|Year : 2023 | Volume
| Issue : 1 | Page : 46-50
Prevalence of depression and depressive symptoms among patients using beta-blockers in King Khalid University Hospital, Riyadh Saudi Arabia: A cross-sectional study
Mohammed A Al-Jaffer, Ibrahim Bader Al-Shaqrawi, Omar H Al-Omar, Abdullah A Al-Jammaz, Meshaal K Al-Ghanim, Albaraa M Al-Saif, Mohammed N Al-Shunayf
Department of Psychiatry, Collage of Medicine, King Saud University, Riyadh, Saudi Arabia
|Date of Submission||24-May-2022|
|Date of Decision||02-Oct-2022|
|Date of Acceptance||10-Oct-2022|
|Date of Web Publication||3-Jan-2023|
Ibrahim Bader Al-Shaqrawi
Collage of Medicine, King Saud University, Riyadh
Source of Support: None, Conflict of Interest: None
Background: The relationship between depression and beta-blockers (BBs) use is a controversial topic for many decades. Due to the interference with adrenergic and serotonin receptors, BB use has been linked to depression in many early cross-sectional and case studies. Others have investigated the indirect relationship between BB use and novice antidepressant use. However, larger trials have yielded inconsistent findings. The objective of this study is to identify the presence of depression and depressive symptoms among patients using BBs in the internal medicine, cardiology, and psychiatry Departments in King Khalid University Hospital (KKUH) and to measure its prevalence. Research Design and Methods: A cross-sectional study included patients visiting Internal Medicine, Cardiology, and Psychiatry clinics at the KKUH in Riyadh, Saudi Arabia, who is known using BBs for any indication and excluded patients previously diagnosed with depression before taking BBs. This study was carried out from December 2018 to October 2019. Either physically or over the phone, patients were requested to complete the Patient Health Questionnaire-9 questionnaire. Drug names and pictures were provided for ease of drug identification. The sample size was 291, with a confidence interval of 95% and 5% margin of error. Written consent was acquired from all participants. Results: Two hundred and ninety-one surveys were collected, among 151 (52%) were females and 140 (48%) were males. Females were more likely to report depressive symptoms and had higher scores of symptom severity on average (P < 0.016). Only 17 patients (5.8%) were found to report no depressive symptoms, while most patients reported mild depressive symptoms (35%). We have not found a statistically significant relationship between BB type and the magnitude of depressive symptoms severity. Conclusions: Although the usage of BBs and the prevalence of depressive symptoms were not directly correlated in our study, compared to the local prevalence, our patients demonstrated a higher prevalence trend of depressed symptoms. In addition, our observations did reveal fascinating information on the gender disparity in depression.
Keywords: Beta-blockers, depression, Patient Health Questionnaire-9
|How to cite this article:|
Al-Jaffer MA, Al-Shaqrawi IB, Al-Omar OH, Al-Jammaz AA, Al-Ghanim MK, Al-Saif AM, Al-Shunayf MN. Prevalence of depression and depressive symptoms among patients using beta-blockers in King Khalid University Hospital, Riyadh Saudi Arabia: A cross-sectional study. J Nat Sci Med 2023;6:46-50
|How to cite this URL:|
Al-Jaffer MA, Al-Shaqrawi IB, Al-Omar OH, Al-Jammaz AA, Al-Ghanim MK, Al-Saif AM, Al-Shunayf MN. Prevalence of depression and depressive symptoms among patients using beta-blockers in King Khalid University Hospital, Riyadh Saudi Arabia: A cross-sectional study. J Nat Sci Med [serial online] 2023 [cited 2023 Jan 28];6:46-50. Available from: https://www.jnsmonline.org/text.asp?2023/6/1/46/366999
| Introduction|| |
}Depression is one of the most common psychiatric disorders. Worldwide, It is considered to be the leading cause of disability as measured by years lost due to disability and the fourth-leading contributor to global disease burden as reported by the WHO. In Saudi Arabia, depression prevalence has high regional variability. Among residents of central Saudi Arabia, depression was estimated to be 18%–20%.,, However, one multicenter study in Riyadh found that nearly half of patients presenting to primary health care have depressive symptoms. Moreover, in Jazan, a cross-sectional study was conducted among T2DM patients and found that the overall prevalence of depression among T2DM patients was 37.6%.
Beta-blockers (BB) are a major class of drugs commonly used for hypertension, arrhythmias, angina, anxiety, and migraine headache, among other indications. Although they are no longer recommended as first-line therapy in patients with uncomplicated hypertension, they are beneficial for the treatment of hypertension in specific situations, such as symptomatic angina, for heart rate control, postmyocardial infarction, heart failure with reduced ejection fraction, and as an alternative to angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers in younger hypertensive women planning a pregnancy or of child-bearing potential. Shortly, after introducing propranolol, the first BB agent, to the American market in 1967, case reports about a possible link with depression appeared.,,,,,,,,, Moreover, there was evidence suggesting that the use of hydrophilic BBs (e.g., atenolol), instead of the hydrophobic propranolol, may decrease drug concentration in the brain and thus decrease its depressive effects.,, Furthermore, beta-1-selective BBs were reported to cause impairment in incidental learning, raising more evidence to its possible central effects. Another interesting study found that the odds of developing depression were increased for short-term use of any BB, whereas current long-term use was not associated with the risk of depression.
However, a systematic review and meta-analysis of psychiatric adverse events during BB therapy, which analyzed large-scale data from double-blinded, randomized controlled trials, does not support an association between BB therapy and depression. Similarly, no effect for BBs was found for other psychiatric adverse events, with the possible exceptions of sleep-related disorders.
BBs are a heterogeneous group of antihypertensive agents. What they have in common is competitive antagonistic action on beta-adrenoreceptors (B1, B2, and B3). They differ in their receptor selectivity, intrinsic sympathomimetic activity, vasodilating properties, and metabolism.
However, the exact mechanism of action of BBs in the central nervous system is yet to be fully understood, and also, the depressive symptoms among the Saudi Arabia patients who is administered with BBs were not thoroughly explored.
A cross-sectional study was conducted on 3326 students from multiple universities in Saudi Arabia and assessed the self-prescription of BBs and its relation to undiscovered anxiety and found that 2.2% of the students had depression. However, studies measured the actual prevalence of depression among BBs users in Saudi Arabia are not many. Our objective is to identify the presence of depression and depressive symptoms among patients using BBs in internal medicine, cardiology, and psychiatry departments at King Khalid University Hospital (KKUH) and to measure its prevalence.
| Research Design and Methodology|| |
Study design and subject selection
The KKUH in Riyadh, Saudi Arabia, served as the site of this cross-sectional investigation, which was carried out between December 2018 and October 2019. KKUH is one of the biggest hospitals in Saudi Arabia and a tertiary facility. The Arabic validated Patient Health Questionnaire-9 (PHQ-9) questionnaire was used to assess patients utilizing BB who were visiting KKUH Internal Medicine, Cardiology, and Psychiatry clinics who is known to taking BBs for whatever reason were included in the study, but those who had been diagnosed with depression before taking BBs were not. The sample size was calculated to be 291 with a margin of error of 5% and a 95% confidence range. All participants provided their written consent.
The ethical approval for this study was obtained from King Saud University College of Medicine Institutional Review Board with Approval number (E-18-3509) on 31/12/2018, Verbal informed consent was obtained from subjects before the study, and this Cross-Sectional study was conducted in accordance with the Declaration of Helsinki. Either physically or over the phone, patients were requested to complete the PHQ-9 questionnaire. For simplicity of drug identification, drug names and images were provided. A self-administered version of the Primary Care Evaluation of Mental Disorders diagnostic tool for common mental diseases is called the PHQ. The PHQ-9 has a depression module that assigns a score from "0" (not at all) to "3" (almost every day) for each of the nine Diagnostic and Statistical Manual of Mental Disorder-IV criteria for depressed symptoms, with a maximum score of 27 Patients who score 1–4 are considered to have minor depression, those who score 5–9 mild depression, those who score 10–14 moderate depression, those who score 15–19 moderately severe depression, and those who score 20 or higher are considered to have severe depression. Based on meta-analysis that was done in 2012, they mention that the optimal cut-off score may differ depending on the setting of the study.. Thus, after many trials, a cut-off score of 9 was chosen in contrast with local study.
Data were analyzed using the Statistical Package for the Social Studies (SPSS 22; IBM Corp., New York, NY, USA). Categorical variables are expressed as percentages. The Chi-square test is used for categorical variables. A P < 0.06 will be considered statistically significant.
| Results|| |
Demographic characteristics of the study's patients
A total of 291 surveys were gathered, of which 151 (52%) were completed by women and 140 (48%) by men. Our sample population's median age was between 40 and 70-year-old for 75% (218 patients). Demographic details about our patients are included in [Table 1]. Among the 206 patients, bisoprolol was the most frequently prescribed BB (71%), and the most popular treatment schedule (84%) was once daily (244 patients). Overall, women were more likely than men to report having depressed symptoms, and they also scored their symptoms on average as being more severe (P < 0.016). The PHQ-9 scores showed a statistically significant difference between once-daily and twice-daily regimens. Patients on a once-daily regimen were more likely to say they had no depression symptoms (P = 0.063). [Table 2] illustrates the connection between dose and depression severity.
|Table 2: Relationship between frequency of administration and severity of depression (n=291)|
Click here to view
Depressive symptoms severity stratification
Only 17 patients (5.8%) were discovered to have no depressive symptoms, whereas 103 individuals claimed to have only mild depressive symptoms (35%). Only 13 patients (4.4%) had ratings that indicated they were suffering from severe depression, and it is interesting to note that they were all on a once-daily regimen.
Beta-blockers types and relation to depression severity stratification
There is no statistically significant correlation between the type of BB and the intensity of depressive symptoms. However, 12 of the patients (92%) who reported having severe depression were also on Bisoprolol [Table 3]. None of the Atenolol (25), Carvedilol (15), or Propranolol (21), or their respective patients, reported experiencing significant symptoms. In addition, all individuals receiving metoprolol (22) reported having mild-to-severe depressive symptoms.
|Table 3: Stratification of beta-blocker types and relation to depression severity|
Click here to view
| Discussion|| |
Overall, our data suggest that there is no statistically significant difference in the prevalence of depressive symptoms between patients taking different types of BBs visiting Internal Medicine, Cardiology, and Psychiatry clinics, which was the main objective of this study. However, almost 64.3% (187 of our patients) reported having depressive symptoms ranging from mild to severe. This is in contrast with the local prevalence of depressive symptoms among primary health care patients being around 50% with the same cut-off point. Moreover, we have not found age to carry a significant relationship with symptomatic severity, Whereas a prior study assessing the relationship between use of BBs and novice use of trichloracetic acid (TCA) found out that the prevalence of patients taking TCA is highest among younger patients between 20 and 44 years of age and that the prevalence declines with time.
When compared to hydrophilic-blockers, lipophilic-blockers were reported to have a greater incidence of incident depression.,, The authors hypothesized that the higher occurrence of negative effects could be explained by a higher concentration of lipophilic-blockers in brain tissue compared to hydrophilic drugs. Atenolol is quite hydrophilic, but bisoprolol has a lipophilic profile similar to that of propranolol., The proposed mechanism for an elevated risk based on physicochemical features, therefore, cannot account for our findings., It was postulated that lipophilic BBs (e.g., propranolol), given their ability to readily cross the blood-brain–barrier, have the ability to cause higher prevalence of depressive symptoms compared to its hydrophilic counterparts.,,
Hence, such relationship could not be demonstrated in our study. Interestingly, our study found that females were more likely to report depressive symptoms; similar relation was reported in local studies.,,, Furthermore, females were likely to have more severe symptoms (P < 0.016). This is in accordance with the findings of a retrospective cohort study assessing the relationship of BB use and antidepressant use. For yet unclear reasons, the relationship between gender and depression consistently shows that females are more likely to be diagnosed with depression. This gender gap has been extensively investigated through possible genetic, environmental, hormonal, and psychological causes.
The results of our cross-sectional study would be strengthened with a larger sample size and a stronger study design, such as cohort studies. Moreover, being a single-center study may limit the generalizability of our findings. Furthermore, patients who participated were only from Internal Medicine, Cardiology, and Psychiatry clinics. Primary health-care patients were not included in the study to establish a relation of BBs use and developing of depressive symptoms among them. One more limiting factor would be the inability of many patients to remember the exact dosing of their medication even after identifying the specific BB drug they are using, which could interfere with the analysis of this variable.
| Conclusions|| |
No statistically significant difference between the different drugs of BB class that has associations with developing depressive symptoms. Majority of patients surveyed experienced some depressive symptoms of varying severity following the use of BBs, with the majority of them experiencing minimal to mild depressive symptoms severity. Our findings yielded interesting results regarding the gender gap of depression, and females were associated with the development of depressive symptoms more than males; females were also found to have higher average symptom severity scores on average. Although our study could not provide a direct link between BB use and the prevalence of depressive symptoms, our patients did show a higher prevalence trend of depressive symptoms when compared to the local prevalence. To our perspective, this is the earliest investigation to demonstrate that there is no meaningful association involving the usage of BBs and the prevalence of depressive symptoms; thus, more research is necessary to validate these findings.
Prospective large-scale studies are needed to delve deeper into the relationship between BB use and depression. We would suggest conducting studies in association with primary health care departments locally to determine if there is an association between BBs use and developing depressive symptoms. It is also recommended to implement screening programs for depressive symptoms to counter it at an early stage, preventing it from reaching a severe point. It is also suggested that patients, particularly those who use BBs be made more aware of the benefits of early diagnosis to avoid major forms of depression and save the cost for the health-care system.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
WHO. The World Health Repor, Mental Health: New Understanding, New Hope. In: Haden A, Campanini B, editors. Geneva: World Health Organization; 2001. p. 30.
Al-Khathami AD, Ogbeide DO. Prevalence of mental illness among Saudi adult primary-care patients in central Saudi Arabia. Saudi Med J 2002;23:721-4.
Becker S, Al Zaid K, Al Faris E. Screening for somatization and depression in Saudi Arabia: A validation study of the PHQ in primary care. Int J Psychiatry Med 2002;32:271-83.
Becker SM. Detection of somatization and depression in primary care in Saudi Arabia. Soc Psychiatry Psychiatr Epidemiol 2004;39:962-6.
Al-Qadhi W, Ur Rahman S, Ferwana MS, Abdulmajeed IA. Adult depression screening in Saudi primary care: Prevalence, instrument and cost. BMC Psychiatry 2014;14:190.
Albasheer OB, Mahfouz MS, Solan Y, Khan DA, Muqri MA, Almutairi HA, et al.
Depression and related risk factors among patients with type 2 diabetes mellitus, Jazan area, KSA: A cross-sectional study. Diabetes Metab Syndr 2018;12:117-21.
Yudofsky SC. Beta-blockers and depression. The clinician's dilemma. JAMA 1992;267:1826-7.
Riemer TG, Villagomez Fuentes LE, Algharably EA, Schäfer MS, Mangelsen E, Fürtig MA, et al.
Do β-Blockers cause depression?: Systematic review and meta-analysis of psychiatric adverse events during β-blocker therapy. Hypertension 2021;77:1539-48.
Waal HJ. Propranolol-induced depression. Br Med J 1967;2:50.
Petrie WM, Maffucci RJ, Woosley RL. Propranolol and depression. Am J Psychiatry 1982;139:92-4.
Nolan BT. Acute suicidal depression associated with use of timolol. JAMA 1982;247:1567.
Kalayam B, Shamoian CA. Propranolol, psychoneuroendocrine changes, and depression. Am J Psychiatry 1982;139:1374-5.
Patterson JF. Depression associated with enalapril. South Med J 1989;82:402-3.
McNeil GN, Shaw PK, Dock DS. Substitution of atenolol for propranolol in a case of propranolol-related depression. Am J Psychiatry 1982;139:1187-8.
Faber R. Nadolol and antidepressant response. Biol Psychiatry 1983;18:1338-9.
Oppenheim G. Propranolol-induced depression: Mechanism and management. Aust N Z J Psychiatry 1983;17:400-2.
Pollack MH, Rosenbaum JF, Cassem NH. Propranolol and depression revisited: Three cases and a review. J Nerv Ment Dis 1985;173:118-9.
Cremona-Barbaro A. Propranolol and depression. Lancet 1983;1:185.
Thiessen BQ, Wallace SM, Blackburn JL, Wilson TW, Bergman U. Increased prescribing of antidepressants subsequent to beta-blocker therapy. Arch Intern Med 1990;150:2286-90.
Westerlund A. Central nervous system side-effects with hydrophilic and lipophilic beta-blockers. Eur J Clin Pharmacol 1985;28 Suppl: 73-6.
Conant J, Engler R, Janowsky D, Maisel A, Gilpin E, LeWinter M. Central nervous system side effects of beta-adrenergic blocking agents with high and low lipid solubility. J Cardiovasc Pharmacol 1989;13:656-61.
Burkauskas J, Noreikaite A, Bunevicius A, Brozaitiene J, Neverauskas J, Mickuviene N, et al
. Beta-1-selective beta-blockers and cognitive functions in patients with coronary artery disease: A cross-sectional study. J Neuropsychiatry Clin Neurosci 2016;28:143-6.
Bornand D, Reinau D, Jick SS, Meier CR. β-blockers and the risk of depression: A matched case-control study. Drug Saf 2022;45:181-9.
Gorre F, Vandekerckhove H. Beta-blockers: Focus on mechanism of action. Which beta-blocker, when and why? Acta Cardiol 2010;65:565-70.
Alsini A, Alkhodaidi I, Alsini Y, Alsseeni S, Alkhodaidi S, Alsini E, et al
. A national survey of self-prescription of beta-blockers and their relation to undiscovered anxiety among medical and pharmacological students in Saudi Arabia. Neuropsychiatr Dis Treat 2021;17:797-807.
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. J Gen Intern Med 2001;16:606-13.
Manea L, Gilbody S, McMillan D. Optimal cut-off score for diagnosing depression with the patient health questionnaire (PHQ-9): A meta-analysis. CMAJ 2012;184:E191-6.
Avorn J, Everitt DE, Weiss S. Increased antidepressant use in patients prescribed beta-blockers. JAMA 1986;255:357-60.
Johnell K, Fastbom J. The association between use of cardiovascular drugs and antidepressants: A nationwide register-based study. Eur J Clin Pharmacol 2008;64:1119-24.
Ko DT, Hebert PR, Coffey CS, Sedrakyan A, Curtis JP, Krumholz HM. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 2002;288:351-7.
Luijendijk HJ, van den Berg JF, Hofman A, Tiemeier H, Stricker BH. β-blockers and the risk of incident depression in the elderly. J Clin Psychopharmacol 2011;31:45-50.
Tarentino AL, Maley F. A comparison of the substrate specificities of endo-beta-N-acetylglucosaminidases from Streptomyces griseus
and Diplococcus Pneumoniae
. Biochem Biophys Res Commun 1975;67:455-62.
Frishman WH. The beta-adrenoceptor blocking drugs. Int J Cardiol 1982;2:165-78.
Patten SB. Propranolol and depression: Evidence from the antihypertensive trials. Can J Psychiatry 1990;35:257-9.
Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry 2017;4:146-58.
el-Rufaie OE, Albar AA, Al-Dabal BK. Identifying anxiety and depressive disorders among primary care patients: A pilot study. Acta Psychiatr Scand 1988;77:280-2.
Abdelwahid HA, Al-Shahrani SI. Screening of depression among patients in family medicine in Southeastern Saudi Arabia. Saudi Med J 2011;32:948-52.
[Table 1], [Table 2], [Table 3]