Comparing the Effect of Melatonin, Diazepam, and Placebo on Decreasing the Level of Anxiety Preoperatively

Comparing Melatonin to Diazepam as a Premedication: a Triple-blind, Randomized, Placebo Controlled Clinical Trial

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06103188

Enrollment

Registered

2023-10-26

Start date

2023-10-02

Completion date

2023-10-30

Last updated

2025-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anxiety, Preoperative Anxiety

Keywords

Preoperative anxiety, Anxiolytic, Melatonin, Diazepam, Sedation, Premedication

Brief summary

The goal of this clinical trial is to compare the effect of melatonin, diazepam, and placebo on the level of anxiety in patients undergoing surgery. The main question it aims to answer is: • Is melatonin effective in reducing the anxiety of patients undergoing surgery? Participants will be asked to answer a questionnaire then they will receive either melatonin, diazepam, or placebo, and then after an hour, they will answer the same questionnaire again. Researchers will compare melatonin, diazepam, and placebo to see if melatonin is as effective in reducing the level of anxiety as diazepam in patients undergoing surgery.

Detailed description

Anxiety is a tense unpleasant sensation experienced by many individuals secondary to their concerns or due to the anticipation of an unpleasant experience like a surgery. Even with the advancement of medical treatment, preoperative anxiety remains a widespread complaint that affects the patients psychologically and physically, and at the same time adversely affecting the outcome of the operation and the experience of the patient. In this triple-blind, randomized clinical study, we aim to compare melatonin to diazepam regarding its efficacy in reducing preoperative anxiety, as well as assessing multiple other effects such as sedation, orientation, and cognition, by applying validated tools to patients undergoing elective surgeries before and after administering the premedication.

Interventions

DRUGPlacebo

The placebo pill will be given to the patients 1 hour prior to their planned surgery.

DRUGDiazepam

Diazepam will be given to the patients 1 hour prior to their planned surgery.

DRUGMelatonin

Melatonin will be given to the patients 1 hour prior to their planned surgery.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* ASA 1 or 2 * Posted for general anesthesia * Aging between 18 and 65 years

Exclusion criteria

* Allergy to any of the drugs under study * Pregnancy * Illiteracy * Any mental illness * Taking antipsychotics, antidepressants, anxiolytics, or sedatives

Design outcomes

Primary

Measure	Time frame	Description
Change in the Anxiety Score Using the Visual Analogue Score for Anxiety Between Treatment Arms	Before administration of premedication, and after 1 hour from the administration of the premedication.	VAS (Visual Analogue Score) Anxiety Scale is a 100 mm long scale. The scale is marked in millimeters from 0 to 100, where 0 correlates with no anxiety at all, and 100 correlates to anxiety as bad as possible. The maximum score is 100 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The more the reduction in anxiety from baseline, the better the outcome.
Change in Anxiety Score Based on The Amsterdam Preoperative Anxiety and Information Scale (APAIS) Between Treatment Arms	Before administration of premedication, and after 1 hour from the administration of the premedication.	The Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a self-reported questionnaire. The scale consists of six items, four of which assess the patient's anxiety, while the last two assess the patients' need-for-information and the patient must choose how much he agrees with each item on a scale of 1 (not at all) to 5 (very much). The scores of each item are summed to provide the total score. The minimum score possible is 6 and the maximum score is 30, the higher the score the higher the anxiety level and need for information. The scale consists of two subscales: Need for Information subscale: consists of two items (minimum score of 2 and maximum score of 10, the higher the score the more need for information). Anxiety subscale: consists of four items (minimum score of 4 and maximum score of 20, the higher the score the higher the anxiety level). The total scale is the sum of the two subscales.

Secondary

Measure	Time frame	Description
Change in Sedation Between Treatment Arms	Before administration of premedication, and after 1 hour from the administration of the premedication.	Ramsay sedation scale (RSS) is scored based on the level of sedation. It consists of six levels scored from 1 to 6: 1. \- Patient is anxious and agitated or restless, or both 2. \- Patient is cooperative, oriented, and tranquil 3. \- Patient responds to commands only 4. \- Patient exhibits brisk response to light glabellar tap or loud auditory stimulus 5. \- Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus 6. \- Patient exhibits no response. As the patient becomes more sedated he receives a higher score on the scale (minimum of 1 and maximum of 6).
Change in Orientation Between Treatment Arms	Before administration of premedication, and after 1 hour from the administration of the premedication.	Orientation will be assessed with a three-point scale as follows: 0 - None 1. \- Orientation in either time or place 2. \- Orientation in both

Other

Measure	Time frame	Description
Change in the Anxiety Score Using the Visual Analogue Score for Anxiety Between Genders	Before administration of premedication, and after 1 hour from the administration of the premedication.	VAS (Visual Analogue Score) Anxiety Scale is a 100 mm long scale. The scale is marked in millimeters from 0 to 100, where 0 correlates with no anxiety at all, and 100 correlates to anxiety as bad as possible. The maximum score is 100 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The more the reduction in anxiety from baseline, the better the outcome.
Change in Anxiety Score Based on The Amsterdam Preoperative Anxiety and Information Scale (APAIS) Between Genders	Before administration of premedication, and after 1 hour from the administration of the premedication.	The Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a self-reported questionnaire. The scale consists of six items, four of which assess the patient's anxiety, while the last two assess the patients' need-for-information and the patient must choose how much he agrees with each item on a scale of 1 (not at all) to 5 (very much). The scores of each item are summed to provide the total score. The minimum score possible is 6 and the maximum score is 30, the higher the score the higher the anxiety level and need for information. The scale consists of two subscales: Need for Information subscale: consists of two items (minimum score of 2 and maximum score of 10, the higher the score the more need for information). Anxiety subscale: consists of four items (minimum score of 4 and maximum score of 20, the higher the score the higher the anxiety level). The total scale is the sum of the two subscales.
Change in Sedation Between Genders	Before administration of premedication, and after 1 hour from the administration of the premedication.	Ramsay sedation scale (RSS) is scored based on the level of sedation. It consists of six levels scored from 1 to 6: 1. Patient is anxious and agitated or restless, or both 2. Patient is cooperative, oriented, and tranquil 3. Patient responds to commands only 4. Patient exhibits brisk response to light glabellar tap or loud auditory stimulus 5. Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus 6. Patient exhibits no response. As the patient becomes more sedated he receives a higher score on the scale (minimum of 1 and maximum of 6).
Change in Orientation Between Genders	Before administration of premedication, and after 1 hour from the administration of the premedication.	Orientation will be assessed with a three-point scale as follows: 0 - None 1. \- Orientation in either time or place 2. \- Orientation in both

Countries

Jordan

Participant flow

Participants by arm

Arm	Count
Melatonin A 5mg melatonin pill Melatonin: Melatonin will be given to the patients 1 hour prior to their planned surgery.	28
Diazepam A 5mg diazepam pill Diazepam: Diazepam will be given to the patients 1 hour prior to their planned surgery.	23
Placebo A 5mg vitamin B12 pill Placebo: The placebo pill will be given to the patients 1 hour prior to their planned surgery.	25
Total	76

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Lost to Follow-up	1	6	4

Baseline characteristics

Characteristic	Melatonin	Diazepam	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	28 Participants	23 Participants	25 Participants	76 Participants
Age, Continuous	36 years	43 years	37 years	38.5 years
Baseline Amsterdam Preoperative Anxiety and Information Scale Baseline APAIS	10 units on a scale	11 units on a scale	6 units on a scale	10 units on a scale
Baseline Amsterdam Preoperative Anxiety and Information Scale Baseline APAIS Anxiety subscale	7.5 units on a scale	6 units on a scale	4 units on a scale	6 units on a scale
Baseline Amsterdam Preoperative Anxiety and Information Scale Baseline APAIS Need for Information subscale	3.5 units on a scale	5 units on a scale	2 units on a scale	4 units on a scale
Baseline orientation score	2 units on a scale	2 units on a scale	2 units on a scale	2 units on a scale
Baseline Ramsay sedation score	2 units on a scale	2 units on a scale	2 units on a scale	2 units on a scale
Baseline Visual Analogue Scale for Anxiety score (VAS-A)	10 units on a scale	30 units on a scale	20 units on a scale	30 units on a scale
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants	23 Participants	25 Participants	76 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	16 Participants	13 Participants	10 Participants	39 Participants
Sex: Female, Male Male	12 Participants	10 Participants	15 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 28	0 / 23	0 / 25
other Total, other adverse events	0 / 28	0 / 23	0 / 25
serious Total, serious adverse events	0 / 28	0 / 23	0 / 25

Outcome results

Primary

Change in Anxiety Score Based on The Amsterdam Preoperative Anxiety and Information Scale (APAIS) Between Treatment Arms

The Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a self-reported questionnaire. The scale consists of six items, four of which assess the patient's anxiety, while the last two assess the patients' need-for-information and the patient must choose how much he agrees with each item on a scale of 1 (not at all) to 5 (very much). The scores of each item are summed to provide the total score. The minimum score possible is 6 and the maximum score is 30, the higher the score the higher the anxiety level and need for information. The scale consists of two subscales: Need for Information subscale: consists of two items (minimum score of 2 and maximum score of 10, the higher the score the more need for information). Anxiety subscale: consists of four items (minimum score of 4 and maximum score of 20, the higher the score the higher the anxiety level). The total scale is the sum of the two subscales.