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반복 경두개자기자극술의 우울증 치료효과 및 최신동향에 대한 고찰

Clinical Efficacy of Repetitive Transcranial Magnetic Stimulation for Treatment of Depression and Latest Trends in TMS Techniques

김혜원|강지인|김세주|김신태
대한생물정신의학회 (The Korean Society Of Biological Psychiatry)|2017.08|생물정신의학 (Journal of Korean Society of Biological Psychiatry)|제24권 제3호|pp. 95-109|DOI 10.22857/kjbp.2017.24.3.002

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키워드

항우울효과·안전성·우울증·반복 경두개자기자극술·뇌자극술.
주제분류정신과학

초록

반복 경두개자기자극술(repetitive transcranial magnetic stimulation, 이하 rTMS)은 전자기코일을 통해 국소적으로 자기장을 형성하여 대뇌 특정부위 뇌세포의 활성도를 조절할 수있는 치료기술이다.1) rTMS는 뇌심부자극술(deep brain stimulation) 에서 요하는 개두술이나 전기경련요법(electroconvulsive therapy, 이하 ECT)에서 요하는 발작 유도 없이 뇌 신경계 조절이 가능하여 비침습적이고 안전한 치료법으로 인정받고 있다.2) 이러한 장점들이 있는 rTMS는 지난 30년간 우울증, 조현병, 강박장애, 뚜렛증후군 등을 포함한 다양한 정신질환의 치료에 시도되고 있다.3)4) 특히, rTMS 임상연구는 치료저항성 우울증(treatment-resistant depression)에서 가장 활발히 이루어지고 있다.5) 우울증 환자에서 배부외측 전전두피질(dorsolateral prefrontal cortex, 이하 DLPFC)의 뇌혈류 이상이 있다고 알려져 있어좌측 DLPFC 부위의 고빈도(5~20 Hz) rTMS 적용 또는 우측DLPFC 부위의 저빈도(1 Hz 이하) rTMS 적용이 유의한 항우울효과가 있는 것으로 보고되었다.6) 우울증 환자에서의rTMS 임상연구들이 통계적으로 유의한 항우울효과와 안전성을 입증하면서 미국 식품의약품안전처(Food and Drug Administration, 이하 FDA)는 2008년에 좌측 DLPFC에 고빈도자극을 주는 rTMS를 우울증 치료에 공식적으로 허가하였다.7) 또한 2013년에 한국 식품의약품안전처에서도 우울증에 rTMS 치료를 승인하였다. 최근 TMS 전문가들이 결성한 Clinical TMS Society(cTMSs)는 consensus review를 통해 좌측DLPFC 고빈도 rTMS를 이용한 우울증 치료지침을 ‘TMS 치료는 항우울제 치료반응이 낮은 환자들에게 우울증 증상 경감의 급성기 치료에 병용 또는 단독요법으로 추천된다.’고 제안하였다.8) 그러나 rTMS의 우울증 치료효과에 대해서는 아직 논란이 있다. 최근 우울증 환자를 대상으로 한 63개의 rTMS 연구를 포함시킨 한 체계적 고찰연구(n = 3236)에서는 우울증상 평가척도를 Clinical Global Impression-Improvement scale (이하 CGI-I)로 변환하여 메타분석했을 때 rTMS의 항우울효과가 통계적으로 유의한 수준이었지만, 증상호전의 정도가 CGI-I 점수 기준으로 평균 0.5점 정도를 감소시키는 데그쳐 임상효과가 불분명하였다.9) 이러한 rTMS의 연구결과들을 해석할 때에는 각 연구들의표본 특성과 TMS 적용방법의 제한성을 고려해야 한다.10) 지금까지의 많은 rTMS 연구들은 작은 표본 크기로 인해 통계적검정력이 낮은 한계점을 가지고 있었고11)12) rTMS 연구에 참여한 우울증 대상자들의 임상특성과 약물복용 여부 등에서 차이가 있었다.6)13) 연구결과에 영향을 끼칠 수 있는 TMS 적용지표 측면에서는 자극 빈도(frequency), 자극 강도(intensity), 치료 동안의 총 자극 횟수(total pulses), 치료적용 횟수(sessions), 사용한 코일의 종류 등이 연구마다 달랐다.6) 또한TMS 코일의 위치를 좌측 혹은 우측의 DLPFC 영역에 적용할 때 정확하게 해당 부위를 자극했는지 확실하지 않은 제한점이 있었다. 최근에는 우울증에 대한 TMS의 제한적 효과를개선하기 위하여 TMS 강도와 자극빈도를 높이거나 심부 뇌를 자극하는 코일을 사용하거나 자극기간을 늘이는 등의 새로운 시도들이 이루어지고 있다. 본 종설에서는 우울증에서 rTMS의 임상연구를 체계적으로 고찰하여 우울증의 임상특성에 따라 분류하여 그 치료효과를 기술했으며 TMS 적용지표를 고려하여 정리하였다. 특히, 2008년 FDA 승인 이후에 치료저항성 우울증 환자를 대상으로 시행된 무작위 허위자극 통제(sham-controlled) 연구와 메타분석 연구의 결과들을 중심으로 항우울효과와 적합성을 기술하였다. 또한 뇌피질을 좀 더 깊이 자극할 수 있는코일을 이용한 deep TMS를 이용하거나 표적위치를 보다 정확하게 자극하는 기술을 이용한 TMS 임상연구들을 살펴보았다. 이와 더불어 기존의 rTMS 적용기법을 넘어 우울증 치료에 새롭게 시도되고 있는 고용량(high-dose) rTMS 적용, 세타돌발자극(Theta-burst Stimulation, 이하 TBS), 자기경련치료(magnetic seizure therapy, 이하 MST) 등의 치료기술을 적용한 연구들을 고찰하여 TMS 치료의 최신 동향을살펴보고자 하였다.

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique which can change cortical excitability in targeted area by producing magnetic field pulses with an electromagnetic coil. rTMS treatment has been used to treat various neuropsychiatric disorders including depression. In this review, we evaluate the literature on rTMS for depression by assessing its efficacy on different subtypes of depression and different technical parameters. In particular, we focus on the results of randomized clinical trials and meta-analyses for depression after the US Food and Drug Administration approval in 2008, which acknowledged its efficacy and acceptability. We also review the new forms of rTMS therapy including deep TMS, theta-burst stimulation, and magnetic seizure therapy (MST) that have been under recent investigation. High frequency rTMS over left dorsolateral prefrontal cortex (DLPFC), low frequency rTMS over right DLPFC, or bilateral rTMS is shown to be effective and acceptable in treatment for patients with non-psychotic, unipolar depression either as monotherapy or adjuvant. Deep TMS, theta-burst stimulation and MST are promising new TMS techniques which warrant further research.

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