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Maintenance or Discontinuation of Antidepressants in Primary Care

Author/s: 
Lewis, G., Marston, L., Duffy, L., Freemantle, N., Gilbody, S., Hunter, R., Kendrick, T., Kessler, D., Mangin, D., King, M., Lanham, P., Moore, M.

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.)

Post COVID-19 Syndrome (Long Haul Syndrome): Description of a Multidisciplinary Clinic at the Mayo Clinic and Characteristics of the Initial Patient Cohort

Author/s: 
Vanichkachorn, G., Newcomb, R., Cowl, C. T., Trenary, M., Higgins, S., Neveau, D., Murad, M. H., Breeher, L., Miller, S.

Objective

To describe characteristics of a series of patients reporting prolonged symptoms after an infection with COVID-19.

Methods

This study describes the multidisciplinary COVID-19 Activity Rehabilitation Program (CARP), established at Mayo Clinic to evaluate and treat post-COVID-19 syndrome (PCS) patients, and reports the clinical characteristics of the first 100 patients receiving evaluation and management during the timeframe of June 1, 2020 and December 31, 2020.

Results

The cohort consisted of 100 patients (mean age 45 years, 68% women, BMI 30.2, presenting a mean of 93 days after infection). Common pre-existing conditions were respiratory (23%) and mental health, including depression and/or anxiety (34%.) The majority (75%) had not been hospitalized for COVID-19. Common presenting symptoms ware fatigue (80%), respiratory complaints (59%), and neurologic complaints (59%) followed by subjective cognitive impairment, sleep disturbance, and mental health symptoms. More than one-third of the patients (34%) reported difficulties with performing basic activities of daily living. Only 1 in 3 patients had returned to unrestricted work duty at the time of the analysis. For most patients, laboratory and imaging studies were normal or non-diagnostic despite debilitating symptoms. Most patients required physical therapy, occupational therapy, or brain rehabilitation. Face-to-face and virtual care delivery modalities were feasible.

Conclusion

Many of the patients did not experience COVID-19-related symptoms that were severe enough to require hospitalization, were younger than 65 years of age, more likely to be female, and most had no pre-existing comorbidities prior to SARS-CoV-2 infection. Symptoms including mood disorders, fatigue, and perceived cognitive impairment resulted in severe negative impacts on resumption of functional and occupational activities in patients experiencing prolonged effects.

Keywords 
COVID-19 depression anxiety fatigue,

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis

Author/s: 
Slee, April, Nazareth, Irwin, Bondaronek, Paulina, Liu, Yifeng, Cheng, Zhihang, Freemantle, Nick

BACKGROUND:

Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices.

METHODS:

A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106.

FINDINGS:

Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias.

INTERPRETATION:

To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of networkanalysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy.

Keywords 
anxiety global anxiety disorder

Treatment of Adult ADHD: A Clinical Perspective

Author/s: 
Geffen, Josh, Forster, Kieran

Adult attention deficit/hyperactivity disorder (ADHD) has moved from the blurred edge of clinical focus to clear recognition as a prevalent and significant disorder in its own right. It is a relatively common comorbidity which if identified and treated may open the door to better outcomes for hard-to-treat patients. Conversely, failure to identify and treat adult ADHD is linked to negative outcomes. The recognition of the importance of adult ADHD in a subset of our patients challenges us to overcome our anxiety about this diagnosis and prevent the societal marginalization of vulnerable patients. Adult ADHD responds well to integrated pharmacological and psychotherapeutic intervention. Its treatment responsiveness reduces disability and allows the comorbidity which is typically present to be addressed. Mastering this challenge can make the diagnosis and treatment of adult ADHD a rewarding experience.

Keywords 
ADD ADHD attention deficit disorder with hyperactivity
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