Oral Melatonin Research Articles

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

Systematic Review and Meta-analysis of Efficacy and Safety of Melatonin and Triclofos for Inducing Adequate Sedation for Sleep Electroencephalogram in Children.

Introduction Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. Objectives The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. Methods A systematic search was conducted on “MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar” till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: “sleep EEG,” “electroencephalogram,” “triclofos,” “melatonin” OR “ramelteon” AND “epilepsy,” “seizure,” OR “convulsion.” ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's I 2 method was utilized. When I 2 was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. Results For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, p = 0.058) and repeat dose ( p = 0.054), detection of epileptiform abnormalities ( p = 0.06), and sleep onset latency ( p = 0.06), but more proportion of children receiving triclofos had adverse effects ( p = 0.001) and duration of sleep was also higher with triclofos ( p = 0.001). Conclusion Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.

Effect of melatonin on paclitaxel-associated acute and chronic pain: a randomized, double-blind, placebo-controlled clinical trial

Background: Taxane-induced pain is a disabling condition. This trial was conducted to assess the effects of melatonin on preventing paclitaxel-associated acute and chronic pain or decreasing its severity in patients with breast cancer. Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on breast cancer women who received weekly paclitaxel (80 mg/m2) with or without trastuzumab after using doxorubicin + cyclophosphamide. The intervention group randomly received oral melatonin (10 mg/day) or placebo, which started from the first night of chemotherapy and continued through the planned 12 weeks of chemotherapy. The level of arthralgia-myalgia as acute pain was assessed every day in both groups using the Brief Pain Inventory (BPI). The Douleur Neuropathique 4 questionnaire (DN4) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 were used to measure chemotherapy-induced peripheral neuropathy as chronic pain. Results: Seventeen patients were enrolled in each group randomly. The incidence of neuropathy according to a DN4 score ≥ 4 was significantly lower in the melatonin group versus the placebo group at week 12 compared to baseline (5 vs 11, P-value= 0.039). In addition, the mean neuropathy severity was significantly lower in the melatonin group over time (β= -0.051, P-value= 0.01). However, there were no significant differences in the mean worst and least pain scores over the twelve cycles of treatment between arms (P-value= 0.633, 0.341 respectively). Conclusion: Co-administration of melatonin in women with breast cancer decreased the incidence of severe paclitaxel-associated neuropathy but melatonin was not effective against acute pain.

Effect of oral melatonin on plasma growth hormone concentration in rhesus monkeys (Macaca mulatta)

Effect of oral melatonin on plasma growth hormone concentration in rhesus monkeys (Macaca mulatta)

Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer's disease.

While melatonin is known to have protective effects in mitochondria-related diseases, aging, and neurodegenerative disorders, there is poor understanding of the effects of melatonin treatment on mitophagy in Alzheimer's disease (AD). We used proteomic analysis to investigate the effects and underlying molecular mechanisms of oral melatonin treatment on mitophagy in the hippocampus of 4-month-old wild-type mice versus age-matched 5×FAD mice, an animal model of AD. 5×FAD mice showed disordered mitophagy and mitochondrial dysfunction as revealed by increased mtDNA, mitochondrial marker proteins and MDA production, decreased electron transport chain proteins and ATP levels, and co-localization of Lamp1 and Tomm20. Melatonin treatment reversed the abnormal expression of proteins in the signaling pathway of lysosomes, pathologic phagocytosis of microglia, and mitochondrial energy metabolism. Moreover, melatonin restored mitophagy by improving mitophagosome-lysosome fusion via Mcoln1, and thus, ameliorated mitochondrial functions, attenuated Aβ pathology, and improved cognition. Concurrent treatment with chloroquine and melatonin blocked the positive behavioral and biochemical effects of administration with melatonin alone. Taken in concert, these results suggest that melatonin reduces AD-related deficits in mitophagy such that the drug should be considered as a therapeutic candidate for the treatment of AD.

Effects of Microwave Oven Exposed Diet on Animal Weight and Testicular Tissue and Relative Role of Mentha Piperita

Background: Usage of electronic gadgets like microwave oven is increasing day by day that heats the food by exposing it to electromagnetic radiations which has many hazardous effects on human health including fertility. Aim: To find the effects of microwave oven exposed diet on weight and testis of mice along with protective effects of Mentha Piperita and Melatonin Study Design: Randomized control trial. Methodology: Adult male mice (n=32) were divided into four groups. Control group (G1) received standard pellets prepared for mice. Second group (G2) was given mice pellets exposed to microwave oven. Third group (G3) received Mentha Piperita leaf extract along with mice pellets exposed to microwave oven and the fourth group (G4) received oral melatonin along with pellets exposed to microwave oven. After experimental period, wt of each mice was again recorded and then mice were sacrificed. Data analyzed by SPSS 21.0v. Results: There was no statistically significant difference of weight gain of animals but there was significant reduction in weight of testis in group G2 but in G3 and G4 wt of the testis was close to control. Conclusion: It was concluded that microwave oven exposed diet had no significant effect on overall weight gain of the animal but it significantly reduced weight of the testis in group G2. However, Mentha Piperita and Melatonin both had ameliorative effects on the wt of the testicular tissue. Keywords: Mice, Testis, Weight, Mentha piperita and Melatonin

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study

BackgroundMelatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. MethodsSixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n...=...32 each). Melatonin group received two tablets (3...mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120...min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15...minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. ResultsPostintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1...min, respectively) (p...<...0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p...<...0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01...mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. ConclusionPremedication with 6...mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.

Melatonin Enhances the Mitochondrial Functionality of Brown Adipose Tissue in Obese—Diabetic Rats

Developing novel drugs/targets remains a major effort toward controlling obesity-related type 2 diabetes (diabesity). Melatonin controls obesity and improves glucose homeostasis in rodents, mainly via the thermogenic effects of increasing the amount of brown adipose tissue (BAT) and increases in mitochondrial mass, amount of UCP1 protein, and thermogenic capacity. Importantly, mitochondria are widely known as a therapeutic target of melatonin; however, direct evidence of melatonin on the function of mitochondria from BAT and the mechanistic pathways underlying these effects remains lacking. This study investigated the effects of melatonin on mitochondrial functions in BAT of Zücker diabetic fatty (ZDF) rats, which are considered a model of obesity-related type 2 diabetes mellitus (T2DM). At five weeks of age, Zücker lean (ZL) and ZDF rats were subdivided into two groups, consisting of control and treated with oral melatonin for six weeks. Mitochondria were isolated from BAT of animals from both groups, using subcellular fractionation techniques, followed by measurement of several mitochondrial parameters, including respiratory control ratio (RCR), phosphorylation coefficient (ADP/O ratio), ATP production, level of mitochondrial nitrites, superoxide dismutase activity, and alteration in the mitochondrial permeability transition pore (mPTP). Interestingly, melatonin increased RCR in mitochondria from brown fat of both ZL and ZDF rats through the reduction of the proton leak component of respiration (state 4). In addition, melatonin improved the ADP/O ratio in obese rats and augmented ATP production in lean rats. Further, melatonin reduced mitochondrial nitrosative and oxidative status by decreasing nitrite levels and increasing superoxide dismutase activity in both groups, as well as inhibited mPTP in mitochondria isolated from brown fat. Taken together, the present data revealed that chronic oral administration of melatonin improved mitochondrial respiration in brown adipocytes, while decreasing oxidative and nitrosative stress and susceptibility of adipocytes to apoptosis in ZDF rats, suggesting a beneficial use in the treatment of diabesity. Further research regarding the molecular mechanisms underlying the effects of melatonin on diabesity is warranted.

Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial.

This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID‐19) patients. This was an open‐label, randomized controlled clinical trial in hospitalized COVID‐19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10‐day mortality, white blood cell count, lymphocyte count, C‐reactive protein status, and peripheral capillary oxygen saturation. Ninety‐six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID‐19 patients.

Consequences of Microwave oven Exposed Diet on The Basal Lamina of Seminiferous Tubules of Mice

Usage of electronic gadgets like microwave oven is increasing day by day that heats the food by exposing it to electromagnetic radiations which has many hazardous effects on human health including fertility. Aim: To find the effects of microwave oven exposed diet on basal lamina of seminiferous tubules of mice alongwith protective effects of Mentha piperita and melatonin on the same tissue. Study Design: Randomized control trial. Methodology: Adult male mice (n=32) were divided into four groups. Control group (G1) received standard pellets prepared for mice. Second group (G2) was given mice pellets exposed to microwave oven. Third group (G3) received Mentha Piperita leaf extract along with mice pellets exposed to microwave oven and the fourth group (G4) received oral melatonin along with pellets exposed to microwave oven. Later their testicular tissue was removed for histological examination while basal lamina disruption was assessed by scoring. Data analyzed by SPSS 22.0v. Results: In group G2, there was slight disruption in the basal lamina in 75% of the cases while in experimental group G3, there was slight disruption of basal lamina only in 12.5% of the cases. However, in group G4, only 25% specimen had slight disruption of basal lamina Conclusion: It was concluded that microwave oven exposed diet produced severe disruption of basal lamina in group G2 that decreased in Mentha piperita and melatonin treated groups. However, Mentha piperita treated group produced better results than melatonin treated group. Keywords: Mice, Testis, Basal Lamina, Mentha piperita and Melatonin

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BackgroundAlthough tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear.MethodsThe current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742.FindingsOverall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control.InterpretationThe current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin.Fundingnone.

A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement

No effective antiviral drugs and vaccines are available for the treatment of patients with severe coronavirus 2019 (COVID-19). Therefore, available, safe, and inexpensive drugs and supplements such as melatonin are among the proposed options for controlling inflammation. We did a randomized, single-blind study in Imam Khomeini Hospital between June 30, 2020, and August 5, 2020. Mild to moderate COVID-19 patients aged 25-65 years were eligible to enter the study based on chest CT scan, clinical symptoms, and physician diagnosis. The intervention group was prescribed 6 mg of oral melatonin for 2 weeks, which consumed half an hour before bedtime every night in low light conditions. Clinical symptoms and C-reactive protein (CRP) were measured before and after treatment in the melatonin received and control (regular medications) groups. Among screened patients with COVID-19, 14 patients were assigned to receive melatonin, and 17 patients were considered as controls. A significant difference (p=0.005) between CRP 1 and CRP 2 levels (before and after using melatonin) was found in the melatonin group while this difference (p=0.069) was not significant in the control group. Also, the percentage of recovery (based on symptoms) in patients who took melatonin was higher than that of patients in the control group (85.7% VS 47.1%). The result of this study confirmed the effectiveness of melatonin in mild to moderate outpatients with COVID-19. More clinical trials on elderly, diabetic, obese patients and severe cases are suggested in future studies.

The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage.

To investigate the role of NLRP3 inflammasome in cardiac aging, we evaluate here morphological and ultrastructural age-related changes of cardiac muscles fibers in wild-type and NLRP3-knockout mice, as well as studying the beneficial effect of melatonin therapy. The results clarified the beginning of the cardiac sarcopenia at the age of 12 months, with hypertrophy of cardiac myocytes, increased expression of β-MHC, appearance of small necrotic fibers, decline of cadiomyocyte number, destruction of mitochondrial cristae, appearance of small-sized residual bodies, and increased apoptotic nuclei ratio. These changes were progressed in the cardiac myocytes of 24 old mice, accompanied by excessive collagen deposition, higher expressions of IL-1α, IL-6, and TNFα, complete mitochondrial vacuolation and damage, myofibrils disorganization, multivesicular bodies formation, and nuclear fragmentation. Interestingly, cardiac myocytes of NLRP3−/− mice showed less detectable age-related changes compared with WT mice. Oral melatonin therapy preserved the normal cardiomyocytes structure, restored cardiomyocytes number, and reduced β-MHC expression of cardiac hypertrophy. In addition, melatonin recovered mitochondrial architecture, reduced apoptosis and multivesicular bodies’ formation, and decreased expressions of β-MHC, IL-1α, and IL-6. Fewer cardiac sarcopenic changes and highly remarkable protective effects of melatonin treatment detected in aged cardiomyocytes of NLRP3−/− mice compared with aged WT animals, confirming implication of the NLRP3 inflammasome in cardiac aging. Thus, NLRP3 suppression and melatonin therapy may be therapeutic approaches for age-related cardiac sarcopenia.

What if melatonin could help patients with severe COVID-19?

What if melatonin could help patients with severe COVID-19?

Oral melatonin as part of multimodal anxiolysis decreases emergence delirium in children whereas midazolam does not: A randomised, double-blind, placebo-controlled study.

Pre-operative anxiety is a risk factor for emergence delirium in children and a multimodal approach including sedatives and nonpharmacological measures is the current strategy to tackle this anxiety. The efficacy of oral melatonin as a component of multimodal anxiolytic strategy to decrease emergence delirium is not well studied. The aim of this study was to evaluate the efficacy of a multimodal anxiolytic strategy including oral melatonin or midazolam to decrease emergence delirium after sevoflurane anaesthesia. A randomised, double-blind, parallel arm, placebo-controlled trial. Tertiary care teaching hospital from July 2019 till January 2020. Children in the age group of 3 to 8 years who received sevoflurane anaesthesia for elective ambulatory procedures. Children were randomised to receive oral premedication with either melatonin 0.3 mg kg-1, midazolam 0.3 mg kg-1 or honey as placebo. All the children received standardised nonpharmacological measures involving multiple techniques to allay anxiety. The anaesthetic plan was also standardised. The primary outcome was the incidence of emergence delirium as assessed by the Watcha scale in the postanaesthesia care unit. The secondary outcomes were pre-operative anxiety assessed using a modified Yale Preoperative Anxiety scale, patient compliance with mask induction using the Induction Compliance Checklist and postoperative sedation. Data from 132 children were analysed. Melatonin significantly reduced the incidence of emergence delirium compared to placebo: 27 vs. 50%, respectively, an absolute risk reduction of 23.3 [95% confidence interval 3.7 to 42.9), P = 0.03]. Melatonin also significantly reduced the risk of emergence delirium compared with midazolam: 27 vs. 56%, respectively, an absolute risk reduction of 29.2 (95% CI 9.5 to 48.8). The midazolam group had a similar incidence of emergence delirium as placebo. Sedation scores were similar in the three groups postoperatively. The incidence and score of pre-operative anxiety as well as the compliance with mask induction were similar in the three groups. A multimodal anxiolytic approach including oral melatonin, as opposed to oral midazolam, significantly reduced emergence delirium after sevoflurane anaesthesia. CTRI/2019/06/019850 in Clinical Trial Registry of India (www.ctri.nic.in).

Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants’ sleep disturbances, anxiety/depression and health-related quality of life. A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline, and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. The most relevant results were the significant reduction in the perception of physical fatigue in the Mel-Zinc group at the final treatment follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Urinary 6-sulfatoxymelatonin levels were significantly elevated though the treatment in experimental group vs. placebo (p < 0.0001); however, no significantly differences were observed for zinc concentration among participants. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS. This clinical study was registered on ClinicalTrials.gov (NCT03000777).

Prophylactic drug management for febrile seizures in children.

Prophylactic drug management for febrile seizures in children.

Protective effects of oral melatonin against cadmiuminduced neurotoxicity in Wistar rats

Protective effects of oral melatonin against cadmiuminduced neurotoxicity in Wistar rats

Melatonin and the health of menopausal women: A systematic review

Melatonin is involved in multiple changes that characterize the aging and can potentially be a safe and effective treatment for menopausal women. The aim of this study was to carry out a systematic review of the medical literature on the health benefits of oral melatonin administration on menopausal women. The electronic databases PubMed, Scopus, and Web of Science were searched systematically on interventional studies that evaluated the association between oral melatonin administration and the health of menopausal women. Risk for bias was assessed for randomized, controlled studies by the RoB v.2 tool and for non-randomized trials by the ROBINS-I tool. Twenty-four studies on melatonin treatment in various aspects of women's health were included in the final systematic review. The studies included 1,173 participants. No evidence was found for an independent effect of melatonin on hemodynamic measures or markers of glucose metabolism. There is some evidence that very low-density lipoprotein and triglycerides levels increase during melatonin administration. There is a fair amount of evidence that melatonin treatment has a favorable effect on bone density and BMI. Melatonin treatment improves EEG patterns and subjective sleep quality in postmenopausal women with preexisting sleep impairment. In a dose of 3mg and above, melatonin improves climacteric symptoms in one or more domains. The vast majority of the studies had a low risk for bias. In light of multiple health benefits and an excellent safety profile, melatonin administration should be considered in menopausal women.

Effects of preoperative melatonin on postoperative pain following cesarean section: A randomized clinical trial

BackgroundData regarding the analgesic effects of melatonin after the surgery is scare. So far, only one study has investigated the analgesic effect of melatonin during cesarean section. Objective: The present study was performed to investigate the effect of preoperative oral melatonin on pain intensity after cesarean section during spinal anesthesia. MethodsIn a double-blind randomized controlled clinical trial study, 204 patients undergoing elective cesarean section with class 1 and 2 anesthesia (ASA) were enrolled. Patients were randomly divided into 3 groups of 68 patients. Patients in group A were given 5 mg melatonin tablets, patients in group B were given 10 mg melatonin tablets, and group C was given placebo. All patients underwent spinal anesthesia with the same anesthesia protocol. Pain intensity, nausea, vomiting, pruritus and headache were assessed and recorded 2, 6, 12 and 24 h after surgery. The time of first dose of analgesia, the amount of opioid consumed within 24 h, and the time to resume physical activity was also recorded. Statistical analysis of data was performed using SPSS 20 software. ResultsRepeated measurements of pain intensity during the study showed that in all 3 groups pain intensity was significantly reduced during the study, p < 0.001, respectively. The intensity of pain was significantly different in groups B and C, groups B and A and groups A and C, P < 0.001, respectively. The pain reduction was greatest in group B, followed by group A and group C, respectively. The time interval between the end of surgery and the patient's need for analgesia was significant in group B compared to group A (P = 0.035) and C (P < 0.001) and also in group A compared to group C (P = 0.011). The mean dose of opioid was significantly least in group B, p < 0.001. The mean time to resume physical activity was also shortest in group B, p < 0.001 Headache and nausea/vomiting were observed in 7 patients (10.7%) group A and 7 patients (10.7%) in group C. None of the patients in group B developed complications. ConclusionThe results of the present study showed that the use of 10 mg of melatonin before cesarean section with spinal anesthesia is not only safe, but also reduces the severity of patients' pain, increases the duration of postoperative analgesia, reduces the need for analgesics after surgery and resumption of physical activity.