quality of life

BACKGROUND
Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.

METHODS
We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.

RESULTS
A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.

CONCLUSIONS
Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)

Background: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope.

Objective: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions.

Design: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481).

Setting: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom.

Patients: Patients with recurrent vasovagal syncope and no serious comorbid conditions.

Intervention: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months.

Measurements: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up.

Results: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups.

Limitation: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center.

Conclusion: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden."

Importance: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs) for moderate to severe asthma remain unclear.

Objective: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma.

Data sources: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction.

Study selection: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma.

Data extraction and synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence.

Main outcomes and measures: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events.

Results: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence).

Conclusions and relevance: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.

Importance: Fibromyalgia is a chronic condition that results in a significant burden to individuals and society.

Objective: To investigate the effectiveness of therapies for reducing pain and improving quality of life (QOL) in people with fibromyalgia.

Data sources: Searches were performed in the MEDLINE, Cochrane, Embase, AMED, PsycInfo, and PEDro databases without language or date restrictions on December 11, 2018, and updated on July 15, 2020.

Study selection: All published randomized or quasi-randomized clinical trials that investigated therapies for individuals with fibromyalgia were screened for inclusion.

Data extraction and synthesis: Two reviewers independently extracted data and assessed risk of bias using the 0 to 10 PEDro scale. Effect sizes for specific therapies were pooled using random-effects models. The quality of evidence was assessed using the Grading of Recommendations Assessment (GRADE) approach.

Main outcomes and measures: Pain intensity measured by the visual analog scale, numerical rating scales, and other valid instruments and QOL measured by the Fibromyalgia Impact Questionnaire.

Results: A total of 224 trials including 29 962 participants were included. High-quality evidence was found in favor of cognitive behavioral therapy (weighted mean difference [WMD], -0.9; 95% CI, -1.4 to -0.3) for pain in the short term and was found in favor of central nervous system depressants (WMD, -1.2 [95% CI, -1.6 to -0.8]) and antidepressants (WMD, -0.5 [95% CI, -0.7 to -0.4]) for pain in the medium term. There was also high-quality evidence in favor of antidepressants (WMD, -6.8 [95% CI, -8.5 to -5.2]) for QOL in the short term and in favor of central nervous system depressants (WMD, -8.7 [95% CI, -11.3 to -6.0]) and antidepressants (WMD, -3.5 [95% CI, -4.5 to -2.5]) in the medium term. However, these associations were small and did not exceed the minimum clinically important change (2 points on an 11-point scale for pain and 14 points on a 101-point scale for QOL). Evidence for long-term outcomes of interventions was lacking.

Conclusions and relevance: This systematic review and meta-analysis suggests that most of the currently available therapies for the management of fibromyalgia are not supported by high-quality evidence. Some therapies may reduce pain and improve QOL in the short to medium term, although the effect size of the associations might not be clinically important to patients.