J&J Medical Connect
SPRAVATO®

(esketamine)

+ Save link
J&J Medical Connect

Connect with us

Connect with us

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

SPRAVATO® (esketamine)

Medical Information

Effect of SPRAVATO on Brain Volume and Structure in Treatment-Resistant Depression

Last Updated: 12/11/2025

SUMMARY

  • Lorente et al (2025)1 conducted a 6-month, open-label, proof-of-concept study to evaluate clinical and molecular effects of SPRAVATO on brain volume in 7 adults with treatment-resistant depression (TRD) receiving SPRAVATO adjunctive to oral antidepressants. Neuroimaging showed significant increases in volume within frontal, limbic, and hippocampal regions, along with improved microstructural integrity. Serum neurofilament light chain (sNfL) levels, a potential biomarker of neuronal damage, decreased from 14.67±1.64 to 12.14±1.51 pg/mL (P=0.0781).

EFFECT ON BRAIN VOLUME AND STRUCTURE

Neuroimaging Proof-of-Concept Study

Lorente et al (2025)1 conducted a 6-month, prospective, open-label study (depTesk) in adults with TRD receiving SPRAVATO adjunctive to oral antidepressants and other psychotropic medications (N=7; mean age, 48.2 years; female, 71%). Patients received SPRAVATO twice weekly for 4 weeks, followed by weekly administration for 20 weeks. At baseline and 6 months, structural MRI imaging was performed to measure brain changes and at baseline and 6 months, and blood samples were taken to measure sNfL levels.  Depressive symptoms (e.g., MADRS and PHQ-9) were also assessed.

Baseline brain volume, particularly in the nucleus accumbens, putamen, thalamus, basal forebrain, hippocampus, and cortical regions, including insula and frontal lobe, were significantly lower in TRD patients compared with 21 matched healthy controls.

At 6 months, both MADRS (from 31.7 to 11.9) and PHQ-9 (from 20.1 to 9.1) improved from baseline. Brain volume changes and tractography changes after 6 months of treatment are presented in Table: Comparative Brain Volumes Before and After SPRAVATO Treatment and in Table: Tractography Analysis After SPRAVATO Treatment.


Comparative Brain Volumes Before and After SPRAVATO Treatment1
Brain Region, mm3
Baseline,
Mean±SEM
After 6 Months of Treatment, Mean±SEM
P-Value
FDR-adjusted qa
Frontal lobe
824.6±19.20
+20.86±8.13
0.0159
0.0626
Superior frontal gyrus
-
+7.39±2.93
0.0164
0.0428
Frontal operculum
27.15±1.09
+1.98±0.92
0.0036
0.0686
Subcallosal frontal gyrus
-
+0.34±0.13
0.0017
0.1188
Limbic anterior cingulate
-
+2.46±1.09
0.0033
0.2810
Hippocampus
21.69±0.32
+1.50±0.57
0.0015
0.0375
   CA1
7.65±0.17
+0.59±0.29
0.0017
0.0514
   CA4-DG
5.82±0.10
+0.38±0.13
0.0016
0.0784
Abbreviation: FDR, false discovery rate; SEM, standard error of mean.
aMultiple comparisons were controlled using the Benjamini–Hochberg FDR procedure, with a significance threshold set at q<0.05

Tractography Analysis After SPRAVATO Treatment1
Brain Region
After 6 Months of Treatment,
Mean±SEM
P-Value
Volume Change (mm3)
   Fronto-parahippocampal
+991.3±371.2
0.0156
   Frontoparietal
+2189±1110
0.0496
   Frontal aslant fascicles
+4014±1688
0.0469
Fiber Count Change
   Fronto-parahippocampal
+80.57±17.55
0.0313
   Frontoparietal
+392.1±128.5
0.0156
   Frontal aslant fascicles
+248.7±61.68
0.0156
Fractional anisotropy
   Fronto-hippocampal
Increase from 0.362±0.006 to 0.414±0.005
0.0156
   Frontoparietal
Increase from 0.357±0.007 to 0.409±0.008
0.0156
   Frontal aslant fascicles
Increase from 0.364±0.006 to 0.401±0.010
0.0257
Mean Diffusivity
   Fronto-hippocampal
Increase from 0.216±0.011 to 0.154±0.015
0.0088
   Frontoparietal
Increase from 0.245±0.017 to 0.196±0.026
0.0088
   Frontal aslant fascicles
Increase from 0.235±0.016 to 0.181±0.024
0.0105
Abbreviation: SEM, standard error of mean.

Decreased sNfL were observed after 6 months of treatment (mean±SEM) from 14.67±1.64 pg/mL to 12.14±1.51 pg/mL (P=0.0781).

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 10 December 2025.

 

References

Show
1 Lorente AR, Campos-Navarro MP, Montoya ÁG, et al. Rebuilding the atrophied brain: 6-month nasal esketamine therapy expands key frontal and hippocampal regions and reduces serum neurofilament levels in patients with major depressive disorder. A proof-of-concept study of the depTesk (DEPression treatment with ESKetamine) study. CNS Spectr. 2025;30(1):e83.