Methylphenidate use in geriatric depression: A systematic review.

OBJECTIVES: Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression. METHODS: PubMed (1946-December 2020) and Embase (1947-December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late-life depression, and MPH. Studies were included if they were a randomized-controlled trial or open-label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older. RESULTS: After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day. CONCLUSIONS: Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short-term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long-term trials are needed to further define the role of MPH in this population.

Impact of prophylactic oseltamivir on INR in patients on stable warfarin therapy.

Influenza prophylaxis with oseltamivir is recommended for exposed high-risk patients. Patients with many comorbidities have an increased likelihood of co-administration of oseltamivir and warfarin. Evidence of a drug interaction is conflicting in the literature and is limited to a 5-day treatment course. This study evaluates the impact of prophylactic oseltamivir on international normalized ratio (INR) in patients taking warfarin. This retrospective cohort study conducted within the Veterans Health Administration included patients on warfarin who received oseltamivir for influenza prophylaxis. The primary endpoint was change in INR from baseline to day 10 of oseltamivir treatment. Secondary endpoints included change in INR based on renal function and duration of oseltamivir prophylaxis, trend in INR, and frequency of bleeding and thrombosis events. A total of 1041 patients were included and received oseltamivir for a mean of 12.9 days. The mean post-oseltamivir INR was significantly increased compared to the pre-oseltamivir INR (2.39 to 2.52; p < 0.001). Patients with a creatinine clearance of 31-60 mL/min had a significant increase in INR (2.40 to 2.59; p < 0.01). There was an increase in INR when oseltamivir was used for 7 or 8-10 days. Of included patients, 5.1% and 1.8% had a recorded thrombosis or bleeding event, respectively. There was a significant increase in INR in patients on chronic warfarin therapy and concomitant prophylactic oseltamivir, but this change may only be clinically significant for certain patient populations. The most impact on INR was within 7-10 days of oseltamivir initiation and in patients with impaired renal function.

PARADIGM-HF Trial: Secondary Analyses Address Unanswered Questions.

Our aim was to summarize published secondary analyses of the PARADIGM-HF trial. In the original trial, published in September 2014, sacubitril/valsartan significantly reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared to enalapril. This summary provides a resource for clinicians to review subsequent analyses of the landmark trial evaluating the benefit of sacubitril/valsartan in various subgroups and providing information regarding optimal use of this new therapy in the broader heart failure population. A full list of publications of the existing PARDADIGM-HF post hoc analyses was obtained and summarized, grouped by focus (e.g., severity of illness, tolerability). Twenty-six publications and one abstract analyzing the PARADIGM-HF trial were reviewed, summarizing the most important results that compared the benefits of sacubitril/valsartan to enalapril, including pertinent subgroup information from each analysis. Key publications evaluated the treatment effect of sacubitril/valsartan based on heart failure severity (i.e., ejection fraction or heart failure risk scores), impact on alternate outcomes, influence of additional therapies, tolerability in patients with comorbidities (i.e., diabetes), long-term benefits, and cost-effectiveness. In addition, nine ongoing phase III and phase IV clinical trials with sacubitril/valsartan were briefly summarized to address potential future uses in more extensive heart failure settings. The benefit of sacubitril/valsartan over enalapril for the primary endpoint in the PARADIGM-HF trial is maintained throughout numerous secondary analyses. Though the subgroups analyzed are based on participants from a single clinical trial, clinicians can more confidently incorporate this novel therapy into practice with expanded knowledge of these existing analyses as well as ongoing prospective trials.