KISEP Special Articles 14 2 2003 우울증치료를위한좌측미주신경자극법 김형섭마음사랑병원 ABSTRACT Left Vagus Nerve Stimulation (VNS) for the Treatment of Depression Hyeong-Seob Kim, MD Maeum Sarang Hospital, Wanjoo, Korea Depressive disorder is one of the very serious mental diseases in terms of personal, social, economical losses. It is not clear for the pathogenesis of the depression, however, even though decreased 5-HT and NE may be the biological causing factors in the neuronal synapses. Moreover, there are many depressive patients who are treatment resistant or partial responders. Thus, we have been needed the other therapeutic methods for those cases. Repeated transcranial magnetic stimulation (rtms) & VNS are the newly introduced methods for the treatment of refractory or partial responders with depression, which nature of therapeutic effect is the stimulation of the CNS. VNS has been used to treat the refractory epilepsy patients. Despite of numerous empirical and preclinical data, although VNS may be effective for the treatment of depression, the parameters for the treatment of depression using the VNS device have not been confirmed yet. However, from the several reports clinical effectiveness were described about 40%, thus, it is interested that VNS will be able to use for the treatment of depression in a future. (Korean J Psychopharmacol 2003;14(2):84-89) KEY WORDS:CNS stimulation Refractory depression Vagus nerve stimulation. 서 - 교신저자 84 론
미주신경자극 (VNS) 의역사 - - - 우울증과관계되는미주신경의해부학적특성 Table 1. The list of human studies in VNS 1988 First Human Implant Dr. Kiffin Penry 1992 First Randomized Active Control Study 1994 European Community Approval 1996 5 completed controlled studies N454 1997 USA FDA Commercial Approval 1998 2,500Implants ever worldwide 1999 Substantial mood improvements 2000 Detailed rationale for depression Figure 1. Application of VNS. - - 85
Insular Cortx Thalamus Amygdala Hippocampus Hypothalamus Pons Parabrachial Nucleus Dorsal Raphe Medulla Medial Reticular Formation Nuclcus of the Solitary Tract Solitary Tract Nodose Ganglion Spinal Cord Arca Postrema DMN Nucleus Cunneatus Figure 2. Afferent Pathway to the Brain, Epilepsia, 31Sup.2S1-S7, 199. 86 1. VNS 의우울증치료기전 1) 전간환자의 VNS 시행경험 2) 신경생화학적변화및 PET 연구 3) 항경련제의항우울효과 2. 도구장착과치료 Parameters 및부작용 Korean J Psychopharmacol 2003;14(2):84-89
Table 2. Research parameters for VNS Range Nominal value Output current 0.0 to 3.50 ma in 0.25 ma steps 0.00 ma OFF Pulse width 130 to 1000 sec 500 sec Frequency 1 to 30 Hz 20 Hz ON time 7 to 90 sec 30 sec OFF time 0.2 to 60 minutes in 5-minute steps, 5 min 60 to 80 minutes in 30-minute steps Magnetcurrent to 3.50 ma in 0.25-mA steps 0.0 ma Magnet pulse width 130 to 100 sec 500sec Magnet on time 7 to 90 sec 30 sec Table 3. Adverse profiles of VNS Potential surgery related risks; 01. adverse reaction to anesthesia 02. incision pain 03. blood clot 04. infection 05. cyst formation 06. inflammation 07. facial numbness 08. localized surgery related pain 09. facial paralysis 10. nausea 11. fluid accumulation 12. paresthesia 13. hematoma 14. scarring 15. histotoxic reaction 16. skin irritation 17. hoarseness 18. tissue reaction 19. nerve damage possible Potential device & sitimualtion related risks % of previous patients reports 01. aspiration pneumonia 0.1 02. hypesthesia 2.1 03. cardiovascular effects 0.1 04. increased coughing 52.6 05. device migration 1 06. laryngismus 7.4 07. dyspepsia 21.1 08. muscle twitching during stimulation 3.2 09. dysphagia 2.1 10. nausea & vomiting 17.9 11. dyspnea 27.4 12. pain 33.7 13. ear pain 4.2 14. paresthesia 17.9 15. facial paresthesis or paralysis 0.1 16. pharyngitis 42.1 17. hemidiaphragm paralysis 1 18. Tinnitus 4.2 20. Hiccuping 3.2 21. Voice alteration 66.3 Potential Adverse Effects possible but not reported to date Duodenal ulcer or gastric ulcer 87
Table 4. Improved rates of VNS in each studies Authors Year No. of subject Duration of study Improved rate Rush et al 2000 30 10 Wks 40% Marangell et al 2000 30 2 years 11/12 of acute responder, 16/18 of acute cases nonrespond Sackeim et al 2000 60 10 Wks 30.5% in HDRS, 34.0% in MDRS, 37.3% in CGI-I Sackeim et al 2001 27 10 Wks Cognitive improvement Ellen et al 2001 60 2 years 46% in 1 year, 54% in 2 years Martinez et al 2002 60 312 Mo 3145%, 1527%remission Mahas 2002 60 10 Wks 30.5%, partial 27%, full 15.3% Armitage 2002 4 10 Wks Improved sleep quality Marangell 2002 30 12 Wks 40% 3. 치료효과 4. 시술비용 88 맺음말 중심단어 참고문헌 1) Bailey P, Bremer F. A sensory cortical representation of the vagus nerve. J Neurophysiol 1938;(40):405-412. 2) Dell P, Olson R. Projections secondaries mesencephaliques, diencephaliques et amygdaliennes des afferences viscerales vagales. C R Soc Biol 1951;145:1088-1091. 3) Maclean PD. The tribune in evolution: role in paleocerebral functions. 1990; New York: Plenum press Korean J Psychopharmacol 2003;14(2):84-89
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