1. INTRODUCTION:

Blood pressure is caused by the pressure exerted on the walls of the arteries of the body. This pressure is influenced by factors such as cardiac output, vascular systemic resistance and the hardness of arterial walls.¹

Hypertension is a chronic disease in which the blood pressure in the arteries is consistently increased.^2,3 This situation is associated with an increase in the incidence of stroke and heart diseases, being the two leading causes of death.^4,5 In addition, hypertension can lead to disorders such as peripheral artery disease, vision loss, kidney damage and dementia.^6-8 However, about 50% of the disease burden is related to levels lower than this cross-sectional level.⁹ In most national and international guidelines, the level of blood pressure that is considered as hypertension is 140 mmHg and 90 mmHg diastolic pressure or both.^10,11 The latest findings from the Global Burden of Disease (GBD) show that increased blood pressure (systolic pressure>115mmHg) is still the single most important factor affecting the global burden of disease and causes the total annual death rate of over nine million and four hundred thousand people.^12,13 As a result of a 10% increase in the prevalence of high blood pressure between 2000 and 2025, about 560 million new cases will suffer from this disease and its complications worldwide.¹⁴The most common hypertensive emergency is a sudden and unexplained increase in blood pressure in patients who have a history of primary chronic hypertension.¹⁵ Most of the patients who suffer from hypertensive emergencies mention a history of inadequate blood pressure treatment or sudden discontinuation of the treatment process.^16,17Hypertensive crises are cases where systolic and diastolic blood pressure are higher than 180 mmHg and 120 mmHg, respectively.¹⁸The initial assessment of a patient with primary hypertension referred to the medical emergency includes measuring blood pressure, taking the medical history, conducting targeted examinations and performing routine laboratory tests (FBS, HbA1c, Na, k, Cr, Ca, Lipid profile) along with a 12-lead ECG.^19,20 Proper management of hypertensive crises patients requires the cooperation of the patient and the doctor to coordinate drug and non-drug treatments and prevent end organ damage.²¹ The current European guideline is based on clinical observations with frequent blood pressure measurement and its gradual reduction by prescribing oral antihypertensive drugs in patients with hypertensive crises.²² On the other hand, these patients should immediately receive pharmacological and non-pharmacological interventions in order to reduce blood pressure levels from critical values. Also, special treatment protocols for managing clinical conditions related to stroke, acute coronary syndromes, eclampsia, pulmonary edema and aortic dissection should be considered. A similar guideline has been provided by the United States for the management of hypertension.²³ Anxiety is one of the most common psychiatric diseases in adults and is considered as one of the major public health problems in many regions of the world.^24,25 According to statistical estimates, anxiety is the most common psychiatric disorder worldwide, and the sixth cause of disability.^26,27 About one third of all people have the possibility of having some type of anxiety disorder in their lifetime. Despite the multifactorial nature of hypertension, psychological factors have been confirmed as one of the underlying causes of hypertension, yet the mechanisms involved have not been well identified.^28-30 It has also been shown in several studies that anxiety disorders are associated with a higher incidence of hypertension.^31,32,33 On the other hand, there are studies rejecting these findings and even indicating a decrease in blood pressure regarding anxiety. Therefore, this study was conducted to investigate the effectiveness of anti-anxiety treatment in helping to control hypertension in hypertensive crises patients referred to Shahid Rajaei Hospital of Karaj in 2020.

2. MATERIALS AND METHODS:

2.1 Study design:

The present stud is a randomized clinical trial. The study subjects included patients with hypertensive crisis who referred to Shahid Rajaei Medical and Teaching Center of Karaj in 2020. Information was collected using researcher-made questionnaires, Hospital Anxiety and Depression Scale (HADS) and the same device and operator for each patient.

2.2 Inclusion/ exclusion criteria:

Inclusion criteria were: failure to respond to standard oral antihypertensive treatment at the same time of admission, received HADS score> 8 at admission, systolic pressure > 180mmHg with or without symptoms of end organ damage, diastolic pressure > 120mmHg with or without symptoms of end organ damage.

Exclusion criteria were: symptoms of focal neurological disorder, history of brain pathology, changes indicative of myocardial infarction in the ECG, any finding in favor of myocardial infarction, history of major depressive disorder, any conditions that facilitate dependence on benzodiazepines, and any contraindication for using anti-anxiety drugs.

2.3 HADS:

This tool includes two scales of anxiety and depression, each consisting of 7 questions. In total, the range of scores for each domain is from 0 to 21. A score of 0-7 means being healthy, a score of 8 to 10 means an interstitial disorder, and a score of 11 and above is considered a suspected disorder. Cronbach’s alpha coefficient for depression and anxiety scores has been reported to be between 0.80 and 0.90.³⁴

2.4 Interventions:

Patients who met the conditions for entering the study were randomly divided into three groups receiving 1 mg oral lorazepam and 2mg oral olanzapine and not receiving anti-anxiety medication. In all patients, vital signs and blood pressure, systolic and diastolic pressure and heart rate were monitored according to the standard method. In patients receiving anti-anxiety drug, systolic and diastolic blood pressure and heart rate were measured at the beginning of anti-anxiety medication administration and then 40 minutes after anti-anxiety drug administration. The patients were advised to return for re-evaluation one week and then three weeks later after being discharged from the emergency room and taking the anti-hypertensive and anti-anxiety oral diet of their own group. Systolic blood pressure and diastolic blood pressure and heart rate were re-evaluated in both visits and the acquired HADS score in the second follow-up visit.

2.5 Statistical analysis:

After coding the data, they were analyzed using version 22 of the SPSS software. Backwards general regression test and repeated measure tests using Bonferroni post hoc were used to solve the problem of non-homogeneity of the groups and to adjust the age and gender of the participants to evaluate Greenhouse-Geisser. A p-value less than 0.05 was considered to be statistically significant.^35,36

2.6 Ethical considerations:

All eligible subjects were included in the study after obtaining informed consent.The present study was presented in approved by the Research Ethics Committee of Alborz University of Medical Sciences under IR.ABZUMS.REC.1399.170.

4. RESULTS:

In the present study, 120 patients, including 59 women and 61 men, under antihypertensive oral treatment, who came to the emergency room with a hypertensive crisis and did not respond to the mentioned treatment, were included in the HADS questionnaire if they met the conditions. No patients were excluded from the study and all participated in the follow-up evaluations. The average age of the participants was 52.24 years, the youngest of whom was 25 and the oldest was 85. The lowest systolic pressure at the beginning of the study was 160mmHg, the highest was 193mmHg, and the average value was 179.06mmHg. Also, the lowest diastolic pressure at admission was 86 mmHg, the highest was 121mmHg, and the average was 104.83 mmHg. The minimum and maximum recorded heart rates of the patients at the beginning of the study were 80 and 115bpm. The highest frequency of HADS related to the medium range with frequency was 71 people (59.2 percent). The results indicated that the decrease in systolic pressure is statistically significant compared to the non-prescription of anti-anxiety drug (P=0.001). However, no significant difference was observed in the follow-up i.e. 1 week and 3 weeks later (P=0.392) (Table 1). The results related to changes in diastolic pressure in two drug groups after anti-anxiety drug administration were statistically significant (P=0.002). However, no significant difference was observed in the follow-up i.e. 1 week and 3 weeks later (P=0.284) (Table 2). The results of the Greenhouse-Geisser testafter adjusting for age and gender were significant in relation to systolic pressure (P˂0.05), but no significant relation was observed regarding the diastolic pressure (P˃0.05). Evaluations related to the effect of anti-anxiety drugs on heart rate also did not show significant changes before and after the administration of drugs (P=0.953). Also, the changes in the HADS level of the subjects at the time of second re-evaluation i.e. 3 weeks after the start of the study had no significant relationship with the values obtained at the beginning of the study (P=0.547).

Table 1: Systolic pressure at the beginning of the study and after the administration of drugs

Systolic blood pressure	Type of the anti-anxiety medication administered	Mean	Standard deviation	Number	P-value
Systolic bp at presentation	Loarzepam	179.65	7.385	60	0.000
	Olanzapin	178.47	7.017	60
	Total	179.06	7.197	120
Systolic bp after administration of anxiolytic	Loarzepam	160.98	10.291	60	0.392
	Olanzapin	167.15	12.256	60
	Total	164.07	11.686	120

Table 2: Diastolic pressure at the beginning of the study and after the administration of drugs

Diastolic blood pressure	Type of the anti-anxiety medication administered	Mean	Standard deviation	Number	P-value
Diastolic bp at presentation	Loarzepam	104.37	8.743	60	0.000
	Olanzapin	105.30	8.838	60
	Total	104.83	8.766	120
Diastolic bp after administration of anxiolytic	Loarzepam	87.12	7.484	60
	Olanzapin	93.77	11.726	60
	Total	90.44	10.348	120

7. DISCUSSION:

Anxiety disorders are one of the most common mental disorders and 33.7% of the populations are affected by it during their lifetime.^37,38By affecting the sympathetic nervous system and releasing noradrenaline, anxiety causes vasoconstriction, increased myocardial work, and increased breathing rate and heart rate.³⁹ The review of studies shows the severity of the results and complications of high blood pressure in patients with anxiety disorders.^40,41 Therefore, in the present study, it was attempted to investigate the importance and effectiveness of anti-anxiety treatment in helping to control high blood pressure in hypertensive crises patients referred to Rajaei Karaj Hospital in 2020. The results of the present study showed that the administration of anti-anxiety drugs in patients with hypertensive crises and anxiety disorders leads to a decrease in systolic and diastolic pressure. In the study conducted by Yilmaz et al, 2011, which was conducted in order to compare alprazolam with captopril in high blood pressure, it was reported that the therapeutic results of both sublingual captopril and diazepam treatment groups succeeded in lowering blood pressure compared to the control group. In this study, the changes in heart rate were not statistically significant.⁴² In the study conducted by Herhaus et al.(2022), the effects of biofeedback on reducing heart rate and blood pressure in patients with anxiety and panic disorders were reported to be positive.⁴³ This was despite the fact that prescribed anti-anxiety drugs in the present study did not have a significant effect on heart rate and HADS despite the reduction of systolic and diastolic blood pressure of the patients. In the study of Al-Qudah et al.(2021), it was reported that in triple resistant hypertension that included diuretics, a decrease in pressure was observed following the administration of benzodiazepine,⁴⁴ which is in line with the results of the present study. Also, the results of the present study showed that the reduction of systolic and diastolic pressure compared to the pre-administration of anti-anxiety phase in the follow-up i.e. 1 week and 3 weeks later is not significantly different. Pastrovic et al. (2020) have reported that the administration of anti-anxiety drugs in the control of urgent hypertension in the emergency ward has an effective role in controlling blood pressure.⁴⁵This confirms the results of the present study. In a study reported by Pich et al.(1993), the absence of neuropeptide Y in people suffering from anxiety disorders was associated with an increase in blood pressure, and this substance can be effective in reducing blood pressure by creating anti-anxiety effects.⁴⁶ These results are directly related to the findings of the present study regarding blood pressure reduction with anxiety control. Also, in the study conducted by Komsiyska et al.(2015), which was conducted in order to investigate the role of anti-anxiety drugs in the treatment of patients suffering from arterial blood pressure with anxiety disorders, the results showed that patients who had obtained a score indicating anxiety from the STAI questionnaire after receiving anti-anxiety treatment along with standard antihypertensive treatment experienced a significant systolic pressure decrease, but there were no statistically significant changes in heart rate and diastolic pressure.⁴⁷This is in line with the results of the present study. The study conducted by Kulkarni et al.(2019) indicated the negative effect of taking anti-anxiety drugs before pregnancy on high blood pressure trend in pregnant women.⁴⁸This is contrary to the results of the present study.

5. CONCLUSION:

The results of the present study showed that the evaluation of patients with hypertensive crisis in terms of anxiety disorder with an appropriate scale and the prescription of anti-anxiety drugs in patients with indicators of anxiety disorders during a hypertensive crisis help to improve and accelerate blood pressure control in the emergency room. This reduction in systolic and diastolic pressure of patients was significant. However, our findings regarding the continuation of treatment outside the hospital did not show significant changes. It is suggested that further studies be designed and conducted with a longer duration and a larger sample size in the future.

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Received on 19.09.2023 Modified on 16.11.2023

Research J. Pharm. and Tech 2024; 17(5):2093-2098.

DOI: 10.52711/0974-360X.2024.00331