Dexmedetomidine prophylaxis helps reduce postpartum depression

Administering dexmedetomidine after childbirth may safely lower the incidence of postpartum depression (PPD), as shown in a study.

In a cohort of 338 women (mean age 31.5 years) who underwent caesarean delivery, those who were given dexmedetomidine 0.5 μg/kg (n=169) versus saline 0.9% (n=169, control) were less likely to screen positive for PPD at postpartum days 7 (12.6 percent vs 32.1 percent; risk ratio [RR], 0.39, 95 percent confidence interval [CI], 0.25–0.62; p<0.001) and 42 (11.4 percent vs 30.3 percent; RR, 0.38, 95 percent CI, 0.23–0.61; p<0.001). [JAMA Netw Open  2024;7:e2353252]

PPD was defined as a postpartum Edinburgh Postnatal Depression Scale (EPDS) score of more than 9. Accordingly, the median EPDS score was significantly lower in the dexmedetomidine than in the group at both timepoints (7 days postpartum: 3.0 vs 6.0, p<0.001; 42 days postpartum: 3.0 vs 6.0; p<0.001).

The findings suggests that pre-emptive dexmedetomidine administration has the potential to lower the frequency of positive PPD screenings and improve EPDS scores among women at high risk of developing PPD, according to the investigators.

Safety profile

In terms of safety, the frequency of adverse events did not significantly differ between the dexmedetomidine group and the control group (27.2 percent vs 19.5 percent; p=0.10), except for hypotension, which occurred with significantly greater frequency in the dexmedetomidine group (18.3 percent vs 9.5 percent; RR, 2.15, 95 percent CI, 1.13–4.10; p=0.02).

“In this study, a loading dose of dexmedetomidine, 0.5 μg/kg, combined with a maintenance low-dose patient-controlled intravenous analgesia (PCIA) was used to make up for the short duration of drug effect after a single administration, to reduce the adverse effects related to blood concentration dependence, and to facilitate postoperative management,” the investigators said. [Anesthesiol Clin 2011;29:587-605]

Immediately after delivery, dexmedetomidine 0.5 μg/kg or saline 0.9% was intravenously infused for 10 minutes. After the infusion, dexmedetomidine plus sufentanil or sufentanil alone was administered via PCIA for 48 hours to women in the dexmedetomidine and control groups, respectively.

Other outcomes

Aside from the lower incidence of PPD and improved EPDS score, significant improvements were also seen for sleep quality (measured using Insomnia Severity Index [ISI]) and postoperative pain (measured using Numerical Rating Scale [NRS] pain score) with dexmedetomidine than with control.

The dexmedetomidine group had significantly lower median ISI scores at postpartum days 1 (11.0 vs 13.0; p=0.002) and 2 (6.0 vs 7.0; p<0.001), as well as significantly decreased median NRS pain scores at rest at postpartum hours 6 (p=0.03), 24 (p<0.001), and 48 (p=0.002). There were no significant between-group differences in ISI scores at postpartum days 7 and 42 and in NRS pain scores during movement.

The improvements observed in sleep quality and postoperative pain did not come as a surprise for the investigators, with dexmedetomidine having shown to have central antisympathetic, antianxiety, and sedative effects similar to natural sleep and certain analgesic effects. [Proc (Bayl Univ Med Cent) 2001;14:13-21]

“However, our results show that dexmedetomidine improved sleep only within 48 hours during infusion, and whether dexmedetomidine-improved sleep is related to PPD needs further clarification… [Meanwhile,] the unremarkable improvement in pain on movement can be attributed to the dose we administered (0.04 μg/kg/h), which is much lower compared with the standard clinical dose (0.6 μg/kg/h),” they acknowledged. [Anesth Analg 2000;90:699-705; Pain Physician 2021;24:E997-E1006]

Additional data showed that the brain-derived neurotrophic factor (BDNF) and pro-BDNF levels, which have been linked to the pathogenesis and prognosis of PPD, had no significant association with the incidence of PPD. The investigators attributed this finding to the insufficient sample size, with a low number of positive PPD screenings in the dexmedetomidine group.