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Njengoko ucelomngeni lomsebenzi, iingxaki zolwalamano, noxinezeleko lwasekuhlaleni lusanda, ukudandatheka kusenokuzingisa. Kwizigulane ezinyangwa ngamachiza okudakumba okokuqala, ngaphantsi kwesiqingatha bafumana uxolelo oluzinzileyo. Izikhokelo malunga nendlela yokukhetha ichiza emva kokuba unyango lwesibini lwe-antidepressant lungasebenzi luyahluka, lubonisa ukuba nangona kukho amachiza amaninzi akhoyo, kukho umahluko omncinane phakathi kwawo. Kula machiza, kukho obona bungqina buxhasayo bokunyusa i-atypical antipsychotics.

Kuvavanyo lwamva nje, idatha yovavanyo lwe-ESCAPE-TRD ixeliwe. Ulingo lwalubandakanya izigulane ze-676 ezinexinzelelo ezingazange ziphendule ngokubonakalayo ubuncinane kwii-antidepressants ezimbini kwaye zisathatha i-serotonin reuptake inhibitors okanye i-serotonin-norepinephrine reuptake inhibitors, njenge-venlafaxine okanye i-duloxetine; Injongo yolingo yayikukuthelekisa ukusebenza kwe-esketamine nasal spray kunye nequetiapine ukukhululwa okuqhubekayo. Isiphelo esiphambili sasiyi-remission kwiiveki ze-8 emva kokwenza i-randomization (impendulo yexesha elifutshane), kwaye isiphelo sesibini esiphambili sasingenakuphindaphinda kwiiveki ze-32 emva kokuxolelwa kwiiveki ze-8.

Iziphumo zibonise ukuba akukho chiza libonisa ukusebenza kakuhle, kodwa i-esketamine nasal spray yayisebenza kancinci (27.1% vs. 17.6%) (Figure 1) kwaye yaba neziphumo ezibi ezimbalwa ezikhokelele ekuyekisweni konyango lolingo. Ukusebenza kwawo omabini amachiza kwanda ngokuhamba kwexesha: ngeveki yama-32, i-49% kunye ne-33% yezigulane kwi-Esketamine nasal spray kunye ne-quetiapine eqhubekayo yokukhululwa kwamaqela aphumelele ukuxolelwa, kwaye i-66% kunye ne-47% baye basabela kunyango, ngokulandelelana (Umfanekiso 2). Bekukho ukuphinda kubuye okumbalwa phakathi kweeveki 8 kunye ne 32 kuwo omabini amaqela onyango

Inqaku elihlabayo lophononongo yayikukuba izigulane eziye zaphuma kulingo ziye zavavanywa njengeziphumo ezibi (okt, zidityaniswe nezigulane ezinezifo ezingakhange zixolelwe okanye zibuyele umva). Ubungakanani obuphezulu bezigulane eziyekiweyo unyango kwiqela le-quetiapine kuneqela le-esketamine (40% vs. 23%), umphumo onokuthi ubonise ubude obufutshane be-dizziness kunye nemiphumo emibi yokwahlula ehambelana ne-Esketamine nasal spray kunye nobude bexesha elide le-sedation kunye nokuzuza ubunzima obuhambelana nokukhululwa okuqhubekayo kwe-quetiapine.

Yayilulingo olunelebhile evulekileyo, okuthetha ukuba izigulane zazisazi ukuba loluphi uhlobo lwechiza eziluthathayo. Abaphononongi abaqhube udliwano-ndlebe lweklinikhi ukumisela amanqaku e-Montgomery-Eisenberg yoxinzelelo lweScale yayingoogqirha bendawo, hayi abasebenzi abakude. Kukho ukunqongophala kwezisombululo ezigqibeleleyo kubumfama obunzulu kunye nokulindela ukulindela okunokuthi kwenzeke kulingo lwamachiza aneziphumo zexesha elifutshane zengqondo. Ngoko ke, kuyimfuneko ukupapasha idatha malunga nemiphumo yamachiza ekusebenzeni komzimba kunye nomgangatho wobomi ukuqinisekisa ukuba umahluko obonakalayo ekusebenzeni akukona nje umphumo we-placebo, kodwa nokuba umahluko unentsingiselo yeklinikhi.

I-paradox ebalulekileyo yolingo olunjalo kukuba ii-antidepressants zibonakala zenza ukuwohloka ngokukhawuleza kweemvakalelo kunye nokwandisa utyekelo lokuzibulala kwinani elincinci lezigulane. I-SUSTAIN 3 luphononongo lwexesha elide, oluvulelekileyo lweSigaba sesi-3 solingo lwe-SUSTAIN, apho ukulandelwa okuqokelelweyo kwezigulane ze-2,769 - i-4.3% yafunyanwa ukuba ifumene isiganeko esibi kakhulu sengqondo emva kweminyaka. Nangona kunjalo, ngokusekelwe kwidatha evela kulingo lwe-ESCAPE-TRD, umlinganiselo ofanayo wezigulane kwi-esketamine kunye namaqela e-quetiapine bafumana iziganeko ezimbi kakhulu zengqondo.

Amava asebenzisekayo nge-esketamine nasal spray nawo ayakhuthaza. I-cystitis kunye nokukhubazeka kwengqondo kuhlala kuyingcingane kunokuba yingozi yangempela. Ngokufanayo, ekubeni izitshizi ngeempumlo kufuneka zilawulwe kwizigulana zangaphandle, ukusetyenziswa ngokugqithiseleyo kunokuthintelwa, nto leyo ephucula amathuba okuphononongwa rhoqo. Ukuza kuthi ga ngoku, indibaniselwano ye-racemic ketamine okanye ezinye iziyobisi ezinokuthi zisetyenziswe kakubi ngexesha lokusetyenziswa kwe-esketamine nasal spray ayiqhelekanga, kodwa kusenobulumko ukubeka iliso ngokusondeleyo.

Ziziphi iimpembelelo zolu phononongo kumsebenzi wezonyango? Owona myalezo ubalulekileyo ngowokuba xa isigulana singaphenduli ubuncinane kwii-antidepressants ezimbini, amathuba okuba afumane uxolelo olupheleleyo kwiinyanga ezimbini nokongezwa kwamachiza onyango ahlala ephantsi. Xa kujongwa ukuphelelwa lithemba kwezinye izigulana kunye nokunganyangeki kwazo kumachiza, ukuzithemba kunyango kunokujongelwa phantsi ngokulula. Ngaba umntu onengxaki yoxinzelelo olukhulu uyasabela kunyango? Ngaba umguli angonwabanga ngokwezonyango? Olu lingo nguReif et al. iqaqambisa imfuneko yokuba oogqirha babonise ithemba kunye nokuzinza kunyango lwabo, ngaphandle apho izigulane ezininzi aziphathwa kakuhle.

Ngoxa umonde ubalulekile, kunjalo nangesantya esisingathwa ngaso isifo sokudandatheka. Ngokwendalo izigulane zifuna ukuchacha ngokukhawuleza kangangoko kunokwenzeka. Ekubeni ithuba lesigulana lenzuzo liyancipha ngokuthe ngcembe ngokusilela ngakunye konyango lwe-antidepressant, kufuneka kuqwalaselwe ukuzama olona nyango lusebenzayo kuqala. Ukuba ngaba ekuphela kwezinto ezimisela ukuba zeziphi na isithonga sokudakumba esinokukhetha emva kokusilela kunyango lwamachiza amabini lusebenza kunye nokhuseleko, ngoko ke ulingo lwe-ESCAPE-TRD lunokugqiba ngokusengqiqweni ukuba i-esketamine nasal spray kufuneka ikhethwe njengonyango lodidi lwesithathu. Nangona kunjalo, unyango lolondolozo nge-esketamine nasal spray ludla ngokufuna utyelelo lweveki okanye kabini ngeveki. Ke ngoko, iindleko kunye nokuphazamiseka kunokuba zizinto ezithatha isigqibo esichaphazela ukusetyenziswa kwazo.

I-Esketamine nasal spray ayisayi kuba kuphela kwe-glutamate antagonist yokungena kwikliniki. Uhlalutyo lwamva nje lwe-meta lubonisa ukuba i-ketamine ye-racemic ye-intravenous inokusebenza ngakumbi kune-esketamine, kwaye iimvavanyo ezimbini ezinkulu zentloko ukuya kwentloko zixhasa ukusetyenziswa kwe-intravenous racemic ketamine kamva kwindlela yonyango njengendlela yokukhetha izigulane ezifuna unyango lwe-electroconvulsive. Ibonakala inceda ukuthintela ukudandatheka ngakumbi kwaye ilawule ubomi bomguli.