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BMJ (Clinical Research Ed.) Jan 2022To identify drug classes and individual selective serotonin reuptake inhibitors (SSRIs) with high rates of remission and low risk of adverse events in the treatment of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To identify drug classes and individual selective serotonin reuptake inhibitors (SSRIs) with high rates of remission and low risk of adverse events in the treatment of panic disorder with or without agoraphobia.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Embase, Medline, and ClinicalTrials.gov from inception to 17 June 2021.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised controlled trials that included adults aged ≥18 years with a diagnosis of panic disorder, compared drugs used to treat the panic disorder, and measured the outcomes of interest, including remissions, dropouts, and adverse events.
METHODS
Risk of bias in the included studies was assessed using the revised Cochrane risk of bias tool for randomised trials. Direct meta-analyses were performed using random effects models. A two stage network meta-analysis with surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of drug classes and individual SSRIs.
RESULTS
87 studies including a total of 12 800 participants and 12 drug classes were eligible for inclusion. Almost all the studies (86/87) had some concern or were at high risk of bias. Network meta-analysis of remission with consistent results indicated that tricyclic antidepressants, benzodiazepines, monoamine oxidase inhibitors, SSRIs, and serotonin-noradrenaline reuptake inhibitors (SNRIs) were associated with significantly higher remission rates than placebo, with risk ratios of 1.39 (95% confidence interval 1.26 to 1.54), 1.47 (1.36 to 1.60), 1.30 (1.00 to 1.69), 1.38 (1.26 to 1.50), and 1.27 (1.12 to 1.45), respectively. SUCRAs identified benzodiazepines (84.5%, mean rank=2.4), tricyclic antidepressants (68.7%, 3.8), and SSRIs (66.4%, 4.0) as the top three best treatments for remission. However, tricyclic antidepressants, benzodiazepines, and SSRIs were also significantly associated with increased risk of adverse events compared with placebo, with risk ratios of 1.79 (1.47 to 2.19), 1.76 (1.50 to 2.06), and 1.19 (1.01 to 1.41), respectively. Consistency assumption of adverse events was upheld but could still be present on removal of studies with high percentages of women participants and those with agoraphobia. A SUCRA cluster ranking plot considering both remission and adverse events among all drug classes indicated that SSRIs were associated with high remission and low risk of adverse events. Among individual SSRIs, sertraline and escitalopram provided high remission with an acceptable risk of adverse events.
CONCLUSION
The findings suggest that SSRIs provide high rates of remission with low risk of adverse events for the treatment of panic disorder. Among SSRIs, sertraline and escitalopram were associated with high remission and low risk of adverse events. The findings were, however, based on studies of moderate to very low certainty levels of evidence, mostly as a result of within study bias, inconsistency, and imprecision of the findings reported.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020180638.
Topics: Adult; Agoraphobia; Escitalopram; Female; Humans; Induction Chemotherapy; Male; Network Meta-Analysis; Panic Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome
PubMed: 35045991
DOI: 10.1136/bmj-2021-066084 -
The World Journal of Biological... Feb 2023This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety,...
World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part I: Anxiety disorders.
AIM
This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008).
METHOD
A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications.
RESULT
This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence.
CONCLUSION
It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.
Topics: Adult; Adolescent; Child; Humans; Stress Disorders, Post-Traumatic; Biological Psychiatry; Anxiety Disorders; Selective Serotonin Reuptake Inhibitors; Anxiety; Obsessive-Compulsive Disorder
PubMed: 35900161
DOI: 10.1080/15622975.2022.2086295 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
Brain Sciences Feb 2023Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a... (Review)
Review
Anxiety disorders are the most common group of mental disorders, but they are often underrecognized and undertreated in primary care. Dysfunctional breathing is a hallmark of anxiety disorders; however, mainstays of treatments do not tackle breathing in patients suffering anxiety. This scoping review aims to identify the nature and extent of the available research literature on the efficacy of breathwork interventions for adults with clinically diagnosed anxiety disorders using the DSM-5 classification system. Using the PRISMA extension for scoping reviews, a search of PubMed, Embase, and Scopus was conducted using terms related to anxiety disorders and breathwork interventions. Only clinical studies using breathwork (without the combination of other interventions) and performed on adult patients diagnosed with an anxiety disorder using the DSM-5 classification system were included. From 1081 articles identified across three databases, sixteen were included for the review. A range of breathwork interventions yielded significant improvements in anxiety symptoms in patients clinically diagnosed with anxiety disorders. The results around the role of hyperventilation in treatment of anxiety were contradictory in few of the examined studies. This evidence-based review supports the clinical utility of breathwork interventions and discusses effective treatment options and protocols that are feasible and accessible to patients suffering anxiety. Current gaps in knowledge for future research directions have also been identified.
PubMed: 36831799
DOI: 10.3390/brainsci13020256 -
Contemporary Clinical Trials Apr 2020Anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia) are common, distressing, and impairing. While pharmacotherapy...
Anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia) are common, distressing, and impairing. While pharmacotherapy and psychotherapy are first-line treatment strategies for anxiety disorders, many patients are reluctant to take psychiatric medication, and many prefer to avoid any kind of mental health treatment due to stigma or distrust of traditional medical care. We present the trial protocol for the first study comparing first-line medication treatment with Mindfulness-Based Stress Reduction (MBSR), a popular mindfulness meditation training program, for the treatment of anxiety disorders. We will use a non-inferiority, comparative effectiveness trial design, in which individuals with diagnosed anxiety disorders will be randomized to either pharmacotherapy with escitalopram or MBSR for 8 weeks of treatment. Treatment outcome will be based on gold standard symptom severity measures assessed by trained independent evaluators blind to treatment allocation. Secondary outcomes will include key symptom and function measures, as well as tolerability and satisfaction with treatment. Findings will provide crucial information to inform decision making about the relative benefits of MBSR versus a first line medication for anxiety disorders by patients, medical care providers, healthcare insurers and other stakeholders.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Anxiety Disorders; Citalopram; Equivalence Trials as Topic; Meditation; Mindfulness; Research Design; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index
PubMed: 32087339
DOI: 10.1016/j.cct.2020.105965 -
Journal of Autism and Developmental... Jun 2020Effective treatments of highly prevalent stress-related outcomes such as depression and anxiety are understudied in adults with autism spectrum disorder (ASD). A... (Randomized Controlled Trial)
Randomized Controlled Trial
Effective treatments of highly prevalent stress-related outcomes such as depression and anxiety are understudied in adults with autism spectrum disorder (ASD). A randomized controlled trial with baseline, post-intervention, and 10-week follow-up, that explores the effects of animal assisted therapy (AAT) was conducted. In total, 53 adults with ASD with normal to high intelligence were randomized in an intervention (N = 27) versus waiting list control group (N = 26). The remarkable adherence to the therapy program by study participants and the program's clinically relevant effects indicate that AAT with dogs can be used to reduce perceived stress and symptoms of agoraphobia, and to improve social awareness and communication in adults with ASD with normal to high intelligence.
Topics: Adult; Agoraphobia; Animal Assisted Therapy; Animals; Anxiety; Anxiety Disorders; Autism Spectrum Disorder; Communication; Depression; Dogs; Female; Humans; Male
PubMed: 30900194
DOI: 10.1007/s10803-019-03971-9 -
Psychiatry Research Mar 2020Anxiety disorders are highly prevalent in the general population and associated with high rates of impairment and disability. This burden highlights the need to identify...
Anxiety disorders are highly prevalent in the general population and associated with high rates of impairment and disability. This burden highlights the need to identify risk factors that individuals can modify without professional intervention. A systematic review was conducted to identify studies that examined modifiable risk and protective factors for anxiety disorders among adults in the general population. Searches were conducted in PubMed, PsycINFO and MEDLINE using medical subject headings and text words related to risk factors, protective factors, and each anxiety disorder. Screening, data extraction, and quality assessment were performed by three study authors. Modifiable risk and protective factors from 19 studies across seven countries were identified. Risk factors identified included cigarette smoking, alcohol use, cannabis use, negative appraisals of life events, avoidance, and occupational factors. Protective factors included social support, coping, and physical activity. Cigarette smoking was the most studied risk factor. Support was found for cigarette smoking as a risk factor for agoraphobia and panic disorder. Mixed results were found for generalized anxiety disorder and specific phobia. Across disorders, smoking frequency was associated with greater risk. Results indicate an important gap in the literature in that few studies have examined modifiable risk factors for anxiety disorders.
Topics: Adult; Agoraphobia; Anxiety Disorders; Avoidance Learning; Cigarette Smoking; Cross-Sectional Studies; Female; Humans; Male; Occupational Health; Panic Disorder; Prevalence; Protective Factors; Retrospective Studies; Risk Factors; Substance-Related Disorders
PubMed: 31839417
DOI: 10.1016/j.psychres.2019.112705