, R. Kahn
7 The Study: （研究效度）- 1A 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 symptomsany antipsychotic had been used exceeding 2 weeks in the previous year or 6 weeks lifetimepatients had a known intolerance to one of the study drugspatients met any of the contraindications for any of the study drugs as mentioned in the (local) package insert texts.
8 The Study: （研究效度）- 2Patients 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.
9 The Study: （研究效度）- 3The 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)
10 The Study: （研究效度）- 2 (multicenter, open randomized clinical trial) Level of Evidence: 1b(multicenter, open randomized clinical trial)
11 The Study: （研究效度）- 3 本篇文獻的PICO (T) Patient / ProblemPatients of first episode schizophrenia and schizophreniform disorderInterventionAtypical antipsychoticsComparisonHaloperidolOutcomeResponse and remission on PANSS scoreTime12 months
12 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)
13 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.
14 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.
17 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.
18 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 observationsFor response, missing observations were substituted by the LOCF method.
19 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
20 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..
21 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 rateKill or Update By（下次更新日期）:May. 15, 2010