정신분열병 환자의 우울증에서 Paroxetine과 삼환계 항우울제 병용치료

심주철,공보금,박정환,윤영란,신재국,김정익,안동성,김용관,차인준,김영훈 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.4

저자들은 마산동서병원에 입원중인 우울증이 동반된 정신분열증 환자 10명을 대상으로 사용중인 항정신병약물에 paroxetine과 저용량의 삼환계 항우울제를 6주간 병용투여한 후 우울증상에 대한 효과와 치료의 안전성 및 약물상호작용을 알아보았다. Paroxetine은 고정량의 항정신병약물과 삼환계 항우울제에 부가하여 일일 20㎎을 6주간 병용하게 하였으며, 임상상태는 HDRS, HARS, UKU Side Effect Rating Scale등의 평가척도를 사용하여 평가하였다. 또한 약동학적 약물상호작용은 삼환계 항우울제들의 혈장농도를 HPLC로 측정하여 분석하였다. 결과는 다음과 같다. 1) 10명의 전체 대상환자에서의 HDRS 평균점수는 TCA와 paroxetine 병용투여 6주후에 통계적으로 유의하게 감소되었다. 이중 40%의 환자에서는 병용투여 6주후에 HDRS 점수상 50% 이상의 감소를 보여, 일부의 환자들에서는 정신분열병에 동반된 우울증상의 치료에 소량의 삼환계 항우울제와 paroxetine의 병용치료가 효과가 있음을 확인하였다. 2) 두 명의 환자에게서 심각한 약물독성이 발생하였다. 이중 한 명은 삼환계 항우울제의 높은 혈중농도로 인한 항콜린성 위기(anticholinergic crisis) 소견을 보였으며, 다른 한 명은 인지기능 및 의식수준은 명료하였으나 망상과 환각증상이 약화되는 소견을 보였다. 따라서 본 연구에서 시도된 복합적 약물치료의 경우, 삼환계 항우울제의 혈중농도의 측정을 포함한 세심한 임상적 추적이 필요하다고 생각된다. 3) 기저치의 amitriptyline과 그 대사물인 nortriptyline의 농도합. imipramine과 대사물인 desipramine의 농도합은 각각 47.8-226.5ng/㎖. 80.5-395.6ng/㎖였으며 일반적으로 이들 약물들의 단독사용시에 문헌에 보고된 혈중농도를 훨씬 상회하고 있었다. 이는 병용투여된 항정신병 약물 약시 강력한 CYP2D6 효소억제제로서 기저치의 삼환계 항우울제들의 혈장농도를 이미 상당히 증가시켰던 것으로 판단되며, 그러한 결과로 인해 본 연구에서는 paroxetine이 이전의 문헌보고들과는 달리 뚜렷하게 삼환계 항우울제들의 혈장농도를 증가시키지 못하였다. 본 연구는 SSRI와 삼환계 항우울제의 병합 투여가 우울증의 개선 효과를 빠르게 하고, 치료역을 넓히고, 약물상호작용의 결과 paroxetine이 삼환계 항우울제의 혈중농도를 증가시킨다는 기존의 연구결과를 이용하여 정신분열병 우울증상의 치료에 parotextine과 소량의 삼환계 항우울제를 병용하는 방법을 시도해 본 연구이다. 저자들은 이러한 약물치료가 일부의 환자들에게서 효과가 있음을 관찰하였으나, 항정신병약물과 삼환계 항우울제를 병용투여 할 경우는 물론 이에 paroxetine과 같은 선택적 세로토닌 재흡수 억제제를 병용할 경우 복합약물상호작용의 결과로 약물독성의 위험성이 크며 세심한 주의가 필요함을 경험하였다. Depression is well-known to comorbid with several psychiatric disorders. Many schizophrenics also suffer from depression in the course of their illness. Combined therapy of SSRI and tricyclic antidepressants were reported to have benefits in some depressed patients. Paroxetine, a potent CYP2D6 inhibitor, increases the blood levels of tricyclic antidepressant markedly. Using paroxetine, we tried this combined therapy in the treatment of depressive symptoms in 10 chronic schizophrenic inpatients and evaluated its efficacy and drug interactions between paroxetine and tricyclic antidepressants. The following results were obtained : 1) The mean score of Hamilton's Depression Rating Scale(HDRS) was reduced significantly after 6 weeks-trials of this combined therapy for the mild depressive symptoms in 10 chronic schizophrenics. In four patients, 50% or more reductions in the scores of HDRS were noticed at final evaluation. 2) Two among our 10 subjects experienced severe toxic behavioral problems. Anticholinergic crisis with toxic confusion due to high blood levels of tricyclics was found in one patient and the other showed rapid clinical deterioration in his psychotic symptoms such as delusion and hallucination without any consciousness alternation. 3) Baseline plasma levels of tricyclics before adding paroxetine were higher than expected in our chronic schizophrenic subjects maintained with their antipsychotic medications. Several antipsychotics were also known as a potent CYP2D6 inhibitors and to increase the blood levels of tricyclics. Because the blood levels of tricyclics had already increased significantly by the use of antipsychotics, adding paroxetine to antipsychotics and tricyclic antidepressant in our subjects could increase the blood levels of tricyclics not so much as previously reported in the literatures.

기분장애 환자의 다중약물치료 시 고려해야 할 대사적 약물상호작용

문은수,장재승,하규섭,하태현 대한정신약물학회 2008 대한정신약물학회지 Vol.19 No.6

Polypharmacy has recently become usual practice in the treatment of patients with mood disorders. In this article, we review the results of recent studies on metabolic drug interactions between anticonvulsants, atypical antipsychotics, and antidepressants. Important drug interactions in clinical practice may be summarized as follows. First, valproate may increase the serum level of carbamazepine and its active metabolite carbamazepine-epoxide, quetiapine, and lamotrigine. In particular, in combined regimens of lamotrigine and valproate, the dose of lamotrigine needs to be downwardly titrated, due to the potential risk of skin lesions. Second, there are numerous carbamazepine- associated interactions that need careful monitoring, because carbamazepine is a well-known inducer of CYP1A2, CYP2C9, and CYP2C19. Thus, in patients receiving carbamazepine, clinically significant decreases in serum levels may be found for drugs metabolized by these enzymes. Third, atypical antipsychotics are primarily metabolized by CYP2D6 and CYP3A4, thereby compromising the use of inhibitors of these enzymes. Fourth, most selective serotonin-reuptake inhibitors (SSRIs) are actually inhibitors of diverse enzyme systems, indicating at least potential problems with increased serum levels. While paroxetine, fluoxetine, and fluvoxamine strongly inhibit CYP enzymes, citalopram, venlafaxine, mirtazapine, and bupropion do so weakly. In conclusion, understanding drug-drug interactions is essential in planning individualized pharmacotherapy with diverse therapeutics. In treating patients with mood disorders, special concern should be paid to combination therapy using valproate, carbamazepine, and some SSRIs. 기분장애 환자의 약물치료 시 항경련제나 비정형 항정 신병약물 및 항우울제들을 서로 병용하는 다중약물치료가 증가하고 있다. 약물상호작용에 대한 이해는 다중약물치 료 시 적정 약물용량의 결정에 있어 중요하다고 볼 수 있 다. 본고에서는 약동학적 약물상호작용 중에서 약물 대 사와 관련된 대사적 약물상호작용을 중심으로 약물대사 효소 및 유도제나 억제제로 작용할 수 있는 약물과 대사 적 약물상호작용에 관한 기존의 연구결과들을 정리하였 다. 대사적 약물상호작용의 연구결과들을 요약해 보면, carbamazepine이 CYP1A2, CYP2C9 및 CYP2C19에 의해 대사되는 약물의 혈중농도를 감소시킬 수 있으며, 항우울제 중에서 fluoxetine, paroxetine, sertraline 및 fluvoxamine은 CYP1A2, CYP2D6 및 CYP2C19에 의 해 대사되는 약물의 혈중농도를 감소시킬 수 있다. 또한 lamotrigine의 경우 valproate에 의해 혈중농도가 증가 할 수 있고, carbamazepine에 의해 혈중농도가 감소할 수 있다. 그리고 비정형 항정신병약물은 억제제나 유도 제로서의 작용이 거의 없으므로 다른 약물의 농도변화에 큰 영향이 없다고 볼 수 있다. 대사적 약물상호작용은 다 중약물치료 시 적정 약물용량 결정에 있어 중요하게 고 려되어야 하며, 향후 약물대사와 관련된 유전자 다형성 에 대한 정보가 보완된다면, 임상진료 시에 실제적인 도 움을 얻을 수 있을 것이다.

새로운 항정신병약물의 약물상호작용

김용식,강웅구,노명선,Kim, Yong Sik,Kang, Ung Gu,Roh, Myoung Sun 대한생물정신의학회 2000 생물정신의학 Vol.7 No.1

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

임상의사가 흔히 실수할 수 있는 노인 약물치료의 사례와 그 대처방안

오병훈(Byoung Hoon Oh) 대한노인정신의학회 2003 노인정신의학 Vol.7 No.1

Psychotropic drug use in the aged from 7-92% in institutional settings and up to 30% in medical settings. And older patients received an average of 5-12 medications per day in general hospitals. I reviewed common errors during psychotropic drug treatment and suggest the proper management guideline. In general, physical illness, medical drugs, drug-drug interactions and age-related physiological changes may alter psychotropic drug pharmacokinetics and it induced the severe adverse reactions from psychotropic agents. To proper management for the elderly patients with psychotropic drug treatment, the clinician must have skilled experiences of the effective drug administration and understand the unique characteristics of elderly individuals. And in addition, geriatric psychiatrist must be emphasized the psychosocial problems that may decrease drug compliance.

조현병 환자의 입원 치료시 약물처방 경향의 변화 : 일 대학병원에서 1996~2000년과 2006~2010년의 차이 비교

황인환,김대호,오대영,Hwang, In-Hwan,Kim, Daeho,Oh, Dae-Young 대한생물정신의학회 2014 생물정신의학 Vol.21 No.2

Objectives Previous 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. Methods All 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). Results The 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. Conclusions Increased 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.

조현병 환자의 아동기 외상과 정신작용약물 사용 경향에 대한 예비 연구

김총기,김대호,이현지,김양석,Kim, Chonggi,Kim, Daeho,Lee, Hyunji,Kim, Yangsuk 대한생물정신의학회 2016 생물정신의학 Vol.23 No.3

Objectives Experience of early childhood abuse elevates the risk of developing schizophrenia in later period of life, incidence of psychiatric comorbidity, symptomatic severity and complexity. In this context, we hypothesized that the pattern of psychotropic medication used would reflect this; those with childhood trauma will received more types and higher doses of psychotropic medication. Methods From our database of 102 outpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) schizophrenia, we analyzed experiences of childhood trauma measured by the Childhood Trauma Questionnaire-Short Form and types and dose of prescribed psychotropic medication. Results We found significant positive correlations between child sexual abuse and the number of psychotropic medications (p = 0.029) and between child emotional neglect and the number of psychotropic medications other than antipsychotics (p = 0.045). Conclusions This preliminary study suggests that the pattern of psychotropic use may be affected by types of childhood trauma. Further studies will have to shed light on mediating factors such as symptoms or comorbid conditions that lead to prescription of certain psychotropic class.

정신과 영역에서의 약물 상호작용

홍현주,김찬형 대한생물치료정신의학회 2003 생물치료정신의학 Vol.9 No.1

In current psychiatric practice, pharmacotherapy combination are commonly used to treat comorbid psychiatric or medical disorders, to increase its efficacy. Although many interactions have little clinical significances, some may interfere with treatment or even be life-treatening. If the pharmacokinetic properties and pharmacodynamic mechanisms of action of the ineraction drugs are known, many drug interactions and explores underlying pharmacokinetic and pharmacodynamic considerations for interactions in psychiatric practice.