Albzea W, Almonayea L, Aljassar M, et al. Efficacy and Safety of Preoperative Melatonin for Women Undergoing Cesarean Section: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Medicina (Kaunas). 2023;59(6):1065. Published 2023 Jun 1. doi:10.3390/medicina59061065
This systematic review and meta-analysis of randomized placebo-controlled trials investigated the effectiveness and safety of using melatonin to assist in pain management following a cesarean section. Seven studies that included 754 women found that the melatonin-treated group experienced significantly less pain (p<0.001) when melatonin was administered up to 2 hours before surgery.
Our comments/takeaway from the article
Melatonin has been cited in the literature for its use in various surgical procedures such as reducing pain following back surgery and reducing sepsis following surgery. The exploration of melatonin therapy for c-section pain is clinically relevant since over 32% of all women undergo cesarean section for childbirth. Due to melatonin’s safety profile, the use of melatonin pre-operatively to assist in pain management may be a plausible therapy for surgeons and clinicians to consider, with the greatest benefit resulting from a single dose of 10 mg of melatonin prior to surgery.
This systemic review and meta-analysis followed PRISMA guidelines and created the search criteria using PICO:
Population: Women who had an elective) cesarean section
Comparator: Placebo or no treatment
Outcomes: Changes in at least one of the following: hemoglobin, heart rate, arterial pressure, anxiety score, pain score, time for first analgesic request, total blood loss, and adverse events.
The dose of melatonin ranged from 3 mg to 10 mg and was administered orally and sublingually 20 minutes to 2 hours before spinal anesthesia or skin incision.
The results reported were:
Hemoglobin: No significant difference in melatonin vs. placebo/non-treated groups
Heart rate: No significant difference in melatonin vs. placebo/non-treated groups
Mean arterial pressure: No significant difference in melatonin vs. placebo/non-treated groups
Pain score: significant reduction in pain (p<0.001) in melatonin-treated groups at 6 and 12 hours post-surgery for all doses, but it was only significant at 24 hours post-surgery at the 10 mg dose.
Time to first analgesic request: significantly longer time (p<0.001) in the melatonin-treated group vs. placebo/non-treated groups in the request for pain medication, with the longest time recorded in the group taking 10 mg.
Total blood loss: No significant difference in melatonin vs. placebo/non-treated groups
Adverse events: no significant difference in the risk for adverse events (nausea, vomiting, headache) following surgery, with the exception of the 6 mg dose significantly increasing the risk of headache (p=0.004).
There are several mechanisms of action of melatonin that the authors suggest are responsible for reducing pain post-surgery, such as its ability to:
reduce inflammation to suppress pro-inflammatory cytokines.
modulate pain through the opioid system in the brain.
modulate neurotransmitters such as serotonin and dopamine, which are involved in pain perception.
improve sleep quality and length, lowering pain indirectly.
reduce the sympathetic nervous system, indirectly lowering pain by reducing pre-surgery anxiety.
reduce muscle tension and spasms.
Limitations noted by Author(s)
A small number of studies (7 total)
The lack of all desired outcomes being reported.
A large difference in dosing among the studies
The sample sizes of all studies may not have been large enough to result in statistically significant findings.
Other limitations noted in this review
Though anxiety scores were one of the outcome measures this was not reported.
Article review completed by Kim Ross, DCN
Content reviewed by Deanna Minich, PhD
July 12, 2023