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Frontiers in Psychiatry 2020Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress... (Review)
Review
Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.
PubMed: 33424664
DOI: 10.3389/fpsyt.2020.595584 -
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 -
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 -
Neuropsychiatric Disease and Treatment 2020Any type of sexual dysfunction is an important problem in half of the patients with depressive disorder. On the other hand, one to a quarter of people without any... (Review)
Review
Any type of sexual dysfunction is an important problem in half of the patients with depressive disorder. On the other hand, one to a quarter of people without any depressive disorder experience sexual dysfunction. Antidepressant agents can lead to all types of sexual side effects including arousal, libido, orgasm and ejaculation problems. Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drugs which are prescribed for the treatment of a variety of disorders, including major depressive disorder, obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, generalized anxiety disorder, and impulse control disorders. It has been reported that one in eight people have utilized one of the SSRIs in the past 10 years. Some studies reported up to 80% of SSRI-induced sexual side effects. Management of SSRI-induced sexual dysfunction seems to be complex and hard. In this paper, SSRI-induced sexual dysfunction and new perspectives in the management of this problem were reviewed.
PubMed: 32368066
DOI: 10.2147/NDT.S185757 -
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