D . Himanshu Ni an, e al. E icacy and Sa e y o Ke amine in T ea men -Resis an Dep ession: A P ospec i e
Clinical S udy. In . J Med. Pha m. Res., 6 (6): 553‐555, 2025
553
In e na ional Jou nal o Medical
and Pha maceu ical Resea ch
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O iginal A icle
E icacy and Sa e y o Ke amine in T ea men -Resis an Dep ession: A
P ospec i e Clinical S udy
D . Himanshu Ni an¹, D . Isha Yada ², D . Ji end a Kuma ³
¹Assis an P o esso , Depa men o Psychia y, Noida In e na ional Ins i u e o Medical Sciences, G ea e , Noida.
²Assis an P o esso , Depa men o Anaes hesia, UCMS and GTB Hospi al, New Delhi.
³Assis an P o esso , Depa men o Psychia y, AMU, Aliga h.
A B S T R A C T
Co esponding Au ho :
D . Himanshu Ni an
Assis an P o esso , Depa men o
Psychia y, Noida In e na ional
Ins i u e o Medical Sciences,
G ea e , Noida.
Recei ed: 15‐10‐2025
Accep ed: 14‐11‐2025
A ailable online: 20‐11‐2025
Backg ound: T ea men - esis an dep ession (TRD) is a majo challenge in clinical
psychia y. Ke amine, an NMDA ecep o an agonis , has eme ged as a no el
he apeu ic op ion due o i s apid an idep essan e ec s. This s udy aimed o
e alua e he e icacy and sa e y o ke amine in pa ien s wi h TRD.
Me hods: This was a p ospec i e, open-label clinical s udy conduc ed on pa ien s
diagnosed wi h majo dep essi e diso de no esponding o a leas wo adequa e
an idep essan ials. In a enous ke amine (0.5 mg/kg) was adminis e ed o e 40
minu es wice weekly o wo weeks. Pa ien s we e assessed using he Hamil on
Dep ession Ra ing Scale (HDRS) and Mon gome y-Asbe g Dep ession Ra ing
Scale (MADRS) a baseline, Day 3, Day 7, and Day 14. Ad e se e ec s we e
moni o ed using a s anda dized checklis .
Resul s: A o al o 40 pa ien s wi h TRD we e en olled. Mean HDRS sco es
educed signi ican ly om 25.3±3.2 a baseline o 12.4±2.8 a Day 14 (p<0.001).
MADRS sco es showed a simila decline om 32.1±4.5 o 14.8±3.7 (p<0.001).
Response a e (≥50% educ ion in HDRS) was obse ed in 67.5% o pa ien s, and
emission (HDRS ≤7) in 22.5%. Ad e se e ec s we e mild and ansien , wi h
dissocia ion (20%), dizziness (12.5%), and nausea (10%) being mos common.
Conclusion: In a enous ke amine demons a es apid and signi ican
an idep essan e ec s in pa ien s wi h ea men - esis an dep ession and is
gene ally well- ole a ed. Fu he con olled s udies wi h la ge sample sizes and
long- e m ollow-up a e wa an ed o es ablish i s sus ained e icacy and sa e y.
Copy igh © In e na ional Jou nal o
Medical and Pha maceu ical Resea ch
Keywo ds: Ke amine, T ea men ‐ esis an dep ession, NMDA ecep o
an agonis , Rapid‐ac ing an idep essan .
INTRODUCTION
Majo dep essi e diso de (MDD) is one o he leading causes o disabili y wo ldwide. Despi e he a ailabili y o mul iple
classes o an idep essan s, app oxima ely 30–40% o pa ien s do no achie e adequa e esponse e en a e ials o wo o
mo e an idep essan s, he eby ul illing he c i e ia o ea men - esis an dep ession (TRD). This clinical challenge
unde sco es he need o no el he apeu ic agen s wi h as e onse and g ea e e icacy.
Ke amine, a phencyclidine de i a i e and NMDA ecep o an agonis , has gained a en ion o i s apid an idep essan
e ec s obse ed wi hin hou s o adminis a ion. I modula es glu ama e gic ansmission and enhances neu oplas ici y
h ough downs eam ac i a ion o AMPA ecep o s and mTOR signaling. This s udy was designed o p ospec i ely e alua e
he e icacy and sa e y o in a enous ke amine in Indian pa ien s diagnosed wi h TRD.
MATERIALS AND METHODS
This p ospec i e, open-label s udy was conduc ed a he Depa men o Psychia y, Noida In e na ional Ins i u e o Medical
Sciences, G ea e Noida, in collabo a ion wi h he Depa men o Anaes hesia, UCMS and GTB Hospi al, New Delhi,
be ween Janua y 2024 and July 2025.
Inclusion c i e ia included adul s aged 18–60 yea s, diagnosed wi h MDD as pe DSM-5, and non esponsi e o a leas wo
D . Himanshu Ni an, e al. E icacy and Sa e y o Ke amine in T ea men -Resis an Dep ession: A P ospec i e
Clinical S udy. In . J Med. Pha m. Res., 6 (6): 553‐555, 2025
554
adequa e an idep essan ials. Exclusion c i e ia we e psycho ic diso de s, subs ance use diso de , uns able medical illness,
o p egnancy.
Pa icipan s ecei ed six in usions o ke amine (0.5 mg/kg IV) o e 40 minu es wice weekly o wo weeks. Dep ession
se e i y was measu ed using HDRS and MADRS a baseline, Day 3, Day 7, and Day 14. Vi al pa ame e s and side e ec s
we e closely moni o ed.
RESULTS
A o al o 40 pa icipan s me inclusion c i e ia and comple ed he wo-week s udy p o ocol. The mean age was 37.2 ± 9.6
yea s ( ange 19–58 yea s), wi h a gende dis ibu ion o 22 emales (55%) and 18 males (45%). The a e age du a ion o
dep essi e illness was 4.8 ± 2.3 yea s. Mos pa icipan s (60%) had ailed wo p io an idep essan egimens, while 40%
had ailed h ee o mo e.
A baseline, he mean HDRS sco e was 25.3 ± 3.2, which signi ican ly dec eased o 12.4 ± 2.8 by Day 14 (p < 0.001).
Simila ly, he mean MADRS sco e declined om 32.1 ± 4.5 o 14.8 ± 3.7 (p < 0.001). No ably, 27 pa ien s (67.5%) achie ed
a clinical esponse (≥50% HDRS educ ion), and 9 pa ien s (22.5%) achie ed emission (HDRS ≤ 7) by he end o
ea men . Imp o emen was e iden as ea ly as Day 3 pos - i s in usion.
Ad e se e en s we e epo ed in 14 pa ien s (35%). The mos equen we e dissocia ion (20%), dizziness (12.5%), and
nausea (10%). All side e ec s we e mild o mode a e and esol ed spon aneously wi hin one hou pos -in usion. No cases
o psychosis, hemodynamic ins abili y, o pe sis en cogni i e impai men we e eco ded.
O e all, he ea men was well- ole a ed, and no pa ien s discon inued due o ad e se e ec s. These indings ein o ce
ke amine’s po en ial as a sa e, apid-ac ing, and e ec i e in e en ion o pa ien s wi h TRD.
Assessmen Timepoin
Mean HDRS (±SD)
Mean MADRS (±SD)
Baseline
25.3 ± 3.2
32.1 ± 4.5
Day 3
18.2 ± 2.9
24.6 ± 3.9
Day 7
14.5 ± 2.5
18.7 ± 3.4
Day 14
12.4 ± 2.8
14.8 ± 3.7
Response a e (≥50% HDRS educ ion) was 67.5%, while emission (HDRS ≤7) was achie ed in 22.5%. No se ious
ad e se e en s we e epo ed. The mos equen side e ec s we e ansien dissocia ion (20%), dizziness (12.5%), and
nausea (10%).
DISCUSSION
The indings o his p ospec i e s udy highligh ke amine’s ema kable e icacy in apidly alle ia ing dep essi e symp oms
among indi iduals wi h ea men - esis an dep ession (TRD). The apid educ ion in HDRS and MADRS sco es wi hin
he i s week o ea men emphasizes ke amine’s dis inc ad an age o e adi ional an idep essan s, which o en ake
se e al weeks o achie e he apeu ic e ec s. This apid esponse is clinically signi ican , especially in pa ien s a high isk
o suicide, as ke amine has been shown o exe po en an i-suicidal e ec s h ough i s modula ion o he glu ama e gic
sys em.
Mechanis ically, ke amine’s an idep essan ac ion is a ibu ed o NMDA ecep o an agonism, leading o an acu e su ge in
glu ama e elease. This, in u n, s imula es AMPA ecep o ac i i y, enhancing synap ic plas ici y and p omo ing
neu ogenesis h ough downs eam ac i a ion o he mTOR signaling pa hway and inc eased exp ession o b ain-de i ed
neu o ophic ac o (BDNF). Neu oimaging and p eclinical s udies u he sugges ha ke amine e e ses s ess-induced
synap ic de ici s in he p e on al co ex and hippocampus, egions implica ed in mood egula ion.
In he p esen s udy, he esponse a e o 67.5% and emission a e o 22.5% align wi h exis ing li e a u e, such as he
indings o Za a e e al. (2006) and Mu ough e al. (2013), who epo ed compa able e icacy ollowing a single o epea ed
in usion egimen. The consis en decline in HDRS and MADRS sco es ac oss all ime poin s unde sco es ke amine’s obus
and ep oducible an idep essan po en ial. Impo an ly, no se ious ad e se e en s we e obse ed, e lec ing i s sa e y when
adminis e ed unde p ope supe ision and dose egula ion.
The obse ed ad e se e ec s—dissocia ion, dizziness, and nausea—we e mild, ansien , and sel -limi ing, consis en wi h
p e ious sa e y p o iles. Dissocia ion ypically appea ed wi hin minu es o in usion onse and esol ed wi hin 60 minu es
pos -in usion. These e ec s a e belie ed o s em om ke amine’s ansien co ical dys egula ion and can be mi iga ed wi h
ca e ul dose i a ion and pa ien moni o ing.
Ou esul s also con ibu e o he g owing e idence ha ke amine may induce a neu obiological ' ese ' in dys unc ional
neu al ci cui s associa ed wi h dep ession. Func ional MRI s udies ha e demons a ed no maliza ion o connec i i y wi hin
D . Himanshu Ni an, e al. E icacy and Sa e y o Ke amine in T ea men -Resis an Dep ession: A P ospec i e
Clinical S udy. In . J Med. Pha m. Res., 6 (6): 553‐555, 2025
555
he de aul mode ne wo k (DMN) and limbic s uc u es ollowing ke amine ea men . Such neu oadap i e changes may
explain he sus ained mood imp o emen obse ed e en a e cessa ion o in usions.
Howe e , limi a ions o his s udy include he ela i ely small sample size, open-label design, and sho - e m ollow-up
pe iod. The absence o a placebo con ol p e en s de ini i e causal in e ence ega ding ke amine’s supe io i y. Long- e m
e ec s, elapse a es, and cogni i e impac s equi e u he explo a ion h ough andomized, double-blind, con olled ials.
None heless, he p esen indings o e aluable eal-wo ld da a om an Indian popula ion, highligh ing ke amine’s
he apeu ic iabili y and ole abili y p o ile in di e se clinical se ings.
Fu u e di ec ions should include s udies on al e na i e ou es such as in anasal eske amine, e alua ion o main enance
p o ocols, and explo a ion o bioma ke s p edic i e o ea men esponse. In eg a ion o ke amine he apy wi hin
comp ehensi e psychia ic ca e, including psycho he apy and psychosocial suppo , may u he enhance and sus ain
clinical ou comes.
CONCLUSION
Ke amine demons a es obus , apid, and sa e an idep essan e ec s in ea men - esis an dep ession. I s inclusion in
ea men algo i hms may e olu ionize dep ession managemen , especially o pa ien s un esponsi e o adi ional
he apies. Fu u e andomized con olled ials wi h ex ended obse a ion a e necessa y o alida e and ex end hese
indings.
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