Augmentation with prazosin for patients with depression and a history of trauma: A randomised, double-blind, placebo-controlled study.

INTRODUCTION: Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation. AIMS OF THE STUDY: This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population. METHODS: This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy. RESULTS: There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate. CONCLUSION: Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension. CLINICAL TRIAL REGISTRATION: ChiCTR2200063642.

[Therapeutic efficacy and safety of monotherapy Alfuprost MR 10 mg/day in clinical practice].

INTRODUCTION: Alpha-blockers are the first-line therapy for men with BPH/LUTS. They have similar efficiency, but different uroselectivity. Therefore, when choosing a-blockers, their safety and adverse events should be taken into account. AIM: To evaluate the efficiency and safety of using Alfuprost MR 10 mg/day for 12 months in clinical practice. MATERIALS AND METHODS: A total of 55 men aged 55-80 years with BPH/ LUTS were included in the study, which was carried out on the basis of 6 outpatient clinics in St. Petersburg from June 2020 to September 2021. Along with standard methods, the examination included an assessment of male sexual function, hemodynamic parameters, and satisfaction with the treatment of patients and physicians using the Likert scale. The follow-up scheme included 7 visits (every 60+/-5 days) and lasted 12 months. RESULTS: After 2 months of therapy with Alfuprost MR, a significant decrease in the number of patients complaining of pain was observed. The proportion of patients with urgency and difficulty with urinating decreased by 50% and 30%, respectively. By the end of the treatment, the total IPSS score decreased by 1.9 times and averaged 9.98 points, the quality of life improved by 2.5 points, the average maximum urine flow rate significantly increased by 1.4 times, reaching 17.4 ml/sec, and the post-void residual volume decreased to 12.5 ml (3.8 times). By the last visit, there was a decrease in prostate volume by 4.3%. Moreover, the proportion of patients with an initial level of total PSA 2.5-4 ng/ml decreased by 25.4%. The level of PSA after treatment less than 2.5 ng/ml was seen in 70.9% of cases. All patients were satisfied with the treatment after 2 months, as well as investigators at visit 5. There was a significant improvement in all components of the sexual function, especially erectile function. In addition, there were no significant changes in ejaculation. CONCLUSION: Long-term therapy with Alfuprost MR 10 mg/day has high therapeutic efficacy and safety in elderly patients with LUTS/BPH, regardless of comorbidities.

Silodosin versus naftopidil for the treatment of benign prostatic hyperplasia: a multicenter randomized trial.

This was a multicenter randomized trial to investigate the clinical efficacy and the impact on sexual function of alpha-1A selective silodosin and alpha-1D selective naftopidil for treatment of benign prostatic hyperplasia. A total of 97 patients with lower urinary tract symptoms/benign prostatic hyperplasia who had an International Prostate Symptom Score of 8 or more were randomly assigned to receive silodosin (8 mg/day, n = 53) or naftopidil (75 mg/day, n = 44). Before and 4, 8 and 12 weeks after treatment, International Prostate Symptom Score and its quality of life score were used to assess lower urinary tract symptoms. Also, International Index of Erectile Function-5, and an original questionnaire were used to evaluate erectile function and ejaculation for sexually active patients, respectively. The silodosin group showed advantages in terms of voiding symptoms and quality of life of International Prostate Symptom Score when compared with the naftopidil group. Both silodosin and naftopidil showed no significant effect on International Index of Erectile Function-5. A total of 23 sexually active patients in the silodosin group experienced more ejaculatory impairment than 21 patients in the naftopidil group, with a decrease of ejaculation volume (87% vs 40%, P = 0.003), prolonged time to ejaculation (56% vs 33%, P = 0.027) and decrease of orgasm (50% vs 39%, P = 0.027). These results suggest that alpha-1A selective blockers are more effective for voiding symptoms, whereas alpha-1D selective blockers offer a minor degree of ejaculatory dysfunction.

Risk of Severe COVID-19 in Prevalent Users of Alpha-1 Adrenergic Receptor Antagonists: A National Case-Control Study of Medicare Beneficiaries.

BACKGROUND: Alpha-1 adrenergic receptor antagonists prevent cytokine storm in mouse sepsis models. This led to the hypothesis that alpha-1 blockers may prevent severe coronavirus disease 2019 (COVID-19), which is characterized by hypercytokinemia and progressive respiratory failure. METHODS: We performed an observational case-control study in male Medicare beneficiaries aged 65 years or older, with or without benign prostatic hyperplasia (BPH), and treated with alpha-1 receptor blockers or 5-alpha reductase inhibitors. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated for outcomes of uncomplicated and severe COVID-19 hospitalization (intensive care unit admission, invasive mechanical ventilation, or death). RESULTS: There were 20,963 cases of hospitalized COVID-19 matched to 101,161 controls on calendar date and neighborhood of residence. In the primary analysis (males with BPH), there was no difference in risk of uncomplicated COVID-19 hospitalization (aOR 1.08, 95% CI 0.996-1.17) or hospitalization with severe complications (aOR 0.97, 95% CI 0.88-1.08). In the secondary analysis (males with or without BPH), the corresponding aORs were 1.02 (95% CI, 0.96-1.09) (uncomplicated) and 0.99 (95% CI, 0.91-1.07) (complicated), respectively. Subgroup and sensitivity analyses yielded similar results. Of note, there was no difference in risk of severe COVID-19 hospitalization when comparing non-selective vs selective alpha-1 blocker use (aOR 0.98, 95% CI 0.86-1.10), higher- vs lower-dose alpha-1 blocker use (aOR 0.96, 95% CI 0.86-1.08), or current vs remote alpha-1 blocker use (aOR 1.04, 95% CI 0.91-1.18). CONCLUSIONS: Prevalent use of alpha-1 receptor blockers was not associated with a protective or harmful effect on risk of uncomplicated or severe hospitalized COVID-19.

Cost analysis of alpha blocker treatments for benign prostatic hyperplasia in Medicare beneficiaries.

OBJECTIVES: Tamsulosin is the most widely used alpha-1 blocker medication for managing benign prostatic hyperplasia (BPH) as indicated in the current practice guideline. The aim of this study was to compare all-cause medical costs and BPH-specific medical costs in older male adults with BPH treated with tamsulosin vs other alpha-1 blockers (i.e., doxazosin, terazosin, and alfuzosin). METHODS: This was a retrospective propensity-score matched cohort study based on 2006-2012 Medicare claims data. All-cause medical costs and BPH-specific medical costs were compared between tamsulosin and other alpha-1 blockers treatment groups using baseline-adjusted quantile regression analyses. The comparisons were performed at different percentiles of the cost distributions. RESULTS: 176,793 older male adults with BPH who used alpha-1 blockers were included in the analysis. All-cause medical costs in 75th and 95th percentiles of the cost distribution are substantially higher in tamsulosin treatment group when compared to other alpha-1 blocker medications (p < 0.05 for all). Tamsulosin treatment group had substantially higher BPH-specific medical costs in 99th percentile of the cost distribution when compared to doxazosin and terazosin (p < 0.001 for all). Overall, the top 5% of the patients with the highest all-cause medical costs accounted for approximately 45% of the overall all-cause medical costs, and the top 1% of the patients with the highest BPH-specific medical costs accounted for 39-51% of those costs. CONCLUSION: Older adults with BPH who encountered higher medical expenses had substantially higher medical costs when treated with tamsulosin than other common alpha blockers. Cost-related quality of measures should be assessed to improve health outcomes in older adults with BPH.

Beneficial Effect of Increasing the Dose of Tamsulosin to 0.4 mg in Japanese Patients with Benign Prostatic Hyperplasia.

OBJECTIVE: Tamsulosin is often administered at a dose of 0.2 mg in Japan, Korea, and elsewhere in Asia, while a dose of 0.4 mg is more common in the West. In order to determine the higher dose might also be appropriate in the North-East Asian setting, we studied whether the effect of increasing the dose to 0.4 mg in Japanese patients who had dysuria associated with benign prostatic hyperplasia. PATIENTS AND METHODS: Twenty-two cases with a voiding volume ≥ 100 ml assessed by uroflowmetry out of 31 patients with benign prostatic hyperplasia and an IPSS (International Prostate Symptom Score) ≥ 8 whose symptoms were controlled with 0.2 mg of tamsulosin were entered into this study. We evaluated IPSS and QOL (quality of life) score, urinary flow parameters and residual urine volume before and 4 weeks after increasing the dose of tamsulosin. RESULTS: Statistical analyses performed using the Wilcoxon test showed no significant alteration in IPSS total score or QOL score with the increased dose, but Qmax (maximum urinary flow rate) improved from 10.1 ± 5.5 ml/s to 12.1 ± 6.5 ml/s (p = 0.013), and residual urine volume improved from 37.6 ± 26.4 ml to 22.2 ± 24.3 ml (p = 0.012). Two of the 31 patients complained of new symptoms; 1 complained of breast pain and the other complained of dizziness. CONCLUSIONS: From the lack of side effects of more than moderate grade in the present study, increasing the dose of tamsulosin might be recommended before switching patients to other drugs.