The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment
Abstract
1. Introduction
1.1. Treatment Resistant Depression
1.2. Ketamine
1.2.1. Pharmacology of Ketamine
1.2.2. Ketamine Mechanism of Action
1.2.3. Molecular Pathways Underlying Ketamine’s Rapid Antidepressant Effects
1.2.4. Psychotherapy and Molecular Correlates
1.2.5. Molecular Synergy in Ketamine-Assisted Psychotherapy (KAP)
1.2.6. Epigenetic Mechanisms of Ketamine
1.2.7. Non-Ketamine Psychotherapy and Comparative Molecular Profiles
1.3. Ketamine Safety and Tolerability
Ketamine-Induced Bladder Toxicity
1.4. Ketamine for Treatment Resistant Depression
1.4.1. Dissociation
1.4.2. Rapid Onset
1.4.3. Antidepressant Effects of Ketamine on TRD
2. Results
2.1. Clinical Characteristics
2.2. The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for TRD
2.3. Depression Categorizations Pre- and Post-Infusion(s)
2.4. Tolerability and Safety
3. Discussion
3.1. Limitations
3.2. Directions for Future Research
4. Materials and Methods
4.1. Participants
4.2. Measures
4.2.1. Beck Depression Inventory
4.2.2. Antidepressant Treatment History Form
4.2.3. Inclusion Criteria
4.2.4. Exclusion Criteria
4.3. Study Design
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
TRD | Treatment-resistant depression |
MDD | Major depressive disorder |
SSRIs | Selective serotonin reuptake inhibitors |
SNRIs | Serotonin–norepinephrine reuptake inhibitors |
MAOIs | Monoamine oxidase inhibitors |
TCAs | Tricyclic antidepressants |
IV | Intravenous |
IM | Intramuscular |
NMDA | N-methyl-D-aspartate |
AMPA | α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid |
BDNF | Brain-derived neurotrophic factor |
mTOR | Rapamycin |
CBT | Cognitive Behavioral Therapy |
HPA | Hypothalamic–pituitary–adrenal |
IL-6 | Interleukin-6 (IL-6) |
TNF-α | Tumor necrosis factor-alpha |
PTSD | Post-traumatic stress disorder |
KAP | Ketamine-assisted psychotherapy |
KIC | Ketamine-induced cystitis |
GAG | Glycosaminoglycan |
ANCOVA | Analysis of covariance |
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Parameter | Details |
---|---|
Administration Routes | |
Dosage Ranges | |
Treatment Protocols |
|
Targeted Clinical Conditions |
|
(a) | |
Diagnosis pre-treatment | Frequency (Percentage) |
Mild depression | 3/9 (33%) |
Moderate depression | 5/9 (55%) |
Severe depression | 1/9 (11%) |
Diagnosis post-treatment | Frequency (Percentage) |
Clinically ‘normal’ | 5/9 (55%) |
Mild depression | 4/9 (44%) |
Moderate depression | 0/9 (0%) |
Severe depression | 0/9 (0%) |
(b) | |
Diagnosis pre-treatment | Frequency (Percentage) |
Mild depression | 0/5 (0%) |
Moderate depression | 0/5 (0%) |
Severe depression | 5/5 (100%) |
Diagnosis post-treatment | Frequency (Percentage) |
Clinically ‘normal’ | 0/5 (0%) |
Mild depression | 0/5 (0%) |
Moderate depression | 3/5 (60%) |
Severe depression | 2/5 (40%) |
(c) | |
Diagnosis pre-treatment | Frequency (Percentage) |
Mild depression | 2/6 (33%) |
Moderate depression | 2/6 (33%) |
Severe depression | 2/6 (33%) |
Diagnosis post-treatment | Frequency (Percentage) |
Clinically ‘normal’ | 2/6 (33%) |
Mild depression | 1/6 (16%) |
Moderate depression | 2/6 (33%) |
Severe depression | 1/6 (16%) |
(d) | |
Diagnosis pre-treatment | Frequency (Percentage) |
Mild depression | 0/4 (0%) |
Moderate depression | 2/4 (50%) |
Severe depression | 2/4 (50%) |
Diagnosis post-treatment | Frequency (Percentage) |
Clinically ‘normal’ | 0/4 (0%) |
Mild depression | 2/4 (50%) |
Moderate depression | 0/4 (0%) |
Severe depression | 2/4 (50%) |
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Sakopoulos, S.; Todman, M. The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment. Int. J. Mol. Sci. 2025, 26, 6673. https://doi.org/10.3390/ijms26146673
Sakopoulos S, Todman M. The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment. International Journal of Molecular Sciences. 2025; 26(14):6673. https://doi.org/10.3390/ijms26146673
Chicago/Turabian StyleSakopoulos, Sofia, and McWelling Todman. 2025. "The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment" International Journal of Molecular Sciences 26, no. 14: 6673. https://doi.org/10.3390/ijms26146673
APA StyleSakopoulos, S., & Todman, M. (2025). The Effects of Psychotherapy on Single and Repeated Ketamine Infusion(s) Therapy for Treatment-Resistant Depression: The Convergence of Molecular and Psychological Treatment. International Journal of Molecular Sciences, 26(14), 6673. https://doi.org/10.3390/ijms26146673