Age: 18 - 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Montefiore Medical Center
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of the study is to assess if melatonin given for three nights before wisdom tooth surgery decreases post-operative pain and pain medication consumption. Patients will receive either melatonin or a placebo for three nights prior to surgery and we will measure pre-operative anxiety, preoperative sleep quality, post op pain medication consumption, post op pain scores, and blood values.
What safety data exists for melatonin treatment?Melatonin is generally well-tolerated and considered safe in short-term studies, with low toxicity reported. It is effective for sleep disorders in various populations, including children and adolescents, and is available over the counter. However, there is a lack of long-term safety data, and its effects during pregnancy and interactions with other medications are not fully understood. Indiscriminate use of unlicensed preparations is not advisable.158911
Is melatonin a promising drug for reducing pain after surgery?Yes, melatonin is a promising drug for reducing pain after surgery. It has been shown to lower pain levels and help patients feel calmer and more cooperative after surgery.3471012
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking melatonin or have a history of using psychotropic drugs.
What data supports the idea that Melatonin for Postoperative Pain is an effective drug?The available research shows that melatonin can be effective in reducing postoperative pain. For example, a study on patients undergoing colorectal surgery found that those who took melatonin before surgery experienced less pain compared to those who took a placebo. Another study on lumbar disc surgery patients also suggested that melatonin could help reduce pain after surgery. However, some studies have shown mixed results, indicating that more research is needed to confirm its effectiveness. Overall, melatonin appears to have potential as a pain-relief option after surgery, but its effectiveness can vary.2671213
Eligibility Criteria
This trial is for healthy adults aged 18-35 needing wisdom tooth surgery under IV sedation, without allergies to melatonin or pain meds, no chronic pain or psychiatric conditions, not pregnant, and not currently using melatonin. They must be able to understand and sign the consent form.Inclusion Criteria
I need 3-4 wisdom teeth removed with surgery under IV sedation.
I am between 18 and 35 years old.
Exclusion Criteria
I have used or am using medication for mental health issues.
My BMI is over 35.
I am allergic to melatonin, opioids, or some over-the-counter pain medications.
I am currently taking melatonin.
I have a sleep disorder like insomnia or narcolepsy.
Treatment Details
The study tests if taking melatonin for three nights before wisdom tooth removal can reduce post-surgery pain and need for painkillers. Participants will randomly receive either melatonin or a placebo pill (lactose) to compare effects on anxiety, sleep quality, post-op pain, medication use, and blood values.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Experimental Treatment - MelatoninExperimental Treatment1 Intervention
Premedication for three nights with 10mg melatonin
Group II: Control Treatment - LactosePlacebo Group1 Intervention
Premedication for three nights with lactose capsules
Find a clinic near you
Research locations nearbySelect from list below to view details:
Montefiore Medical Center Department of DentistryBronx, NY
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Who is running the clinical trial?
Montefiore Medical CenterLead Sponsor
References
Treatment of circadian rhythm disorders--melatonin. [2019]Melatonin has clear acute and delayed effects on sleep and circadian rhythms. Decrements in core temperature and alertness have been found at different times of day following low pharmacological and physiological doses of melatonin. When correctly timed, melatonin induces both phase advances and phase delays of the circadian system in humans. When timed to advance, the decrement in temperature and alertness and the degree of shift are closely related to dose. In both simulation and field studies, correctly timed melatonin can alleviate some of the problems of shiftwork and jet lag, notably enhancing sleep and alertness and hastening adaptation of rhythms to the imposed schedule. Performance effects and changes in sleep architecture need to be fully evaluated. The optimization of dose and formulation is also an area that requires further work. Whether or not recently developed melatonin analogs (72) will prove more or less useful than melatonin in adapting to phase shift remains to be seen. If incorrectly timed, melatonin has the potential to induce deleterious effects. While short-term studies indicate that it has very low toxicity, there are no long-term safety data. All of the studies reported here concern healthy adult volunteers and the use of a preparation licensed for human experimental use and available on a named patient basis on prescription. There are no data on uncontrolled preparations available over the counter in some countries. Its effects in pregnancy, interaction with other medications, and many other considerations remain to be addressed. Thus, while melatonin is useful in well-controlled conditions, the indiscriminate use of unlicensed preparations is not advisable.
Pineal opioid receptors and analgesic action of melatonin. [2019]Physicians have noted since antiquity that their patients complained of less pain and required fewer analgesics at night times. In most species, including the humans, the circulating levels of melatonin, a substance with analgesic and hypnotic properties, exhibit a pronounced circadian rhythm with serum levels being high at night and very low during day times. Moreover, melatonin exhibits maximal analgesic effects at night, pinealectomy abolishes the analgesic effects of melatonin, and mu opioid receptor antagonists disrupt the day-night rhythm of nociception. It is believed that melatonin, with its sedative and analgesic effects, is capable of providing a pain free sleep so that the body may recuperate and restore itself to function again at its peak capacity. Moreover, in conditions when pain is associated with extensive tissue injury, melatonin's ability to scavenge free radicals and abort oxidative stress is yet another beneficial effect to be realized. Since melatonin may behave as a mixed opioid receptor agonist-antagonist, it is doubtful that a physician simply could potentiate the analgesic efficacy of narcotics such as morphine by coadministering melatonin. Therefore, future research may synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics.
Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. [2022]Melatonin possesses sedative, hypnotic, analgesic, antiinflammatory, antioxidative, and chronobiotic properties that distinguish it as an attractive alternative premedicant. A qualitative systematic review of the literature concerning the perioperative use of melatonin as an anxiolytic or analgesic in adult patients was carried out using the recommended guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. Nine of the 10 studies showed statistically significant reduction of preoperative anxiety with melatonin premedication compared with placebo. An opioid-sparing effect or reduced pain scores were evident in five studies whereas three studies were contradictory. Thus, melatonin premedication is effective in ameliorating preoperative anxiety in adults, but its analgesic effects remain controversial in the perioperative period. Additional well designed randomized controlled trials are necessary to compare melatonin premedication with other pharmacological interventions, investigate its effect on more varied surgical populations, and to delineate its optimal dosing regimen.
Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. [2013]Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby may reduce anxiety, which leads to lower levels of pain. In this paper, we review the current evidence regarding the analgesic properties of melatonin in animals and humans with chronic pain.
Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders. [2022]Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non-24-hour sleep-wake disorder (or non-24). However, three additional commercially available melatonin receptor agonists-agomelatine, prolonged-release melatonin, and ramelteon-have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs.
The analgesic effects of exogenous melatonin in humans. [2022]The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a tmax value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.
Changes in Melatonin, Cortisol, and Body Temperature, and the Relationship Between Endogenous Melatonin Levels and Analgesia Consumption in Patients Undergoing Bariatric Surgery. [2019]Melatonin has analgesic, anti-inflammatory, sedative, and anxiolytic properties. However, the relationship between endogenous melatonin levels and postoperative analgesic requirements has not been well elucidated in patients undergoing bariatric surgery. We studied endogenous melatonin levels, cortisol levels, body temperatures, and the relationship between the level of endogenous melatonin and postoperative morphine consumption.
Therapeutic potential of melatonin agonists. [2019]Melatonin, a hormone secreted by the pineal gland, has been successfully employed to improve sleep in both normal patients and insomniacs, and for the treatment of circadian rhythm sleep disorders. Melatonergic MT1 and MT2 receptors exist in high concentrations in the suprachiasmatic nucleus of the hypothalamus and have been shown to be instrumental for the sleep-promoting and circadian rhythm-regulating effects of melatonin. A lack of consistency among reports on the therapeutic efficacy of melatonin has been attributed to differences in melatonin's bioavailability and the short half-life of the hormone. In view of the need for longer acting melatonergic agonists that improve sleep efficiency without causing drug abuse or dependency, ramelteon (Rozerem™, Takeda) was developed. Ramelteon, which acts via MT1/MT2 melatonergic agonism, has been found clinically effective for improving total sleep time and sleep efficiency in insomniacs. Agomelatine (Valdoxan™, Servier) is another MT1/MT2 melatonergic agonist that also displays antagonist activity at 5-HT2C serotonin receptors. Agomelatine has been found effective in treating depression and sleep disorders in patients with major depressive disorder. A slow-release preparation of melatonin (Circadin™, Neurim) has been shown to be effective in treating sleep disorders in the elderly population.
Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. [2022]To evaluate the efficacy and safety of melatonin in the treatment of sleep onset insomnia in children and adolescents.
Phase II double-blind randomised controlled trial of exogenous administration of melatonin in chronic pain (DREAM-CP): a study protocol. [2021]Chronic pain is prevalent, and approximately half of patients with chronic pain experience sleep disturbance. Exogenous melatonin is licensed to treat primary insomnia and there is some evidence for analgesic effects of melatonin.The aim of this study is to investigate the effects of oral melatonin (as Circadin) 2 mg at night in adults with severe non-malignant pain of at least 3 months' duration.
Perspective on Melatonin Use for Sleep Problems in Autism and Attention-Deficit Hyperactivity Disorder: A Systematic Review of Randomized Clinical Trials. [2020]Melatonin is a hormone produced by the pineal gland and is available over the counter for treating sleep problems in the pediatric population. We conducted a systematic review of randomized clinical trials (RCTs) on MEDLINE and included six studies that met our inclusion criteria. RCTs were conducted in patients from two to 18 years of age with a diagnostic and statistical manual of mental disorders (DSM)-IV diagnosis of autism spectrum disease (ASD) and/or attention-deficit hyperactivity disorder (ADHD) in both short-term and long-term RCTs ranging from eight-week to 52-week studies. The mean difference in the children's sleep disorder showed statistically significant improvement in sleep duration and sleep latency onset compared to the placebo. Overall, a high response rate was observed in the melatonin group compared to the placebo in treating sleep problems in children. Melatonin is a well-tolerated and safe medication in the dose range of 2-10 mg/day in the child and adolescent population.
The Effect of Preoperative Sublingual Melatonin on Postoperative Pain Severity in Patients Undergoing Colorectal Surgery: A Triple-Blinded Randomized Trial. [2022]Background: Postoperative pain has detrimental physiologic and psychologic effects on patients' outcomes, such as increased postoperative morbidity, delayed recovery, and reduced patient satisfaction. This study aimed to determine the effect of preoperative sublingual melatonin on pain severity after colorectal surgery. Methods: We performed a randomized, placebo-controlled, triple-blinded study to test the efficacy of 6 mg of sublingual melatonin or placebo 1 hour preoperative on pain severity and sedation of 60 patients after colorectal surgeries. Pain and sedation were assessed by numerical verbal response (NVR) and the Ramsey sedation score, respectively, at the baseline, 1, 2, 6, 12, and 24 hours after surgery. The repeated measures analysis of variance was used to assess group × time interaction, and the Bonferroni adjustment was used for between-group comparisons. Results: A total of 60 patients with a mean ± SD age of 49.35 years were equally randomized to the study groups. There was no significant difference between groups with respect to the baseline characteristics. The mean score of pain severity of patients in the melatonin group was significantly lower compared with the placebo group at 2, 6, 12, and 24 hours after surgery. The total mean pain score for the first 12 hours (mean difference [MD] [SE], 0.41 [0.12]; 95% CI, 0.17-0.65; [P = 0.012]) and the mean score of pain in 24 hours after surgery were significantly lower in the melatonin group in comparison with the placebo group (MD [SE], 0.44 [0.13]; 95% CI, 0.19-0.69; [P = 0.001]). Compared with the placebo group, the percent of patients who were cooperative, aware, and calm was significantly higher in the melatonin group at the baseline (43.3% vs 53.3%) and at 1 (36.7% vs 60%) and 2 hours (33.3% vs 80%). Conclusion: The use of 6 mg preoperative melatonin sublingual tablet in patients with colorectal surgeries could reduce the severity of postoperative pain, patients' restlessness and anxiety, and increase patients' cooperation and calmness. Therefore, it seems that sublingual melatonin is an effective drug in controlling postoperative pain.
The Effect of Preoperative Oral Melatonin on Postoperative Pain after Lumbar Disc Surgery: A Double-Blinded Randomized Clinical Trial. [2023]Despite advances in surgical and anesthesiology techniques, many patients continue to experience postoperative pain after lumbar disc surgeries. The aim of this study was to investigate the effect of preoperative oral melatonin on the severity of postoperative pain after lumbar laminectomy/discectomy.