Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence

A large amount of research has accumulated on the efficacy and effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders including posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and specific phobia. The purpose of the current article is to provide an overview of two of the most commonly used CBT methods used to treat anxiety disorders (exposure and cognitive therapy) and to summarize and discuss the current empirical research regarding the usefulness of these techniques for each anxiety disorder. Additionally, we discuss the difficulties that arise when comparing active CBT treatments, and we suggest directions for future research. Overall, CBT appears to be both efficacious and effective in the treatment of anxiety disorders, but dismantling studies are needed to determine which specific treatment components lead to beneficial outcomes and which patients are most likely to benefit from these treatment components.     

Pharmacotherapy of anxiety disorders: a critical review

Given the enormous contribution of anxiety disorders to the burden of disease, it is key to optimize their prevention and treatment. In this critical review we assess advances in the pharmacotherapy of anxiety disorders, as well as remaining challenges, in recent decades, the field has seen rigorous clinical trial methods to quantify the efficacy and safety of serendipitously discovered agents, more focused development of medications with selective mechanisms of action, and the gradual translation of insights from laboratory research into proof-of-principle clinical trials. On the positive side, a considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents. Significant challenges in the field include barriers to appropriate diagnosis and treatment of anxiety disorders, failure of a significant proportion of patients to respond to first-line pharmacotherapy agents, and a limited database of efficacy or effectiveness studies to guide treatment in such cases.     

Sleep and anxiety disorders

Sleep disturbances-particularly insomnia - are highly prevalent in anxiety disorders and complaints such as insomnia or nightmares have even been incorporated in some anxiety disorder definitions, such as generalized anxiety disorder and posttraumatic stress disorder. In the first part of this review, the relationship between sleep and anxiety is discussed in terms of adaptive response to stress. Recent studies suggested that the corticotropin-releasing hormone system and the locus ceruleus-autonomic nervous system may play major roles in the arousal response to stress. It has been suggested that these systems may be particularly vulnerable to prolonged or repeated stress, further leading to a dysfunctional arousal state and pathological anxiety states, Polysomnographic studies documented limited alteration of sleep in anxiety disorders. There is some indication for alteration in sleep maintenance in generalized anxiety disorder and for both sleep initiation and maintenance in panic disorder; no clear picture emerges for obsessive-compulsive disorder or posttraumatic stress disorder. Finally, an unequivocal sleep architecture profile that could specifically relate to a particular anxiety disorder could not be evidenced; in contrast, conflicting results are often found for the same disorder. Discrepancies between studies could have been related to illness severity, diagnostic comorbidity, and duration of illness. A brief treatment approach for each anxiety disorder is also suggested with a special focus on sleep.     

Nonpharmacological treatments for anxiety disorders

An evidence-based review of nonpharmacological treatments for anxiety disorders is presented. The vast majority of the controlled research is devoted to cognitive behavior therapy (CBT) and shows its efficiency and effectiveness in all the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) anxiety disorders in meta-analyses. Relaxation, psychoanalytic therapies, Rogerian nondirective therapy, hypnotherapy and supportive therapy were examined in a few controlled studies, which preclude any definite conclusion about their effectiveness in specific phobias, agoraphobia, panic disorder, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), CBT was clearly better than psychoanalytic therapy in generalized anxiety disorder (GAD) and performance anxiety Psychological debriefing for PTSD appeared detrimental to the patients in one high-quality meta-analysis. Uncontrolled studies of psychosurgery techniques for intractable OCD demonstrated a limited success and detrimental side effects. The same was true for sympathectomy in ereutophobia. Transcranial neurostimulation for OCD is under preliminary study. The theoretical and practical problems of CBT dissemination are discussed.     

Epidemiology of anxiety disorders in the 21st century

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.     

The epidemiology of anxiety disorders: a review

Epidemiological studies show that anxiety disorders are highly prevalent and an important cause of functional impairment; they constitute the most frequent menial disorders in the community. Phobias are the most common with the highest rates for simple phobia and agoraphobia. Panic disorder (PD) and obsessive-compulsive disorder (OCD) are less frequent (2% lifetime prevalence), and there are discordant results for social phobia (SP) (2%-16%) and generalized anxiety disorder (GAD) (3%-30%). These studies underline the importance of an accurate definition of disorders using unambiguous diagnostic and assessment criteria. The boundaries between anxiety disorders are often ill defined and cases may vary widely according to the definition applied. Simple phobia, agoraphobia, and GAD are more common in vmrnen, while there is no gender différence for SP, PD, and OCD, Anxiety disorders are more common in separated, divorced, and widowed subjects; their prevalence is highest in subjects aged 25 to 44 years and lowest in subjects aged >65 years. The age of onset of the different types of anxiety disorders varies widely: phobic disorders begin early in life, whereas PD occurs in young adulthood. Clinical - rather than epidemiological - studies have examined risk factors such as life events, childhood experiences, and familial factors. Anxiety disorders have a chronic and persistent course, and are frequently comorbid with other anxiety disorders, depressive disorders, and substance abuse. Anxiety disorders most frequently precede depressive disorders or substance abuse, Comorbid diagnoses may influence risk factors like functional impairment and quality of life. It remains unclear whether certain anxiety disorders (eg, PD) are risk factors for suicide. The comorbidity of anxiety disorders has important implications for assessment and treatment and the risk factors should be explored. The etiology, natural history, and outcome of these disorders need to be further addressed in epidemiological studies.     

Neuroimaging in anxiety disorders

Over the last few years, neuroimaging techniques have contributed greatly to the identification of the structural and functional neuroanatomy of anxiety disorders. The amygdala seems to be a crucial structure for fear and anxiety, and has consistently been found to be activated in anxiety-provoking situations. Apart from the amygdala, the insula and anterior cinguiate cortex seem to be critical, and ail three have been referred to as the "fear network." In the present article, we review the main findings from three major lines of research. First, we examine human models of anxiety disorders, including fear conditioning studies and investigations of experimentally induced panic attacks. Then we turn to research in patients with anxiety disorders and take a dose look at post-traumatic stress disorder and obsessive-compulsive disorder. Finally, we review neuroimaging studies investigating neural correlates of successful treatment of anxiety, focusing on exposure-based therapy and several pharmacological treatment options, as well as combinations of both.     

Psychopharmacology of anxiety disorders

Exposure of the general population to a 1:4 lifetime risk of disabling anxiety has inspired generations of fundamental and clinical psychopharmacologists, from the era of the earliest benzodiazepines (BZ) to that of the selective serotonin reuptake inhibitors (SSRIs) and related compounds, eg, the serotonin and norepinephrine reuptake inhibitors (SNRIs). This comprehensive practical review summarizes current therapeutic research across the spectrum of individual disorders: generalized anxiety disorder (GAD), panic disorder (PD) and agoraphobia (social anxiety disorder), compulsive disorder (OCD), phobic disorder (including social phobia), and posttraumatic stress disorder (PTSD). Specific diagnosis is a precondition to successful therapy: despite substantial overlap, each disorder responds preferentially to specific pharmacotherapy. Comorbidity with depression is common; hence the success of the SSRIs, which were originally designed to treat depression. Assessment (multidomain measures versus individual end points) remains problematic, as-frequently-do efficacy and tolerability The ideal anxiolytic remains the Holy Grail of worldwide psychopharmacologic research.     

A systematic review of the neural bases of psychotherapy for anxiety and related disorders

Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions.     

Cognitive behavioral group therapy for anxiety: recent developments

Anxiety disorders occur frequently, and can have a negative impact on the quality of people''s lives. They often begin at an early age and can have some serious consequences. This article is an overview of the recent studies concerning group cognitive-behavioral interventions for anxiety disorders. In the last few years, anxiety disorder prevention for children and adolescents has become an important focus of research work. Group prevention programs are based on standard cognitive behavioral therapy (CBT) strategies and are aimed at preventing anxiety disorders as early as possible. Numerous cognitive behavioral group therapies for children as well as adults have been well studied. There are many CBT protocols that have been developed for treating specific anxiety disorders. Now, specialized CBT programs are available for individuals who suffer from different anxiety disorders, enabling them to be treated together in groups.     

Functional neuroimaging studies of the effects of psychotherapy

It has been long established that psychological interventions can markedly alter patients'' thinking patterns, beliefs, attitudes, emotional states, and behaviors. Little was known about the neural mechanisms mediating such alterations before the advent of functional neuroimaging techniques. Since the turn of the new millenium, several functional neuroimaging studies have been conducted to tackle this important issue. Some of these studies have explored the neural impact of various forms of psychotherapy in individuals with major depressive disorder. Other neuroimaging studies have investigated the effects of psychological interventions for anxiety disorders. I review these studies in the present article, and discuss the putative neural mechanisms of change in psychotherapy. The findings of these studies suggest that mental and behavioral changes occurring during psychotherapeutic interventions can lead to a normalization of functional brain activity at a global level.     

Biological predictors of pharmacological therapy in anxiety disorders

At least one third of patients with anxiety disorders do not adequately respond to available pharmacological treatment. The reason that some patients with anxiety disorders respond well, but others not, to the same classes of medication is not yet fully understood. It is suggested that several biological factors may influence treatment mechanisms in anxiety and therefore could be identified as possible biomarkers predicting treatment response. In this review, we look at current evidence exploring different types of treatment predictors, including neuroimaging, genetic factors, and blood-related measures, which could open up novel perspectives in clinical management of patients with anxiety disorders.     

Prevention: an achievable goal in personalized medicine

In the past 15 years a considerable number of studies have found evidence that it may be possible to prevent the onset of some mental disorders. Most evidence is available for depressive disorders, but a growing number of studies have focused on anxiety disorders and psychotic disorders. This paper reviews the studies which have examined the effects of preventive interventions on the incidence of mental disorders in people who do not meet criteria for a mental disorder at baseline. More than 20 studies have examined prevention of depressive disorders, and they have found an overall reduction in the incidence of about 25% compared with control groups. The problem of identifying the most optimal target groups for preventive interventions is also illustrated. This is a problem because most risk indicators have a low specificity, and most people with a risk indicator do not develop a mental disorder. Finally, this paper will show how other statistics, such as the exposure rate, the attributable fraction, and the number needed to treat can help in identifying the most optimal target groups for preventive interventions.     

Epidemiology of mental disorders in children and adolescents

This article provides a review of the magnitude of mental disorders in children and adolescents from recent community surveys across the world. Although there is substantial variation in the results depending upon the methodological characteristics of the studies, the findings converge in demonstrating that approximately one fourth of youth experience a mental disorder during the past year, and about one third across their lifetimes. Anxiety disorders are the most frequent conditions in children, followed by behavior disorders, mood disorders, and substance use disorders. Fewer than half of youth with current mental disorders receive mental health specialty treatment. However, those with the most severe disorders tend to receive mental health services. Current issues that are now being identified in the field of child psychiatric epidemiology include: refinement of classification and assessment, inclusion of young children in epidemiologic surveys, integration of child and adult psychiatric epidemiology, and evaluation of both mental and physical disorders in children.     

Pharmacotherapy for anxiety disorders in children and adolescents

Anxiety disorders are the most common mental health diagnoses in youth, and carry risks for ongoing impairments and subsequent development of other psychiatric comorbidities into adulthood. This article discusses considerations for assessment and treatment of anxiety disorders in youth, with a focus on the evidence base of pharmacologic treatment and important clinical considerations to optimize care. We then briefly describe the impact of anxiety on neuronal elements of fear circuitry to highlight how treatments may ameliorate impairments through enhanced plasticity Overall, pharmacotherapy for anxiety disorders is effective in improving clinical symptoms, particularly in combination with psychotherapy. Response is typically seen within several weeks, yet longitudinal studies are limited. Selective serotonin reuptake inhibitors are thought to be relatively safe and effective for acute treatment of several classes of anxiety disorders in youth, with increasing evidence supporting the role of neuronal plasticity in recovery.     

Psychiatric aspects of organic sleep disorders

In recent years, a number of studies have attempted to characterize psychological disturbances related to various sleep disorders. The objective of this type of research is to investigate the possibility that psychopathology may represent an etiological factor, a complication, and/or a target for treatment. In addition, disordered sleep can present itself in a complex and atypical fashion in which the primary sleep-related component may not be immediately apparent. This article reviews the evidence for a relationship between organic sleep disorders and psychiatric morbidity. Generally, it can be concluded that organic sleep disorders have a profound negative impact on most domains of health-related quality of life. Results for the sleep disorders that have been studied (narcolepsy idiopathic hypersomnia, sleep apnea/hypopnea syndrome, restless legs syndrome, periodic limb movement disorder, and circadian sleep disorders) show strong evidence for an association with mood disorders. After treatment, depression scores may or may not improve to the level of population norms, suggesting that this relationship is more complex than one of mere cause and effect.     

Neuroplasticity in mood disorders

Neuroimaging and neuropathological studies of major depressive disorder (MDD) and bipolar disorder (BD) have identified abnormalities of brain structure in areas of the prefrontal cortex, amygdala, striatum, hippocampus, parahippocampal gyrus, and raphe nucleus. These structural imaging abnormalities persist across illness episodes, and preliminary evidence suggests they may in some cases arise prior to the onset of depressive episodes in subjects at high familial risk for MDD. In other cases, the magnitude of abnormality is reportedly correlated with time spent depressed. Postmortem histopathological studies of these regions have shown abnormal reductions of synaptic markers and glial cells, and, in rare cases, reductions in neurons in MDD and BD. Many of the regions affected by these structural abnormalities show increased glucose metabolism during depressive episodes. Because the glucose metabolic signal is dominated by glutamatergic transmission, these data support other evidence that excitatory amino acid transmission is elevated in limbic-cortical-striatal-pallidal-thalamic circuits during depression. Some of the subject samples in which these metabolic abnormalities have been demonstrated were also shown to manifest abnormally elevated stressed plasma cortisol levels. The co-occurrence of increased glutamatergic transmission and Cortisol hypersecretion raises the possibility that the gray matter volumetric reductions in these depressed subjects are partly accounted for by processes homologous to the dendritic atrophy induced by chronic stress in adult rodents, which depends upon interactions between elevated glucocorticoid secretion and N-meihyl-D-aspartate (NMDA)-glutamate receptor stimulation. Some mood-stabilizing and antidepressant drugs that exert neurotrophic effects in rodents appear to reverse or attenuate the gray matter volume abnormalities in humans with mood disorders. These neurotrophic effects may be integrally related to the therapeutic effects of such agents, because the regions affected by structural abnormalities in mood disorders are known to play major roles in modulating the endocrine, autonomic, behavioral, and emotional experiential responses to stressors.     

The overlap between anxiety,depression, and obsessive-compulsive disorder

The anxiety disorders include generalized anxiety disorder, specific phobia, social phobia, agoraphobia, and panic disorder. In addition to the specific symptoms of these disorders, there may be a common experience of anxiety and even dysphoria across the conditions, and of course recourse to the same drug or choice of drugs for treatment. This overlap probably occurs because of universal dimensions of distress or negative affectivity, a shared genetic predisposition, and a common neurobiology Evidence of shared genes is still based mainly on twin studies, but the shared neurobiology can be investigated directly by the investigation of emotional or cognitive bias either behaviorally or using functional brain imaging. This intermediate phenotype can then provide a substrate for understanding and developing medicines and psychological treatments.