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1 KISEP Special Article 생물정신의학 Vol. 13, No. 4, November 2006 항우울제의부작용과대처방안 (1) * - 성기능장애를중심으로 - 김정기 ** 이수진 ** Antidepressant-Induced Adverse Effects and Management Strategy * - Focused on Sexual Dysfunction - Jeong-Gee Kim, M.D., Ph.D., ** Soo Jin Lee, M.D. ** ABSTRACT S exual dysfunction is a relatively common adverse effect in the use of antidepressants. The sexual side effects may result in a lack of compliance with the prescribed antidepressants. The author reviewed the prevalence and updated treatment for the antidepressant-induced adverse effects focusing on sexual dysfunction. The incidence of sexual dysfunction is reported to exceed more than 50% especially with SSRIs. In order to obtain a quantified baseline and as an ongoing evaluation tool, clinicians may use some of the established questionnaires and validated instruments such as the Arizona Sexual Experience scale and Changes in Sexual Functioning Questionnaire. Clinicians should be aware that delayed ejaculation and orgasm, symptoms most frequently associated with antidepressants, are not usually associated with depression itself. Although many antidotes have been proposed, few have been subjected to double-blind trials. Some evidences have suggested that bupropion and buspiron may be the effective antidotes for SSRI induced sexual dysfunction. Additional trials will be requied to define what role, if any, bupropion and buspiron might have in the treatment of SSRI-induced sexual side effects. The available evidence is rather limited, with only small number of trials assessing each strategy. While further randomized data is awaited, for men with antidepressant induced erectile dysfunction, the addition of sidenafil or tadalafil may appear to be an effective strategy. KEY WORDS:Antidepressant Adverse effect Sexual dysfunction Management. * 본연구는보건복지부보건의료기술진흥사업의지원에의하여이루어진것임 ( 과제번호 :A050047). This study was supported by a grant of the Korean Health 21 R & D Project, Ministry of health and Welfare, republic of Korea(A050047). ** 메리놀병원정신과 Maryknoll General Hospital, Department of Psychiatry, Busan, Korea 교신저자 : 김정기, 부산광역시중구대청동 4 가 12 전화 ) (051) , 전송 ) (051) ) kjg567@korea.com

2 서론 항우울제는 1950~60년대부터사용되어온삼환계항우울제 (Tricyclic antidepressants, TCAs), MAO 억제제 (Monoamine oxidase inhibitors, MAOIs) 를비롯하여 1980년대이후에우울증의원인이라고생각되는특정신경전달물질에선택적인약리학적효능을가진선택적세로토닌재흥수차단제 (Selective serotonin reuptake inhibitors, SSRIs), 세로토닌- 노에피네프린재흡수차단제 (Serotonin norepinephrine reuptake inhibitors, SNRI) 등의항우울제가속속등장하였다. 이들새로운항우울제들은치료의효과면에서는별다른진전을가져오지못했으나약물의부작용등이연관이된내인성이이전의약물보다개선되었다. 그럼에도불구하고이들약제들이부작용이전혀없는것은아니다. 1) 주요우울증의경과에대한 12년간의장기간추적연구에서전체의절반이상에서주요우울증상이나경한우울증상을가지고있었고절반이하의기간동안만정상적인상태를보였다. 2) 또한항우울제복용을조기중단하는경우증상의재발과만성화로이어지기쉽다. 즉재발또는 3회이상의우울증삽화가있은경우에는재발병율이 80~90% 에이르렀다. 3) 그러나항우울제를지속적으로복용하고있는환자에서는 70% 에서재발의위험율을낮추었고, 위약을복용한군에비해절반이하의재발율을보였다. 4) 따라서최근에는발병이후유지기를포함하여 1년이상의약물치료가필요하다는주장도있으며특히노년에발생한우울장애의경우보다장기간의치료가좋다고추천된다. 5) 약물사용기간의변화에따라서약물치료시나타날수있는부작용들의발생과처치도달라질수있다. 즉약물복용초기에발생하여일시적으로있다가완화되는것이나혹은초기발생하여다소경미하게지속되는것이있고, 약물복용후어느정도기간이지난뒤발생하거나문제가되어지속되는부작용들이있다. 6) 장기유지치료에서는체중증가와성기능장애등의부작용이순응도을낮추는가장큰문제로생각되고있다. 7)8) 이런부작용들은환자들의치료에대한순응을떨어뜨릴뿐만아니라장기약물복용이계속되는한지속적으로나타나므로결과적으로치료에부정적인영향을주게되어치료중단과재발로이어지게되는경우가많다. 따라서장기치료시발생하는 부작용들은환자의치료탈락이나가족과의관계의어려움, 사회, 및직업적능력을감퇴시켜삶의질을떨어뜨린다. 8-10) 특히이런문제는우울증의초기치료단계에서는우울증의여러가지고통으로부터벗어나려는문제가더시급하고또한우울증자체의증상으로나타나기도하므로별반문제가되지않다가초기우울증상이전반적으로완화되는데도불구하고지속될경우문제가될수있다. 따라서본논문에서는항우울제를장기적으로복용할때, 즉주요우울장애로인하여최소한수개월이상투약을받아우울증상에는치료반응을보이나약물복용이후성기능장애를호소하는항우울제에의해유발된성기능장애의기전과대처방안을알아보고자한다. 성기능장애의역학과원인 Kennedy 등 11) 의연구에의하면주요우울증을가진남성의 40%, 여성의 50% 에서성욕이감소되었다는보고가있으며, 이전에항우울제를복용한환자의 15~20% 에서절정감에문제가있다고보고하였다. 또한환자의약 36% 에서항우울제로야기된성기능장애로치료를중단하였다. 12) 이러한자료는항우울제가성기능장애의주된기여인자라는것을보여준다. Nofzinger 등 13) 은남성우울증환자를대상으로 NPT(nocturnal penile tumescences) 를이용한발기능력평가에서 30% 정도에서병적인범위로감소되었다고하였다. 많은수에서기분과성적만족이호전되어도 NPT 감소가지속되므로기분의존적이지않을수있으며, 비록우울한동안에성기능에대한만족도는떨어지나, 기대와달리성적인욕동, 활동또는관심은떨어지지않는다고하였다. 성기능장애의빈도가높은것은 MAOIs, SSRIs, venlafaxine, TCAs 등이다. 항우울제를복용하는환자들은자신의성기능장애에대한담당의사에서자발적으로보고하는경우는 14.2% 에불과하고, 의사의직접적인질문을받을경우훨씬많은 58.1% 에서성기능장애를보고한다. 14) Valerie 등 15) 의보고에의하면영국과프랑스에서실시된항우울제로인한성기능장애의발생빈도조사에서영국인 39.2%, 프랑스인 26.6% 가항우울제로인한성기능장애가있는것으로나타났다. 남성은 34.2%, 여성은 32.5% 를나타난다고하였다. 이들은이러한성기능장애로인하여자존감, 기분, 성파

3 트너와의관계, 그리고삶의질적인면에서부정적인영향을주는것으로보고하였다. 국내의연구에서는김정웅등이 77 명의환자중 SSRIs 사용환자중 30명 (39%) 에서성기능장애가발생하였고여성에서더욱심각하다고보고하였고, 조성일등이항우울제를사용한 122명의환자중 37.7% 인 46명에서성기능장애를보고하였고, 발생빈도에는성별차이가없는것으로보고하였다. 16) 성기능장애에는여러인자들이기여할수있다. 첫째는우울증그자체가원인이될수있다. 우울증은리비도나쾌감을경험하는능력을포함한신체적인욕구를감소시킨다. 따라서급성우울증환자의경우성에대해관심이없으므로이에대한호소를하지않는다. 둘째, 정신분열병, 물질남용, 인격장애를포함한다른정신과적인질환이우울증에병합되는경우가많다. 셋째, 갑상선질환, 심혈관계질환, 당뇨를포함한여러신체적질환이성기능장애와연관된다. 넷째, 이뇨제, clonidine, b-blocker, H2-blocker, phenytoin 등일반신체질환에사용되는약제이외에도, 항정신병약물, 벤조다이아제핀등의항불안제, narcotics 등도연관된다. 다섯째, 우울증환자에서원발성성기능장애가발생할수있다. 마지막으로정신사회및상황적변화가약물및알코올남용등과같이성기능장애를일으키는요인이될수있다. 17) 예를들면, 우울증환자의배우자는감소된가계의수입을보충하기위해일을하게되고, 이로인하여우울증이나치료와는관계없이성적인불만족이증가할수있다. 항우울제유발성성기능장애의기전 1. 항우울제와연관된성기능장애의가설들항우울제는다음의기전을통하여성기능장애를유발할수있다. 첫째, 성욕과성기능에감소를가져오는등 의중추신경계의불특정한효과, 둘째, 투약이중추신경계신경전달물질의기능에영향을주어성욕을감소시키거나성기능부전을일으키는중추신경계특정효과, 셋째, 최종장기에서성기능을중재하는특정신경전달물질을감소시키는약물에의한말초신경계효과, 넷째, 호르몬효과이다. 9)18) 예를들면여성에서 estrogen testosterone, progesterone은모두성적인기능의생리학적인요소이나, 남성에서는 testosterone이가장우선되는생리학적인요소이다. Oxytocin 은 orgasm 과연관되어있고, 성욕에영향을줄수있다. 2. 성기능장애에대한신경전달물질의효과기분조절과인지에주된역할을하는신경전달물질이성기능장애에또한중요한역할을한다. 도파민과노르에피네프린은우울증에서성적인욕구와각성에영향을준다. 도파민은동기유발과연관될뿐만아니라욕구에영향을주어성적인활동에참여하는능력에영향을주고성적인흥미를유지하는역할을수행한다. 19) 노르에피네프린은성적인각성과질수축을자극한다. 또한이완없이지속적인각성상태를피하기위하여세로토닌시스템이활성화되어각성상태를중단시키는등의기전으로성적인기능을조절한다. 20) 더불어세로토닌은 nitric oxide function 을감소시키고성기자극을감소시킨다 ( 표 1). 21) 3. NO-cGMP pathway와연관된성기능의기전 Sildenafil(Viagra ) 이 male erectile dysfunction 치료제로발매되면서성기의발기와이완에중요한작용을하는신경전달물질로각광을받게된 Nitric oxide(no) 는 cyclic guanosine monophosphate(cgmp) 형성을촉발해대뇌의의성적흥분을말초의 penile/clitoral erection 으로바꾸어준다. SSRIs 는 NO synthetase inhibitor 로작용하여성기능장애를유발하며, Ginkgo Biloba 를포함한 antidote는 NO synthetase의 enhancer로 SSRIs Table 1. Neurophysiology of sexual dysfunction 22) DA 5-HT NE ACh Clinical correlation Erection α, β M Antipsychotics may lead to erectile dysfunction(da block):da agonists may lead to enhanced erection and libido;priapism with trazodone(α1 block);β-blockers may lead to impotence α1-blockers(tricyclic drugs, MAOIs, thioridazine) may lead to impaired ejaculation;5-ht agents may inhibit orgasm Ejaculation & orgasm ± α1 M :facilities, :inhibits or decreses, ±:some, Ach:acetylcholine, DA:dopamine, 5-HT:serptonin, M: modulates, NE:norepinephrine, :minimal

4 유발성성기능장애를호전시키는것으로생각된다 ) 대처방안 항우울제로유발된성기능장애는흔히관심의대상이되지않는다. ELIXIR 연구 28) 는 4,557 명의환자에서 SSRIs 로유발된성기능장애에대한치료전략을조사하였고그들은대개적정한치료를받지않는다고결론지었다. 환자의 42% 는자연적인회복을수동적으로기다렸고 39% 는다른항우울제로교체되었다. 또한일부환자에서약물의용량조절, 약물휴일, 약물대체, 해독제치료, 약물의첨가, 비약물학적방법이시도되었으나대부분의경우에서그들의효용성이충분하게입증되지는않았다. 1. 자연적치유를기다리는것약물의부작용이지속되지않을수있다. 이것은치료초기에는적용해볼수있다. 이것은약 5~10% 미만의환자가경험하기때문이다. 한연구에의하면 SRI induced sexual dysfunction 의자연관해는 6개월내에 5.8%, 38개월간지속적으로치료받은환자에서 9.8% 에서일어난다고보고하였다. 29) 또다른연구에서는 SSRI 를처방받은 156 명의환자에서 4~6개월간 19% 만이중등도이상의호전을보고하였다. 30) 이는자연관해가드물다는것을설명한다. 따라서자연적인호전이일어나기를기다리는것은비효과적인전략이다. 2. 약물의용량조절항우울제로야기된성적인부작용은용량과연관될수있으며, 용량의점진적인감소는일부환자에서유용하다. 이런조절전략은특히다른부작용을함께경험하고있는환자에서유용할수있다. 그러나이것은약물에잘반응하고순응하는환자에게만시도되어질수있으며, 용량조절시기와유지기에환자의증상재발을방지를위해서임상가의세심한관찰이필요하다. 31) 3. 약물휴일약물을하루혹은이틀동안거르도록환자에게충고하는약물휴일은효과적일수있으나치료호응도를약화시킬수있다. 31) 예를들면환자가주말을제외하고매일약물을복용하도록처방받는다고해도환자는다른날에도약물을건너뛸수있다. 더욱이반감기가짧은 SSRIs 를복용하고있는경우약물휴일은약물중단증상 이나우울증상의재발을가져올수있다. 4. 추가적인약물치료항우울제로야기된성기능장애치료에효과적인선택이될수있다. 그러나이런결과를지지할만한체계적인자료가부족하다. 추가적인약물의사용혹은해독치료가효율적인항우울제치료처방을고수하도록환자를격려하면서성기능장애의증상을경감시킬수있는방법으로사용될수있다. 1) Bupropion augmentation 일반적으로 SRI 치료를받는동안에발생한성기능장애에서 Bupropion 을첨가하는것이효과적일수있다고알려져있다. 또한병용치료에일반적으로내인성이좋다. Clayton 등 32) 은 endpoint changes in sexual functioning Questionnaire(CSFQ) desire-frequency가 bupropion 을사용한환자들에서더호전되었다고보고하였다. Masand 등 33) 은 Arizona Sexual experiences scale(asex) 상 50% 호전이이루어지지않는참가자들의수가 placebo 와비교하여의미있는차이가없다고하였다. 또다른연구에서 DeBattista 등 34) 은 bupropion 으로치료한군에서 sexual arousal 호전을보고하였으나치료효과및방법론에대한내용이명확하지않았다. 최진혁등 35) 은 SSRI 로치료받고있는주요우울증환자중성기능장애가발생한 14명의환자를 Bupropion SR 로대체투여 8주후 11명에서성기능장애의유의한감소를보고했다. 그러나최근의연구에서효과여부에대한연구들이대부분적은수의대상자를포함하고있고그결과들이일관적이지않아대규모의체계적인연구가향후필요할것으로생각된다. 2) Sildenafil augmentation 남성에항우울제로유발된성기능장애에항우울제에 sildenafil 추가가효과가있다는보고가일관적으로되고있다. Numberg 36,37) 와 Ginsberg 등은 international index of erectile function(iief) 나 ASEX 등을사용한연구에서성기능장애가덜해졌음을보고하였다. 또한 Massachussetts central hospital sexual functioning questionaire(mgh-sfq) 및 Erectile dysfunction inventory of treatment satisfaction score(edits) 에서도호전이있다고하였다. 이러한것들은발기부전을호

5 전시킬뿐만아니라전반적인성적만족을가져오는것으로보고되었다. 최근 Fava 등 38) 의연구에서도같은결과를보고하였다. 3) Tadalafil augmentation Segraves 등 39) 에의하면남성의발기부전에서 Tadalafil 을추가하는것이 IIEF 를사용하여평가한뒤상당한호전이있다는것을보고하였다. 또한발기부전의보고가덜되는것같다고하였다. 4) Yohimbine augmentation Michelson 등 40) 의보고에서여성에게항우울제에 Yohimbin 을추가하는경우성기능장애에효과가있는것같지않다는보고가있었다. 또다른연구에서기전은확실치않으나 SSRIs 사용으로유발된성욕감퇴, 발기부전, 절정감장애등에 5.4~16.2mg 을사용했으나효과가없었다. 5) Cyproheptadine augmentation SSRIs 를사용한남성에서발생한무절정감, 발기기능장애에경우에따라 2~16mg 을사용해효과가있었다는보고 23) 가있었으나 sedation 이과도하게되었다. 이에대한좀더대규모의연구가요구된다. 6) Ginkgo biloba augmentation Kang 등의연구에서질문지를통한조사에서위약과비교시대부분의지표에서차이가없는것으로나타났다. 41) 그러나 satisfaction to orgasm 지표에서는위약에비하여더나은것으로평가하였다. 하루평균 209mg (60mg/qd-120mg/bid) 를사용하였다. 7) Ephedrine augmentation Meston 등은 Brief index of sexual functioning for women 을사용한조사에서위약과의미있는차이가없다고하였다. 42) 8) Buspirone augmentation Landen 등은항우울제에반응이없는남녀를대상으로, 4주경과뒤위약과비교하여성기능장애가 remission 되는것은차이가없었다. 43)44) 그러나 Michelson 등은우울증이회복된여성을대상으로한조사에서 buspirone 을추가한경우보다호전되었다고는하였으나치료를한군과위약군사이에의미있는차이가없다고하였다. 39) 9) Amantadine augmentation Michelson 등은여성에서 amantadine 을추가하는경우, visual analogue scale 을사용하여측정시전반적인성기능에서위약과의미있는차이가없었다. 45) 또한 buspirone 과비교하는경우에도두군간에의미있는차이가있는것은아니라고하였다. 10) Mirtazapine augmentation Michelson 은여성에서 mirtazapine 과위약을추가한연구에서 mirtazapine 군이면담이나 diary 등으로조사시성기능장애에향상이없다고하였다. 40) 11) Granisetron augmentation Jesperson과 Nelson 등은 granisetron을항우울제에추가하는연구에서 Sexual side effects scale(sses) 에서기저치와차이가없다고하였다. 46)47) 더불어 ASEX 나 Feiger sexual function and satisfaction(fsfsq) 에서차이가없다고보고하였다. 5. 약물의 Switching 항우울제로유발된성기능장애는항우울제의특정작용기전이중요한역할을한다는가설은 SSRIs, Buporpion, Mirtazapine 을비교하는연구들을입증되고있다. 주요우울증환자 456 명의무작위연구에서성기능장애에대한 bupropion SR, fluoxetine, placebo의효과를검토하였다. 성기능장애, 특히절정감장애는 fluoxetine 복용환자의 30% 에서치료시도 2주이내에일어났으며연구기간내내지속되었다. 49) 또한 bupropion SR 이나위약을복용한환자와비교했을때 sertraline 을복용한환자에서보다높은비율에서절정감장애를경험했다 (10% bupropion SR VS 11% placebo VS 36% sertraline:p<.05) 환자의보다 10~11% 에서더많이나타났다 (p<.001). 50) Escitalopram, bupropion XR 혹은 placebo를복용하는우울증환자를인터뷰방식으로성장애에대한비교연구결과에서 bupropion, placebo로치료받는환자와비교해 escitalopram 을투여받은환자는치료첫주에절정감장애를경험하는환자의수가의미있게많다는것이입증되었다. 이런차이는 8주연구에서일관되게지속되었으며, CSFQ 전체점수에서자가측정변화들에서도반영되어졌다. 51) SSRIs 로치료하여우울증이호전된환자들중에서 SS

6 RIs 로야기된성기능장애를가진 19 명의환자에게 mirtazapine 으로바꾸어 6주이상사용하였다. 이들환자중에 11명은정상적인성기능으로돌아왔고, 그리고 2명은상당한개선을보여다. 다른연구에서 mirtazapine 으로치료받은우울증환자를 6개월동안자연적인경과를추적해보았더니 baseline 에서 78명중 48명 (61.6%) 환자는성기능장애를경험하였고, 6개월경과추적을완료한 38명중 27명 (71.1%) 에서이문제가해결되었다. 52) 즉사용하는 SSRIs 에서다른종류의 SSRIs 로대체하는것은성적인부작용을없애는데몇몇환자에게 ( 약 10%) 도움을줄수있다. 그러나 bupropion, nefazodone, mirtazapine 을포함해기전이다른약물로대체하는것이보다더효과적인선택이될수있다. 6. 비약물학적치료몇몇비약물학적치료들은어떤환자에서성기능장애를경감시키는것을도울수있다. 그들의성적인문제에관해서대화를하는것만으로도어떤환자에서는도움이되나, 다른환자에게는배우자와함께성치료를받게하거나정신분석치료, 최면요법, 인지행동치료등을시행하거나자위행위, 기구의사용등다른성적인기술을시도하도록해야할때도있다. 또한임상의는환자가성생활을회피하지않고유지하는것이성적인기능의개선에도움이된다. 토론 항우울제사용으로유발되는성기능장애, 특히 SSRIs 의경우 50% 이상에서보고되고있다. 이는장기간의치료가필요한우울증의약물치료시비순응의요소가된다. 치료자는이를염두에두고초기부터관심을가지는것이필요하다. 그러나단순히관심을가지고면담을하는것보다는객관적이든주관적인보고에의한것이든지이를인지하고측정할수있도록하는질문지의개발및활용이필요할것으로생각된다. 아직항우울제로유발된성기능장애를치료하는확립된방법은충분하지않은것같다. 심리치료적인개입, 기계적인장치, 약물을감량하거나약물휴지기를갖는것에대한평가는적절히이루어지지않았다. 항우울제로유발된성기능장애의경우각약제별로처방에따라수용성등에차이가있을것이라고기대하였 으나, 그차이는없었다. 단지 mirtazapine 을추가한경우성기능장애로인한탈락률이떨어졌다는보고가있었다. 그러나이에대한대규모의체계적인연구가필요하다. 1. 항우울제의교체 SSRI(sertraline) 로유발된성기능장애에 nefazodone 으로교체하는것이효과적이라는근거가있다. 하지만임상의들의측정에서는분명한효과가있다고하였으나, 반면에환자들은그렇지않다고보고하였다. 또한유럽에서는 nefazodone의사용이중단되었고, 그사용이제한적이다. 2. 항우울제에다른약제를추가항우울제로유발된발기부전의경우 sildenafil 을추가하는것이효과적이라는보고가일관적이다. 또한비슷한작용기전을가진 tadalafil 에서도동일한결과가보고되고있다. 일반적으로항우울제로유발된성기능장애에효과가있다고알려져있는 bupropion이나 buspirone을추가하는것은소규모연구에서그효과가있음을보고하기도하고, 그렇지않다는보고가있는등결과가일관적이지않다. 최근의연구에서 bupropion 을사용하는것이다소효과가있다는보고가늘어나고있다. 그러나보다정확한결과를얻기위해서는이에대한대규모의체계적인연구가필요하다. Mirtazapine, yohimbine, amantadine, Gingko biolba 등은현재는추가하는것이효과가있는지여부가확실히증명되지않고있는상태이다. 결론 최근까지항우울제로유발된성기능장애의치료에대한연구는현재까지그개입각각에대한자료가제한적이고소규모의수준에서진행되고있다. 따라서이문제에대처하려면첫째, 가장중요한것이임상의사가이문제에관심을가지는것이다. 이는면담시나질문지등을통하여장애여부를정확하게인지하는것이그첫단계이다. 둘째, 이에대한대처로성기능장애가발생시저절로호전되는것을기다려볼수있으나, 이는 10% 미만의낮은빈도에서나타나므로적극적인개입을하는것이좋다. 셋째, 심리적접근및약물휴일등과같은개입방법에대한것은연구가더이루어져야하므로이에대한언급을하기는충분하지않지만, 성기

7 능에대해심리적인측면가지는중요성을고려하면효과가있을것으로기대된다. 넷째, 항우울제를사용하고있는약물에서다른종류의약물로교체하거나다른약물을추가하는것은현재까지는가장효과적으로널리사용되는방법이나환자의증상등다양한요소를고려해야사용하여야한다. 다양한약물들이그효과가있음을언급하고있으나, 현재까지일관되게효과가입증되고있는것은항우울제사용후발생한남성의발기부전에 sildenafil 을추가하는것이다. 하지만 bupropion, tadalafil, buspiron 등을추가하는방법에대한결론을내리기위해서는충분한연구가더필요한것으로생각된다. 중심단어 : 항우울제 역효과 성기능장애 처치. 참고문헌 1. Bahk WM, Lim W. Long-Tenn Tolerability of New Antidepressants: Focusing on Bupropion SR(Wellbutrin SR ) Kor J Psychopharma 2005;16: Judd LL, Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, et al. A prospective 12-year study of subsyndromal and syndromal depressive symptomatology in unipolar depressive disorders. Arch Gen Psychiatry 1998;55: Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991;52: Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM. Relapse prevention with antidepres-sant drug treatment in depressive disorders: a systematic review. The Lancet 2003;361: Khan A, Detke M, Khan SR. Mallinckrodtc: placebo response and antidepressant clinical trial outcome. J Nerv Ment Dis 2003;191: Balon R, Yeragani Vk, Pohl R, Ramesh C. Sexual dysfunction during antidepressant treatment. J Clin Psychiatry 1993;54: Adam Keller Ashton, Brenda D. Jamerson, Wendy L. Weinstein. Antidepressant-related adverse effects impacing treatment compliance: Results of a patient survey. Current Therapeutic Research 2005;66: Ferguson JM. SSRI Antidepressant Medications: Adverse Effects and Tolerability Primary Care Companion. J Clin Psychiatry 2001;3:1. 9. Lee SJ, Kang BJ. Antidepressant-induced sexual dysfunction: Focused on Serotonin-specific Reuptake inhibitors. J the Korean Society of Biological Therapies in Psychiatry 1989;5: Rothschild AJ. Selective serotonin reuptake inhibitor induced sexual dysfunction: efficacy of a drug holiday. Am J Psychiatry 1995;152: Kennedy SH, dickens SE, Eisfeld BS. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord 1999;56: Lawrence AL. Sex and serotonin reuptake inhibitor antidepressants. Psychiatr Ann 1999;29: Nofzinger EA, Thase ME, Reynolds CF 3rd, Frank E, Jennings JR, Garamoni GL, et al. Sexual function in depressed men: assessment by self-report, behavioural and nocturnal penile tumescence measures before and after treatment with cognitive behavioral therapy. Arch Gen Psychiatry 1993;50: Motejo-Gonzalez AL, Liorca G, Izquierdo JA. SSRI induced sexual dysfunction: Fluoxetine, paroxetine, sertraline and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997;23: Williams VS, Baldwin DS, Hogue SL, Fehnel SE, Hollis KA, Edin HM, et al. Estimating the prevalence and impact of antidepressant-induced Sexual Dysfunction in 2 European Countries: A Cross-Sectional Patient Survey. J Clin Psychiatry 2006;67: Cho SI, Lee YS, Suh DS, Na Ch, Min KJ. A Survey of Sexual Dysfunction by Antidepressants. Kor J Psychosomatic Med 2003;11: Kang BJ. Drugs and Human Sexual Function. Kor J Psychopharma 1993;4: Gitlin MJ. Psychotropic medications and their effects on sexual function: diagnosis, biology and treatment approaches. J Clin Psychiatry 1994;55: Segraves T. Effects of psychotropic drugs on human erection and ejaculation. Arch Gen Psychiatry 1989;46: Birtan D, Hull EM. Pharmacological analysis of male rat sexual behavior. Neurosci Biobehav Rev 1987;11: Sussman N, Ginsberg D. Rethinking side effects of the selective serotonin reuptake inhibitor: Sexual dysfunction and weight gain. Psychiatry Ann 1998;28: Benjamin James Sadok. Virginia Alcott Sadok Kaplan & Sadock s Synopsis of Psychiatry. 9 th ed. Lippincott Williams & Wilkins;p Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric oxide: A Physiologic mediator of penile erection. Science; Raifer J, Anderson WJ, Bush PA, et al. Nitric oxide as a mediator of relaxation of the corpus cavenosum in response to noradrenergic, noncholinergic neurotransmission. N Eng J Med 1992;326: Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sidenafil: A novel effective oral therapy for male erectile disorder. Br J Urol 1996;78: Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Sildenafil Study Group. Oral sildenafil in the treatment of erectile dysfunction. J Urol 2002;167: Sullivan G, Lukoff D. Sexual side effects of antipsy

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R