Comparison of Anxiolytic Drugs of Diazepam and Zolpidem in Patients Undergoing Extraction

Anxiolytic drugs are a class of drugs that reduce the anxiety levels in the individuals by nonspecifically binding to the GABAα located throughout the central nervous system. The aim of this study was to compare the anxiolytic effects of diazepam and Zolpidem in patients undergoing extraction. This was a cross-sectional study conducted at a university setting, with a sample size of 100 patients, of the age group 25-45 years. 50 patients were administered with Tab. Diazepam and 50 patients with Tab. Zolpidem one hour before the surgical procedure. The Hamilton Anxiety Rating Scale (HAM-A Scale) was used to record the patient's anxiety levels before and during the extraction procedure. These data were then recorded in MS Excel Sheet and imported to SPSS for statistical analysis. From this study, it can be seen that most of the patients were females and mainly between the age group 25-35 years. Diazepam had significantly lesser post sedation anxiety levels in comparison with its post sedation levels than zolpidem with, a statistically significant difference (p<0.001). Therefore, it can be concluded that diazepam had better post sedation effects than zolpidem in patients undergoing extraction as patients presented with lesser severity in their anxiety levels. Original Research Article Deepak et al.; JPRI, 32(18): 178-187, 2020; Article no.JPRI.59810 179


INTRODUCTION
Sedatives have been known for their efficacy in managing anxiety during dental treatment. Patients generally present with a moderate to a high level of fear and anxiety during a surgical procedure [1,2]. Oral sedation helps the patients to combat mild to moderate levels of fear and anxiety, but they are commonly less effective in patients with higher levels of anxiety, and for these patients, drugs can be administered intravenously for better action. On intravenous sedation, few individuals with higher levels of anxiety require a deeper level of sedation or general anesthesia. The patient's age is an important factor in the selection of an oral sedative drug and it's dosage. The widely accepted is the oral route of administration as it is easy, painless, and inexpensive. Sedatives used to produce anxiolysis or minimal sedation in healthy adults are safe and effective at a required dosage [3]. For geriatric patients, it is important to select a particular dosage and drug as it may interact with the physiological and psychological changes, as older adults can have a higher risk of systemic diseases [4].
One of the commonly used sedatives is benzodiazepines such as diazepam, zaleplon, etc. They promote the binding to the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) receptors in the brain. They are receptors of multi-subunit complexes associated with gated chloride ion (Cl−) channels that are seen within the cell membrane of neurons. When the receptor gets activated by GABA, the channel opens allowing a greater influx of chloride ions and results in more negative resting membrane potential. This thereby results in sedation in individuals.

Zolpidem
is also an anxiolytic nonbenzodiazepine drug that binds to the omega 1 benzodiazepine recognition sites located within the GABAA receptor complex [5]. This is a highly lipophilic molecule and has a fast onset of action (usually within 20-40 minutes), and peak plasma levels 1-2 hours after oral administration. Diazepam has 100% oral bioavailability and commonly used dosages are 2-10 mg for adults [6]. Zolpidem produces muscle relaxation and anticonvulsant effects in patients only at a higher dose than the hypnotic dose [7]. Zolpidem has a rapid onset of action, usually within 30 minutes whereas it has a short half-life and no active metabolites. Flumazenil is the antagonist drug used for higher zolpidem sedation [8].
Extraction is one of the commonly performed surgical procedures in a dental clinic, and it is important to undergo a painless extraction in patients. Sedatives drugs play a major role in painless extractions as they block the neurotransmitters and suppress the anxiety levels and this will help in performing a successful procedure. Previously our department has published extensive research on various aspects of prosthetic dentistry [9][10][11][12][13][14][15][16][17][18][19], this vast research experience has inspired us to research about the comparison of anxiolytic drugs of diazepam and zolpidem in patients undergoing extraction.

MATERIALS AND METHODS
This was a cross-sectional study conducted at a university setting, Chennai. The sample size was 100 patients, of the age group 25-45 years, with 50 males and 50 females. There were certain inclusion and exclusion criteria for sample selection. Inclusion Criteria included only patients undergoing extraction of root stumps and grossly decayed tooth. Exclusion Criteria were patients with systemic diseases and on medications, third molar impactions, mobile tooth, pregnant females, root canal treated tooth advised for extraction, and in patients older than 45 years. Anxiolytic drugs Tab. Diazepam (10mg) and Tab. Zolpidem (10mg) were administered in patients undergoing extraction. 50 patients were administered with Tab. Diazepam and 50 patients were administered with Tab. Zolpidem one hour before undergoing the surgical procedure. Both drugs have adequate bioavailability for sustained pharmacological effects. All the patients included in the study ad body weight ranging from 75-90 kg and hence 10 mg of drug was chosen.
The Hamilton Anxiety Rating Scale (HAM-A Scale) was used to record the patient's anxiety levels before and during the extraction procedure. This was distributed to patients undergoing extraction, before and after the drug was administered orally. This sheet had a series of scores from 0-4, and for each patient, it was summed up to a total score of 56, in which a score of 17 or less indicates mild anxiety severity, 18 to 24 indicates mild to moderate anxiety severity, 25 to 30 indicates a moderate to severe anxiety severity.
These data were then recorded in MS Excel Sheet and imported to SPSS for statistical analysis. The statistical tests used were the inferential tests (chi-square test) and the descriptive statistics. The software used was SPSS by IBM. The independent variables were age and gender. The dependent variables were HAM-A scale scores for Diazepam and Zolpidem, pre and post sedation. The graphical illustration was done using SPSS Version 20.0.

RESULTS AND DISCUSSION
In this study, it can be seen that 58.0% of the patients were distributed in the age group between 25-35 years and 42.0% were in the age group between 36 1) and 51% of the study population were females and 49% of subjects were males (Fig on pre sedation HAM-A scores for diazepam, 68.9% of the patients had a score between 18 18% had a score between 25-30, and 14% had a score of <17 (Fig. 3). Based on post sedation HAM-A scores of diazepam, 58% of t had a score between 18-24, 34% had a score of <17 and 8% had a score between 25 Based on pre sedation HAM zolpidem, 56% of the patients had a score between 18-24, 24% had a score of <17 and 20% e then recorded in MS Excel Sheet and imported to SPSS for statistical analysis. The statistical tests used were the square test) and the descriptive statistics. The software used was SPSS by IBM. The independent variables were nd gender. The dependent variables were A scale scores for Diazepam and Zolpidem, pre and post sedation. The graphical illustration was done using SPSS Version 20.0.

RESULTS AND DISCUSSION
In this study, it can be seen that 58.0% of the ere distributed in the age group 35 years and 42.0% of the patients were in the age group between 36-45years ( Fig.  1) and 51% of the study population were females and 49% of subjects were males (Fig. 2). Based A scores for diazepam, 68.9% of the patients had a score between 18-24, 30, and 14% had a 3). Based on post sedation A scores of diazepam, 58% of the patients 24, 34% had a score of <17 and 8% had a score between 25-30 ( Fig. 4). Based on pre sedation HAM-A scores for zolpidem, 56% of the patients had a score 24, 24% had a score of <17 and 20% had a score between 25-30 (Fig post sedation HAM-A scores for zolpidem, 54% of the patients had a score between 18 had a score of <17 and 4% had a score between 25-30 ( Fig. 6). On the association between age and HAM-A scores of pre and post sedation with diazepam, in 25-35 years age gr mean score of 1.76 was seen for pre sedation and there was a decrease in the mean score (1.41) after post sedation with diazepam, whereas in 36-45 years age group, a higher mean score of 2.43 was seen for pre sedation and there was a decrease (2.19) after post sedation with diazepam, p value-0.00 (<0.05), statistically significant ( Fig  7). On the association between age and HAM scores of pre and post sedation with zolpidem, in 25-35 years age group, a higher mean score of 1.59 was seen for pre sedation and there was a decrease in the mean score (1.28) after post sedation with zolpidem, whereas in 36 age group, a higher mean score of 2.48 was seen for pre sedation and there was a decrease in the mean score (2.10) after post sedation with zolpidem, p-value-0.01 (<0.05), statistically significant ( Fig. 8). On the association between gender with pre and post sedation with diazepam, in females, a higher mean score of 1.73 was seen for pre sedation and there was a decre Bar graph represents the distribution of patients based on age, where the X represents the age group of the patients and the Y-axis represents the number of patients in percentage. 58.0% of the patients were distributed in the age group between 25 of the patients were in the age group between 36-45years (red) 187, 2020; Article no.JPRI.59810 30 (Fig. 5). Based on A scores for zolpidem, 54% of the patients had a score between 18-24, 42% had a score of <17 and 4% had a score between 6). On the association between age A scores of pre and post sedation with 35 years age group, a higher mean score of 1.76 was seen for pre sedation and there was a decrease in the mean score (1.41) after post sedation with diazepam, 45 years age group, a higher mean score of 2.43 was seen for pre sedation and there was a decrease in the mean score (2.19) after post sedation with diazepam, p-0.00 (<0.05), statistically significant (Fig.  7). On the association between age and HAM-A scores of pre and post sedation with zolpidem, in 35 years age group, a higher mean score of 1.59 was seen for pre sedation and there was a decrease in the mean score (1.28) after post sedation with zolpidem, whereas in 36-45 years age group, a higher mean score of 2.48 was seen for pre sedation and there was a decrease fter post sedation with 0.01 (<0.05), statistically 8). On the association between gender with pre and post sedation with diazepam, in females, a higher mean score of 1.73 was seen for pre sedation and there was a decrease Bar graph represents the distribution of patients based on age, where the X-axis axis represents the number of patients in percentage. 58.0% of the patients were distributed in the age group between 25-35 years (blue) 45years (red) in the mean score (1.33) after post sedation with diazepam, whereas in males, a higher mean score of 2.37 was seen for pre sedation and there was a decrease in the mean score (2.16) after post sedation with diazepam, p (>0.05), statistically insignificant (Fig. 9). On the association between gender with pre and post sedation with zolpidem, in females, a higher in the mean score (1.33) after post sedation with diazepam, whereas in males, a higher mean score of 2.37 was seen for pre sedation and s a decrease in the mean score (2.16) after post sedation with diazepam, p-value-0.20 (>0.05), statistically insignificant (Fig. 9). On the association between gender with pre and post sedation with zolpidem, in females, a higher mean score of 1.53 was se and there was a decrease in the mean score (1.18) after post sedation with zolpidem, whereas in males, a higher mean score of 2.41 was seen for pre sedation and there was a decrease in the mean score (2.08) after post sedation with zolpidem, p-value-0.019 (<0.05), statistically significant (Fig. 10). mean score of 1.53 was seen for pre sedation and there was a decrease in the mean score (1.18) after post sedation with zolpidem, whereas in males, a higher mean score of 2.41 was seen for pre sedation and there was a decrease in the mean score (2.08) after post sedation with 0.019 (<0.05), statistically Bar graph represents the distribution of patients based on gender, where the X-axis axis represents the number of patients in percentage. 51% of the study population were females (blue) and 49% of subjects were males

Fig. 4. Bar graph represents the distribution of patients based on Post sedation HAM atients administered with Diazepam, where the X-axis represents the post sedation HAM axis represents the number of patients in percentage. 58% of the patients had a score between 18-24 (red), 34% had a score of <17 (blue) and
between 25-30 (green)

Fig. 5. Bar graph represents the distribution of patients based on Pre sedation HAM A scores in patients administered with Zolpidem, where X-axis represents the pre sedation HAM A axis represents the number of patients in percentage. 56% of the patients had a score between 18-24 (red), 24% had a score of <17 (blue) and 20% had a score between 25-30 (green)
187, 2020; Article no.JPRI.59810

Fig. 7. Bar graph represents the association between age with Pre and posts sedation HAM
scores in patients administered with Diazepam where the X patients and the Y-axis represents the Mean HAM age group, a higher mean score of 1.76 was seen for pre sedation and there was a decrease in the mean score (1.41) after post sedation with diazepam, whereas in 36 higher mean score of 2.43 was seen for pre sedation and there w score (

Bar graph represents the distribution of patients based on Post sedation HAM A scores in patients administered with Zolpidem, where X-axis represents the post sedation HAM A axis represents the number of patients in percentage. patients had a score between 18-24 (red), 42% had a score of <17 (blue) and 4% had a score between 25-30 (green)
Bar graph represents the association between age with Pre and posts sedation HAM scores in patients administered with Diazepam where the X-axis represents the age of the axis represents the Mean HAM-A scores for Diazepam. In the 25 age group, a higher mean score of 1.76 was seen for pre sedation and there was a decrease in the mean score (1.41) after post sedation with diazepam, whereas in 36-45 years age group, a higher mean score of 2.43 was seen for pre sedation and there was a decrease in the mean score (

Bar graph represents the distribution of patients based on Post sedation HAM A scores axis represents the post sedation HAM A axis represents the number of patients in percentage. 54% of the 24 (red), 42% had a score of <17 (blue) and 4% had a score
Bar graph represents the association between age with Pre and posts sedation HAM-A axis represents the age of the A scores for Diazepam. In the 25-35 years age group, a higher mean score of 1.76 was seen for pre sedation and there was a decrease in 45 years age group, a as a decrease in the mean 0.00 (<0.05), statistically significant] Bar graph represents the association between gender with Pre and posts sedation A scores in patients administered with Diazepam where the X-axis represents the gender axis represents the Mean HAM-A scores for Diazepam. In fem higher mean score of 1.73 was seen for pre sedation and there was a decrease in the mean score (1.33) after post sedation with diazepam, whereas in males, a higher mean score of 2.37 was seen for pre sedation and there was a decrease in the mean score (

Fig. 8. Bar graph represents the association between age with Pre and posts sedation HAM-A axis represents the age of the A scores for Zolpidem. In the 25-35 years
and there was a decrease in 45 years age group, a higher mean score of 2.48 was seen for pre sedation and there was a decrease in the mean

(<0.05), statistically significant]
Bar graph represents the association between gender with Pre and posts sedation axis represents the gender A scores for Diazepam. In females, a higher mean score of 1.73 was seen for pre sedation and there was a decrease in the mean score (1.33) after post sedation with diazepam, whereas in males, a higher mean score of 2.37 ore (2.16) after post

Fig. 10. Bar graph represents the association between gender with Pre and post sedation HAM A scores in patients administered with Zolpidem where X patients and Y-axis represents the Mean HAM A scores for
Zolpidem. In females, a higher mean score of 1.53 was seen for pre sedation and after post sedation with zolpidem, whereas in males, a higher mean score of 2.41 was seen for pre sedation and there was decrease in the mean score (2.08) after post sedation with

[Pearson chi square test, chi square value
There is a wide variety of drugs that can be used to sedate patients undergoing extraction However, there are a few studies that relatively compare the effectiveness of different kinds of sedatives. Benzodiazepines are the class of drugs mostly used to induce a state of anxiolysis, sedation, or amnesia [21]. It can also be seen that a lesser dose of diazepam also produces better post sedation zolpidem, and hence can be used to prevent any adverse effects in the adults. Diazepam is known to attain the sedative level about 30 minutes after oral administration, and deepest sedative effects after 60 [22]. Although diazepam and zolpidem are known to produce adverse effects such as nausea, vomiting, and respiratory depression, our study revealed no such effects during and after the procedure [23].

CONCLUSION
Within the limitations of this study, it can be concluded that diazepam had better post sedation effects than zolpidem in patients undergoing extraction. Diazepam had There is a wide variety of drugs that can be used to sedate patients undergoing extraction [20]. However, there are a few studies that relatively compare the effectiveness of different kinds of sedatives. Benzodiazepines are the class of drugs mostly used to induce a state of anxiolysis, It can also be seen that a lesser dose of diazepam also produces better post sedation zolpidem, and hence can be used to prevent any adverse effects in the adults. Diazepam is known to attain the sedative level ministration, and deepest sedative effects after 60-90 minutes . Although diazepam and zolpidem are known to produce adverse effects such as nausea, vomiting, and respiratory depression, led no such effects during and Within the limitations of this study, it can be concluded that diazepam had better post sedation effects than zolpidem in patients dergoing extraction. Diazepam had significantly lesser post sedation anxiety levels than zolpidem. However, further studies have to be done to evaluate the anxiolytic effects of these drugs in patients undergoing surgical procedures. Randomized control tri sample size and multi-centered studies in different geographical locations can further enhance understanding and provide more clinical evidence for using anxiolytic drugs in clinical scenarios.

DISCLAIMER
Authors have declared that no interests exist. The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors. significantly lesser post sedation anxiety levels than zolpidem. However, further studies have to be done to evaluate the anxiolytic effects of these drugs in patients undergoing surgical procedures. Randomized control trials with larger centered studies in different geographical locations can further enhance understanding and provide more clinical evidence for using anxiolytic drugs in clinical Authors have declared that no competing interests exist. The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts

CONSENT AND ETHICAL APPROVAL
As per university standard guideline, patients consent and ethical approval have been collected and preserved by the authors.