In 2019, the US Preventive Services Task Force (USPSTF) issued recommendations that each one pregnant and postpartum women must be evaluated with a purpose to determine risk for depressive illness and beneficial that girls at increased risk must be referred for counseling interventions. Ultimately the goal is to discover women at highest risk for depressive illness while pregnant and the postpartum period, in order that we will introduce interventions designed to stop depression on this setting.

Of utmost importance is the number of an efficient intervention. The medical literature reports on a big selection of interventions designed to stop PPD; nonetheless, a lot of these interventions haven’t been tested in multiple settings. In a recent study, researchers explored using dexmedetomidine to cut back the chance of postpartum depression after delivery in a bunch of ladies undergoing Cesarean section. 

What’s Dexmedetomidine? Why Did They Test It?

Dexmedetomidine or DEX is a highly selective α2 -adrenergic receptor ( α2 -AR) agonist. It’s used commonly throughout the perioperative period and has sedative, anxiolytic, and analgesic properties. It produces these effects by inhibiting central sympathetic outflow by blocking alpha receptors within the brainstem and inhibiting the discharge of norepinephrine.

Plainly the concept that DEX could also be used as an antidepressant got here from a 2014 study from India where DEX was used for anesthesia in patients receiving ECT; this study noted that patients receiving DEX experienced less agitation and a greater reduction in depressive symptoms. Animal studies later demonstrated DEX’s antidepressant effects. Exactly how DEX works as an antidepressant will not be fully understood; nonetheless, DEX appears to have anti-inflammatory effects and upregulates the production of brain-derived neurotrophic factor (BDNF).

Dexmedetomidine in Postpartum Women

On this randomized, double-blind, placebo-controlled clinical trial, Zhou and colleagues recruited women who were undergoing a Cesarean section and who experienced depression while pregnant, defined as an Edinburgh Postnatal Depression Scale (EPDS) rating of 9 or greater.

After delivery, 338 participants were randomized and received either an intravenous infusion of DEX (0.5 μg/kg) or saline. Following this infusion, women within the DEX group received DEX (2.0 μg/kg) and the opioid analgesic sufentanil (2.2 μg/kg); the control group received only sufentanil (2.2 μg/kg).

At 1 and 6 weeks after delivery, depressive symptoms were measured using the EPDS. The participants were also asked about sleep, pain, and other adversarial events.

Prevalence of Postpartum Depressive Symptoms

At Week 1, 12.6% of the ladies within the dexmedetomidine group screened positive for PPD versus 32.1% of the ladies within the control group. At 6 weeks, 11.4% of the dexmedetomidine group versus 30.3% of the control group screened positive. 

In addition they observed another differences between the DEX and control groups:

• Insomnia scores within the DEX group were significantly decreased from baseline to 1 and a pair of days postpartum in comparison with the control group. Nevertheless, there have been no differences in insomnia symptoms between the groups at 1 and 6 weeks postpartum.
• Women within the DEX group reported less pain at 6, 24, and 48 hours after delivery than women within the control group.

The 2 groups experienced similar rates of adversarial events; nonetheless, those within the DEX group had higher rates of hypotension (systolic blood pressure lower than 90 mm Hg or 20% lower than baseline).

Interesting Study, But Still More questions

It is a very interesting study. In a bunch of ladies who had elevated EPDS scores while pregnant, postpartum treatment with the α2-adrenergic receptor agonist dexmedetomidine was related to a 60% reduction within the prevalence of postpartum dpepressive symptoms at weeks 1 and at week 6. This represents a big reduction of risk in a bunch of ladies who, because they already had experienced depressive symptoms during regnancy, were at increased risk for PPD. As well as, treatment with DEX was related to improved sleep and higher pain control.

The authors of the study ask whether DEX could be used to “prevent” postpartum depression. The undeniable fact that these women already had depressive symptoms while pregnant raises the likelihood that some (or many?) women were already depressed on the time they were treated with DEX. This is predicated on the finding that girls with PPD often experience the onset of depressive symptoms while pregnant, typically throughout the last trimester. So it is feasible that DEX may prevent postpartum depression, but we must also entertain the likelihood that DEX may additionally alleviate or prevent the worsening of already present depressive symptoms. This publication didn’t include data on changes in depressive symptoms in individual participants, information which may help to separate these possibilities. 

Another questions to think about:

• Would treatment with DEX reduce risk for PPD in women with other risk profiles, reminiscent of women with a history of PPD? Or in women with a pregravid history of depression? Or women in the final population?
• Provided that women with insomnia during late pregnancy and early postpartum period are at increased risk for PPD, could the helpful effects of DEX be related to improvements in sleep throughout the early postpartum period?
• Previous studies have indicated lower risk of PPD in women with higher peripartum pain control; could the advantages seen with DEX be related to raised pain relief?

Nonetheless, this study provides one other avenue of exploration for the treatment of postpartum depression, an option that may very well be administered once on the time of delivery. Further studies are needed to raised understand which women are most definitely to learn from this intervention. 

Several other α2-adrenergic receptor ( α2-AR) agonists are currently available on the market but will not be used as antidepressants. Clonidine or Catapres is used to treat ADHD, anxiety and hypertension. Tizanidine or Zanaflex is used as a muscle relaxant. To one of the best of my knowledge, now we have not seen any antidepressants that specifically goal adrenergic receptors. 

Ruta Nonacs, MD PhD

References

Al-Mahrouqi T, Al Alawi M, Freire RC. Dexmedetomidine within the Treatment of Depression: An Up-to-date Narrative Review. Clin Pract Epidemiol Ment Health. 2023 Aug 30;19:e174501792307240. 

Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015 Spring;62(1):31-9.

Zhou Y, Bai Z, Zhang W, Xu S, Feng Y, Li Q, Li L, Ping A, Chen L, Wang S, Duan K. Effect of Dexmedetomidine on Postpartum Depression in Women With Prenatal Depression: A Randomized Clinical Trial. JAMA Netw Open. 2024 Jan 2;7(1):e2353252.