online ML Comm ORIGINAL ARTICLE ISSN 1225-8709 / eissn 2005-7571 Korean J Biol Psychiatry 2014;21(2):49-56 : 1996~2000 2006~2010 한양대학교의료원정신건강의학과, 1 CHA 의과학대학교분당차병원정신건강의학교실 2 황인환 1 김대호 1 오대영 2 Psychotropic Prescription Patterns for Inpatients with Schizophrenia : 10-Year Comparison in a University-Affiliated Hospital in South Korea In-Hwan Hwang, MD, 1 Daeho Kim, MD, 1 Dae-Young Oh, MD 2 1 Department of Psychiatry, Hanyang University Medical Center, Seoul, Korea 2 Department of Psychiatry, Bundang CHA Medical Center, CHA University, Seongnam, Korea ObjectivesZZPrevious literature on the prescription change among patients with schizophrenia mainly focused on antipsychotics. This study investigated chronological change in the patterns of discharge medication among inpatients with schizophrenia at a psychiatric inpatient unit of a university-affiliated hospital. MethodsZZAll admission records at a psychiatric unit of Hanyang University Guri Hospital with discharge diagnosis of schizophrenia during two different five-year time frames (1996-2000 and 2006-2010) were reviewed including the demographic and clinical data and discharge medications. The data were gathered from a total of 207 patients (95 in 1990s and 112 in 2000s). ResultsZZThe frequency in use of atypical antipsychotics (p < 0.01), antidepressants (p < 0.05), beta-blockers (p < 0.01), and benzodiazepine (p < 0.01) was significantly higher in 2000s. Anticholinergic drugs were less likely used in 2000s (p < 0.01). We did not find significant differences in the equivalent dose of antipsychotic drugs, the use of mood stabilizers and cholinergic drugs between two time frames. ConclusionsZZIncreased proportion of atypical antipsychotics and decreased use of anti-parkinsonian drugs are in line with literature. Our results show that more diverse classes of psychotic medications are used for schizophrenia in recent years. It is likely that psychiatrists are becoming more conscious of negative symptoms, anxiety, and depression in the pharmacotherapy of schizophrenia as well as positive symptoms of the illness. Key WordsZZSchizophrenia ㆍ Medication ㆍ Prescription ㆍ Psychotropic drugs ㆍ Antipsychotics. Received: February 24, 2014 / Revised: March 17, 2014 / Accepted: April 9, 2014 Address for correspondence: Daeho Kim, MD Department of Psychiatry, Hanyang University Guri Hospital, 153 Gyeongchun-ro, Guri 471-701, Korea Tel: +82-31-560-2274, Fax: +82-31-554-2599, E-mail: dkim9289@hanyang.ac.kr 조현병치료에항정신병약물의사용은필수적이며, 조현병의호전혹은악화와밀접한관련이있다. 즉, 꾸준한약물복용은조현병의재발을방지하기때문에, 환자들의약물순응도는조현병의예후와직결되고, 정신의학자들은약물순응도들치료의매우중요한요소로간주해왔다. 1)2) 조현병환자들에게서약물순응도가떨어지고, 자의적으로 약물복용을중단하는데는병식의부족과도관련이있지만약물의부작용과도밀접한관련이있다. 1) 때문에환자들에게꾸준한약물복용을강조하기위해선, 우선처방하는정신과의사들이적절한항정신병약물을처방하고, 특히약물의부작용을적극적으로관리해주어야한다. 3) 항정신효과의증대와약물로인한부작용의감소를위한방향으로항정신병약물이개발되어왔다. 1950년대에전형항정신병약물이개발되고, 이로인한추체외로부작용이보고되 Copyright 2014 Korean Society of Biological Psychiatry 49
Korean J Biol Psychiatry 2014;21(2):49-56 며항정신병약물의부작용이인식되기시작하였고, 이러한신경운동계통의부작용을줄이기위해 1990년대에들어 risperidone, olanzapine, quetiapine과같은비정형항정신병약물이개발되었다. 비정형항정신병약물은기존의전형항정신병약물에비해치료효과가좋으면서, 추체외로부작용등의부작용은줄어들어, 점차로전형항정신병약물을대체하게되었다. 4) 우리나라에서는 1995년이후에 risperidone이소개된후, olanzapine, quetiapine 순으로도입이되었고, 이후로도새로운비정형항정신병약물이지속적으로도입되며, 약물처방경향의변화도나타났다. 이런변화에발맞추어 2006년에는국내실정을반영하여 한국형정신분열병약물치료지침서 2006 이개발되었다. 지침서에는 1차선택약제로 risperidone, olanzapine과같은비전형항정신병약물을추천하였고, 우울증상이있는경우우울장애와마찬가지로항우울제를사용하며, 안전성과효능의이유로선택적세로토닌재흡수억제제 (selective serotonin reuptake inhibitor) 가 1차선택약제로추천되었다. 추체외로부작용에대해서는항콜린제와같은항파킨슨약물이추천되었으며, 좌불안석증에서는베타차단제 (beta-blockers) 와벤조다이아제핀 (benzodiazepine), 항콜린제 (anticholinergenic drugs) 의조심스러운사용이권유되었다. 또한공격성이두드러지는경우를제외하고는기분조절제의병합은효과적이라는근거가제한적이었다는치료지침을발표하였다. 5) 그럼에도실제임상상황에서조현병환자들의약물처방의변화와추세에대한문헌은부족한실정이다. 그리고이전연구들대부분은항정신병약물사용에국한되어연구가진행되었다. 또한임상상황에서다종약물요법 (polypharmacy) 은흔히사용되고있지만, 이에대한알고리즘이나진료가이드라인문헌은부족하며, 처방의사의개인적인성향이많이반영되기도한다. 6)7) 이연구는한대학병원정신건강의학과에입원하여조현병으로최종진단된환자들의퇴원처방을조사하여정신작용제 (psychotropic agent) 의종류및용량을시기별로분석하였다. 이번연구는한대학병원단위이기는하지만, 정신과약물처방변화를이해하고, 실제로임상에서처방되는다양한정신작용제의내용이나처방패턴을이해하는기초자료로서의의미가있을것으로생각된다. 연구대상및과정 이연구는 1996~2000 년, 2006~2010 년기간중한양대학교구리병원정신건강의학과에서퇴원한환자중국제질병분류 10판 (International Classification of Diseases-10) 의진단기준에따라조현병으로진단된환자 244명을조사대상으로하여, 의무기록지조사를통해퇴원약물로처방된정신작용제의내용과용량을조사하였다. 1990년대의 37명은의무기록이소실되어제외하였고, 총 207명중 1990년대 (1996~2000 년 ) 에퇴원한 95명, 2000년대 (2006~2010 년 ) 에퇴원한 112명을대상군으로하였다. 이상의의무기록을한명의정신과전문의가조사하여사회인구학적특성 ( 성별, 연령, 결혼상태, 교육, 고용상태, 수입, 종교 ) 과임상적변인 ( 유병기간, 입원횟수, 해당입원의재원일 ), 퇴원시점에서처방된정신과약물을조사하였다. 이연구는해당병원의연구윤리위원회의사전승인후진행되었다. 보다자세한소견은같은자료를이용한사전연구에나타나있다. 8)9) 정신작용제정신작용제는퇴원시처방된전형항정신병약물, 비정형항정신병약물, 주사제형의항정신병약물, 항우울제, 기분조절제, 항콜린성약물, 콜린성약물, 베타차단제, 벤조다이아제핀으로분류하였다. 항정신병약물은개개약물과용량을조사하였고, 용량은 chlorpromazine 등가용량으로환산하였고, 10-12) 특히처방된항정신병약물의종류가 2가지이상인경우에는각약물의등가용량을더하여처방용량을비교하였다. 그외정신작용제는해당계통약물의유무로평가하였다. 자료분석수집된자료는통계프로그램인 Statistical Package for the Social Sciences( 이하 SPSS) 18 for Windows(SPSS Inc., Chicago, IL, USA) 를이용하여분석하였고, 두시점의차이를비교하기위해 t 검정이나카이제곱검정 (chi-squared test) 을실시하여유의성을검토하였다. 통계적유의수준은양방향 p < 0.05로하였으며, 항목별값이자유도 (df) 에상응하는기대빈도에미치지못한경우에는통계적유의성을두지않았다. 또한 Fisher s exact test는셀값이 5보다작을때카이제곱검정을대신하여사용하였다. 양군의차이, 즉성별등이다른변인의차이에영향을주는지알아보기위해로그회귀분석을시행하였으며, 영향을주지않음을확인하였다. 기본적특징 환자의기본적특징은 Table 1에나타나있다. 전체대상군의사회인구학적특성을보면전체 207명중남자 101명 (48.8%), 여자 106명 (51.2%) 이고, 평균나이는 33.1세 [standard devia- 50
Change in Psychotropic Prescription in Schizophrenia Hwang IH, et al Table 1. Sociodemographic characteristics of patients with schizophrenia in the 1990s and 2000s (n = 207) 1990s (n = 95) 2000s (n = 112) χ 2 p Sex 10.56 0.001 Male 58 (61.1) 43 (38.4) Female 37 (38.9) 69 (61.6) Marital status 01.22 0.75 Married Divorced Widowed Never married 29 (32.6) 04 (4.5) 00 56 (62.9) 41 (36.6) 05 (4.5) 01 (0.9) 65 (58.0) Education 03.03 0.39 Less than high school High school graduate University graduate Graduate school 23 (25.8) 52 (58.4) 13 (14.6) 01 (1.1) 18 (16.1) 73 (65.2) 20 (17.9) 01 (0.9) Employment 02.23 0.53 Unemployed Employed Student Housewife 44 (50.6) 15 (17.2) 09 (10.3) 19 (21.8) 47 (42.0) 28 (25.0) 13 (11.6) 24 (21.4) Monthly income* 02.91 0.41 Less than 2000 2000-3999 4000-5999 More than 6000 34 (39.5) 36 (41.9) 13 (15.1) 03 (3.5) 34 (30.6) 60 (54.1) 14 (12.6) 03 (2.7) Religion 06.25 0.28 Christianity Catholicism Buddhism Others 22 (25.9) 08 (9.4) 07 (8.2) 03 (3.5) 45 (52.9) 45 (40.2) 11 (9.8) 09 (8.0) 02 (1.8) 44 (39.3) Data are n (%). Statistical analysis used either chi-square or Fisher s exact test. * : household income in US dollars tion( 이하 SD) = 10.40] 였다. 유병기간은평균 66.4개월 [95% confidence interval( 이하 CI) = 31.6-34.4], 입원횟수는평균 1.6회 (95% CI = 1.2-2.0), 재원일수는평균 56.5일 (95% CI = 51.5-61.5) 이었다. 1990년대와 2000년대두시대의환자군을비교했을때결혼상태, 교육정도, 고용상태, 수입, 종교는통계적차이를보이지않았으나, 2000년대환자군의연령이 34.9세 (SD = 11.0) 였고, 1990년대가평균 30.8세 (SD = 9.2) 로 2000년대환자가연령이높았다 (p = 0.01). 그리고 2000년대환자군에처방된정신작용제의수는 3.0가지 (SD = 1.3) 였고, 1990년대가 2.5가지 (SD = 1.0) 로 2000년대환자군에처방된약물수가더많았다 (p = 0.004). 그러나입원기간및입원횟수, 유병기간은두군사이에통계적차이를보이지않았다 (Table 2). 항정신병약물 1990년대, 2000년대두시기에조현병진단으로퇴원한총 207명의대상군은모두항정신병약물을처방받고있었다. 처 방되고있는항정신병약물중전형항정신병약물은 bromperidol, chlorpromazine, haloperidol, loxapine, perphenazine, pimozide가있었고, 비정형항정신병약물로는 amisulpride, aripiprazole, olanzapine, paliperidone, quetiapine, sulpiride, risperidone, ziprasidone 이있었다. 1990년대퇴원시환자들의항정신병약물처방은 risperidone(41.2%), chlorpromazine(18.%), haloperidol(16.7%), olanzapine(7.9%) 순으로많았고, 2000년대에는 risperidone (30.4%), quetiapine(17.7%), amisulpride(13.9%), olanzapine (10.1%) 순으로많았다. 2000년대퇴원환자군의항정신병약물처방분포중 haloperidol, chlorpromazine, loxapine 과 pimozide 는 1990년대퇴원환자군에비하여유의하게적었으며, quetiapine, amisulpride, aripiprazole, paliperidone, ziprasidone, sulpiride 은 2000년대에만사용했었기때문에유의하게많았다. 양시대에사용된약중 risperidone, olanzapine, clozapine 등의비전형약물은유의한차이가없었다. 1990년대에만사용되었던 thioridazine, perphenazine, bromperidol journal.biolpsychiatry.or.kr 51
Korean J Biol Psychiatry 2014;21(2):49-56 Table 2. Clinical characteristics of patients with schizophrenia in the 1990s and 2000s (n = 207) 1990s (n = 95) 2000s (n = 112) Statistics Mean SD Mean SD t p Age 030.8 009.2 034.9 011.0-2.82-0.005 Hospital days 056.8 035.8 056.3 037.4-0.09-0.930 No. of hospitalization 001.6 003.1 001.6 002.9-0.07-0.950 Duration of illness 057.3 080.4 074.0 083.9-1.46-0.150 Psychotropics (no) 002.5 001.0 003.0 001.3-2.95-0.004 CPZ equivalent 760.9 542.2 834.0 510.0-0.99-0.320 n (%) n (%) χ 2 p No. of antipsychotics 06.64 < 0.04 1 2 3 70 (73.7) 25 (26.3) 00 (0) 064 (57.1) 047 (42.0) 001 (0.9) Antipsychotics 66.56 < 0.001 Only typical Only atypical Both 36 (37.9) 39 (41.1) 20 (21.1) 002 (1.8) 104 (92.9) 006 (5.4) Antidepressant 06.34 < 0.012 01 (1.1) 94 (98.9) 010 (8.9) 102 (91.2) Mood stabilizer 00.35 < 0.76 06 (6.3) 89 (93.7) 005 (4.5) 107 (95.5) Beta blocker 08.13 < 0.006 15 (15.8) 80 (84.2) 037 (33.0) 075 (97.0) Benzodiazepine 10.60 < 0.002 19 (20.0) 76 (80.0) 046 (41.1) 066 (58.9) Anticholinergic 07.48 < 0.007 73 (76.8) 22 (23.2) 066 (58.9) 046 (41.1) Cholinergic 00.06 < 1.000 04 (4.2) 91 (95.8) 004 (3.6) 108 (96.4) Statistical analysis used either chi-square or Fisher s exact test. CPZ : chlorpromazine 은통계적유의성이없었다. 항정신병약물처방경향을보면, 1990년대에는전형항정신병약물만사용한경우가 37.9% 인것에비해 2000년대에는단지 1.8% 만이전형항정신병약물만을사용하고있었고, 98.3% 는비정형항정신병약물단독혹은병용처방이이루어지고있었다 (Table 2). 또한비정형항정신병약물은 2000년대에들어유의한처방증가를보이고있었으며 (98.2% vs. 62.1%, chisquare test = 44.7, p < 0.01)(Table 3), chlorpromazine 등가용량으로계산한항정신병약물의처방용량은두시대에서차이를보이지않았다 (Table 2). 기타정신작용제항우울제 (8.9% vs. 1.1%, chi-square test = 6.3, p < 0.05), 베타차단제 (33.0% vs. 15.8%, chi-square test = 8.1, p < 0.01), 그리고벤조다이아제핀 (41.1% vs. 20.0%, chi-square test = 10.6, p < 0.01) 의사용빈도는 1990년대에비하여 2000년대에유의한증가를보였다. 반면, 항콜린성약물은 2000년대에유의한감소를보였다 (58.9% vs. 76.8%, chi-square test = 7.5, p < 0.01). 기분안정제, 콜린성약물의사용빈도는 1990 년대, 2000년대간유의한차이가나타나지않았다 (Table 3). 두시대사이에빈도의유의미한차이를보인항콜린성약물, 베타차단제, 벤조다이아제핀, 항우울제와비정형항정신병약물의처방유무와의상관관계를확인해보았고, 베타차단제만이상관성을보였다 (Table 4). 항정신병약물별로항콜린성약물, 베타차단제, 벤조다이아제핀, 항우울제와의상관관계의결과는 Table 5에나타나있 52
Change in Psychotropic Prescription in Schizophrenia Hwang IH, et al Table 3. Frequency of psychotropic prescription in the discharge medication for schizophrenia in the 1990s and 2000s Total (n = 207) 1990s (n = 95) 2000s (n = 112) Atypical antipsychotics 59 (62.1) 110 (98.2) 66.56 < 0.001 Antidepressant 01 (1.1) 010 (8.9) 06.34 0.012 Mood stabilizer 06 (6.3) 005 (4.5) 00.35 0.758 Benzodiazepine 19 (20.0) 046 (41.1) 10.60 0.002 Beta blocker 15 (15.8) 037 (33.0) 08.13 0.006 Anticholinergics 73 (76.8) 066 (58.9) 07.48 0.007 Cholinergics 04 (4.2) 004 (3.6) 00.06 1.000 Data are n (%). Statistical analysis used either chi-square or Fisher s exact test χ 2 p Table 4. Use of psychotropic medications in atypical vs. typical antipsychotics Anticholinergic Beta blocker Benzodiazepine Antidepressant Atypical antipsychotics (n = 169) Typical antipsychotics (n = 38) 110 (65.1) 059 (34.9) 048 (28.4) 121 (71.6) 056 (33.1) 113 (66.9) 011 (6.5)0 158 (93.5) Data are n (%). Statistical analysis used either chi-square or Fisher s exact test 29 (76.3) 09 (23.7) 04 (10.5) 34 (89.5) 09 (23.7) 29 (76.3) 00 (0.0)0 38 (100). χ 2 Statistics p 1.77 0.251 5.27 0.023 1.29 0.334 2.61 0.222 다. 이중통계적으로유의미한결과를보인것은 risperidone 과항콜린성약물, haloperidol 과항콜린성약물및베타차단제, chlorpromazine 과항콜린성약물및베타차단제, paliperidone 처방과베타차단제처방, quetiapine 과항콜린성약물및베타차단제처방이었다. 1996~2000 년과 2006~2010 년에이르는 10년사이에변화된정신작용제의사용경향을살펴보면, 비정형항정신병약물사용의유의미한증가를보이고있었으며, 이는기존의국내외의여러연구들과비슷한결과를보였다. 국내의기존연구결과를보면, 일대학병원에서비정형항정신병약물이처방되어퇴원한환자수를비교한연구에서, 1997년에는 57.6%, 2003~2004년에는 93.7%, 2009~2010년에는 98.7% 로점차증가하는것으로나타났다. 또한 2가지이상의항정신병약물이사용된경우도, 1997년 4.8%, 2003~2004년에는 9.0%, 2009~2010 년에는 16.1% 로증가하였다. 13) 또다른연구에서는 2002년에일대학병원정신건강의학과외래환자를대상으로항정신병약물의처방경향을분석하였고, 처방되고있는 항정신병약물중비정형약물의처방비율이 88.1% 로높은비중을차지하는등여러국내의연구결과는본연구의결과와비슷한경향을보였다. 14-16) 또한국외의기존연구결과를보면, 미국샌디에이고자치주에서의료보장 (Medicaid) 자료를이용하여 1999년과 2004 년사이 15962명의조현병환자에게처방된항정신병약물사용을비교한결과, 1999년은전형항정신병약물이비율이 24.9%, 비정형약물이 61.1% 였던것에비해, 2004년에는전형항정신병약물이 7.6% 로감소하였고, 비정형약물이 71.0% 로증가한것을보이고있다. 17) 호주의의료보험 (Health Insurance Commission) 자료를통해, 1995년과 2001년에처방된항정신병약물을비교한연구도있는데, 세계보건기구 (World Health Organization) 에서정한 1000명당하루에처방받는약물의용량을표현한 defined daily dose( 이하 DDD) 라는단위를이용하여비교한결과, 1995년에는비정형항정신병약물의사용이 0.3 DDD였던것에반해, 2001년에는 3.8 DDD로증가한것을확인하였다. 18) 또한스페인보건부자료를통하여 1985 년부터 2000년까지처방된항정신병약물의처방빈도를조사한결과, 비정형항정신병약물의처방이 1985년에 1.5 DDD, 2000년에는 5.7 DDD로증가하는등 19) 국외의여러연구들 journal.biolpsychiatry.or.kr 53
Korean J Biol Psychiatry 2014;21(2):49-56 에서와마찬가지로본연구에서도비정형항정신병약물처방 Table 5. Concurrent psychotropic prescription with individual vs. other antipsychotics in the patients with schizophrenia (n = 207) Risperidone Haloperidol Olanzapine Chlorpromazine Clozapine Amisulpride Aripiprazole Paliperidone Quetiapine Ziprasidone 11 (39.3%) 5 (62.5%) p = 0.001 p = 0.522 5 (62.5%) 5 (50.0%) 16 (72.7%) 5 (41.7%) 23 (92.0%) 14 (56.0%) 19 (86.4%) Anticholinergic 71 (74.7%) p = 0.522 p = 0.198 p = 0.371 p = 0.056 p = 0.003* p = 0.150 p = 0.031* p = 0.023* 4 (50.0%) 12 (42.9%) 5 (62.5%) 2 (20.0%) 07 (31.8%) 3 (25.0%) 03 (12.0%) 02 (9.1%) 08 (32.0%) p = 0.050 p = 0.268 Beta blocker 24 (25.3%) p = 0.111 p = 0.021* p = 0.025* p = 0.520 p = 0.298 p = 0.647 p = 0.080 p = 0.546 Benzodiazepine 34 (35.8%) 06 (27.3%) 08 (32.0%) 07 (28.0%) 2 (16.7%) 08 (36.4%) 4 (40.0%) 3 (37.5%) 11 (39.3%) 4 (50.0%) p = 0.135 p = 0.431 p = 0.555 p = 0.445 p = 0.213 p = 0.379 p = 0.387 p = 0.485 p = 0.225 p = 0.216 Antidepressant 08 (8.4%) 00 (0.0%) 00 (0.0%) 00 (0.0%) 0 (0.0%) 02 (9.1%) 2 (20.0%) 0 (0.0%) 01 (3.6%) 1 (12.5%) p = 0.063 p = 0.281 p = 0.234 p = 0.234 p = 0.510 p = 0.330 p = 0.092 p = 0.641 p = 0.547 p = 0.359 Beta blocker with haloperidol vs. other antipsychotics was significant at 0.0497. * : positive, : negative correlation 의증가를확인하였다. 본연구에서는비정형항정신병약물의유의미한처방증가외의다양한정신작용제의처방경향에대해서도살펴보았으며, 2000년대에들어항우울제, 베타차단제, 벤조다이아제핀사용의유의미한증가와항콜린성약물의유의미한감소를확인하였다. 이는비정형항정신병약물의임상적효능과낮은빈도의추체외로부작용과같은장점을시사하며, 비정형항정신병약물을 1차약물로선택하는최근의알고리즘도잘반영하고있는것으로보인다. 15) 그러나일부전형약물, loxapine, chlorthio, bromperidol 등은 2000년대에는생산되지않았으며, 비정형약물중 risperidone과 olanzapine을제외하고는 1990년대는상용화되지않았다는점도고려해야겠다. 또한, 2000년대에는한가지종류의항정신병약물을처방한단독요법보다는 2가지이상의항정신병약물을처방한복합요법이더증가하였다. 이는필요이상으로많은약물투여가능성의우려도있으나, 본연구에서는 chlorpromazine 등가용량으로환산하여계산한총합은시대별로차이를보이지않았다 (Table 2). 항우울제처방도 2000년대에증가하는것으로나타났는데이는조현병환자들의우울증상조절의중요성이대두된맥락으로이해할수있다. 조현병환자들에게우울장애의동반율이높고, 이러한경우우울감, 절망감과관련한부정적평가로인하여삶의질의저하, 자살사고및자살시도의증가와같은여러부정적영향을미친다는것이알려져있다. 20-24) 정신병증상의개선만을목표로항정신병약물만처방하는것이아니라, 항우울제처방과같은복합약물요법의경향성은환자들의여러증상적측면에관심을가지고이에대한개입을통해주관적고통을줄이고, 사회적기능과삶의질을개선하려는노력의일환으로볼수있겠다. 베타차단제와벤조다이아제핀의처방증가도관찰되었다. 베타차단제는항정신병약물의부작용인좌불안석증, 진전, 불안 ( 특히사회불안이나수행불안 ) 에주로사용되는약물이며, 벤조다이아제핀은추체외로부작용, 불안, 불면에주로사용되고있는약물이다. 5) 조현병의치료에서베타차단제가주로추체외로부작용의일종인좌불안석증에주로쓰이는현실을고려할때, 이는예상외의경향이다. 왜나하면추체외로부작용은전형항정신병약물에비해비정형항정신병약물에서덜나타난다고알려져있기때문이다. 25) 이연구는사용된약물의이유나추체외로부작용여부를조사하지않았기때문에정확한이유는알수는없지만, 다음과같은추론은가능하다. Table 5의각항정신병약물과베타차단제의상관을보면, paliperidone 과 quetiapine 사용과정적, haloperidol 과부적 54
Change in Psychotropic Prescription in Schizophrenia Hwang IH, et al 관계였다. Paliperidone에비해 quetiapine은좌불안석증의빈도가낮은것으로알려졌으나좌불안석증의경우불면이나불안이동반하기때문에이를조절하기위한결과로도추론할수있겠다. Haloperidol 의경우전형약물이기때문에오히려베타차단제의사용이적은것은반대의결과이나, 약물용량, 동시투여약물들을고려해야하기때문에현재의자료로는원인을추정하기어렵다. 베타차단제는좌불안석증외에진전이나불안조절을목적으로사용될가능성도있다. 벤조다이아제핀처방증가는우선 clozapine 과 olanzapine 을제외한비정형약물의진정효과가적은것과관련있는것으로보인다. 특히이연구의대상이된급성기입원환자의경우정신병증상으로인한흥분, 불면, 초조, 불안에대한진정이필요했을것이며이에대한추가로처방되었을가능성이다. 또한조현병의불안증상에대한적극적대처로볼수있다. 과거에는조현병환자의불안은양성증상에가려지거나, 항정신병부작용과연관지어생각되며저평가되어왔고, 평가를위한척도도부족한실정이다. 26) 하지만조현병환자의불안은정신운동초조를유발하여환자들의삶의질을저하시킨다고알려졌기때문에, 27) 양성증상의조절뿐만아니라불안, 초조, 불면등에고려가처방경향에나타난것으로보인다. 2000년대에들어항콜린성약물사용은감소한것으로나타나고있다. 항콜린성약물은급성근육긴장이상증, 파킨슨증후군과같은추체외로부작용의예방및치료에사용되는대표적인약물이다. 28) 반면항콜린성약물의사용은인지기능저하 29) 와지연발생운동이상증를악화시킬수있다는보고 30) 가있어, 장기적인처방에대해서는논란의여지가있다. 따라서본연구의결과는비정형항정신병약물의추체외로부작용감소와같은장점을반영한다고볼수있다. 1990년대와 2000년대를비교하였을때기분안정제와콜린성약물의처방은비슷한경향을보였다. 조현병환자들에게서충동성, 기분불안정, 특히공격성이있는경우에기분안정제를처방하는것이효과적이라는의견이있지만, 현재까지축적된근거로볼때기분조절제의병합이효과적이라는근거는제한적이다. 조현병환자들에게서보이는충동성, 공격성은주로양성증상과관련되어있는경우가많아, 이런경우항정신병약물의증량이이루어지는경우가많을것으로생각되며, 기분안정제처방의제한된효과로인해두시대에서처방경향의변화는보이지않고있다. 콜린성약물은항정신병약물의항콜린성부작용에대해사용되고있으며, 항콜린성부작용은전형항정신병약물, 비정형항정신병약물의차이로나타나기보다는각약물의무스카린성 (muscarinic) 수용체의친화성정도에따라나타나는부작용이다. 2000년대에들어비정형항정신병약물의사용증가와항콜린성부작용과는큰 연관이없으며, 이는콜린성약물의큰변화없는처방경향으로나타나고있다. 새로운항정신병약물에기대하는것은, 항정신병효과의증가와부작용의감소이고, 이로인해약물의종류와용량을최소화하여환자의순응도증가일것이다. 조현병에대한이해가증가하고새로운항정신병약물개발이이루어졌음에도, 환자에게처방되는약물의종류가증가한것은조현병의다양한증상군 ( 불안, 우울등 ), 또한환자의삶의질, 정신사회적기능회복과사회복귀, 사회적비용저하와같은다측면적개입과고려를반영한것으로판단된다. 31) 그렇다고새로운항정신병약물에이점만있는것은아니다. 대표적으로여러비정형항정신병약물은비만, 대사증후군, 심혈관계질환과관련이있으며, 필요한경우이와관련된모니터링이권장되며, 경우에따라내과적처치의추가, 항정신병약물의변경등이가능하다. 32) 이연구의제한점은일대학병원입원환자를대상하여그대표성의문제다. 외래기반이나정신병원, 의원의환자군에비해유병기간이적은급성기의환자또한양성증상이심한환자군이과도표현될가능성이있다. 이는처방되는약물수의증가로나타날수있을것이다. 또한최근연구나처방가이드라인에접근이용이하며, 비교적보험삭감과약제비용에대한예민성이적은대학병원의처방패턴은의원이나정신병원과다를수있다. 또한차트리뷰를통한정보수집으로인해처방된약물의종류와용량을통해환자들의증상, 부작용의유무등을유추하였다는제한점이있다. 그리고처방하는의사의성향이약물처방경향에영향을미칠수있는데, 1990 년대에서 2000년대로오며 2명의의사가바뀐점도제한점이라할수있겠다. 마지막으로이연구는퇴원시점의횡적인조사로입원이나외래치료중의약물종류나용량변화, 특히약물변경에대한점은고려하지못하였고향후이런경향에대한연구가필요하다. 그리고치료반응과부작용을같이조사하여보다효과와부작용측면을처방패턴에대입하여분석하는연구도필요할것이며, 약물경제적측면의변화, 타대학병원과의비교를보는연구도필요하겠다. 이러한제한점에도불구하고, 이연구를통해최근수년간조현병환자에게더욱다양한종류의정신과약물이사용되었음을확인하였다. 또한, 항정신병약물뿐만아니라, 다양한정신작용제의처방경향을분석하여환자들의정신병적증상뿐만아니라약물부작용, 우울, 불안등을조절하여삶의질을개선하고자하는최근의경향을살펴본점에서의의가있다고생각한다. 중심단어 : 조현병 약물 처방 정신작용제 항정신병약물. journal.biolpsychiatry.or.kr 55
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