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Dialogues in Clinical Neuroscience Jun 2017Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are... (Review)
Review
Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are associated with a high burden of illness. Anxiety disorders are often underrecognized and undertreated in primary care. Treatment is indicated when a patient shows marked distress or suffers from complications resulting from the disorder. The treatment recommendations given in this article are based on guidelines, meta-analyses, and systematic reviews of randomized controlled studies. Anxiety disorders should be treated with psychological therapy, pharmacotherapy, or a combination of both. Cognitive behavioral therapy can be regarded as the psychotherapy with the highest level of evidence. First-line drugs are the selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Benzodiazepines are not recommended for routine use. Other treatment options include pregabalin, tricyclic antidepressants, buspirone, moclobemide, and others. After remission, medications should be continued for 6 to 12 months. When developing a treatment plan, efficacy, adverse effects, interactions, costs, and the preference of the patient should be considered.
Topics: Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Cognitive Behavioral Therapy; Humans; Psychotherapy; Selective Serotonin Reuptake Inhibitors
PubMed: 28867934
DOI: 10.31887/DCNS.2017.19.2/bbandelow -
Advances in Experimental Medicine and... 2020This chapter reviews the role of benzodiazepines (BZs) in the treatment of anxiety disorders, specifically panic disorder with or without agoraphobia, generalized... (Review)
Review
This chapter reviews the role of benzodiazepines (BZs) in the treatment of anxiety disorders, specifically panic disorder with or without agoraphobia, generalized anxiety disorder, and social anxiety disorder (social phobia). BZs pharmacology, classification, efficacy, adverse effects, withdrawal symptoms, possible dependence, and abuse; their positioning among pharmacological treatment; and guidance on how to use them are discussed.
Topics: Agoraphobia; Anxiety Disorders; Benzodiazepines; Humans; Panic Disorder
PubMed: 32002938
DOI: 10.1007/978-981-32-9705-0_20 -
Deutsches Arzteblatt International Sep 2018Anxiety disorders are the most common type of mental illness in Europe, with a 12-month prevalence of 14% among persons aged 14 to 65. Their onset is usually in...
BACKGROUND
Anxiety disorders are the most common type of mental illness in Europe, with a 12-month prevalence of 14% among persons aged 14 to 65. Their onset is usually in adolescence or early adulthood. The affected patients often develop further mental or somatic illnesses (sequential comorbidity).
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed.
RESULTS
The group of anxiety disorders includes generalized anxiety disorder (GAD), phobic disorders, panic disorders, and two disorders that are often restricted to childhood-separation anxiety and selective mutism. A comprehensive differential diag- nostic evaluation is essential, because anxiety can be a principal manifestation of other types of mental or somatic illness as well. Psychotherapy and treatment with psychoactive drugs are the therapeutic strategies of first choice. Of all types of psycho- therapy, cognitive behavioral therapy has the best documented efficacy. Modern antidepressants are the drugs of first choice for the treatment of panic disorders, agoraphobia, social phobia, and GAS; pregabalin is a further drug of first choice for GAS.
CONCLUSION
In general, anxiety disorders can now be effectively treated. Patients should be informed of the therapeutic options and should be involved in treatment planning. Current research efforts are centered on individualized and therefore, it is hoped, even more effective treatment approaches than are available at present.
Topics: Adolescent; Adult; Aged; Antidepressive Agents; Anxiety Disorders; Child; Cognitive Behavioral Therapy; Female; Humans; Male; Middle Aged; Phobic Disorders; Sex Factors; Treatment Outcome
PubMed: 30282583
DOI: 10.3238/arztebl.2018.0611 -
Dialogues in Clinical Neuroscience Sep 2015Anxiety disorders, including panic disorder with or without agoraphobia, generalized anxiety disorder, social anxiety disorder, specific phobias, and separation anxiety...
Anxiety disorders, including panic disorder with or without agoraphobia, generalized anxiety disorder, social anxiety disorder, specific phobias, and separation anxiety disorder, are the most prevalent mental disorders and are associated with immense health care costs and a high burden of disease. According to large population-based surveys, up to 33.7% of the population are affected by an anxiety disorder during their lifetime. Substantial underrecognition and undertreatment of these disorders have been demonstrated. There is no evidence that the prevalence rates of anxiety disorders have changed in the past years. In cross-cultural comparisons, prevalence rates are highly variable. It is more likely that this heterogeneity is due to differences in methodology than to cultural influences. Anxiety disorders follow a chronic course; however, there is a natural decrease in prevalence rates with older age. Anxiety disorders are highly comorbid with other anxiety disorders and other mental disorders.
Topics: Age of Onset; Anxiety Disorders; Global Health; History, 17th Century; History, 21st Century; Patient Acceptance of Health Care; Psychiatric Status Rating Scales; Sex Characteristics
PubMed: 26487813
DOI: 10.31887/DCNS.2015.17.3/bbandelow -
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 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 -
Neuropsychopharmacology : Official... Jan 2017The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate... (Review)
Review
The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.
Topics: Anxiety Disorders; Brain; Fear; Humans; Inflammation; Stress Disorders, Post-Traumatic
PubMed: 27510423
DOI: 10.1038/npp.2016.146 -
Presse Medicale (Paris, France : 1983) May 2018Traumatic events and their consequences are often hidden or minimised by patients for reasons linked to the post-traumatic stress disorder itself (inexpressibility,... (Review)
Review
Traumatic events and their consequences are often hidden or minimised by patients for reasons linked to the post-traumatic stress disorder itself (inexpressibility, shame, depressive thoughts, fear of stigmatisation, etc.). Although post-traumatic stress disorder (PTSD) remains the most widely known disorder, chronic post-traumatic psychiatric disorders are many and varied. After a trauma, the practitioner has to check for the different clinical forms of post-traumatic psychological consequences: PTSD is not the only diagnosis. Based on our own clinical experience compared to the international literature, we think necessary to build a didactic classification describing chronic post-traumatic symptoms and syndromes. Post traumatic depressions and bereavement lead to high risk of suicidal crisis and self-harm behaviours. Re-experiencing are felt with anxiety, hyper arousal increases anxious reactivity, and avoidance strategies increase anticipatory anxiety, indicating post-traumatic anxiety disorders (agoraphobia, specific phobia, obsessive compulsive disorder, separation anxiety, social phobia). Characterising an often-severe clinical picture, the co-occurrence of post-traumatic and chronic psychotic symptoms is not unusual (post-traumatic schizophrenia, post-traumatic depression with mood-congruent psychotic features, non-schizophrenic post-traumatic psychotic disorder, and bipolar reaction to trauma). A physical injury occurring at the same time as a traumatic exposure increases the risk of developing post-traumatic stress disorder later which, in turn, afflicts the subjective perception of the physical health (development of somatoform and psychosomatic disorders, comorbidity with a post-concussion syndrome). The trauma may cause a rupture in the biography of a person, also in his/her internal physiological functioning as in his/her social activities (impacts of instinctive functions and behaviours, personality changes, and adjustment difficulties on professional and personal life). Although a nomenclature is necessary for semiological descriptions, a thorough analysis of the patient's general psychological functioning must also be conducted.
Topics: Comorbidity; Diagnosis, Differential; Emotions; Female; Humans; Male; Mental Disorders; Stress Disorders, Post-Traumatic
PubMed: 29580906
DOI: 10.1016/j.lpm.2017.12.006 -
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