Abstract
Background:
The aim of this randomized, double-blind placebo-controlled clinical trial was to study the effects of subclinical doses of esketamine on postpartum depression and pain following elective cesarean sections.
Methods:
This randomized, double-blind placebo-controlled trial included 150 pregnant women undergoing elective cesarean sections. After umbilical cord clamping, participants received either subclinical doses of esketamine (0.25 mg/kg, diluted in 10 mL of 0.9% saline) or a placebo (10 mL of 0.9% saline). The primary outcome measures were the incidence of postpartum depression (PPD) and postoperative pain. The Edinburgh Postnatal Depression Scale was used to evaluate PPD on days 3, 7, and 14 postpartum, with an Edinburgh Postnatal Depression Scale score ≥ 10 indicating PPD. Postoperative pain was assessed using the Visual Analog Scale (VAS) at 4, 24, and 48 hours post-surgery. Secondary outcomes included adverse reactions and Ramsay sedation scores at 5 and 15 minutes post-administration.
Results:
There were no significant differences in the incidence of PPD between the 2 groups on days 3, 7, and 14 postpartum (P > .05). The VAS scores showed significant differences between the 2 groups at 4 and 24 hours postoperatively (P < .05), but not at 48 hours (P > .05). The experimental group had significantly higher adverse reactions and Ramsay sedation scores 5 minutes post-administration compared to the control group (P < .05), but no significant differences were observed upon leaving the operating room (P > .05).
Conclusion:
Subclinical doses of esketamine did not reduce the incidence of PPD at 14 days postpartum but did significantly lower VAS scores at 24 hours post-surgery. The experimental group experienced temporary increases in adverse reactions and Ramsay sedation scores shortly after administration.
Keywords: cesarean section, esketamine, pain, postpartum depression
1. Introduction
Postpartum depression (PPD) is a debilitating but treatable mental disorder characterized by the onset of depressive symptoms during or after pregnancy.[1] Clinical manifestations include depression, anxiety, irritability, fear, pessimism, excitement, and poor coping abilities; in severe cases, suicide may occur.[2] In economically developed countries, PPD prevalence ranges from 6.9% to 12.9%, while in less developed or impoverished countries, it may exceed 20%.[3] PPD peaks around 6 weeks postpartum, with most cases occurring within the first week and a few within 3 years postpartum.[4] The DSM-5 defines depression that occurs during pregnancy or up to 4 weeks after delivery as PPD.[5] The psychological state of PPD patients not only affects the mother’s physical and mental health but also severely impacts breastfeeding infants and family harmony. Currently, clinical treatments for PPD include psychotherapy and pharmacotherapy. However, long-term medication may adversely affect infants’ cognitive, behavioral, neurological, and emotional development through breastfeeding.[6] Thus, preventing PPD is crucial.
The exact mechanism of PPD remains unclear. Many factors contribute to its development, including prenatal stress, low socioeconomic status, genetic factors, and other psychological factors.[7] Additionally, postoperative pain has been reported to increase the risk of postoperative depression.[8] Therefore, preventing and reducing postoperative pain might be a strategy to prevent PPD after cesarean sections.
Esketamine has twice the affinity for the N-methyl-d-aspartate (NMDA) receptor as racemic ketamine. Recent studies have found that esketamine has significant antidepressant effects, particularly in treating treatment-resistant depression.[9] In 2019, the US Food and Drug Administration approved esketamine nasal spray for treatment-resistant depression.[10] Wang et al found that the administration of 0.2 mg/kg esketamine after delivery significantly reduced the incidence of PPD at 1 and 6 weeks postpartum.[11] Jiang et al found that the use of esketamine during cesarean section can reduce postoperative pain.[12] However, clinical reports on the effects of esketamine on PPD and pain after cesarean sections are scarce. This clinical study aims to investigate the effects of a single intravenous injection of subclinical doses of esketamine on PPD and pain after cesarean sections.
2. Materials and methods
2.1. Ethics and trial registration
This study follows the Consolidated Standards of Reporting guidelines.[13] It was approved by the Ethics Committee of the Affiliated Yongchuan Hospital of Chongqing Medical University (2023LLS038) and registered with the Chinese Clinical Trial Registry (ID: ChiCTR2400080884) on February 15, 2024. All participants provided written informed consent before enrollment.
2.2. Participants
This clinical trial was conducted from February 16, 2024, to April 30, 2024, at the Affiliated Yongchuan Hospital of Chongqing Medical University and the Yongchuan Maternity and Child Health Hospital. A total of 150 pregnant women with full-term singleton pregnancies undergoing elective cesarean sections were included. The inclusion criteria were: (1) full-term singleton pregnancy, age 18 to 40 years; (2) no history of depression before or during pregnancy; (3) body mass index ≤ 30 kg/m²; (4) willingness to cooperate and provide written consent; and (5) ASA classification I–II. The exclusion criteria included: (1) mothers with a history or symptoms of depression before delivery; (2) premature delivery; (3) pregnant women with severe obstetric diseases or significant organ diseases before delivery; (4) allergy to esketamine; (5) unwillingness to sign the consent form; (6) participation in other studies; and (7) multiple pregnancies.
2.3. Sample size
The sample size was calculated based on a previous meta-analysis that found the incidence of PPD in China to be between 10% and 22%.[14] We hypothesized that the incidence of PPD after esketamine intervention would be 5%. Using PASS15 software (NCSS LLC, Kaysville, UT) for 2 independent samples, with a 1:1 ratio between the trial and control groups, a power value of 0.8, and an α value of 0.05, a bilateral Z test was conducted. The result indicated that each group required 60 cases. Considering a 20% dropout rate, each group needed 75 cases, totaling 150.
2.4. Study design and concealment
Participants were randomly divided into the esketamine group (S group) and the control group (C group), with 75 cases in each group. A total of 150 sealed opaque envelopes containing patient group allocation were prepared by a statistician who was not involved in the study. Esketamine (Jiangsu Hengrui Medicine Co., Ltd., Jiangsu, China) was administered intravenously to the S group at a dose of 0.25 mg/kg 10 minutes after umbilical cord clamping. The control group received an equivalent volume of saline at the same time. Both observers and participants were blinded to group assignments.
2.5. Anesthesia management and intervention
Standard preoperative fasting and water restrictions were followed. No other medications were used preoperatively, and vital signs were routinely monitored. Combined spinal-epidural anesthesia was administered to all women between L3 and L4. A dose of 0.66% heavy ropivacaine (2 mL of 1% ropivacaine [Renfu Pharmaceutical Co., Ltd., Hubei, China] + 1 mL of 10% glucose injection [Taiji Pharmaceutical Co., Ltd., Hebei, China]), totaling 2.5 mL, was injected at a speed of 5 seconds/mL, and an epidural lumen tube was inserted 4 cm. Anesthesia levels were controlled between T4 and T6. Norepinephrine was administered intravenously if necessary. After the umbilical cord was clamped, esketamine or saline was administered by the chief anesthetist within 10 minutes. Postoperatively, preemptive analgesia was provided utilizing an ultrasound-guided transversus abdominis plane block. Simultaneously, a patient-controlled intravenous analgesia pump (PCIA) containing the following formula was connected: 1.0 µg/kg sufentanil injection (Renfu Pharmaceutical Co., Ltd., Hubei, China) + 4.0 mg/kg tramadol injection (Xinghua Pharmaceutical Co., Ltd., Hubei, China) + normal saline, totaling 100 mL (Kelun Pharmaceutical Co., Ltd., Sichuan, China). The loading dose was 5 mL, the background dose was 2 mL/h, the bolus dose was 1 mL, and the lockout time was 15 minutes.
Postoperative follow-up was performed by another anesthesiologist. During follow-up, the following measures were assessed: visual analog scale (VAS) scores during rest and movement at 4 hours (T1), 24 hours (T2), and 48 hours (T3) post-surgery; the effective compression times of PCIA at 48 hours post-surgery; the duration of adjuvant analgesic use; Edinburgh Postnatal Depression Scale (EPDS) scores at 3, 7, and 14 days post-surgery; and the occurrence of postoperative side effects.
2.6. Outcomes
All patients were followed up for 2 weeks, and those lost to follow-up were excluded from the study. The primary outcome measures were the incidence of PPD and postoperative pain. PPD was assessed using the EPDS, a questionnaire designed to screen for postpartum depression. It consists of 10 multiple-choice questions, each with 4 possible answers, scored from 0 to 3. The total score ranges from 0 to 30. Studies have reported that a score of 9/10 is the critical threshold for initial clinical screening of postpartum depression.[15] For Chinese patients, an EPDS score > 9 indicates PPD, with a sensitivity and specificity of 82% and 86%, respectively.[16] In this study, an EPDS score ≥ 10 was used as the threshold for assessing PPD. Postoperative pain was assessed using the VAS, which consists of a 10 cm horizontal line with 0 indicating no pain and 10 indicating severe pain. Secondary outcomes included analgesia-related adverse events (nystagmus, dizziness, tearing, drowsiness, hallucinations, nausea, headache, vomiting, and diplopia) and Ramsay sedation scores. The Ramsay Sedation Scale ranges from 1 to 6: 1 = anxious or irritable; 2 = cooperative and quiet with good orientation; 3 = responds to commands; 4 = drowsy and quick to respond to tapping between the eyebrows or loud auditory stimulation; 5 = drowsy and slow to respond to tapping between the eyebrows or loud auditory stimulation; and 6 = drowsy and unresponsive.
2.7. Statistical analysis
Data were analyzed using IBM SPSS software version 25.0 (SPSS Inc., Chicago, IL). Continuous variables are presented as mean ± SD or median (interquartile range), and categorical variables are presented as numbers (percentages). Normality assumptions for continuous variables were assessed using the Shapiro–Wilk test. Between-group differences were evaluated using independent samples t tests or the Mann–Whitney U test for continuous, normally distributed, or non-normally distributed variables, respectively. Categorical variables were compared between groups using the chi-square test. A P-value of <.05 was considered statistically significant.
3. Results
A total of 191 participants were evaluated for participation in this study, and 150 parturients were included in the clinical trial, with 75 patients in each group. Twenty-one women were excluded from the study: 6 cases had intraoperative blood loss > 500 mL (4 from the control group and 2 from the experimental group), and 15 were lost to follow-up (8 from the control group and 7 from the experimental group). Therefore, a total of 129 cases completed the study and were included in the final analysis (Fig. 1). The demographic and clinical characteristics of the participants are detailed in Table 1. There were no significant differences between the 2 groups in demographic characteristics or intraoperative maternal and neonatal general parameters (Table 1).
Figure 1.
CONSORT flow diagram. In total, 191 participants were evaluated for participation in this study, and 150 parturients were included in the clinical trial, with 75 patients in each group. Twenty-one women were excluded from the study: 6 cases had intraoperative blood loss > 500 mL (4 from the control group and 2 from the experimental group), and 15 were lost to follow-up (8 from the control group and 7 from the experimental group). A total of 129 cases completed the study and were included in the final analysis.
Table 1.
Demographic and clinical characteristics of the puerperae.
| Variables | S group (N = 66) |
C group (N = 63) |
Statistical value | P value |
|---|---|---|---|---|
| Age | 29.86 ± 4.78 | 29.30 ± 4.95 | 0.656 | .513 |
| BMI (kg/m2) | 27.32 ± 2.24 | 27.76 ± 2.02 | 1.187 | .238 |
| Married (yes/no) | 66/0 (100%) | 63/0 (100%) | 1.000 | |
| Education | ||||
| Junior college or below | 29 (43.9%) | 32 (50.8%) | ||
| Bachelor or above | 37 (56.1%) | 31 (49.2%) | 0.608 | .436 |
| Scarred uterus | 33 (50%) | 39 (61.9%) | 1.852 | .174 |
| ASA classification II | 66 (100%) | 65 (100%) | 1.000 | |
| Accompanying diseases during pregnancy* | 9 (14.6%) | 4 (6.3%) | 1.889 | .169 |
| Gestational age (days) | 273.67 ± 6.01 | 270.03 ± 6.83 | 3.211 | .127 |
| Duration of anesthesia (min) | 74.68 ± 13.72 | 80.92 ± 11.97 | ‐2.747 | .07 |
| Duration of operation (min) |
57.68 ± 13.67 | 67.24 ± 12.04 | ‐3.201 | .06 |
| Amount of bleeding (mL) | 337.88 ± 48.88 | 341.27 ± 55.75 | ‐0.368 | .127 |
| Newborn sex (m/f) | 31/35 | 34/29 | 0.632 | .427 |
| Vasoactive drug use | 8 (12.1%) | 10 (15.9%) | 0.378 | .539 |
Data are presented as the mean ± SD, number of patients (%), or median (range).
ASA = American Society of Anesthesiologists, BMI = body mass index (calculated as weight in kilograms divided by height in meters squared).
Including mild gestational diabetes and well-controlled gestational hypertension.
Five minutes post-administration of the drug, the incidences of nystagmus, dizziness, drowsiness, lacrimation, nausea, blurred vision, hallucinations, and the Ramsay sedation score in group S were significantly higher than those in group C (P < .05). Fifteen minutes post-administration, the incidences of hallucinations and lacrimation remained significantly higher in group S. Upon leaving the operating room, there were no significant differences in the incidence of side effects between the 2 groups. Additionally, the traction reflex in group S was significantly lower than that in group C during surgery (P < .05) (Table 2).
Table 2.
Side effects after esketamine administration during cesarian section.
| S group (n = 66) | C group (n = 63) | P value | |
|---|---|---|---|
| Nystagmus | |||
| 5 min | 65 (98.48) | 0 (0%) | <.001 |
| 15 min | 4 (6.1%) | 0 (0%) | .140 |
| Out of operating room | 0 (0%) | 0 (0%) | 1.00 |
| Dizziness | |||
| 5 min | 63 (95.5%) | 0 (0%) | <.001 |
| 15 min | 6 (9.1%) | 0 (0%) | .042 |
| Out of operating room | 1 (0%) | 0 (0%) | 1.000 |
| Drowsiness | |||
| 5 min | 40 (60.6%) | 0 (0%) | <.001 |
| 15 min | 2 (3.0%) | 0 (0%) | .496 |
| Out of operating room | 0 (0%) | 0 (0%) | 1.000 |
| Lacrimation | |||
| 5 min | 29 (44.0%) | 0 (0%) | <.001 |
| 15 min | 7 (10.6%) | 0 (0%) | .013 |
| Out of operating room | 0 (6.1%) | 0 (0%) | 1.000 |
| Diplopia | |||
| 5 min | 7 (10.6%) | 0 (0%) | .013 |
| 15 min | 1 (1.5%) | 0 (0%) | 1.000 |
| Out of operating room | 1 (0%) | 0 (0%) | 1.000 |
| Hallucinations | |||
| 5 min | 25 (37.9%) | 0 (0%) | <.001 |
| 15 min | 8 (12.1%) | 0 (0%) | .012 |
| Out of operating room | 0 (0%) | 0 (0%) | 1.000 |
| Nausea | |||
| 5 min | 5 (7.6%) | 0 (0%) | .058 |
| 15 min | 28 (42.4%) | 26 (40.0%) | .894 |
| Out of operating room | 6 (9.1%) | 5 (7.7%) | .814 |
| Vomiting | |||
| 5 min | 4 (6.1%) | 0 (0%) | .140 |
| 15 min | 27 ((40.9%) | 25 (37.9%) | .887 |
| Out of operating room | 3 (4.5%) | 4 (6.2%) | .953 |
| Ramsay score > 3# | |||
| 5 min | 63 (95.5%) | 0 (0%) | <.001 |
| 15 min | 0 (0%) | 0 (0%) | 1.000 |
| Out of operating room | 0 (0%) | 0 (0%) | 1.000 |
| Visceral traction pain | 7 (10.6%) | 39 (60.0%) | <.001 |
Data are presented as the number of patients (%).
Postoperative follow-up results showed that, compared with the control group, the VAS scores of patients in the experimental group at T1 and T2 were significantly lower during rest and movement (coughing or turning over) (P < .05). However, there were no significant differences at T3. The effective compression times of PCIA 48 hours after surgery were fewer in group S than in group C (P < .05). The number of additional analgesic drugs needed postoperatively was significantly reduced in the experimental group (P < .05). There were no significant differences in the incidence of depression at 3, 7, and 14 days post-surgery between the 2 groups. However, the EPDS scores of the experimental group were significantly lower than those of the control group at 3 and 7 days after surgery (P < .05). There was no significant difference in EPDS scores between the 2 groups 14 days after surgery (Table 3).
Table 3.
Outcome measures.
| Variables | S group (n = 66) | C group (n = 65) | P value |
|---|---|---|---|
| T1 VAS score (static) | 4.24 ± 0.70 | 4.98 ± 0.13 | <.001 |
| T1 VAS score (move) | 5.24 ± 0.70 | 5.98 ± 0.13 | <.001 |
| T2 VAS score (static) | 3.50 ± 0.50 | 4.17 ± 0.38 | <.001 |
| T2 VAS score (move) | 4.50 ± 0.54 | 5.17 ± 0.38 | <.001 |
| T3 VAS score (static) | 2.00 ± 0.00 | 2.06 ± 0.25 | .38 |
| T3 VAS score (move) | 3.00 ± 0.00 | 3.06 ± 0.25 | .38 |
| Total number of PCIA compressions in 48 hours | 7.58 ± 1.50 | 14.75 ± 1.78 | <.001 |
| Postoperative adjuvant analgesia | 2 (3.00%) | 19 (30.2%) | <.001 |
| EPDS score | |||
| Before operation | 4.12 ± 0.64 | 4.08 ± 0.63 | .406 |
| 3 days after surgery | 6.42 ± 0.75 | 6.95 ± 0.58 | <.001 |
| Occurrence of postpartum depression | 0 (0%) | 0 (0%) | 1.000 |
| 7 days after surgery | 8.58 ± 0.88 | 9.05 ± 0.63 | <.001 |
| Occurrence of postpartum depression | 8 (12.1%) | 8 (12.7%) | .921 |
| 14 days after surgery | 5.86 ± 0.76 | 6.21 ± 0.68 | .07 |
| Occurrence of postpartum depression | 0 (0%) | 0 (0%) | 1.000 |
Data are presented as the mean ± SD, number of patients (%).
EPDS = Edinburgh Postnatal Depression Scale, VAS = Visual Analogue Scale.
4. Discussion
The results of this clinical trial showed that a subclinical dose of esketamine given to “healthy” full-term women after umbilical cord ligation did not reduce the incidence of PPD at 3, 7, and 14 days after delivery. However, the VAS scores of the experimental group at 4 and 24 hours after delivery were significantly lower. The incidence of side effects and the Ramsay sedation score were significantly increased in the experimental group, albeit briefly.
A recent study reported that esketamine (0.01 mg/kg/hour), as an adjunct analgesic for PCIA 48 hours after surgery, significantly reduced the incidence of PPD at 3 and 14 days but had no effect on PPD at 28 days post-surgery.[17] Yao et al conducted a randomized controlled trial (RCT) and reported that intravenous administration of 0.25 mg/kg esketamine or normal saline of the same volume 5 minutes after fetal delivery significantly reduced the incidence of PPD 1 week postpartum but had no effect on PPD at 2 weeks and 1 month after surgery.[18] A meta-analysis of single-dose esketamine for the treatment of unipolar and bipolar depression indicated that depressive symptoms were significantly relieved 40 to 60 minutes after administration of 0.5 mg/kg esketamine, and the antidepressant effects lasted 5 to 8 days.[19] Therefore, in this study, patients were followed up at 3, 7, and 14 days post-operation. A recent meta-analysis showed that a single intravenous subanesthetic dose of esketamine (0.5 mg/kg) during the cesarean section period prevented PPD in the first week postpartum, but 0.2 mg/kg had no significant effect on PPD.[20] Esketamine, the S-isomer of ketamine, is twice as potent in humans. Xu et al reported that although 0.25 mg/kg esketamine administered before skin incision could pass the placental barrier, the Apgar scores of fetuses in the experimental group were not significantly affected, and the drug did not cause significant neonatal depression.[4] Therefore, a single dose of 0.25 mg/kg esketamine was used to study the incidence of PPD in this trial.
The antidepressant mechanism of esketamine is not entirely clear, but it may involve: (1) activation of the a-amino-3-hydroxy-5methyl-4-isoxazole-propionate receptor by inhibiting synaptic or selective GluN2B NMDA receptors, followed by inhibition of NMDA receptors in Gamma-aminobutyric acid interneurons, leading to the activation of NMDA receptor-dependent lateral cingulate neurons to produce antidepressant effects[21]; (2) blockade of the NMDA receptor and activation of the a-amino-3-hydroxy-5methyl-4-isoxazole-propionate receptor, promoting neurotrophic effects, including the release of downstream neurotrophic signals such as brain-derived neurotrophic factor and eukaryotic elongation factor 2, resulting in the growth of cerebral cortex dendrites and synapse formation[22]; (3) induction of the activation of the mTORC1 signaling pathway and extracellular regulatory protein kinase[23]; (4) improvement of mood by regulating the midbrain dopamine system (D2 receptors and D3 receptors), opioid receptors, and monoamine transporters.[24]
Han et al[17] demonstrated that the injection of esketamine (0.01 mg/kg/hour) as an adjunct in PCIA reduced the incidence of PPD within 14 days after cesarean section. Furthermore, Wang et al[25] reported that the injection of esketamine (0.1, 0.2, or 0.4 mg/kg) with sufentanil for PCIA reduced the incidence of PPD, the consumption of sufentanil, and postoperative analgesia. These findings are partially consistent with those of this clinical trial. The possible reasons are as follows: (1) the timing of administration was different. In previous studies, esketamine was used as an adjuvant medication for PCIA after surgery, while in this study, it was used as a preventive medication; (2) the dosage of the drug was different. In previous studies, the dosages were 1.5 mg/kg/h or 0.1/0.2/0.4 mg/kg, while a conservative and safe dose of 0.25 mg/kg was used in this trial.
Esketamine, as an intravenous anesthetic, has sedative and analgesic effects. Wang et al found that intraoperative intravenous injections of low-dose esketamine (0.25 mg/kg) and high-dose esketamine (0.5 mg/kg) affected postoperative pain in patients with cervical cancer, but the difference was not significant.[26] Li et al conducted an RCT and found that adding 1.5 mg/kg esketamine to postoperative PCIA significantly reduced post-obstetric NRS scores and postoperative sufentanil consumption, especially the NRS score during movement.[27] This trial also confirmed that esketamine can reduce maternal pain at 4 and 24 hours post-surgery, as well as the number of effective PCIA compressions 48 hours after surgery.
Wang et al conducted an RCT and found that esketamine combined with sufentanil used for PCIA after elective cesarean section reduced sufentanil consumption, improved postoperative analgesia, and decreased the incidence of PPD at 1 week and 6 weeks.[25] Wang et al also found that esketamine combined with ropivacaine hydrochloride for labor analgesia significantly reduced the VAS score and the incidence of PPD.[28] Alipoor et al found that perinatal acute pain and postpartum chronic pain were risk factors for PPD.[6] The prevention and reduction of postoperative pain may help reduce the incidence of postpartum PPD. This clinical trial showed that intravenous administration of a subclinical dose of esketamine during cesarean section reduced VAS scores at 4 and 24 hours post-surgery, and EPDS scores at 3 and 7 days post-surgery were significantly decreased. It confirms that esketamine, administered at a subclinical dose, can reduce acute postoperative pain but does not significantly reduce the incidence of PPD in the short-term postpartum period. This highlights the importance of dosing and timing in determining the efficacy of esketamine for PPD prevention. Clinicians can consider the use of subclinical doses of esketamine for short-term postoperative pain relief after cesarean sections, as it was shown to lower VAS scores without causing long-lasting side effects. However, for preventing PPD, higher doses or alternative administration strategies (such as using esketamine in combination with other analgesics in PCIA) may need to be explored. Further studies with large sample sizes and multi-center clinical trials are needed to confirm this conclusion.
In this study, we observed higher rates of side effects such as nystagmus, drowsiness, dizziness, hallucinations, and diplopia in the experimental group. However, their duration was short, and all were completely relieved before leaving the operating room. Moreover, the Ramsay sedation score of the experimental group was significantly increased 5 minutes after drug administration. No long-term psychiatric side effects were reported, but these short-term side effects highlight the need to ensure the safe use of esketamine. It is important to recognize that there are gaps in our understanding of the safety of esketamine, and future studies need to address these outstanding questions.[29]
5. Limitations
There are some limitations of this clinical trial that should be noted. First, the EPDS scores were measured by an anesthesiologist instead of a professional psychologist, which may have introduced bias in the scoring process. Additionally, in this study, patients were only followed up for 14 days after delivery, so their subsequent PPD status remains unknown. Second, according to a meta-analysis,[30] obstetric factors associated with postoperative PPD include cesarean section, perioperative acute and chronic pain, preterm birth, obesity, hyperemesis, and severe obstetric comorbidities. The exclusion criteria for this clinical trial eliminated most of these factors, focusing only on the effect of pain on PPD, which may have led to selection bias. Third, this study excluded participants who had previously been diagnosed with depression.[31] These individuals may have additional confounding mental health factors compared to those who have never experienced depression. However, studying the prevention of PPD in this population could have greater clinical significance. Therefore, future studies should consider including individuals with a history of depression.
6. Conclusions
In conclusion, the results of this clinical trial indicated that the use of a subclinical dose of esketamine during elective cesarean section did not reduce the incidence of PPD at 14 days postpartum, but it did reduce EPDS scores at 7 days postpartum, VAS scores at 24 hours postoperatively, and decreased the use of adjuvant analgesics at 48 hours postoperatively. However, esketamine was associated with a temporary increase in the risk of intraoperative complications. Therefore, larger sample sizes and multicenter clinical trials are needed in the future to further confirm these findings.
Acknowledgments
The author thanks all researchers for providing the requested data.
Author contributions
Conceptualization: Xiangqian Wan, Ming Li, Mingqing Peng.
Data curation: Xiangqian Wan, Ming Li, Xiantao Li, Huan Dai, Mingqing Peng.
Formal analysis: Xiangqian Wan, Ming Li, Xiantao Li, Huan Dai, Mingqing Peng.
Investigation: Xiangqian Wan.
Methodology: Xiangqian Wan, Mingqing Peng.
Project administration: Mingqing Peng.
Software: Xiangqian Wan, Mingqing Peng.
Supervision: Mingqing Peng.
Validation: Xiangqian Wan, Xiantao Li, Huan Dai, Mingqing Peng.
Visualization: Mingqing Peng.
Writing – original draft: Xiangqian Wan, Mingqing Peng.
Writing – review & editing: Xiangqian Wan, Mingqing Peng.
Abbreviations:
- EPDS
- Edinburgh Postnatal Depression Scale
- NMDA
- N-methyl-d-aspartate
- PCIA
- patient-controlled intravenous analgesia pump
- PPD
- postpartum depression
- RCT
- randomized controlled trial
- VAS
- Visual Analog Scale
The authors have no funding and conflicts of interest to disclose.
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
How to cite this article: Wan X, Li M, Li X, Dai H, Peng M. The effect of a subclinical dose of esketamine on depression and pain after cesarean section: A prospective, randomized, double-blinded controlled trial. Medicine 2024;103:44(e40295).
Contributor Information
Xiangqian Wan, Email: 286624122@qq.com.
Ming Li, Email: 505030235@qq.com.
Xiantao Li, Email: 505030235@qq.com.
Huan Dai, Email: 1015104578@qq.com.
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