Njengoba izinselele zomsebenzi, izinkinga zobudlelwane, nezingcindezi zomphakathi zanda, ukucindezeleka kungase kuqhubeke. Ezigulini ezilashwa ngama-antidepressants okokuqala, zingaphansi kwesigamu ezithola ukuxolelwa okuqhubekayo. Iziqondiso zokuthi ungawukhetha kanjani umuthi ngemva kokwehluleka kokwelashwa kwesibili kwe-antidepressant ziyehluka, okuphakamisa ukuthi nakuba kunemithi eminingi etholakalayo, kukhona umehluko omncane phakathi kwayo. Kule mithi, kunobufakazi obusekela kakhulu bokwandisa ama-antipsychotic atypical.
Ekuhlolweni kwakamuva, idatha yokuhlolwa kwe-ESCAPE-TRD iyabikwa. Ukuhlolwa kwakuhlanganisa iziguli ze-676 ezinokucindezeleka ezingazange ziphendule ngokuphawulekayo okungenani ama-antidepressants amabili futhi zisathatha i-serotonin reuptake inhibitors ekhethiwe noma i-serotonin-norepinephrine reuptake inhibitors, njenge-venlafaxine noma i-duloxetine; Inhloso yocwaningo bekuwukuqhathanisa ukusebenza kahle kwe-esketamine nasal spray nokukhululwa okuqhubekayo kwe-quetiapine. Isiphetho esiyinhloko kwaba ukukhululwa emavikini angu-8 ngemva kokungahleliwe (impendulo yesikhashana esifushane), futhi isiphetho esiyinhloko sesibili sasingekho ukuphindaphinda emavikini e-32 ngemva kokuxolelwa emavikini angu-8.
Imiphumela yabonisa ukuthi awukho umuthi obonisa ukusebenza kahle okuhle, kodwa i-esketamine nasal spray yayisebenza kancane kakhudlwana (27.1% vs. 17.6%) (Umfanekiso 1) futhi yaba nemiphumela emibi embalwa eholele ekuyekisweni kokwelashwa kocwaningo. Ukusebenza kahle kwayo yomibili le mithi kukhuphuke ngokuhamba kwesikhathi: ngeviki lama-32, ama-49% kanye nama-33% eziguli ezisesifuthoni samakhala se-Esketamine kanye namaqembu akhululwa isikhathi eside e-quetiapine ayesethole ukuxolelwa, futhi ama-66% nama-47% abesephendulile ekwelashweni, ngokulandelana (Umfanekiso 2). Kube khona ukuphindeka okumbalwa kakhulu phakathi kwamaviki 8 kanye nama-32 kuwo womabili amaqembu okwelapha
Isici esiphawulekayo socwaningo kwakuwukuthi iziguli eziyekile ocwaningweni zahlolwa njengezinomphumela omubi (okungukuthi, zihlanganiswe neziguli ezinesifo esingazange sixole noma esiphinde sabuyela emuva). Ingxenye ephezulu yeziguli eziyekiswe ukwelashwa eqenjini le-quetiapine kuneqembu le-esketamine (40% vs. 23%), umphumela ongabonisa ubude besikhathi esifushane sesiyezi kanye nemiphumela emibi yokuhlukaniswa ehambisana ne-Esketamine nasal spray kanye nesikhathi eside sokudambisa kanye nesisindo somzimba esihambisana nokukhululwa okuqhubekayo kwe-quetiapine.
Kwakuwuhlolo olunelebula evulekile, okusho ukuthi iziguli zazazi ukuthi hlobo luni lomuthi eziwudlayo. Abahloli abenze izinhlolokhono zomtholampilo ukuze banqume izikolo ze-Montgomery-Eisenberg Depression Rating Scale bekungodokotela bendawo, hhayi izisebenzi ezikude. Kukhona ukushoda kwezixazululo eziphelele zokuchema okuphuphuthekisa okukhulu nokulindela okungenzeka ekuhlolweni kwezidakamizwa ezinemiphumela yesikhashana esebenza ngokwengqondo. Ngakho-ke, kuyadingeka ukushicilela idatha ngemiphumela yezidakamizwa ekusebenzeni ngokomzimba kanye nekhwalithi yokuphila ukuze kuqinisekiswe ukuthi umehluko obonwayo ekusebenzeni akuwona nje umphumela we-placebo, kodwa futhi ukuthi umehluko ubalulekile ngokomtholampilo.
Indida ebalulekile yocwaningo olunjalo ukuthi ama-antidepressants abonakala enza ukuwohloka kwemizwa kungazelelwe futhi andise ukuthambekela kokuzibulala enanini elincane leziguli. I-SUSTAIN 3 iwucwaningo olunwetshiwe lwesikhathi eside, olunelebula evulekile lwesivivinyo seSigaba 3 i-SUSTAIN, lapho ukulandelelwa okuhlanganisiwe kweziguli ezingu-2,769 - 4.3% kwatholakala ukuthi babe nesenzakalo esibi kakhulu sengqondo ngemva kweminyaka. Kodwa-ke, ngokusekelwe kudatha evela ocwaningweni lwe-ESCAPE-TRD, ingxenye efanayo yeziguli emaqenjini e-esketamine kanye ne-quetiapine yabhekana nezenzakalo ezimbi ezimbi zengqondo.
Okuhlangenwe nakho okuwusizo nge-esketamine nasal spray nakho kuyakhuthaza. I-cystitis kanye nokukhubazeka kwengqondo kuhlala kuyithiyori kunezingozi zangempela. Ngokufanayo, njengoba izifutho zekhala kufanele zinikezwe ngesisekelo sokulaliswa esibhedlela, ukusetshenziswa ngokweqile kungavinjelwa, okuthuthukisa namathuba okubuyekezwa njalo. Kuze kube manje, inhlanganisela ye-racemic ketamine noma ezinye izidakamizwa ezingase zihlukunyezwe ngesikhathi sokusetshenziswa kwe-esketamine nasal spray akuvamile, kodwa kusewukuhlakanipha ukuqapha lokhu okungenzeka eduze.
Iyini imiphumela yalolu cwaningo ekusebenzeni komtholampilo? Umlayezo obaluleke kakhulu ukuthi uma isiguli singaphenduli okungenani kuma-antidepressants amabili, amathuba okuthola ukukhululwa okuphelele phakathi nezinyanga ezimbili ngokungezwa kwemithi yokwelapha ahlala ephansi. Uma kubhekwa ukuphelelwa ithemba kwezinye iziguli kanye nokungazweli kwazo emithini, ukuzethemba ekwelashweni kungase kuncishiswe kalula. Ingabe umuntu onenkinga enkulu yokucindezeleka uyasabela emithini? Ingabe isiguli asijabule ngokwezempilo? Lokhu kuhlolwa kukaReif et al. igqamisa isidingo sokuthi odokotela bakhombise ithemba kanye nokuqina ekwelashweni kwabo, ngaphandle kwalokho iziguli eziningi aziphathwa kahle.
Nakuba ukubekezela kubalulekile, kunjalo nangesivinini esisingathwa ngaso isifo sokucindezeleka. Iziguli ngokwemvelo zifuna ukululama ngokushesha ngangokunokwenzeka. Njengoba ithuba lesiguli lokuhlomula lincipha kancane kancane ngokwehluleka ngakunye kokwelashwa kwe-antidepressant, kufanele kucatshangelwe ukuzama ukwelashwa okuphumelelayo kakhulu kuqala. Uma okuwukuphela kwayo okunqumayo ukuthi iyiphi i-antidepressant engakhethwa ngemva kokwehluleka kokwelashwa kwezidakamizwa ezimbili kungukusebenza nokuphepha, khona-ke uhlolo lwe-ESCAPE-TRD lungaphetha ngokunengqondo ngokuthi i-esketamine nasal spray kufanele ikhethwe njengokwelashwa komugqa wesithathu. Kodwa-ke, ukwelashwa kwesondlo nge-esketamine nasal spray ngokuvamile kudinga ukuvakasha kwamasonto onke noma kabili ngeviki. Ngakho-ke, izindleko kanye nokuphazamiseka kungenzeka kube yizici ezibalulekile ezithinta ukusetshenziswa kwazo.
I-Esketamine nasal spray ngeke kube ukuphela komphikisi we-glutamate ukungena emtholampilo. Ukuhlaziywa kwe-meta kwakamuva kusikisela ukuthi i-ketamine ye-racemic emithanjeni ingase iphumelele kakhulu kune-esketamine, futhi izivivinyo ezimbili ezinkulu zekhanda kuya kwekhanda zisekela ukusetshenziswa kwe-intravenous racemic ketamine kamuva endleleni yokwelashwa njengendlela yokuzikhethela ezigulini ezidinga ukwelashwa kwe-electroconvulsive. Kubonakala kusiza ukuvimbela ukucindezeleka okwengeziwe futhi ukulawula ukuphila kwesiguli.
Isikhathi sokuthumela: Oct-08-2023