Academische Commu-
nicatie B-B2AS17
1
1
2 Mini Review
3 Exploring Ketamine’s Potential in Major
4 Depressive Disorder: Short-Term Effects and Long-
5 Term Sustainability
6
7 1 Universiteit Utrecht, bachelor biologie; 1260529 ;
8
9 Abstract: Major Depressive Disorder (MDD) is a common mental health condition
10 that affects millions of people worldwide, with treatment-resistant depression (TRD)
11 being a significant clinical challenge. Traditional antidepressants, such as selective
12 serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake in-
13 hibitors (SNRIs), often require weeks to be effective or fail to provide symptom relief.
14 Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has
15 appeared to be a promising alternative due to its rapid antidepressant effects. By en-
16 hancing glutamatergic neurotransmission and synaptic plasticity, ketamine provides
17 symptom relief within hours, even in individuals suffering from TRD. This review dis -
18 cusses ketamine’s mechanism of action, highlighting its short-term effects on gluta-
19 matergic modulation and its ability to reverse synaptic deficits. Additionally, the long-
20 term effects of ketamine on neuroplasticity, brain structure and cognitive function are
21 discussed. While increasing evidence suggests that ketamine induces persistent neu-
22 robiological changes, caution remains over the sustainability of its antidepressant ef-
23 fects and potential risks, such as cognitive impairments
24 Citation: Lastname, F.; and neurotoxicity. Future research should focus on opti-
Lastname, F.; Lastname, F.
25 Title. Biology 2024, 11, x.
mizing ketamine’s clinical potential by determining the
26 https://doi.org/10.3390/xxxxx most effective dosing strategies and minimizing adverse
27 Academic Editor: Firstname effects. Finding the balance between ketamine’s thera-
28 Lastname peutic potential and its risks is crucial for establishing it
29 Received: date as a sustainable long-term treatment for MDD.
Accepted: date
Published: date
30 Keywords: Ketamine; Major Depressive Disorder; Treatment Resistant Depression;
31 Publisher’s Note: MDPI stays NMDA Receptor Antagonist; Synaptic Plasticity; Neurogenesis
32 neutral with regard to
jurisdictional claims in
published maps and
33 institutional affiliations. 1. Introduction
34 Major Depressive Disorder (MDD), also known as depres-
35 sion, affects an estimated 3.8% of the global population
Copyright: © 2022 by the au-
36 thors. Submitted for possible
(WHO, 2023). A major challenge in treating MDD is the
37 open access publication under increasing frequency of treatment resistant depression
the terms and conditions of the
38 (TRD), which affects at least 30% of MDD patients (McIn-
Creative Commons Attribution
(CC BY) license (https://cre-
ativecommons.org/licenses/by/
2
4.0/).
3 Biology 2024, 11, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/biology
nicatie B-B2AS17
1
1
2 Mini Review
3 Exploring Ketamine’s Potential in Major
4 Depressive Disorder: Short-Term Effects and Long-
5 Term Sustainability
6
7 1 Universiteit Utrecht, bachelor biologie; 1260529 ;
8
9 Abstract: Major Depressive Disorder (MDD) is a common mental health condition
10 that affects millions of people worldwide, with treatment-resistant depression (TRD)
11 being a significant clinical challenge. Traditional antidepressants, such as selective
12 serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake in-
13 hibitors (SNRIs), often require weeks to be effective or fail to provide symptom relief.
14 Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has
15 appeared to be a promising alternative due to its rapid antidepressant effects. By en-
16 hancing glutamatergic neurotransmission and synaptic plasticity, ketamine provides
17 symptom relief within hours, even in individuals suffering from TRD. This review dis -
18 cusses ketamine’s mechanism of action, highlighting its short-term effects on gluta-
19 matergic modulation and its ability to reverse synaptic deficits. Additionally, the long-
20 term effects of ketamine on neuroplasticity, brain structure and cognitive function are
21 discussed. While increasing evidence suggests that ketamine induces persistent neu-
22 robiological changes, caution remains over the sustainability of its antidepressant ef-
23 fects and potential risks, such as cognitive impairments
24 Citation: Lastname, F.; and neurotoxicity. Future research should focus on opti-
Lastname, F.; Lastname, F.
25 Title. Biology 2024, 11, x.
mizing ketamine’s clinical potential by determining the
26 https://doi.org/10.3390/xxxxx most effective dosing strategies and minimizing adverse
27 Academic Editor: Firstname effects. Finding the balance between ketamine’s thera-
28 Lastname peutic potential and its risks is crucial for establishing it
29 Received: date as a sustainable long-term treatment for MDD.
Accepted: date
Published: date
30 Keywords: Ketamine; Major Depressive Disorder; Treatment Resistant Depression;
31 Publisher’s Note: MDPI stays NMDA Receptor Antagonist; Synaptic Plasticity; Neurogenesis
32 neutral with regard to
jurisdictional claims in
published maps and
33 institutional affiliations. 1. Introduction
34 Major Depressive Disorder (MDD), also known as depres-
35 sion, affects an estimated 3.8% of the global population
Copyright: © 2022 by the au-
36 thors. Submitted for possible
(WHO, 2023). A major challenge in treating MDD is the
37 open access publication under increasing frequency of treatment resistant depression
the terms and conditions of the
38 (TRD), which affects at least 30% of MDD patients (McIn-
Creative Commons Attribution
(CC BY) license (https://cre-
ativecommons.org/licenses/by/
2
4.0/).
3 Biology 2024, 11, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/biology
