Dexmedetomidine found effective for reducing postpartum depression risk

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A recent study revealed that early postpartum administration of dexmedetomidine significantly reduces the risk of postpartum depression among women with prenatal depression.

Dexmedetomidine found effective for reducing postpartum depression risk | Image Credit: © LUMEZIA.com - © LUMEZIA.com - stock.adobe.com.

Dexmedetomidine found effective for reducing postpartum depression risk | Image Credit: © LUMEZIA.com - © LUMEZIA.com - stock.adobe.com.

The risk of postpartum depression (PPD) is significantly reduced by early postpartum administration of dexmedetomidine among women with prenatal depression, according to a recent study published in JAMA Network Open.

Takeaways

  1. The study suggests that the risk of postpartum depression (PPD) is significantly decreased by administering dexmedetomidine early in the postpartum period, particularly among women with prenatal depression.
  2. Prenatal depression is identified as a known risk factor for PPD, and the study emphasizes the importance of prenatal screening to implement interventions aimed at reducing the risk of postpartum depression.
  3. The research explores the association between increased α2-adrenoreceptor (α2-AR) expression and PPD. Dexmedetomidine, an α2-AR antagonist, is suggested to potentially reduce α2-AR density, which tends to be elevated in patients with PPD.
  4. The study conducted a randomized, double-blind, placebo-controlled clinical trial involving women who had undergone elective cesarean delivery and had prenatal depression. Dexmedetomidine was administered, and various outcomes, including PPD screening, suicidal ideation, and blood biomarker levels, were evaluated.
  5. The results indicate a significant reduction in positive PPD screening results, decreased suicidal ideation, and increased plasma brain-derived neurotrophic factor (BDNF) levels in the dexmedetomidine group. The study concludes that dexmedetomidine shows both safety and efficacy in reducing PPD, suggesting a potential connection to BDNF upregulation or pro-BDNF downregulation.

Approximately 10% to 20% of women experience PPD after birth, leading to severe adverse outcomes in mothers, young children, and family members. Prenatal depression is a known risk factor of PPD, with prenatal screening recommended to implement interventions to reduce PPD risk.

Data has indicated increased α2-adrenoreceptor (α2-AR) expression in multiple brain regions among patients who completed suicide. Dexmedetomidine, an α2-AR antagonist, may be able to reduce α2-AR density, which is increased in patients with PPD. However, there is little data evaluating the impact of dexmedetomidinefor PPD.

To evaluate the association between dexmedetomidine and PPD, investigators conducted a randomized, double-blind, placebo-controlled clinical trial. The study occurred at The Third Xiangya Hospital of Central South University and Hunan Maternal and Child Health Hospital between March 28, 2022, and April 16, 2023.

Participants were aged 18 years or older, had received elective cesarean delivery, had prenatal depression based on the Edinburgh Postnatal Depression Scale (EPDS), and were capable of communicating with investigators. Patients with a dexmedetomidine allergy and a heart rate below 50 beats per minute or a presence of cardiac conduction or rhythm abnormalities were excluded.

Patients were randomized 1:1 to receive either dexmedetomidine or placebo. Additionally, venous blood sampling was performed in 60 randomly selected participants in each group. All participants underwent preoperative assessment and baseline data collection.

Dexmedetomidine was administered at 0.5 μg/kg in 20 mL of 0.9% saline for 10 minutes in the dexmedetomidine group. In the placebo group, participants received 20 mL of 0.9% saline for 10 minutes. Patient-controlled intravenous analgesia was administered to all patients for 48 hours immediately following infusion, set at a rate of 2 mL per hour.

A positive PPD screening result was the primary outcome of the analysis, determined by EPDS scores at days 7 and 42 after the procedure. EPDS scores of 9 or greater indicated PPD. 

Secondary outcomes included suicidal ideation at7 and 42days, Insomnia Severity Index (ISI) scores at 1, 2, 7, and 42 days, and plasma brain-derived neurotrophic factor (BDNF) and pro-BDNF levels. Safety outcomes included adverse outcomes (AEs), vital signs, Ramsay Sedation Scale score, and other safety indicators.

There were 338 women included in the final analysis, aged a mean 31.5 years. A significant decrease in positive PPD screening results was observed in the dexmedetomidine group compared to the control group.On day 7, rates of positive PPD screening were 12.6% and 32.1%, respectively. At day 42, these rates were 11.4% and 30.3%, respectively.

Suicidal ideation was also significantly reduced in the dexmedetomidine group at day 7 compared to the control group, but this difference was not observed at day 42. Median ISI scores also significantly decreased in the dexmedetomidine at days 1 and 2 postpartum compared to the control group. Day 1 scores were 11 and 13, respectively, and day 2 scores were 6 and 7, respectively.

Plasma BDNF and pro-BDNF levels were significantly increased in the dexmedetomidine group compared to the control group, with a difference of 61.53 ng/L for the mean level and 71.57 ng/L for the mean change in value. AEs did not significantly differ between groups, but hypotension was reported in 18.3% of the dexmedetomidine group and 9.5% of the control group.

These results indicated safety and efficacy from dexmedetomidine in reducing PPD. Investigators concluded its antidepressant effect may be related to BDNF upregulation or pro-BDNF downregulation.

Reference

Zhou Y, Bai Z, Zhang W, et al. Effect of dexmedetomidine on postpartum depression in women with prenatal depression: A randomized clinical Trial. JAMA Netw Open. 2024;7(1):e2353252. doi:10.1001/jamanetworkopen.2023.53252

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