Managing preoperative anxiety is a major issue in anaesthesia, directly influencing patient well-being and postoperative results. Melatonin, mainly known for regulating the sleep-wake cycle, plays a crucial role in this context. What are the mechanisms of action of this hormone and how can it improve the pre-operative experience of patients? This article explores the anxiolytic effects of melatonin and its potential as an adjuvant in anaesthesia.
Is it a good idea to take melatonin before an operation?
Melatonin, synthesised by the pineal gland, regulates the circadian rhythm and has antioxidant, anti-inflammatory and immunomodulatory properties. Its main receptors, MT1 and MT2, are involved in a variety of neuroendocrine processes, including the modulation of mood and anxiety.
Preoperative anxiety: an underestimated problem
Preoperative anxiety affects around 60% of patients prior to surgery. This condition is associated with cardiovascular complications, increased anaesthetic requirements and prolonged postoperative recovery. Conventional treatments include benzodiazepines, but these have side effects such as excessive sedation and cognitive impairment.
Does melatonin calm anxiety?
Melatonin plays a key role in modulating anxiety by acting on several interconnected biological systems. It exerts its effect mainly via activation of the MT1 and MT2 receptors present in the central nervous system.
This activation helps to reduce the activity of the neuronal circuits involved in stress responses, thereby promoting a state of calm without excessively altering alertness. Melatonin also interferes with the hypothalamic-pituitary-adrenal (HPA) axis, a central regulator of the stress response. By reducing the release of cortisol, a hormone associated with acute stress, it helps maintain a hormonal balance conducive to relaxation.
Melatonin also influences the GABAergic system, boosting the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter. This action contributes to a soothing effect on the entire nervous system, without inducing marked sedation, unlike other pharmacological anxiolytics.
Thanks to this combination of effects, melatonin is particularly useful for reducing pre-operative anxiety while preserving patients’ cognitive and psychomotor functions.
Clinical efficacy of melatonin in the pre-operative period
The clinical efficacy of melatonin in the pre-operative period has been widely documented, with promising results that position it as a viable alternative to benzodiazepines. A study by Khare et al (2018) (2) demonstrated that an oral dose of 6 mg of melatonin, administered two hours before surgery, significantly reduced preoperative anxiety. This reduction was accompanied by fewer cognitive side effects compared with a dose of 0.25 mg of alprazolam, a commonly used anxiolytic.
The efficacy of melatonin in children has also been confirmed. A paediatric study showed that doses of between 0.5 and 0.75 mg/kg administered before the operation not only reduced anxiety, but also improved the cooperation of young patients during anaesthetic induction. These observations highlight the dual advantage of melatonin: effective anxiolysis without compromising alertness or cognitive functions. (3)
In short, these studies show that melatonin, with its high safety profile and proven anxiolytic effects, is a valuable therapeutic option in the pre-operative setting, particularly in patients for whom a reduction in side-effects is paramount.
Dosage and safety of use
Melatonin is generally well tolerated, with a minimal side-effect profile. The doses used in the pre-operative period vary between 3 and 10 mg, administered one to two hours before the operation. However, further studies are needed to determine the optimal doses according to age, weight and type of surgery.
Precautions for use :
- Avoid in cases of serious hormonal disorders.
- Increased monitoring in elderly patients to limit the risk of prolonged drowsiness.
Is it dangerous to take melatonin before a general or local anaesthetic?
Taking melatonin before anaesthesia, whether general or local, appears to have a high safety profile, according to current data in the scientific literature. (1) As an endogenous hormone, melatonin is well tolerated by the body, with a limited risk of adverse effects, even when administered in exogenous doses. The clinical studies available, particularly those relating to its use in the pre-operative period, show that melatonin can not only effectively reduce anxiety and improve sleep quality, but also exert sedative and analgesic effects without causing excessive sedation or major disruption of cognitive or psychomotor functions.
However, as with any drug or active substance, melatonin should be used with caution, particularly in the context of complex anaesthetic protocols. Potential interactions with certain anaesthetic agents or specific patient conditions (advanced age, co-morbidities, concomitant treatments) require prior medical assessment. Studies have also suggested that melatonin may reduce cortisol secretion, thereby modulating the perioperative stress response, which could have implications for postoperative recovery.
Melatonin therefore appears to be a safe and effective option for improving perioperative management, particularly as an adjuvant in reducing anxiety and pain. However, its use must be supervised by a healthcare professional, in order to optimise the benefits while minimising the risks. Further research is needed to refine recommendations regarding optimal dosages, specific populations and possible contraindications in an anaesthetic context.
Sources
- Front. Pharmacol Sec. Neuropharmacology Volume 14 – 2023: The relationship between anesthesia and melatonin: a review
- Khare et al (2018): Comparison of effects of oral melatonin with oral alprazolam used as a premedicant in adult patients undergoing various surgical procedures under general anaesthesia: A prospective randomized placebo-controlled study. Anesthesia: Essays and Researches, 12(3), 657-662. doi:10.4103/aer.AER_90_18.
- Kurdi and Muthukalai (2016): A comparison of the effect of two doses of oral melatonin with oral midazolam and placebo on pre-operative anxiety, cognition and psychomotor function in children: A randomized double-blind study. Indian Journal of Anaesthesia, 60(10), 744-750. doi:10.4103/0019-5049.191688.
