Dexmedetomidine, an α2-adrenergic receptor agonist, shows promise in preventing postpartum depression, what about PMDD or PME?

Dexmedetomidine (dek·smeh·duh·tow·muh·din aka Dex) is a sedative used in operative procedures. It helps to prolong effects of pain relief in operative procedures. It is also used as an off-label treatment for delirium, chronic pain, insomnia in intensive care units (ICU) and alcohol withdrawal. It shows promise in the treatment of postpartum depression. Currently, there is no evidence for effectiveness of Dex for PMDD or PME.

A recent meta-analysis (i.e., research combining the findings from various clinical trials) assessed studies that administered Dex as an intravenous (IV) infusion to individuals undergoing a C-section. It showed that Dex was effective in reducing symptoms of postpartum depression. Symptoms in those treated with Dex reduced in one week compared to control groups (no Dex). Receiving Dex soon after delivery and younger age (< 30 years) was associated with decreases in symptoms of postpartum depression.

Evidence suggests that Dex is superior in selectively blocking a2-adrenoreceptors. This is a newer target for antidepressant treatment.

Dex blocks the release of norepinephrine in a region of the brain called the brainstem. Norepinephrine is a chemical that helps with alertness and reactions to stress.

By blocking this chemical release, Dex creates a calming and sleep-inducing effect. It reduces anxiety and relieves pain. It stops nerve signals that activate our “fight-or-flight” stress response.

Thus in theory, Dex may help target biological mechanisms in PMDD and PME to reduce symptoms. However, we need laboratory and clinical research to determine whether Dex would help PMDD. Because Dex has not been studied for the treatment of PMDD, we do not know whether Dex would improve PMDD symptoms, have no effect, or worsen PMDD symptoms.

References:

Reel B, Maani CV. Dexmedetomidine. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513303/

Xu S, Zhou Y, Wang S, Li Q, Feng Y, Chen L, et al. Perioperative intravenous infusion of dexmedetomidine for alleviating postpartum depression after cesarean section: A meta-analysis and systematic review. Eur J Obstet Gynecol Reprod Biol. 2024;296:333-41. doi: 10.1016/j.ejogrb.2024.03.024

Bosch, Oliver G et al. “Dexmedetomidine in Psychiatry: Repurposing of Its Fast-Acting Anxiolytic, Analgesic and Sleep Modulating Properties.” Pharmacopsychiatry 56.2 (2023): 44–50. doi: 10.1055/a-1970-3453.

Reviewed by: Dr. Liisa Hantsoo, IAPMD CAB member.