Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Drug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel-Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697). CONCLUSIONS: Medications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

Depression Severity and Depression Stigma Among Students: A Survey of Universities in Five Countries.

In the university setting, mental disorders have come under greater scrutiny and more attention has been given toward addressing the social stigmas associated with mental illness in an effort to promote mental well-being and improve mental health care delivery on-campus. Depression has been previously linked to a reduction in quality of life, suicidal ideation, and poor academic performance. However, few studies have directly compared the burden of depression or stigmatized views between multiple universities. As a result, this cross-sectional study of university students from five countries was performed to determine the burden of depressive disorders, the stigmatizations of beliefs related to depression, and international variation. A questionnaire consisting of a sociodemographic survey, Patient Health Questionnaire-9 (PHQ-9), and Depression Stigma Scale (DSS) was distributed via multiple routes to undergraduate and graduate students at institutions in the United States, Taiwan, United Arab Emirates, Egypt, and Czech Republic. The point prevalence of depression was determined by using the algorithm scoring method of the PHQ-9. Depression severity was determined according to the summed-item scoring method of the PHQ-9. The degree of stigmatization of beliefs was determined by continuous scores on the DSS subscales for personal and perceived stigma. Differences in depression severity, personal stigma, and perceived stigma were determined according to analysis of variance and further studied using post hoc Tukey's tests. Responses were collected from students in the United States (n = 593), United Arab Emirates (n = 134), Taiwan (n = 217), Egypt (n = 105), and Czech Republic (n = 238). Of 1287 responses, 30.7% (n = 396) screened positive for a depressive disorder: 18.0% (n = 232) for major depressive disorder and 12.7% (n = 164) for another depressive disorder. Depression severity differed internationally (p < 0.001). Emirati students significantly exhibited most depression followed by Czech, American, and Taiwanese students (all ps < 0.001). There was also a difference between students of different countries in terms of personal stigma (p < 0.001), with Emirati students holding more stigmatized personal views than Czech, American, Egyptian, and Taiwanese students (all ps < 0.001). Students similarly demonstrated differences in terms of personal stigma (p < 0.001). Egyptian students exhibited the most perceived stigma followed by Emirati, Taiwanese, American, and Czech students (all ps < 0.001). These findings suggest a high point prevalence of depression among university students and differences in the severity of depression, which has implications for the delivery of mental health care in this population. There were significant differences in terms of personal and perceived stigma between university students, indicating resource allocation for university-based campaigns to reduce depression stigma may need to be tailored to the population. After implementation of stigma reduction programs, future follow-up surveys can be done to compare degrees of stigma before and after the intervention.