徐 佳,李 越,付春鳳,于春巖,張聰沛
(1.哈爾濱市第一??漆t(yī)院,黑龍江 哈爾濱 150000;2.哈爾濱醫(yī)科大學(xué)附屬四院,黑龍江 哈爾濱 150000 通信作者:徐 佳,E-mail:xujiaxujia132129@sina.com)
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齊拉西酮序貫治療精神分裂癥患者的影響因素分析
徐佳1,李越2,付春鳳1,于春巖1,張聰沛1
(1.哈爾濱市第一??漆t(yī)院,黑龍江哈爾濱150000;2.哈爾濱醫(yī)科大學(xué)附屬四院,黑龍江哈爾濱150000 通信作者:徐佳,E-mail:xujiaxujia132129@sina.com)
目的觀察應(yīng)用甲磺酸齊拉西酮針劑治療后進(jìn)行序貫口服劑型治療精神分裂癥患者的療效及其影響因素,為合理應(yīng)用序貫治療方案提供臨床依據(jù)。方法參照《精神障礙診斷與統(tǒng)計(jì)手冊(cè)(第4版)》(DSM-Ⅳ),應(yīng)用陽(yáng)性和陰性癥狀量表(PANSS)評(píng)定40例以興奮激越癥狀為主的精神分裂癥患者的精神癥狀。在治療前(基線期)對(duì)患者一般狀況進(jìn)行問(wèn)卷調(diào)查。在甲磺酸齊拉西酮針劑肌注治療72小時(shí)后進(jìn)行口服序貫治療,在基線期和肌注治療72小時(shí)后進(jìn)行PANSS評(píng)定,采用副反應(yīng)量表(TESS)評(píng)定不良反應(yīng),分析療效及其影響因素。結(jié)果24例患者成功序貫;16例患者因?yàn)榀熜Ш湍褪苄詥?wèn)題序貫治療效果不好,其中7例換用其他第二代非經(jīng)典抗精神病藥物;9例第二次應(yīng)用齊拉西酮針劑治療3天,再次序貫為口服劑型,5例序貫成功,4例換用其他第二代非經(jīng)典抗精神病藥物治療。結(jié)論對(duì)第一次序貫治療不成功的患者可以選擇第二次注射治療,第二次序貫后有部分患者成功。序貫治療的效果和患者是否首發(fā)、體重水平、飲酒習(xí)慣有關(guān),還與注射之外的治療因素,如醫(yī)生護(hù)士和患者的交流、治療同盟關(guān)系建立的質(zhì)量有關(guān)。
精神分裂癥;精神分裂癥興奮激越癥狀;甲磺酸齊拉西酮;序貫治療
精神分裂癥是以思維、情感和行為等多方面的障礙和精神活動(dòng)與環(huán)境的不協(xié)調(diào)為主要特征的一種精神障礙,病程遷延,呈反復(fù)加重或惡化,部分患者可產(chǎn)生人格缺損,最終出現(xiàn)衰退和精神殘疾。精神分裂癥的慢性病程導(dǎo)致患者逐步脫離正常的生活軌道,個(gè)人生活陷入痛苦和混亂。有50%的患者企圖自殺,10%的患者最終死于自殺。直接損害社會(huì)生產(chǎn)力,造成醫(yī)療管理和經(jīng)濟(jì)上的沉重負(fù)擔(dān)[1]。臨床研究顯示齊拉西酮速效針劑對(duì)精神分裂癥急性激越的療效至少和氟哌啶醇相當(dāng),而耐受性更好,尤其是錐體外系副反應(yīng)(EPS)風(fēng)險(xiǎn)更低[2]。但是有關(guān)序貫治療依從性的問(wèn)題研究不多。精神科臨床上有部分序貫治療效果不佳,為了分析其療效及可能的影響因素特進(jìn)行本研究,旨在為臨床合理應(yīng)用序貫治療方案提供依據(jù)。
1.1對(duì)象
回顧分析在2014年5月-2015年6月應(yīng)用齊拉西酮針劑治療后進(jìn)行序貫口服劑型治療的40例住院病例。入組標(biāo)準(zhǔn):①符合《精神障礙診斷與統(tǒng)計(jì)手冊(cè)(第4版)》(Diagnostic and Statistical Manual of Mental Disorders Fourth edition,DSM-IV)精神分裂癥診斷標(biāo)準(zhǔn);②在本次發(fā)作的前2周未使用過(guò)抗精神病藥物治療;③年齡18~60歲;④陽(yáng)性和陰性癥狀量表(Positive and Negative Syndrome Scale,PANSS)總評(píng)分≥60分;陽(yáng)性和陰性癥狀量表興奮因子 (PANSS-EC,PANSS中判斷“興奮激越”的條目,包括興奮、身體緊張、敵意、不合作及沖動(dòng)控制障礙)總評(píng)分≥14分,至少有1項(xiàng)評(píng)分≥4分(中度以上);⑤無(wú)藥物濫用史;⑥無(wú)中樞神經(jīng)系統(tǒng)疾病、心血管系統(tǒng)疾病和其他軀體疾病并排除其他精神障礙、嚴(yán)重自殺傾向患者、孕婦和月經(jīng)期女性。
1.2治療方法
1.2.1第一次序貫治療
1.2.1.1第一次甲磺酸齊拉西酮臀部注射治療
單用甲磺酸齊拉西酮臀部注射治療三天,劑量范圍20~40 mg/d,分兩次肌注。甲磺酸齊拉西酮注射劑由美國(guó)輝瑞公司生產(chǎn),劑型為30mg/支。
1.2.1.2第一次肌注治療后口服序貫治療
對(duì)肌注治療有效的病例繼續(xù)進(jìn)行口服齊拉西酮序貫治療,劑量范圍80~120 mg/d,分兩次口服,治療一周。齊拉西酮口服劑型由美國(guó)輝瑞公司生產(chǎn),劑型40 mg/粒。
1.2.2第二次序貫治療
1.2.2.1第二次甲磺酸齊拉西酮臀部注射治療
對(duì)因療效和耐受性問(wèn)題無(wú)法序貫治療的患者,說(shuō)明情況,根據(jù)患者及家屬的意愿,對(duì)愿意繼續(xù)進(jìn)行序貫治療的患者行第二次齊拉西酮針劑治療,共治療三天,劑量范圍20~40 mg/d,分兩次肌注。
1.2.2.2第二次肌注治療后口服序貫治療
對(duì)行第二次甲磺酸齊拉西酮臀部注射治療的患者進(jìn)行口服齊拉西酮序貫治療,劑量范圍80~120 mg/d,兩次隨餐口服,治療一周。
1.3量表評(píng)定
在治療前(基線期)、肌注治療72小時(shí)后及兩次序貫治療1周后分別對(duì)患者進(jìn)行PANSS評(píng)定,以PANSS評(píng)分減分率評(píng)定療效。副反應(yīng)量表(Treatment Emergent Symptom Scale,TESS)分別在第1次和第2次肌注治療第72小時(shí)及第1次和第2次序貫為口服劑型治療1周末評(píng)定。一般狀況問(wèn)卷調(diào)查:在基線期收集40例病例的一般資料。PANSS評(píng)分減分率=(治療前評(píng)分-治療后評(píng)分)/治療前評(píng)分×100%。痊愈:減分率≥75%,有效:50%≤減分率<75%,無(wú)效:減分率<50%。
1.4統(tǒng)計(jì)方法
采用SPSS13.0進(jìn)行統(tǒng)計(jì)分析,采用t檢驗(yàn)、χ2檢驗(yàn)和相關(guān)分析,檢驗(yàn)水準(zhǔn)α=0.05。
40例患者在治療72小時(shí)后PANSS評(píng)分減分率均>50%,故對(duì)所有患者均進(jìn)行序貫治療。其中有24例成功序貫,未見明顯副反應(yīng),有16例患者因?yàn)榀熜Ш湍褪苄詥?wèn)題無(wú)法序貫治療,其中7例換用其他第二代非經(jīng)典抗精神病藥物,9例第二次應(yīng)用齊拉西酮針劑治療72h,再次序貫為口服劑型,同時(shí)和這9例患者及其家屬進(jìn)行溝通,溝通內(nèi)容包括明確藥物的療效,治療中可能出現(xiàn)的副作用的性質(zhì)、種類、可能持續(xù)的時(shí)間;給患者和家屬堅(jiān)持治療的信心支持,建立治療同盟。9例病例中有5例第二次序貫成功,有4例換用其他第二代非經(jīng)典抗精神病藥物治療。
分析兩次序貫治療成功的病例特點(diǎn),發(fā)現(xiàn)序貫治療的療效和患者非首發(fā)(r=0.359,P=0.023),較高體重(r=0.378,P=0.016),有飲酒史(r=0.320,P=0.044)及治療同盟關(guān)系建立的質(zhì)量(r=0.317,P=0.046)相關(guān)。
精神分裂癥在人群中終身患病率為1%,在世界范圍內(nèi)已經(jīng)成為一個(gè)嚴(yán)重的公共衛(wèi)生問(wèn)題,很多患者住院并占用了巨大的醫(yī)療衛(wèi)生和社會(huì)資源。我國(guó)精神分裂癥的患病率高達(dá)0.655% ,精神分裂癥的患者多達(dá)780萬(wàn)[3]。世界衛(wèi)生組織(WHO)指出該病是當(dāng)今世界上導(dǎo)致殘疾的第四大疾病,故也是當(dāng)前我國(guó)精神病防治與科研工作中的重點(diǎn)。
齊拉西酮屬第二代非典型抗精神病藥,體外研究顯示[1],其對(duì)多巴胺D2、D3、5-羥色胺(5-HT2A、5-HT2C、5-HT1A、5-HT1D)、α1-腎上腺素能受體具有較高的親和力,對(duì)組胺H1受體具有中等親和力,對(duì)包括M膽堿能受體在內(nèi)的其他受試受體/結(jié)合位點(diǎn)未見親和力[4-5]。齊拉西酮對(duì)D2、5-HT2A、5-HT1D受體具有拮抗作用,對(duì)5-HTlA受體具有激動(dòng)作用,因此,能有效改善患者的陰性癥狀,強(qiáng)效激動(dòng)5-HTlA受體,改善認(rèn)知癥狀,從而改變患者的內(nèi)向性,也能改善伴發(fā)的抑郁癥狀。該藥抗膽堿能不良反應(yīng)和肝臟毒性較低,無(wú)自主神經(jīng)、心血管及血細(xì)胞改變等不良反應(yīng)[6]。已有臨床研究表明[7],其對(duì)精神分裂癥陽(yáng)性和陰性癥狀均有效,尤其對(duì)陰性癥狀的效果更好;其錐體外系不良反應(yīng)少,沒有明顯體質(zhì)量增加和月經(jīng)改變,不引起血清催乳素升高,是治療精神分裂癥較為理想的藥物。
通過(guò)本回顧性研究發(fā)現(xiàn),序貫治療的效果與患者是否首發(fā)、體重水平、飲酒習(xí)慣有關(guān);對(duì)于第一次注射治療后進(jìn)行序貫治療效果不佳者可以第二次應(yīng)用齊拉西酮針劑治療3天,再次序貫為口服劑型,這時(shí)療效還與注射之外的治療因素有關(guān),如醫(yī)生護(hù)士和患者的交流、治療同盟關(guān)系建立的質(zhì)量也影響療效。
本研究采用PANSS評(píng)價(jià)臨床療效,而以急性激越為主的患者鎮(zhèn)靜后,可能導(dǎo)致有些維度的評(píng)分無(wú)法準(zhǔn)確進(jìn)行,在今后的研究中考慮采用更科學(xué)適用的量表進(jìn)行評(píng)定。另外由于應(yīng)用序貫治療的患者數(shù)量相對(duì)較少,成功率相對(duì)較低,導(dǎo)致本研究能夠入組的病例數(shù)有限,因此沒有在序貫后期設(shè)置對(duì)照組或引用歷史對(duì)照,希望在以后的研究中積累病例數(shù),使研究數(shù)據(jù)更具臨床參考價(jià)值。
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(本文編輯:吳俊林)
Analysis of influencing factors on schizophrenia patients with sequential therapy of ziprasidone
XU Jia1*, LI Yue2, FU Chun-feng1, YU Chun-yan1, ZHANG Cong-pei1
( 1.FirstSpecialHospitalofHarbin,Harbin150000,China;2.FourthAffiliatedHospitalofHarbinMedicalUniversity,Harbin150000,China*Correspondingauthor:XUJia,E-mail:xujiaxujia132129@sina.com)
ObjectiveTo observe curative effect of applying sequential therapy of oral dosage forms after the ziprasidone mesylate injection treatment for people with schizophreniaand and analysis the influencing factors for providing clinical basis in reasonable application of sequential treatment.MethodsTotally 40 patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders Fourth edition (DSM-IV) who mainly showed symptoms of excitation and agitation were evaluated using Positive and Negative Syndrome Scale (PANSS). General situation questionnaire was used to investigate patients before treatment (baseline). After 72 hours of ziprasidone mesylate injection treatment, sequential therapy was conducted with oral ziprasidone. Patients were assessed using PANSS at baseline and 72 hours after treatment of intramuscular injection. Side effects were assessed with Treatment Emergent Symptom Scale (TESS).Results24 patients were succeeded in the sequential treatment. There were 16 patients whose therapeutic effect were poor because of the efficacy and tolerance of treatment, in which 7 patients’ treatment were changed with another second generation of atypical antipsychotics. Second sequential therapy were applied to another 9 patients after 3 days therapy of ziprasidone mesylate for injection, in which 5 patients were succeeded and 4 patients’ treatments were replaced with another second generation of atypical antipsychotics.ConclusionThe second injection treatment can be applied to the patients who were not succeed in the first sequential therapy and some patients were succeeded in the second sequential therapy. The efficacy of sequential therapy is associated with patients’ weight, drinking habits and whether first-episode. It is also related to other factor except injection factors, such as the relationship between patients and doctors, quality of the therapeutic alliance.
Schizophrenia; Excitation and agitation of schizophrenia; Ziprasidone mesylate; Sequential therapy
R749.3
Adoi:10.11886/j.issn.1007-3256.2016.02.015
2015-10-27)