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Available online at ajdhs.com 

Asian Journal of Dental and Health Sciences 
Open Access to Dental and Medical Research 

Copyright  © 2025 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 
which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided 

the original author and source are credited  

 

 

Melatonin as Antianxiety drug in dentistry: A Review 

Sonal Gupta 1* , Rohan Shrivastava 2 , Abhinandan Patra 3 , Charu Aggarwal 2 , Rishi Nanda 4  

1 Head of the department, Department of Pediatric and Preventive Dentistry, K.D. Dental College and Hospital, Mathura, Uttar Pradesh, India 

2 Post Graduate Student, Department of Pediatric and Preventive Dentistry, K.D. Dental College and Hospital, Mathura, Uttar Pradesh, India 

3 Senior Lecturer, Department of Pediatric and Preventive Dentistry, K.D. Dental College and Hospital, Mathura, Uttar Pradesh, India 

4 Professor, Department of Pediatric and Preventive Dentistry, Eklavya Dental College and Hospital, Kotputli, Rajasthan, India 

Article Info: 
_____________________________________________ 
Article History: 

Received   04 Dec 2024     
Reviewed  02 Jan 2025 
Accepted   27 Jan 2025 
Published 15 March 2025 

_____________________________________________ 
Cite this article as:  

Gupta S, Shrivastava R, Patra A, Aggarwal C, 
Nanda R, Melatonin as Antianxiety drug in 
dentistry: A Review, Asian Journal of Dental 
and Health Sciences. 2025; 5(1):50-53    DOI: 
http://dx.doi.org/10.22270/ajdhs.v5i1.112          

Abstract 
_________________________________________________________________________________________________________________ 

Background: Anxiety is a barrier to dental care for many people. According to preliminary research, 
melatonin has sedative and anxiolytic effects. In dentistry, anxiety is a prevalent issue that may 
compromise the effectiveness of appropriate therapy. Many people with anxiety require oral 
premedication. Many people require heavy sedation or even general anesthesia to undergo dental 
care because they are so extremely nervous that oral sedation is ineffective. Even inserting an 
intravenous catheter can be challenging for these people because of their high levels of anxiety. The 
most often prescribed anxiolytic in these situations has been benzodiazepines, although several of 
these may cause paradoxical side effects. Since melatonin promotes natural drowsiness and 
enhances sedation, it has a strong chance of replacing benzodiazepines in this industry. This article 
aims to provide an overview of the use of melatonin as a dental premedication for patients who are 
uncooperative and apprehensive. 

Keywords: Anesthesia, Dental Anxiety, Melatonin, Premedication 

*Address for Correspondence:   

Sonal Gupta, Head of the department, Department of Pediatric and Preventive Dentistry, K.D. Dental College and Hospital, Mathura, Uttar Pradesh, 
India 

 

Introduction 

There is evidence linking general health issues to 
phobias, anxiety, or dread of the dentist. When you 
consider that 20% of patients delay going to the dentist 
because they need to, this is a significant fact. A dentist's 
dread is often persistent and challenging to overcome 
because of their own experiences or anxiety brought on 
by other patients' comments. 1. When a highly anxious 
patient has treatment under general anesthesia, their 
fear of needles may make it difficult to establish an 
intravenous line, or they may be afraid of being under 
anesthesia in addition to the dental surgery itself. One of 
the most efficient ways to assist patients in lowering their 
feelings of worry and panic is by oral premedication. 
Triazolam, midazolam, lorazepam, and diazepam are 
among the benzodiazepine class of medications that are 
most frequently used as oral anxiolytics for dental 
patients 2. There are widely known side effects of 
benzodiazepines class, and rejection on acceptance of 
those drugs on several occasions. In order to combat this, 
a novel pharmaceutical known as melatonin has entered 
the dentistry science and practice sector. It can be used as 
a premedication and has demonstrated anxiolysis 
abilities comparable to those of benzodiazepines, but 
without the majority of their negative effects 3,4. Thus, 

this review focuses on the use of melatonin in the field of 
dentistry with various advantages. 

Review 

The primary secretory product of the pineal gland, 
melatonin (MT), is linked to the control of the human 
body's circadian dark/light cycle. This hormone 
possesses immunomodulatory and antioxidant 
properties. Furthermore, it has no toxicity, but it is a very 
lipophilic substance, which makes it easier for it to pass 
through cell membranes and compartments. This 
suggests that it may be used therapeutically, for example, 
locally (1) in oral cavity damage caused by bacteria, 
viruses, or fungi, and (2) in postsurgical wounds from 
tooth extractions and other oral surgeries, where it 
promotes bone formation and reduces gingival and 
periodontal inflammation. (3) to improve dental implant 
osteointegration, as well as in autoimmune conditions 
including Sjorgen syndrome, lichen planus, aphthous 
ulceration, and herpes lesions, and (4) even to prevent 
oral cancer 5. In this regard, melatonin may have a 
number of positive impacts on oral health, including 
lessening the severity of herpes, which has been shown 
to be at least as effective as the medication acyclovir. Its 
exact mode of action is unknown, although it may be 
because it stimulates NK CD4 cells 6. In terms of oral 

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Gupta et al.                                                                                                                                   Asian Journal of Dental and Health Sciences. 2025; 5(1):50-53 

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health, melatonin may serve as a prognostic indicator for 
conditions like cancer. It may also be regarded as an onco-
static agent of several cancer types, but low plasma levels 
of it are linked to mouth cancer: such is breast, stomach, 
colon, and lung cancer, all of which are associated with 
low melatonin plasma levels. It diffuses passively from 
the blood to the saliva. For this reason, it was observed 
that the concentration of this in saliva was around 30% 
of that in plasma 7. When compared to blood levels, saliva 
contains less melatonin, most likely because it binds to 
albumin in almost 70% of plasma, preventing it from 
freely diffusing into saliva. Through the stimulation of 
type I collagen fiber formation and the control of 
osteoblastic and osteoclastic activity, local melatonin 
injection has been shown to have a number of possible 
effects in the oral cavity and may aid in the regeneration 
of alveolar bone. It should be taken into consideration 
because turning blood into saliva may help prevent oral 
infections and have positive effects on periodontal 
disease, herpes, and oral cancer. It is also significant for 
the treatment and prognosis of some tumors, such as 
epidermoid carcinoma 8-9. 

Biosynthesis 

Tryptophan is transformed into melatonin in 
pinealocytes. This synthesis is carried out in four phases 
10. Melatonin production occurs through a two-step 
mechanism after tryptophan first transforms into 
serotonin. These enzymes are hydroxyindole-O-
methyltransferase (HIOMT)11 and N-acetyl transferase 
(NAT), which inhibits the melatonin molecule. The 
pattern of day and night determines how this synthesis is 
managed, and night 12 is when it peaks. A number of 
factors affect how quickly this process proceeds. For 
example, norepinephrine and b1 adrenergic receptor 
activation play crucial roles in this synthesis. Under these 
conditions, melatonin production increases 12. Folate and 
vitamin B6 are also essential for this process. For the 
methylation process to occur, folate is required. Vitamin 
B6 is also involved in the decarboxylation of tryptophan. 
Melatonin synthesis won't happen if they're not in the 
environment. 

Pharmacokinetics 

Melatonin is quickly distributed (distribution half-life of 
0.5 to 5.6 minutes) and excreted following intravenous 
injection 13. Within 60 minutes of oral treatment, a peak 
in plasma concentration occurs. The decrease in plasma 
concentrations is biphasic, with half-lives of two and 
twenty minutes, respectively. Melatonin concentrations 
10–100 times greater than the physiological nocturnal 
peak can be achieved within an hour of consumption 
when a typical dose of 1–5 mg is taken; the 
concentrations revert to their baseline levels within 4–8 
hours. Melatonin is rapidly metabolized, mostly in the 
liver and subsequently in the kidney, following 
intravenous or oral administration. However, because 
there is no hepatic first pass following intravenous 
injection, the hepatic bio-degradation is less significant. 
It is converted to 6-hydroxymelatonin by the cytochrome 
P450 enzyme CYP1A2, conjugated with either 90% 
sulfuric acid or 10% glucuronic acid, and then eliminated 

in the urine. Urine contains around 5% of the 
unmetabolized melatonin that is expelled from the body. 

Mechanism of action as sedation and 
antianxiety 

Because melatonin binding to the MT1 receptor appears 
to affect the GABAa receptor via the G-coupled protein 
pathway 17, MT's anesthetic action is comparable to that 
of other anesthetics like propofol and benzodiazepines, 
enhancing the binding of GABA to the GABAa receptor 17. 
Faster recovery times and a lower incidence of 
postoperative excitement and sleep disturbances are 
linked to melatonin premedication, which can be taken 
orally in doses of 3 or 5 mg. This reduces the amount of 
propofol needed to achieve a bispectral index score of 45, 
which indicates a sufficient level of hypnosis for tracheal 
intubation without extending the length of the 
postoperative recovery room stay 18. 2 weeks after 
surgery compared to midazolam 19. Melatonin can reduce 
preoperative anxiety 50–100 minutes after 
administration, and it may be just as effective as standard 
treatment with midazolam in reducing preoperative 
anxiety (50–100 minutes after administration) in adults 
twenty, according to a recently published review 
evaluating the effect of melatonin on pre- and 
postoperative anxiety in adults when compared to MT 
given as premedication to placebo 20. Oral melatonin does 
not affect general cognitive and psychomotor abilities 
like midazolam does 21. Six hours after surgery, melatonin 
may help individuals feel less anxious. When children 
require general anesthesia for oesophageal dilatation 
procedures, oral melatonin appears to reduce 
postoperative agitation 22. Melatonin added to 
alprazolam may provide better anxiolysis than other 
medications in the same group, according to a 
randomized controlled factorial experiment 23. The time 
of premedication with melatonin may also be significant. 
Oral melatonin has been shown to have a sleep-onset 
impact within 30 minutes. However, Naguib and 
Samarkandi 19 found that 60 and 90 minutes after 
sublingual melatonin premedication, melatonin-treated 
patients had higher degrees of drowsiness. Melatonin 
appears to have strong potential for usage in lowering 
anxiety and inducing drowsiness in dental patients 
receiving general anesthesia without any notable side 
effects when compared to other drugs, such as 
benzodiazepines, which are currently the gold standard. 
An observational study was also carried out by Gupta S et 
al. 24 and found that postoperative anxiety decreased in 
correlation with cognitive and psychomotor scores. Their 
study also supported that melatonin can be used as a 
potent premedication drug in children as an anti-anxiety 
drug. 

Premedication in Dentistry 

Because oral sedation reduces tension and excitement 
and relaxes the patient for subsequent procedures, it can 
be useful in dentistry. Barbiturates had a low therapeutic 
index, the potential for addiction, and negative effects on 
the heart and lungs, despite their effectiveness in 
sedation. Benzodiazepines' broad margin of safety and 
efficacy in sedation, anxiolysis, and forgetfulness led to 
the ultimate replacement of barbiturate use for sedation. 



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Additionally, individuals with respiratory, hepatic, renal, 
or cardiovascular diseases require extra attention 15. 
Despite their effectiveness, these medications have a 
higher sedative impact that could cause a delay in 
recovery after sedation 3,28. Disorientation, decreased 
psychomotor performance, paradoxical reactions, 
excessive sedation that interacts with opioids, and sleep 
disturbance after surgery are some of the negative effects 
of midazolam. As a result, melatonin has been proposed 
as a pre-medication alternative to midazolam 28. 
Melatonin sublingual administration (0.05 mg kg−1 or 5 
mg) has been linked to preoperative anxiety reduction in 
adults without psychomotor impairment or recovery 
effects. 5–7.5 mL, or 3–4.5 mg of melatonin tablets, is the 
recommended dosage for syrup oral melatonin 25,26. 
Children can safely take up to 0.4 mg/kg of oral melatonin 
without experiencing any serious negative effects 27. 
Doses of up to 10 mg of melatonin have been used for 
youngsters who are uncooperative and as an alternative 
to traditional sedatives. However, a study found that 
premedication with 5 mg of melatonin was linked to 
drowsiness and pre-operative anxiolysis without causing 
post-operative impairment of psychomotor performance 
4. Exogenous melatonin has a peak effect between 45 and 
90 minutes 24. In addition to providing sedation, oral 
melatonin (0.4 mg/kg) administered 60–90 minutes 
before to surgery offers sufficient anxiolysis on par with 
oral midazolam (0.2 mg/kg) 21. For elective procedures 
using oral melatonin, the 2-4-6 fasting rule is applied. For 
clear foods, breast milk, formula milk, and solids, fasting 
before appointment should be of 2-3 hours, 4 hours, 6 
hours and 6-8 hours respectively 29. 

Other benefits of melatonin include: (1) it may also be 
more palatable to people who might find synthetic drugs 
uncomfortable, and (2) it has a short half-life, which 
reduces the likelihood of extended drowsiness compared 
to benzodiazepines 16. The only short-term side effect of 
oral administration of exogenous melatonin is 
drowsiness; however, the long-term effects of melatonin 
use are still unknown. Melatonin use is generally safe 
without significant adverse effects in healthy adults over 
the age of 18, who are not pregnant, and who do not have 
psychiatric disorders. 

Advantages of Melatonin 

Melatonin offers a number of potential advantages such 
as reduced post-operative sedation & less sleep 
disturbance, faster recovery, improved post-operative 
analgesia, and avoidance of respiratory depression, short 
half-life, dose dependent effect, offers greater taste 
expectance, Difficult to overdose Melatonin since it is a 
natural hormone. 

Disadvantages of Melatonin 

Regardless of the level of sedation, it's vital to fast before 
the session since stomach contents can be re-aspirated or 
vomited, which might cause pneumonia or pneumonitis 
29, Headache, Nausea, Daytime drowsiness may also 
occur in some patients. 

 

 

Safety Profile 

In contrast to midazolam, which causes weariness, 
drowsiness, and dizziness, melatonin has a few negative 
side effects, such as drowsiness. When comparing the 
safety profile of Melatonin to Midazolam 30, Ansari et al. 
(2017) found that children who were premedicated with 
Melatonin experienced a considerably decreased 
incidence of nausea, vomiting, and dizziness. In addition, 
Angelo et al. compared the safety profiles of melatonin 
and midazolam as premedication and found that the 
former was just as effective as the latter without causing 
any cognitive or psychomotor impairments. Additionally, 
compared to midazolam, melatonin in children can be 
used without significant adverse effects and requires less 
preoperative monitoring, according to Kain et al. and 
Tushar et al 30. 

Conclusion 

Melatonin has significance of oral sedation as a 
pharmacological behaviour management technique in 
pediatric dentistry. If it is given prior to pre operative 
dental treatment to uncooperative or fearful patient, it 
provides adequate anxiolysis and sedation. Oral 
Melatonin at 0.75 mg/kg appears to be the most effective 
drug for allaying pre-operative anxiety in children 
followed by 0.5 mg/kg. Even the doses of 0.5 mg/kg and 
0.75 mg/kg does not cause sedation or cognition and 
psychomotor dysfunction. In addition, new clinical 
studies are needed to improve therapeutic efficacy of this 
drug. Further experimental and well-designed clinical 
studies are required to explore the protective and 
therapeutic effects of melatonin as premedication in 
dentistry. 

Conflict of Interest: No 

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