anxiety disorders

Nonpharmacologic Treatments for Maternal Mental Health Conditions

Objectives. This systematic review evaluates nonpharmacologic treatments for mental health conditions during the perinatal period (pregnancy and up to 12 months postpartum). We evaluated nonpharmacologic treatments for perinatal individuals with depressive disorders, anxiety disorders, bipolar disorder, post-traumatic stress disorder (PTSD), or obsessive-compulsive disorder (OCD).

Data sources and review methods. We searched MEDLINE®, PsycINFO®, Embase®, CINAHL®, the Cochrane Register of Clinical Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from January 1, 2000, to January 17, 2024, to identify relevant randomized controlled trials (RCTs). Nonpharmacologic interventions of interest included, among others, cognitive behavioral therapy (CBT), interpersonal therapy (IPT), exercise, non-directive counseling, behavioral activation, bright light therapy, eye movement desensitization and reprocessing (EMDR), and acupuncture. Outcomes of interest were improvement in scores on psychological assessment tools, cure or resolution of symptoms, suicide-related outcomes, and adherence to treatment. PROSPERO registration number: CRD42023440650.

Results. We identified 103 RCTs. Nonpharmacologic treatments were compared to control or each other in 101 RCTs and to pharmacologic treatments in 2 RCTs. The risk of bias was moderate for the majority of included studies, mostly related to lack of blinding. For perinatal individuals with depressive disorders, CBT was more effective than treatment as usual (TAU) to reduce depressive and anxiety symptoms (both moderate strength of evidence [SoE]); IPT was more effective than TAU to treat depressive symptoms (moderate SoE) and anxiety symptoms (low SoE); and both behavioral activation (a CBT technique, with low SoE) and exercise interventions (moderate SoE) were more effective than TAU to reduce depressive symptoms. Remission rates for depressive symptoms were higher with CBT and IPT compared to TAU (both low SoE) and higher with specific acupuncture than nonspecific or sham acupuncture (low SoE). There were no differences between CBT and non-directive counseling (an active patient-led intervention), between counseling and TAU, and between bright light and placebo light therapy (all low SoE). CBT was more effective than TAU to reduce anxiety and depressive symptoms for individuals with combined depressive and anxiety disorders (low SoE). Few (or no) eligible studies evaluated individuals with anxiety disorder, PTSD, OCD, or bipolar disorders, precluding conclusions for these conditions. There was also insufficient evidence for suicide-related outcomes, potential harms of treatment, and adherence to treatment, and for comparisons of nonpharmacologic with pharmacologic treatments.

Conclusion. Several nonpharmacologic treatments are more effective than TAU for perinatal mental health conditions, with the strongest evidence for CBT and IPT to reduce depressive symptoms among perinatal individuals with depressive disorders or combined depressive and anxiety disorders. Future research is needed to evaluate the comparative effectiveness of lesser studied nonpharmacologic interventions and lesser studied perinatal mental health conditions.

Management of Depression in Adults: A Review

Author/s: 
Gregory E Simon, Nathalie Moise, David C Mohr

Importance: Approximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.

Observations: Major depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).

Conclusions and relevance: Effective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.

Keywords 

Therapist-guided remote versus in-person cognitive behavioural therapy: a systematic review and meta-analysis of randomized controlled trials

Author/s: 
Sara Zandieh, Seyedeh Maryam Abdollahzadeh, Behnam Sadeghirad, Li Wang, Randi E McCabe, Liam Yao, Briar E Inness, Ananya Pathak, Rachel J Couban, Holly Crandon, Kian Torabiardakani, Peter Bieling, Jason W Busse

Background: Cognitive behavioural therapy (CBT) has been shown to be effective for several psychiatric and somatic conditions; however, most randomized controlled trials (RCTs) have administered treatment in person and whether remote delivery is similarly effective remains uncertain. We sought to compare the effectiveness of therapist-guided remote CBT and in-person CBT.

Methods: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to July 4, 2023, for RCTs that enrolled adults (aged ≥ 18 yr) presenting with any clinical condition and that randomized participants to either therapist-guided remote CBT (e.g., teleconference, videoconference) or in-person CBT. Paired reviewers assessed risk of bias and extracted data independently and in duplicate. We performed random-effects model meta-analyses to pool patient-important primary outcomes across eligible RCTs as standardized mean differences (SMDs). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to assess the certainty of evidence and used the Instrument to Assess the Credibility of Effect Modification Analyses (ICEMAN) to rate the credibility of subgroup effects.

Results: We included 54 RCTs that enrolled a total of 5463 patients. Seventeen studies focused on treatment of anxiety and related disorders, 14 on depressive symptoms, 7 on insomnia, 6 on chronic pain or fatigue syndromes, 5 on body image or eating disorders, 3 on tinnitus, 1 on alcohol use disorder, and 1 on mood and anxiety disorders. Moderate-certainty evidence showed little to no difference in the effectiveness of therapist-guided remote and in-person CBT on primary outcomes (SMD -0.02, 95% confidence interval -0.12 to 0.07).

Interpretation: Moderate-certainty evidence showed little to no difference in the effectiveness of in-person and therapist-guided remote CBT across a range of mental health and somatic disorders, suggesting potential for the use of therapist-guided remote CBT to facilitate greater access to evidence-based care. Systematic review registration: Open Science Framework (https://osf.io/7asrc).

The frequency and impact of undiagnosed benign paroxysmal positional vertigo in outpatients with high falls risk

Author/s: 
Hawke, L. J., Barr, C. J., McLoughlin, J. V.

Background
The frequency and impact of undiagnosed benign paroxysmal positional vertigo (BPPV) in people identified with high falls risk has not been investigated.

Objective
To determine the frequency and impact on key psychosocial measures of undiagnosed BPPV in adult community rehabilitation outpatients identified with a high falls risk.

Design
A frequency study with cross-sectional design.

Setting
A Community Rehabilitation Program in Melbourne, Australia.

Subjects
Adult community rehabilitation outpatients with a Falls Risk for Older People in the Community Screen score of four or higher.

Methods
BPPV was assessed in 34 consecutive high falls risk rehabilitation outpatients using the Dix–Hallpike test and supine roll test. Participants were assessed for anxiety, depression, fear of falls, social isolation and loneliness using the Hospital Anxiety and Depression Scale, Falls Efficacy Scale-International and De Jong Gierveld 6-Item Loneliness Scale.

Results
A total of 18 (53%; 95% confidence interval: 36, 70) participants tested positive for BPPV. There was no significant difference between those who tested positive for BPPV and those who did not for Falls Risk for Older People in the Community Screen scores (P = 0.555), Hospital Anxiety and Depression Scale (Anxiety) scores (P = 0.627), Hospital Anxiety and Depression Scale (Depression) scores (P = 0.368) or Falls Efficacy Scale-International scores (P = 0.481). Higher scores for the De Jong Gierveld 6-Item Loneliness Scale in participants with BPPV did not reach significance (P = 0.056).

Conclusions
Undiagnosed BPPV is very common and associated with a trend towards increased loneliness in adult rehabilitation outpatients identified as having a high falls risk.

Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review

Author/s: 
Groff, D., Sun, A., Ssentongo, A. E., Ba, D. M., Parsons, N., Poudel, G. R., Lekoubou, A., Oh, J. S., Ericson, J. E., Ssentongo, P., Chinchilli, V. M.

Importance
Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region.

Objective
To estimate organ system–specific frequency and evolution of PASC.

Evidence Review
PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references. Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility.

Findings
From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55.0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders.

Conclusions and Relevance
In this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries.

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.

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