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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 -
JAMA Psychiatry Mar 2020Cognitive behavioral therapy is recommended for anxiety-related disorders, but evidence for its long-term outcome is limited. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cognitive behavioral therapy is recommended for anxiety-related disorders, but evidence for its long-term outcome is limited.
OBJECTIVE
This systematic review and meta-analysis aimed to assess the long-term outcomes after cognitive behavioral therapy (compared with care as usual, relaxation, psychoeducation, pill placebo, supportive therapy, or waiting list) for anxiety disorders, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD).
DATA SOURCES
English-language publications were identified from PubMed, PsycINFO, Embase, Cochrane, OpenGrey (1980 to January 2019), and recent reviews. The search strategy included a combination of terms associated with anxiety disorders (eg, panic or phobi*) and study design (eg, clinical trial or randomized controlled trial).
STUDY SELECTION
Randomized clinical trials on posttreatment and at least 1-month follow-up effects of cognitive behavioral therapy compared with control conditions among adults with generalized anxiety disorder, panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, PTSD, or OCD.
DATA EXTRACTION AND SYNTHESIS
Researchers independently screened records, extracted statistics, and assessed study quality. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
Hedges g was calculated for anxiety symptoms immediately after treatment and at 1 to 6 months, 6 to 12 months, and 12 months or more after treatment completion.
RESULTS
Of 69 randomized clinical trials (4118 outpatients) that were mainly of low quality, cognitive behavioral therapy compared with control conditions was associated with improved outcomes after treatment completion and at 1 to 6 months and at 6 to 12 months of follow-up for a generalized anxiety disorder (Hedges g, 0.07-0.40), panic disorder with or without agoraphobia (Hedges g, 0.22-0.35), social anxiety disorder (Hedges g, 0.34-0.60), specific phobia (Hedges g, 0.49-0.72), PTSD (Hedges g, 0.59-0.72), and OCD (Hedges g, 0.70-0.85). At a follow-up of 12 months or more, these associations were still significant for generalized anxiety disorder (Hedges g, 0.22; number of studies [k] = 10), social anxiety disorder (Hedges g, 0.42; k = 3), and PTSD (Hedges g, 0.84; k = 5), but not for panic disorder with or without agoraphobia (k = 5) and could not be calculated for specific phobia (k = 1) and OCD (k = 0). Relapse rates after 3 to 12 months were 0% to 14% but were reported in only 6 randomized clinical trials (predominantly for panic disorder with or without agoraphobia).
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis suggest that cognitive behavioral therapy for anxiety-related disorders is associated with improved outcomes compared with control conditions until 12 months after treatment completion. At a follow-up of 12 months or more, effects were small to medium for generalized anxiety disorder and social anxiety disorder, large for PTSD, and not significant or not available for other disorders. High-quality randomized clinical trials with 12 months or more of follow-up and reported relapse rates are needed.
Topics: Anxiety Disorders; Cognitive Behavioral Therapy; Humans; Obsessive-Compulsive Disorder; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 31758858
DOI: 10.1001/jamapsychiatry.2019.3986 -
Focus (American Psychiatric Publishing) Jun 2021In this review, the author examines the evidence for psychopharmacologic treatments among adults for generalized anxiety disorder, panic disorder, and social anxiety...
In this review, the author examines the evidence for psychopharmacologic treatments among adults for generalized anxiety disorder, panic disorder, and social anxiety disorder derived from clinical trials. For each disorder, major categories of drugs are reviewed, and then the evidence-based medications in each category are discussed. The author reviews key safety and tolerability considerations for each of the medications or classes. Evidence-based dosing for most specific agents is displayed in a comprehensive reference table. Subsequently, the author synthesizes the available information to suggest a pragmatic stepwise approach to treatment that accounts for patient-specific factors. To inform the guidance, the author incorporates and refines perspectives from treatment guidelines already written by clinical professional organizations. The author also briefly reviews the relatively new quantitative systematic review methodology of network meta-analysis (NMA) and discusses how NMA may help guide pharmacologic treatment sequencing decisions in the future by way of ranking treatments according to effect size and the relative amount of study to which treatments have been subject. Caveats of NMA studies are briefly discussed, as are results of recent NMAs regarding the pharmacologic treatment of anxiety disorders.
PubMed: 34690578
DOI: 10.1176/appi.focus.20200048