Peripartum Depression Pharmacotherapies Targeting GABA–Glutamate Neurotransmission
Abstract
1. Introduction
1.1. Epidemiology
1.2. Detection, Screening, and Risk Factors
1.3. Clinical and Biological Correlation with MDD
2. Discussion
Glutamate and GABA Abnormalities in Depression
3. GABAergic Pharmacotherapies (Table 1)
3.1. Brexanolone
3.2. Zuranolone
3.3. Ganaxolone
Drug | Mechanism of Action | Study | Design | Phase | n | Key Findings | Side Effects |
---|---|---|---|---|---|---|---|
BREXANOLONE | GABA-A neuroactive steroid/neurosteroid-positive allosteric modulator (allopregnanolone analog) | Kanes et al., 2017 [45] | RDBPCT—parallel group | II | 10 | Mean total HAMD score changes from baseline to hour 60 and our 84. Total HAMD scores for all patients were ≤7 at all assessments points from hour 24 onward. | Sedation, acute loss of consciousness, flushed skin/face, dry mouth, and vertigo |
Meltzer-Brody et al., 2018 [46] (NCT02942004) | RDBPCT—3-arm | III | 45 | Reduction in total HAMD score from baseline after 60 h in both groups (60 mg and 90 mg) when compared with the placebo group | |||
Meltzer-Brody et al., 2018 [46] (NCT02942017) | RDBPCT—2-arm | III | 54 | Reduction in total HAMD score from baseline after 60 h in both groups (60 mg and 90 mg) when compared with the placebo group | |||
Epperson et al., 2023 [47] | Post hoc analysis of 3 RCTs mentioned above | Pooled analysis | 102 | HAMD-17 score reduction at hour 60 in patients receiving 90 mg compared with placebo | |||
ZURANOLONE | GABA-A neuroactive steroid/neurosteroid Positive allosteric modulator (allopregnanolone analog) | Deligiannidis et al., 2023 [53] | RDBPCT | III | 196 | Statistically significant improvement in depressive symptoms using the HAMD score at day 15 and significant improvement in depressive symptoms reported on days 3, 28, and 45 | Headache, dizziness, nausea, and somnolence |
Clayton et al., 2024 [56] | Integrated data from four RDBPCTs | Pooled analysis | 1003 | Significant changes from baseline for 6 domains of HAMD on day 15 and changes from baseline for all 8 domains of the HAMD on day 42 | |||
GANAXOLONE | GABA-A neuroactive steroid/neurosteroid-positive allosteric modulator (allopregnanolone analog) | Gutierrez-Esteinou et al., 2019 [57] | RDBPCT—3 doses | II | 58 | Reductions in HAMD scores from baseline at 48 hrs, 60 hrs, and day 34 of administration | Sedation and dizziness |
Dichtel et al., 2020 [58] | Pilot OL—adjunctive, uncontrolled | II | 10 | Total MADRS score decreased by 8 weeks, and the decrease persisted over the 2-week taper |
4. Glutamatergic Pharmacotherapies (Table 2)
Ketamine and Esketamine
Drug | Mechanism of Action | Studies | Design | Phase | n | Key Findings | Side Effects |
---|---|---|---|---|---|---|---|
KETAMINE | NMDAR antagonism; AMPAR stimulation | M. Alipoor, M. Loripoor, M. Kazemi, F. Farahbakhsh, and A. Sarkoohi, 2021 [66] | RDBPCT, 2-arm | III | 134 | Mean EPDS score was significantly lower four weeks after the caesarian section in the ketamine group compared to placebo group. | Vomiting, headache, dizziness, hallucinations, nystagmus |
J. Yao, T. Song, Y. Zhang, N. Guo, and P. Zhao, 2020 [67] | RDBPCT, 2-arm | III | 330 | Significant differences were observed in the EPDS score between subjects in the ketamine group and the placebo group at 1 week postpartum. No difference was found between subjects in the two groups at 2 weeks and 1 month postpartum. | |||
Ma et al., 2019 [68] | RDBPCT, 2-arm | III | 654 | PPD prevalence in the ketamine group was significantly lower than in the control group. The EPDS score at postpartum day 4 was significantly lower in the ketamine group compared with the control group, and the prevalence of postpartum blues was significantly lower in the ketamine group than in the control group. | |||
ESKETAMINE | NMDAR antagonism; AMPAR stimulation | W. Wang, H. Xu, B. Ling, Q. Chen, J. Lv, and W. Yu, 2022 [59] | RDBPCT, 4-arm | III | 160 | A lower incidence of PPD was observed at 1 week and 6 weeks in the esketamine + sufentanil group. | Nausea, vomiting, dizziness, hallucinations, somnolence, nightmares, nystagmus and postpartum hemorrhage |
W. Wang, B. Ling, Q. Chen, H. Xu, J. Lv, and W. Yu, 2023 [60] | RDBPCT, 2-arm | III | 120 | The incidence of PPD was significantly lower at 1 week and 6 weeks after cesarean surgery in the esketamine group. | |||
Y. Han, P. Li, M. Miao, Y. Tao, X. Kang, and J. Zhang, 2022 [61] | RDBPCT, 2-arm | III | 275 | The rate of depression in the parturient period on postoperative days 3, 14, 28 was significantly lower in the esketamine group. EPDS scores in the esketamine group were also significantly lower on postoperative days 3,14, and 28. | |||
Yang et al., 2023 [62] | RDBPCT, 3-arm | III | 312 | The results showed that the incidence of depression symptoms at 42 days postpartum was 27.8% for the placebo group, 14.1% for the esketamine group (1 mg/kg), and 9.1% for the esketamine group (2 mg/kg). The incidence of depression symptoms at 7 days postpartum was 29.9% in the placebo group, 11.1% for the esketamine group (1 mg/kg) and 7.1% for the esketamine group (2 mg/kg). | |||
Wang et al., 2024 [63] | RDBPCT, 2-arm | III | 364 | EDPS scores were lower in the esketamine group at day 7. HAMD-17 scores at 42 days postpartum were also lower in the esketamine group. | |||
Chen et al., 2024 [64] | RDBPCT, 2-arm | III | 298 | The prevalence of depression symptoms and EPDS scores were significantly lower among patients given esketamine compared with controls on postpartum day 7 but without differences between the groups at postpartum days 14, 28, and 42. | |||
Liu et al., 2023 [65] | RDBPCT, 2-arm | III | 150 | There were no significant differences in the prevalence of PPD risk and no significant differences in EPDS scores between the two groups at 3 days, 42 days, 3 months, and 6 months postpartum. |
5. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
RDBPCT | Randomized, Double-Blinded, Placebo-Controlled Trial |
EPDS | Edinburgh Postnatal Depression Scale |
PPD | Peripartum Depression |
MDD | Major Depressive Disorder |
NMDAR | NMDA Receptor |
AMPAR | AMPA Receptor |
OL | Open Label |
MADRS | Montgomery–Åsberg Depression Rating Scale |
HAMD | Hamilton Depression Rating Scale |
RCT | Randomized Clinical Trial |
References
- Cimino, S. Epidemiology, Etiology and Intervention Strategies for Peri-Partum Depression in Mothers. J. Clin. Med. 2023, 12, 5822. [Google Scholar] [CrossRef]
- Fox, M.; Sandman, C.A.; Davis, E.P.; Glynn, L.M. A longitudinal study of women’s depression symptom profiles during and after the postpartum phase. Depress. Anxiety 2018, 35, 292–304. [Google Scholar] [CrossRef]
- Putnam, K.T.; Wilcox, M.; Robertson-Blackmore, E.; Sharkey, K.; Bergink, V.; Munk-Olsen, T.; Deligiannidis, K.M.; Payne, J.; Altemus, M.; Newport, J.; et al. Clinical phenotypes of perinatal depression and time of symptom onset: Analysis of data from an international consortium. Lancet Psychiatry 2017, 4, 477–485. [Google Scholar] [CrossRef]
- Shorey, S.; Chee, C.Y.I.; Ng, E.D.; Chan, Y.H.; Tam, W.W.S.; Chong, Y.S. Prevalence and incidence of postpartum depression among healthy mothers: A systematic review and meta-analysis. J. Psychiatr. Res. 2018, 104, 235–248. [Google Scholar] [CrossRef]
- Lindahl, V.; Pearson, J.L.; Colpe, L. Prevalence of suicidality during pregnancy and the postpartum. Arch. Women’s Ment. Health 2005, 8, 77–87. [Google Scholar] [CrossRef] [PubMed]
- Justesen, K.; Jourdaine, D. Peripartum Depression: Detection and Treatment. Am. Fam. Physician 2023, 108, 267–272. [Google Scholar]
- Langan, R.; Goodbred, A.J. Identification and Management of Peripartum Depression. Am. Fam. Physician 2016, 93, 852–858. [Google Scholar] [PubMed]
- Stefana, A.; Mirabella, F.; Gigantesco, A.; Camoni, L.; for the Perinatal Mental Health Nework; Aceti, F.; Adulti, I.; Aite, L.; Bagolan, P.; Barbano, G.; et al. The screening accuracy of the Edinburgh Postnatal Depression Scale (EPDS) to detect perinatal depression with and without the self-harm item in pregnant and postpartum women. J. Psychosom. Obstet. Gynecol. 2024, 45, 2404967. [Google Scholar] [CrossRef] [PubMed]
- Kendall-Tackett, K.A. Screening for Perinatal Depression: Barriers, Guidelines, and Measurement Scales. J. Clin. Med. 2024, 13, 6511. [Google Scholar] [CrossRef]
- Smith-Nielsen, J.; Egmose, I.; Matthey, S.; Stougård, M.; Reijman, S.; Væver, M.S. Proposing a two-stage screening approach to distinguish between transient and enduring postnatal depressive symptoms: A prospective cohort study. Int. J. Nurs. Stud. Adv. 2025, 8, 100284. [Google Scholar] [CrossRef] [PubMed]
- Agrawal, I.; Mehendale, A.M.; Malhotra, R. Risk Factors of Postpartum Depression. Cureus 2022, 14, e30898. [Google Scholar] [CrossRef]
- Klainin, P.; Arthur, D.G. Postpartum depression in Asian cultures: A literature review. Int. J. Nurs. Stud. 2009, 46, 1355–1373. [Google Scholar] [CrossRef]
- Yang, K.; Wu, J.; Chen, X. Risk factors of perinatal depression in women: A systematic review and meta-analysis. BMC Psychiatry 2022, 22, 63. [Google Scholar] [CrossRef] [PubMed]
- Gastaldon, C.; Solmi, M.; Correll, C.U.; Barbui, C.; Schoretsanitis, G. Risk factors of postpartum depression and depressive symptoms: Umbrella review of current evidence from systematic reviews and meta-analyses of observational studies. Br. J. Psychiatry 2022, 221, 591–602. [Google Scholar] [CrossRef] [PubMed]
- Wisner, K.L.; Moses-Kolko, E.L.; Sit, D.K.Y. Postpartum depression: A disorder in search of a definition. Arch. Women’s Ment. Health 2010, 13, 37–40. [Google Scholar] [CrossRef]
- Batt, M.M.; Duffy, K.A.; Novick, A.M.; Metcalf, C.A.; Epperson, C.N. Is Postpartum Depression Different From Depression Occurring Outside of the Perinatal Period? A Review of the Evidence. Focus 2020, 18, 106–119. [Google Scholar] [CrossRef] [PubMed]
- Guintivano, J.; Manuck, T.; Meltzer-Brody, S. Predictors of Postpartum Depression: A Comprehensive Review of the Last Decade of Evidence. Clin. Obstet. Gynecol. 2018, 61, 591–603. [Google Scholar] [CrossRef]
- The APrON Team; Leung, B.M.Y.; Letourneau, N.L.; Giesbrecht, G.F.; Ntanda, H.; Hart, M. Predictors of Postpartum Depression in Partnered Mothers and Fathers from a Longitudinal Cohort. Community Ment. Health J. 2017, 53, 420–431. [Google Scholar] [CrossRef]
- Silverman, M.E.; Reichenberg, A.; Savitz, D.A.; Cnattingius, S.; Lichtenstein, P.; Hultman, C.M.; Larsson, H.; Sandin, S. The risk factors for postpartum depression: A population-based study. Depress. Anxiety 2017, 34, 178–187. [Google Scholar] [CrossRef]
- Silverman, M.E.; Reichenberg, A.; Lichtenstein, P.; Sandin, S. Is depression more likely following childbirth? A population-based study. Arch. Women’s Ment. Health 2019, 22, 253–258. [Google Scholar] [CrossRef]
- Buttner, M.M.; Mott, S.L.; Pearlstein, T.; Stuart, S.; Zlotnick, C.; O’Hara, M.W. Examination of premenstrual symptoms as a risk factor for depression in postpartum women. Arch. Women’s Ment. Health 2013, 16, 219–225. [Google Scholar] [CrossRef]
- Studd, J.; Nappi, R.E. Reproductive depression. Gynecol. Endocrinol. 2012, 28, 42–45. [Google Scholar] [CrossRef] [PubMed]
- Woody, C.A.; Ferrari, A.J.; Siskind, D.J.; Whiteford, H.A.; Harris, M.G. A systematic review and meta-regression of the prevalence and incidence of perinatal depression. J. Affect. Disord. 2017, 219, 86–92. [Google Scholar] [CrossRef]
- Harrington, Y.A.; Fortaner-Uyà, L.; Paolini, M.; Poletti, S.; Lorenzi, C.; Spadini, S.; Melloni, E.M.T.; Agnoletto, E.; Zanardi, R.; Colombo, C.; et al. Disentangling the Genetic Landscape of Peripartum Depression: A Multi-Polygenic Machine Learning Approach on an Italian Sample. Genes 2024, 15, 1517. [Google Scholar] [CrossRef]
- Cheng, B.; Guo, Y.; Chen, X.; Lv, B.; Liao, Y.; Qu, H.; Hu, X.; Yang, H.; Meng, Y.; Deng, W.; et al. Postpartum depression and major depressive disorder: The same or not? Evidence from resting-state functional MRI. Psychoradiology 2022, 2, 121–128. [Google Scholar] [CrossRef]
- Bhatt, S.; Devadoss, T.; Manjula, S.N.; Rajangam, J. 5-HT3 Receptor Antagonism: A Potential Therapeutic Approach for the Treatment of Depression and other Disorders. Curr. Neuropharmacol. 2021, 19, 1545–1559. [Google Scholar] [CrossRef]
- Cipriani, A.; Furukawa, T.A.; Salanti, G.; Chaimani, A.; Atkinson, L.Z.; Ogawa, Y.; Leucht, S.; Ruhe, H.G.; Turner, E.H.; Higgins, J.P.T.; et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet 2018, 391, 1357–1366. [Google Scholar] [CrossRef]
- Racagni, G.; Popoli, M. Cellular and molecular mechanisms in the long-term action of antidepressants. Dialogues Clin. Neurosci. 2008, 10, 385–400. [Google Scholar] [CrossRef] [PubMed]
- Al-Harbi, K.S. Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Prefer. Adherence 2012, 6, 369–388. [Google Scholar] [CrossRef]
- Jiang, Y.; Zou, D.; Li, Y.; Gu, S.; Dong, J.; Ma, X.; Xu, S.; Wang, F.; Huang, J.H. Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders. Pharmaceuticals 2022, 15, 1203. [Google Scholar] [CrossRef] [PubMed]
- Sanacora, G.; Treccani, G.; Popoli, M. Towards a glutamate hypothesis of depression. Neuropharmacology 2012, 62, 63–77. [Google Scholar] [CrossRef]
- Albrecht, J. Glutamine in the central nervous system: Function and dysfunction. Front. Biosci. 2007, 12, 332. [Google Scholar] [CrossRef] [PubMed]
- Lüscher, B.; Möhler, H. Brexanolone, a neurosteroid antidepressant, vindicates the GABAergic deficit hypothesis of depression and may foster resilience. F1000Research 2019, 8, 751. [Google Scholar] [CrossRef] [PubMed]
- Luscher, B.; Shen, Q.; Sahir, N. The GABAergic deficit hypothesis of major depressive disorder. Mol. Psychiatry 2011, 16, 383–406. [Google Scholar] [CrossRef] [PubMed]
- MacQueen, G.; Frodl, T. The hippocampus in major depression: Evidence for the convergence of the bench and bedside in psychiatric research? Mol. Psychiatry 2011, 16, 252–264. [Google Scholar] [CrossRef]
- Lener, M.S.; Niciu, M.J.; Ballard, E.D.; Park, M.; Park, L.T.; Nugent, A.C.; Zarate, C.A. Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine. Biol. Psychiatry 2017, 81, 886–897. [Google Scholar] [CrossRef]
- Arnone, D.; Mumuni, A.N.; Jauhar, S.; Condon, B.; Cavanagh, J. Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: Meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur. Neuropsychopharmacol. 2015, 25, 1109–1117. [Google Scholar] [CrossRef]
- Bhagwagar, Z.; Wylezinska, M.; Jezzard, P.; Evans, J.; Boorman, E.; Matthews, P.M.; Cowen, P.J. Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. Int. J. Neuropsychopharmacol. 2008, 11, 255–260. [Google Scholar] [CrossRef]
- Luscher, B.; Fuchs, T. GABAergic Control of Depression-Related Brain States. In Advances in Pharmacology; Elsevier: Amsterdam, The Netherlands, 2015; Volume 73, pp. 97–144. ISBN 978-0-12-802658-8. [Google Scholar]
- Koolschijn, P.C.M.P.; Van Haren, N.E.M.; Lensvelt-Mulders, G.J.L.M.; Hulshoff Pol, H.E.; Kahn, R.S. Brain volume abnormalities in major depressive disorder: A meta-analysis of magnetic resonance imaging studies. Hum. Brain Mapp. 2009, 30, 3719–3735. [Google Scholar] [CrossRef]
- Cutler, A.J.; Mattingly, G.W.; Maletic, V. Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder. Transl. Psychiatry 2023, 13, 228. [Google Scholar] [CrossRef]
- Licheri, V.; Talani, G.; Gorule, A.A.; Mostallino, M.C.; Biggio, G.; Sanna, E. Plasticity of GABAA Receptors during Pregnancy and Postpartum Period: From Gene to Function. Neural Plast. 2015, 2015, 170435. [Google Scholar] [CrossRef]
- Deligiannidis, K.M.; Kroll-Desrosiers, A.R.; Mo, S.; Nguyen, H.P.; Svenson, A.; Jaitly, N.; Hall, J.E.; Barton, B.A.; Rothschild, A.J.; Shaffer, S.A. Peripartum neuroactive steroid and γ-aminobutyric acid profiles in women at-risk for postpartum depression. Psychoneuroendocrinology 2016, 70, 98–107. [Google Scholar] [CrossRef]
- Payne, J.L.; Maguire, J. Pathophysiological mechanisms implicated in postpartum depression. Front. Neuroendocrinol. 2019, 52, 165–180. [Google Scholar] [CrossRef]
- Kanes, S.J.; Colquhoun, H.; Doherty, J.; Raines, S.; Hoffmann, E.; Rubinow, D.R.; Meltzer-Brody, S. Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression. Hum. Psychopharmacol. Clin. Exp. 2017, 32, e2576. [Google Scholar] [CrossRef] [PubMed]
- Meltzer-Brody, S.; Colquhoun, H.; Riesenberg, R.; Epperson, C.N.; Deligiannidis, K.M.; Rubinow, D.R.; Li, H.; Sankoh, A.J.; Clemson, C.; Schacterle, A.; et al. Brexanolone injection in post-partum depression: Two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet 2018, 392, 1058–1070. [Google Scholar] [CrossRef] [PubMed]
- Epperson, C.N.; Rubinow, D.R.; Meltzer-Brody, S.; Deligiannidis, K.M.; Riesenberg, R.; Krystal, A.D.; Bankole, K.; Huang, M.-Y.; Li, H.; Brown, C.; et al. Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J. Affect. Disord. 2023, 320, 353–359. [Google Scholar] [CrossRef] [PubMed]
- Hutcherson, T.C.; Cieri-Hutcherson, N.E.; Gosciak, M.F. Brexanolone for postpartum depression. Am. J. Health Syst. Pharm. 2020, 77, 336–345. [Google Scholar] [CrossRef]
- Gunduz-Bruce, H.; Silber, C.; Kaul, I.; Rothschild, A.J.; Riesenberg, R.; Sankoh, A.J.; Li, H.; Lasser, R.; Zorumski, C.F.; Rubinow, D.R.; et al. Trial of SAGE-217 in Patients with Major Depressive Disorder. N. Engl. J. Med. 2019, 381, 903–911. [Google Scholar] [CrossRef]
- Kato, M.; Nakagome, K.; Baba, T.; Sonoyama, T.; Okutsu, D.; Yamanaka, H.; Shimizu, R.; Motomiya, T.; Inoue, T. Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double-blind, randomized, placebo-controlled, phase 2 clinical trial. Psychiatry Clin. Neurosci. 2023, 77, 497–509. [Google Scholar] [CrossRef]
- Clayton, A.H.; Lasser, R.; Nandy, I.; Sankoh, A.J.; Jonas, J.; Kanes, S.J. Zuranolone in Major Depressive Disorder: Results From MOUNTAIN—A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial. J. Clin. Psychiatry 2023, 84, 45750. [Google Scholar] [CrossRef]
- Clayton, A.H.; Lasser, R.; Parikh, S.V.; Iosifescu, D.V.; Jung, J.; Kotecha, M.; Forrestal, F.; Jonas, J.; Kanes, S.J.; Doherty, J. Zuranolone for the Treatment of Adults With Major Depressive Disorder: A Randomized, Placebo-Controlled Phase 3 Trial. Am. J. Psychiatry 2023, 180, 676–684. [Google Scholar] [CrossRef] [PubMed]
- Deligiannidis, K.M.; Meltzer-Brody, S.; Maximos, B.; Peeper, E.Q.; Freeman, M.; Lasser, R.; Bullock, A.; Kotecha, M.; Li, S.; Forrestal, F.; et al. Zuranolone for the Treatment of Postpartum Depression. Am. J. Psychiatry 2023, 180, 668–675. [Google Scholar] [CrossRef] [PubMed]
- Cutler, A.J.; Mattingly, G.W.; Kornstein, S.G.; Aaronson, S.T.; Lasser, R.; Zhang, H.; Rana, N.; Brown, C.; Levin, S.; Miller, C.; et al. Long-Term Safety and Efficacy of Initial and Repeat Treatment Courses With Zuranolone in Adult Patients With Major Depressive Disorder: Interim Results From the Open-Label, Phase 3 SHORELINE Study. J. Clin. Psychiatry 2023, 85, 50879. [Google Scholar] [CrossRef] [PubMed]
- Parikh, S.V.; Aaronson, S.T.; Mathew, S.J.; Alva, G.; DeBattista, C.; Kanes, S.; Lasser, R.; Bullock, A.; Kotecha, M.; Jung, J.; et al. Efficacy and safety of zuranolone co-initiated with an antidepressant in adults with major depressive disorder: Results from the phase 3 CORAL study. Neuropsychopharmacology 2024, 49, 467–475. [Google Scholar] [CrossRef] [PubMed]
- Clayton, A.H.; Suthoff, E.; Jain, R.; Kosinski, M.; Fridman, M.; Deligiannidis, K.M.; Meltzer-Brody, S.; Chen, S.-Y.; Gervitz, L.; Huang, M.-Y.; et al. The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials. J. Affect. Disord. 2024, 351, 904–914. [Google Scholar] [CrossRef]
- Gutierrez-Esteinou, R.; Maximos, B.; Riesenberg, R.; Johnson, K.A.; Aimetti, A.; Lappalainen, J.; Masuoka, L. T136. Safety and Efficacy of Intravenous Ganaxolone in Severe Postpartum Depression: Results From a Double-Blind, Placebo-Controlled Phase 2 Study. Biol. Psychiatry 2019, 85, S181–S182. [Google Scholar] [CrossRef]
- Dichtel, L.E.; Nyer, M.; Dording, C.; Fisher, L.B.; Cusin, C.; Shapero, B.G.; Pedrelli, P.; Kimball, A.S.; Rao, E.M.; Mischoulon, D.; et al. Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women: A Pilot Study. J. Clin. Psychiatry 2020, 81, 7602. [Google Scholar] [CrossRef]
- Wang, W.; Xu, H.; Ling, B.; Chen, Q.; Lv, J.; Yu, W. Effects of esketamine on analgesia and postpartum depression after cesarean section: A randomized, double-blinded controlled trial. Medicine 2022, 101, e32010. [Google Scholar] [CrossRef]
- Wang, W.; Ling, B.; Chen, Q.; Xu, H.; Lv, J.; Yu, W. Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial. Medicine 2023, 102, e33086. [Google Scholar] [CrossRef]
- Han, Y.; Li, P.; Miao, M.; Tao, Y.; Kang, X.; Zhang, J. S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: A randomized controlled trial. BMC Anesthesiol. 2022, 22, 49. [Google Scholar] [CrossRef]
- Yang, S.Q.; Zhou, Y.Y.; Yang, S.T.; Mao, X.Y.; Chen, L.; Bai, Z.H.; Ping, A.Q.; Xu, S.Y.; Li, Q.W.; Gao, K.; et al. Effects of different doses of esketamine intervention on postpartum depressive symptoms in cesarean section women: A randomized, double-blind, controlled clinical study. J. Affect. Disord. 2023, 339, 333–341. [Google Scholar] [CrossRef]
- Wang, S.; Deng, C.-M.; Zeng, Y.; Chen, X.-Z.; Li, A.-Y.; Feng, S.-W.; Xu, L.-L.; Chen, L.; Yuan, H.-M.; Hu, H.; et al. Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: Randomised clinical trial. BMJ 2024, 385, e078218. [Google Scholar] [CrossRef]
- Chen, Y.; Guo, Y.; Wu, H.; Tang, Y.-J.; Sooranna, S.R.; Zhang, L.; Chen, T.; Xie, X.-Y.; Qiu, L.-C.; Wu, X.-D. Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery: A Randomized Clinical Trial. JAMA Netw. Open 2024, 7, e240953. [Google Scholar] [CrossRef]
- Liu, Q.-R.; Zong, Q.-K.; Ding, L.-L.; Dai, H.-Y.; Sun, Y.; Dong, Y.-Y.; Ren, Z.-Y.; Hashimoto, K.; Yang, J.-J. Effects of perioperative use of esketamine on postpartum depression risk in patients undergoing cesarean section: A randomized controlled trial. J. Affect. Disord. 2023, 339, 815–822. [Google Scholar] [CrossRef] [PubMed]
- Alipoor, M.; Loripoor, M.; Kazemi, M.; Farahbakhsh, F.; Sarkoohi, A. The effect of ketamine on preventing postpartum depression. J. Med. Life 2021, 14, 87–92. [Google Scholar] [CrossRef] [PubMed]
- Yao, J.; Song, T.; Zhang, Y.; Guo, N.; Zhao, P. Intraoperative ketamine for reduction in postpartum depressive symptoms after cesarean delivery: A double-blind, randomized clinical trial. Brain Behav. 2020, 10, e01715. [Google Scholar] [CrossRef] [PubMed]
- Ma, J.-H.; Wang, S.-Y.; Yu, H.-Y.; Li, D.-Y.; Luo, S.-C.; Zheng, S.-S.; Wan, L.-F.; Duan, K.-M. Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section✰. Psychiatry Res. 2019, 279, 252–258. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Courtes, A.C.; Smitherman, L.; Shahani, L.; Soares, J.C.; Goetzl, L.; Machado-Vieira, R. Peripartum Depression Pharmacotherapies Targeting GABA–Glutamate Neurotransmission. J. Clin. Med. 2025, 14, 6177. https://doi.org/10.3390/jcm14176177
Courtes AC, Smitherman L, Shahani L, Soares JC, Goetzl L, Machado-Vieira R. Peripartum Depression Pharmacotherapies Targeting GABA–Glutamate Neurotransmission. Journal of Clinical Medicine. 2025; 14(17):6177. https://doi.org/10.3390/jcm14176177
Chicago/Turabian StyleCourtes, Alan C., Louisa Smitherman, Lokesh Shahani, Jair C. Soares, Laura Goetzl, and Rodrigo Machado-Vieira. 2025. "Peripartum Depression Pharmacotherapies Targeting GABA–Glutamate Neurotransmission" Journal of Clinical Medicine 14, no. 17: 6177. https://doi.org/10.3390/jcm14176177
APA StyleCourtes, A. C., Smitherman, L., Shahani, L., Soares, J. C., Goetzl, L., & Machado-Vieira, R. (2025). Peripartum Depression Pharmacotherapies Targeting GABA–Glutamate Neurotransmission. Journal of Clinical Medicine, 14(17), 6177. https://doi.org/10.3390/jcm14176177