-
The Psychiatric Quarterly Sep 2020Generalized Anxiety Disorder (GAD) from an official recognition as a residual category in DSM-III has come a long way to be appreciated as a common underlying anxiety...
Generalized Anxiety Disorder (GAD) from an official recognition as a residual category in DSM-III has come a long way to be appreciated as a common underlying anxiety pathway in the literature. Despite still being defined as extreme anxiety and worry upon performance and about one's health, GAD seems to be a general umbrella of anxiety, covering even social anxiety and panic disorder (PD) and even when not treated and chronic, leading to major depressive disorder (MDD). Along the line of some other similar studies and contentions, in the present study we sought to validate the hypothesis of GAD encompassing social anxiety as well as performance anxiety and its extension to PD and MDD. We also examined the onset of each diagnostic category of GAD, PD and MDD and their developmental course in our clinical sample. 113 patients with Generalized Anxiety Disorder (GAD) out of 295 referrals to our mood and anxiety clinic during the three months of May-July 2019, were identified and included in this research. We expanded the definition of GAD as per our clinical observation to include any situations triggering the anxiety including any performance and social situations and did not exclude if the anxiety led to panic attacks. The results of our study showed that an encompassing GAD (including performance and social anxiety) has an early onset, recognized partially in childhood, but mostly during adolescence. An untreated GAD was complicated with panic disorder and episodes of major depression, each with an onset later in life. GAD in our study was also found to be familial and genetic, while its post-morbid depression seemed to be more a reaction to a long-standing untreated anxiety. The findings of our study if replicated has research implication of better understanding the developmental course of mood disorders and hold the promise of more targeted treatments of anxiety, panic and depression in clinical practice.
Topics: Adult; Age of Onset; Anxiety Disorders; Comorbidity; Depressive Disorder, Major; Humans; Panic Disorder; Phobia, Social
PubMed: 32383134
DOI: 10.1007/s11126-020-09747-0 -
General Hospital Psychiatry 2022Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). However, compilations of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Caffeine has been purported to have anxiogenic and panicogenic properties, specifically salient in patients with panic disorder (PD). However, compilations of the magnitude of the effect of caffeine on anxiety and panic attacks are lacking and potential dose-response relationships have not been examined.
OBJECTIVES
In the present systematic review and meta-analysis, we aimed to examine the acute effects of placebo-controlled caffeine challenge on occurrence of panic attacks and subjective anxiety in patients with PD and healthy controls (HC), including dose-response relationships.
METHODS
Systematic searches were performed in six databases. We included blinded placebo-controlled studies of acute caffeine challenge on panic attacks and/or subjective anxiety in adult patients with PD.
RESULTS
Of the 1893 identified articles, ten met our inclusion criteria. The 9 studies investigating panic attacks included 237 patients, of which 51.1% had a panic attack following caffeine, but none after placebo. Six of these studies compared 128 patients with 115 healthy controls (HC), finding that patients (53.9%) were more vulnerable than HC (1.7%) for panic attacks following caffeine (log RR: 3.47; 95% CI 2.06-4.87). Six studies investigated subjective anxiety in 121 patients and 111 HC following caffeine, with an overall effect indicating increased sensitivity to the anxiogenic effects of caffeine in the patient group (Hedges' g = 1.02 [95% CI: 0.09-1.96]). The restricted range of caffeine employed [400-750 mg] and few studies (3) not using 480 mg prevented any meaningful analysis of a dose-response relationship.
LIMITATIONS
Of the ten studies included, only 2 reported anxiety data for the placebo condition, precluding a proper meta-analysis comparing anxiogenic effects of caffeine and placebo. The restricted dose range used prevented assessment of dose-response relationships.
CONCLUSIONS
The results confirm that caffeine at doses roughly equivalent to 5 cups of coffee induces panic attacks in a large proportion of PD patients and highly discriminates this population from healthy adults. Caffeine also increases anxiety in PD patients as well as among healthy adults at these doses although the exact relationship between caffeine-induced anxiety and panic attacks remains uncertain. The results suggest that caffeine targets important mechanisms related to the pathophysiology of PD.
IMPLICATIONS
Future studies should employ a wider range of caffeine doses and investigate contributions of biological and psychological mechanisms underlying the anxiogenic and panicogenic effects of caffeine. In the clinic, patients with PD should be informed about the panicogenic and anxiogenic effects of caffeine, with the caveat that little is known regarding smaller doses than 480 mg. Registration. PROSPERO (www.crd.york.ac.uk/prospero) registration number CRD42019120220.
Topics: Adult; Anxiety; Anxiety Disorders; Caffeine; Humans; Panic Disorder
PubMed: 34871964
DOI: 10.1016/j.genhosppsych.2021.11.005 -
American Family Physician Aug 2022Generalized anxiety disorder (GAD) and panic disorder (PD) are common mental health conditions in adults that are often seen in primary care. Although there is...
Generalized anxiety disorder (GAD) and panic disorder (PD) are common mental health conditions in adults that are often seen in primary care. Although there is insufficient evidence to support universal screening for PD and GAD, evaluation should be considered in patients who express recurrent, pervasive worry or present with somatic symptoms not attributed to underlying medical conditions. The GAD-7 and Patient Health Questionnaire for PD are validated screening tools that can aid in diagnosis and assessment. Anxiety disorders often present with substance use disorders, which should be treated concurrently. Effective therapies for PD and GAD include cognitive behavior therapy and anti-depressants, including selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Benzodiazepines are not recommended for first-line therapy or long-term use because of adverse reactions, risk of dependence, and higher mortality. No consistent evidence currently supports a specific prevention strategy for PD or GAD, but exercise may be beneficial.
Topics: Adult; Anxiety Disorders; Benzodiazepines; Cognitive Behavioral Therapy; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors
PubMed: 35977134
DOI: No ID Found -
Advances in Experimental Medicine and... 2020Anxiety disorders are debilitating psychological disorders characterized by a wide range of cognitive and somatic symptoms. Anxiety sufferers have a higher lifetime... (Review)
Review
Anxiety disorders are debilitating psychological disorders characterized by a wide range of cognitive and somatic symptoms. Anxiety sufferers have a higher lifetime prevalence of various medical problems. Chronic medical conditions furthermore increase the likelihood of psychiatric disorders and overall dysfunction. Lifetime rates of cardiovascular, respiratory, gastrointestinal, and other medical problems are disproportionately high in anxiety and panic/fear sufferers. The heightened comorbidity is not surprising as many symptoms of anxiety and panic/fear mimic symptoms of medical conditions. Panic disorder specifically is strongly linked to medical conditions due to its salient somatic symptoms, such as dyspnea, dizziness, numbness, chest pain, and heart palpitations, all of which can signal danger and deterioration for chronic disease sufferers. This chapter identifies shared correlates of medical illness and anxiety disorders and evidence for misinterpretation of symptoms as medically relevant and offers an analysis of implications for treatment of both types of conditions. We will concentrate on medical conditions with high associations for anxiety and panic by aspects of symptomatology, specifically neurological disorders (fibromyalgia, epilepsy, cerebral palsy), diabetes, gastrointestinal illness (irritable bowel syndrome, gastroesophageal reflux disease), and cardiovascular and respiratory illnesses (asthma).
Topics: Anxiety Disorders; Chronic Disease; Comorbidity; Humans; Panic Disorder
PubMed: 32002933
DOI: 10.1007/978-981-32-9705-0_15 -
Annals of Clinical Psychiatry :... May 2021Panic disorder (PD) is a devastating illness, with numerous patients experiencing significant functional disability and many not achieving full remission with first-line... (Review)
Review
BACKGROUND
Panic disorder (PD) is a devastating illness, with numerous patients experiencing significant functional disability and many not achieving full remission with first-line pharmacologic and psychotherapeutic treatments.
METHODS
A search of PubMed, Cochrane Library, and PsychINFO databases was used to identify publications focused on evidence-based treatment of PD.
RESULTS
Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are standard first-line pharmacologic treatments for PD. Many other antidepressants can be considered as alternatives to SSRIs, including serotonin-norepinephrine reuptake inhibitors, serotonin multimodal agents, tricyclic antidepressants, monoamine oxidase inhibitors, and mirtazapine. Certain anticonvulsants and antipsychotics may be helpful; however, the evidence base is limited. Buspirone, beta blockers, and hydroxyzine can be considered third-line agents. Currently, there is minimal data supporting the use of electroconvulsive therapy or repetitive transcranial magnetic stimulation (rTMS). There is very little evidence justifying the use of medical cannabis or over-the-counter supplements for PD, and these treatments have risk for adverse effects. Research strongly supports the use of cognitive-behavioral therapy (CBT) for PD.
CONCLUSIONS
Many options exist for the management of PD. Treatments with the strongest evidence include SSRIs, other antidepressants, and CBT. Newer interventions approved for the treatment of depression, such as serotonin multimodal agents, esketamine, and rTMS, merit further investigation for use in PD.
Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Humans; Panic Disorder; Psychotropic Drugs; Selective Serotonin Reuptake Inhibitors
PubMed: 33529291
DOI: 10.127788/acp.0014 -
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 -
American Family Physician Dec 2022Anxiety disorders are the most common psychiatric conditions in children and adolescents, affecting nearly 1 in 12 children and 1 in 4 adolescents. Anxiety disorders...
Anxiety disorders are the most common psychiatric conditions in children and adolescents, affecting nearly 1 in 12 children and 1 in 4 adolescents. Anxiety disorders include specific phobias, social anxiety disorder, separation anxiety disorder, agoraphobia, panic disorder, and generalized anxiety disorder. Risk factors include parental history of anxiety disorders, socioeconomic stressors, exposure to violence, and trauma. The U.S. Preventive Services Task Force recommends screening for anxiety disorders in children eight years and older; there is insufficient evidence to support screening in children younger than eight years. Symptoms of anxiety disorders in children and adolescents are similar to those in adults and can include physical and behavioral symptoms such as diaphoresis, palpitations, and tantrums. Care should be taken to distinguish symptoms of a disorder from normal developmental fears and behaviors, such as separation anxiety in infants and toddlers. Several validated screening measures are useful for initial assessment and ongoing monitoring. Cognitive behavior therapy and selective serotonin reuptake inhibitors are the mainstay of treatment and may be used as monotherapies or in combination. Prognosis is improved with early intervention, caretaker support, and professional collaboration.
Topics: Adult; Humans; Adolescent; Anxiety Disorders; Phobic Disorders; Cognitive Behavioral Therapy; Panic Disorder; Selective Serotonin Reuptake Inhibitors
PubMed: 36521463
DOI: No ID Found -
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 -
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 -
Molecular Psychiatry Jan 2022Treatment resistance affects 20-60% of patients with psychiatric disorders; and is associated with increased healthcare burden and costs up to ten-fold higher relative... (Review)
Review
Treatment resistance affects 20-60% of patients with psychiatric disorders; and is associated with increased healthcare burden and costs up to ten-fold higher relative to patients in general. Whilst there has been a recent increase in the proportion of psychiatric research focussing on treatment resistance (R = 0.71, p < 0.0001), in absolute terms this is less than 1% of the total output and grossly out of proportion to its prevalence and impact. Here, we provide an overview of treatment resistance, considering its conceptualisation, assessment, epidemiology, impact, and common neurobiological models. We also review new treatments in development and future directions. We identify 23 consensus guidelines on its definition, covering schizophrenia, major depressive disorder, bipolar affective disorder, and obsessive compulsive disorder (OCD). This shows three core components to its definition, but also identifies heterogeneity and lack of criteria for a number of disorders, including panic disorder, post-traumatic stress disorder, and substance dependence. We provide a reporting check-list to aid comparisons across studies. We consider the concept of pseudo-resistance, linked to poor adherence or other factors, and provide an algorithm for the clinical assessment of treatment resistance. We identify nine drugs and a number of non-pharmacological approaches being developed for treatment resistance across schizophrenia, major depressive disorder, bipolar affective disorder, and OCD. Key outstanding issues for treatment resistance include heterogeneity and absence of consensus criteria, poor understanding of neurobiology, under-investment, and lack of treatments. We make recommendations to address these issues, including harmonisation of definitions, and research into the mechanisms and novel interventions to enable targeted and personalised therapeutic approaches.
Topics: Bipolar Disorder; Depressive Disorder, Major; Humans; Obsessive-Compulsive Disorder; Panic Disorder; Psychiatry
PubMed: 34257409
DOI: 10.1038/s41380-021-01200-3