Emotional Blunting in Patients With Major Depressive Disorder: A Brief Non-systematic Review of Current Research

Emotional blunting is frequently reported by patients with major depressive disorder (MDD) and has been identified as one of the most prominent side effects of antidepressants leading to medication discontinuation. However, antidepressant-induced emotional blunting remains largely unexplored—there lacks a clinical definition of this condition, and no agreeing conclusion has been reached regarding its etiology. Current research suggests that the onset of diminished emotional response may be related to antidepressant dose, with higher doses being more likely to induce emotional blunting. Consequently, most clinicians either reduce the dose or switch to another drug when treating this symptom. Overall, more comprehensive clinical assessments or interviews specifically designed to evaluate antidepressant-induced emotional blunting in MDD patients are in need to elucidate the neuropsychological mechanisms behind this increasingly prevalent symptom.

Erenumab versus topiramate for the prevention of migraine – a randomised, double-blind, active-controlled phase 4 trial

Background We compared the tolerability and efficacy of erenumab, a monoclonal antibody binding to the calcitonin gene-related peptide receptor, to topiramate for migraine prophylaxis in adults. Methods HER-MES was a 24-week, randomised, double-blind, double-dummy, controlled trial conducted in 82 sites in Germany. Patients with ≥4 migraine days per month and naïve to study drugs were randomly assigned (1:1) to either subcutaneous erenumab (70 or 140 mg/month) plus topiramate placebo (erenumab group) or oral topiramate at the individual dose with optimal efficacy (50–100 mg/day) plus erenumab placebo (topiramate group). The primary endpoint was medication discontinuation due to an adverse event during the double-blind phase. The proportion of patients that achieved ≥50% reduction from baseline in monthly migraine days during the last 3 months of the double-blind phase was a secondary endpoint. Results Seven hundred and seventy-seven patients were randomised (from 22 February 2019 to 29 July, 2020) and 95.1% completed the study. In the erenumab group, 10.6% discontinued medication due to adverse events compared to 38.9% in the topiramate group (odds ratio, 0.19; 95% confidence interval 0.13–0.27; p < 0.001). Significantly more patients achieved a ≥50% reduction in monthly migraine days from baseline with erenumab (55.4% vs. 31.2%; odds ratio 2.76; 95% confidence interval 2.06–3.71; p < 0.001). No new safety signals occurred. Conclusions Erenumab demonstrated a favourable tolerability and efficacy profile compared to topiramate. Trial registration: ClinicalTrials.gov NCT03828539, URL: https://clinicaltrials.gov/ct2/show/NCT03828539

Comparative adherence between DOAC and VKA in patients with atrial fibrillation: a 23-year retrospective observational study in Canada

Background A recent systematic review highlighted significant gaps in the evidence on atrial fibrillation (AF) patients' adherence to oral anticoagulants (OAC). Current evidence suffers from short follow-up times, focuses on the first OAC and does not take switching into account. There is also lack of observational data on adherence to warfarin due to its varying dose that complicates the calculations. As such there is lack of evidence on comparative adherence between VKAs and DOACs and whether the convenience of DOACs translates into better adherence in AF patients. Purpose Our objective was to measure AF patients' long-term OAC adherence and compare the impact of taking direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) on adherence, while accounting for switching. Methods Using linked, population-based administrative data containing physician billings, hospitalization and prescription records of 4.8 million British Columbians (1996–2019), incident adult cases of AF were identified. The primary measure of adherence was proportion of days covered (PDC). Consecutive rolling 90-day windows were created for each patient starting from their first OAC prescription fill date until the end of their follow-up. The PDC for each 90-day rolling window was calculated and averaged to yield mean adherence over the follow-up period for each patient. Permanent medication discontinuation resulted in a PDC of 0 for all subsequent rolling windows after their supply ran out. As such, both poor execution and non-persistence were measured simultaneously. The association between drug class and adherence was assessed using generalized mixed effect linear regression models with drug class treated as time-varying covariate to account for switching. Results The study cohort was 30,264 AF patients [mean age 72.2 years (SD11.0), 44.6% female, mean CHA2DS2-VASc 2.94 (SD1.4)] with mean follow-up of 7.7 (SD 4.8) years. The mean PDC was 0.71 (SD 0.27) with 51% of the cohort having mean PDC values below the conventional threshold of adherence (PDC&lt;0.8). Adherence dropped over time with the greatest decline in the first two years after therapy initiation. After controlling for all other confounders and accounting for switching, taking VKA compared to DOAC was, on average, associated with a 1-day decrease in number of days of medication-taking per year. Conclusion AF patients' OAC adherence was below the conventional threshold of 0.8, and dropped over time, particularly in the first two years. Drug class had no clinically meaningful impact on medication adherence. Our study highlights the need for effective adherence interventions particularly early in OAC therapy. Our findings also emphasizes that prescribers should not assume inherently better adherence for DOACs and should instead choose OAC in conversation with the patient and in accordance with their values and preferences. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research grant

Non-vitamin K antagonist oral anticoagulant discontinuation in non-valvular atrial fibrillation patients (ASPECT-NOAC)

Background and aim Data on NOAC discontinuation patterns in Turkey are lacking. We conducted a subgroup analysis in ASPECT-NOAC study to determine anticoagulant discontinuation pattern in AF patients with recently initiated NOAC therapy. Methods ASPECT-NOAC was a national, multicenter, 12-month observational study conducted in 34 outpatient cardiology clinics of state, university, private, and research hospitals covering all geographic regions of Turkey. Adult AF patients who were under NOAC therapy for less than four months were enrolled. Patients who discontinued using their NOACs were recorded at the end of 12 months. A comparative analysis of patients with discontinuation of medication was conducted. Results This study included 991 non-valvular AF patients. NOAC continuation data were available for 854 patients. During study follow-up, 74 patients (8.7%) discontinued their NOAC medication. Mean age of these patients was 67.1±11.3 years old and 38 patients (51.4%) were female. Most commonly seen comorbidities were hypertension (66.2%) and coronary heart disease (39.2%). 29 patients (39.2%) had permanent (chronic) AF, followed by 26 patients (35.1%) with paroxysmal AF. Major reason for NOAC discontinuation was stated as physician request (n=46, 62%). Following reasons were patient request (n=17, 23%), other (n=9, 12%), and bleeding (n=2, 3%). Patients with NOAC discontinuation had a shorter duration of AF (21.7±41.7 vs 26.2±53.7 months, p=0.017). There was no significant difference of educational levels between medication discontinuation subgroups (p=0.637). Other baseline characteristics and patient disease and treatment awareness levels were similar with the patients who continued their medication. Of 74 patients, two patients died during the study because of cardiac failure. Conclusion NOAC continuity rate over 12 months was found to be high. NOAC discontinuation rate were higher in the patients with shorter duration of AF. Further studies with long-term follow-up detailing discontinuation reasons are warranted. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was funded by Pfizer.

Case Report: Risperidone Induced Peripheral Edema

Risperidone is the first line of treatment for bipolar disorder, atypical depression, and Schizophrenia. We present a 55-year-old male with a history of schizoaffective disorder with bipolar type I presented with aggressive behavior and suicidal ideation. Our patient was treated with low-dose Risperidone; after that, he gradually developed leg pain and edema. His leg pain hampers his ambulation, which is clinically improved after a week of medication discontinuation; however, his leg edema did not resolve completely. In addition, we evaluated our patient's compliance with an empathic verbal interview that shows edema and leg pain hampers his quality of life. We have found that not informing edema as one of the possible side effects increases medication non-compliance in our case. There are several case reports about the side effect of Risperidone (such as leg edema) in combination with other medications, but there is no recommendation about patient counseling of forthcoming leg edema and mobility issues.

Adverse Drug Reactions and Their Impact on the Treatment of Pulmonary Tuberculosis

Background: Although there have been some reports about adverse drug reactions (ADRs) in pulmonary tuberculosis treatment, there are few detailed data and the effect of age among elderly patients on ADRs and the period of medication discontinuation due to ADRs is unknown. Purpose: We evaluated the difference in the incidence of ADRs necessitating discontinuation or a change of medication (dADR) among the different age groups and the period of discontinuation in elderly patients undergoing pulmonary tuberculosis treatment. Subjects and Methods: We conducted a retrospective medical record survey of patients who started anti-tuberculosis medication at our hospital from April 1st, 2018 to March 31st, 2020. Results: A total of 120 patients were recruited. There was no significant difference in the incidence of dADR among the different age groups every 10 years in patients ≥50 years of age (p=0.78). The median period of discontinuation was approximately 4 weeks for fever (29.5 days), approximately 3 weeks for rash (18.5 days), approximately 2 weeks for gastrointestinal disorders (16 days), and hepatocellular liver injury (15.5 days), and approximately 1 week for cholestatic liver injury (8 days) and eosinophilia (7 days). Conclusion: The incidence of dADR was not different among the age groups when patients of ≥50 years of age were compared by age. The median times of onset were 1–3 weeks after the start of treatment. The median periods of discontinuation were 1–4 weeks, and the period of discontinuation due to allergic reactions tended to be the longest

Direct-to-consumer Strategies to Promote Deprescribing in Primary Care: A Pragmatic Feasibility Study

Background – Deprescribing, or the intentional discontinuation or dose-reduction of medications, is a patient-centered approach to reduce harms associated with inappropriate medication use. We sought to determine how direct-to-patient educational materials impacted patient-provider discussion about and deprescribing of potentially inappropriate medications.Methods – We conducted a pre-post with historical control group pilot feasibility trial at an urban VA medical center. We included patients in one of two medication-based cohorts: 1) proton pump inhibitor (PPI), defined as use of any dose for 90 consecutive days, or 2) hypoglycemia risk, defined by diabetes diagnosis; prescription for insulin or sulfonylurea; hemoglobin A1c <7%; and age >65 years, renal insufficiency, or cognitive impairment. The intervention consisted of mailing medication-specific patient-centered EMPOWER (Eliminating Medications Through Patient Ownership of End Results) brochures, adapted to a Veteran patient population, two weeks prior to scheduled primary care appointments. Our primary outcome – deprescribing – was defined as clinical documentation of target medication discontinuation or dose-reduction. Our secondary outcome was documentation of a discussion about the target medication (yes/possible vs. no/absent). Covariates included age, sex, race, specified comorbidities, medications, and utilization. We used chi-square tests to examine the association of receiving brochures with each outcome.Results – The 348 subjects (253 intervention, 95 historical control) were primarily age >65 years, white, and male. Compared to control subjects, intervention subjects were more likely to have deprescribing (36 [14.2%] vs. 4 [4.2%], p=0.009) and discussions about the target medication (31 [12.3%] vs. 1 [1.1%], p=0.001). Conclusions – Targeted mailings of EMPOWER brochures temporally linked to a scheduled visit in primary care clinics are a low-cost, low-technology method that successfully increased both deprescribing and documentation of patient-provider medication discussions in a Veteran population. Leveraging the ability of patients to drive medication prescribing changes within clinical encounters has potential to reduce drug burden and decrease adverse drug effects and harms.