Cognitive behavioral therapy in anxiety disorders: current state of the evidence

A plethora of studies have examined the efficacy and effectiveness of cognitive-behavioral therapy (CBT) for adult anxiety disorders. In recent years, several meta-analyses have been conducted to quantitatively review the evidence of CBT for anxiety disorders, each using different inclusion criteria for studies, such as use of control conditions or type of study environment. This review aims to summarize and to discuss the current state of the evidence regarding CBT treatment for panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Overall, CBT demonstrates both efficacy in randomized controlled trials and effectiveness in naturalistic settings in the treatment of adult anxiety disorders. However, due to methodological issues, the magnitude of effect is currently difficult to estimate. In conclusion, CBT appears to be both efficacious and effective in the treatment of anxiety disorders, but more high-quality studies are needed to better estimate the magnitude of the effect.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Obsessive-compulsive disorder and its related disorders: a reappraisal of obsessive-compulsive spectrum concepts

Obsessive-compulsive disorder (OCD) is a clinical syndrome whose hallmarks are excessive, anxiety-evoking thoughts and compulsive behaviors that are generally recognized as unreasonable, but which cause significant distress and impairment. When these are the exclusive symptoms, they constitute uncomplicated OCD. OCD may also occur in the context of other neuropsychiatric disorders, most commonly other anxiety and mood disorders. The question remains as to whether these combinations of disorders should be regarded as independent, cooccurring disorders or as different manifestations of an incompletely understood constellation of OCD spectrum disorders with a common etiology. Additional considerations are given here to two potential etiology-based subgroups: (i) an environmentally based group in which OCD occurs following apparent causal events such as streptococcal infections, brain injury, or atypical neuroleptic treatment; and (ii) a genomically based group in which OCD is related to chromosomal anomalies or specific genes. Considering the status of current research, the concept of OCD and OCD-related spectrum conditions seems fluid in 2010, and in need of ongoing reappraisal.     

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.     

Cognitive behavioral therapy of obsessive-compulsive disorder

Until the mid-1960s, obsessive-compulsive disorder (OCD) was considered to be treatment-resistant, as both psychodynamic psychotherapy and medication had been unsuccessful in significantly reducing OCD symptoms. The first real breakthrough came in 1966 with the introduction of exposure and ritual prevention. This paper will discuss the cognitive behavioral conceptualizations that influenced the development of cognitive behavioral treatments for OCD. There will be a brief discussion of the use of psychodynamic psychotherapy and early behavioral therapy, neither of which produced successful outcomes with OCD. The main part of the paper will be devoted to current cognitive behavioral therapy (CBT) with an emphasis on variants of exposure and ritual or response prevention (EX/RP) treatments, the therapy that has shown the most empirical evidence of its efficacy.     

Anxiety and DSM-5

The DSM-5 process, and the publication of DSM-5 in 2013, have had a considerable impact on the classification of anxiety disorders. Major changes included the reorganization of the chapter structure, individual groupings of disorders within each chapter from a life span viewpoint, and the use of specifiers. The DSM-5 chapter on anxiety disorders does not include obsessive-compulsive disorder or post-traumatic stress disorder. The chapter itself now reflects a developmental approach. The text of each disorder has been enhanced with short sections on development and course, risk and prognostic factors, etc. It is expected that the reformulation of anxiety disorders in DSM-5 will lead to greater precision in a variety of ways, as illustrated in the papers in this issue of Dialogues in Clinical Neuroscience. In summary, these changes in the way we classify anxiety disorders reflect our best view on the clinical empirical data and should prove useful in the assessment of specific anxiety disorders.     

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.     

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.     

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.     

Assessment and Treatment of Anxiety Disorders in Children and Adolescents

This article reviews the current screening and assessment tools for anxiety disorders in children and adolescents, as well as evidence-based treatment interventions for these disorders. The following anxiety disorders are discussed: separation anxiety disorder, generalized anxiety disorder, specific phobia, panic disorder, social anxiety disorder (social phobia), and selective mutism. There are several well-studied screening and assessment tools to identify childhood anxiety disorders early and differentiate the various anxiety disorders. Evaluations of baseline somatic symptoms, severity, and impairment ratings of the anxiety disorders, and collecting ratings from several sources is clinically helpful in assessment and treatment follow-up. Cognitive-behavioral therapy (CBT) has been extensively studied and has shown good efficacy in treatment of childhood anxiety disorders. A combination of CBT and medication may be required for moderate to severely impairing anxiety disorders and may improve functioning better than either intervention alone. Selective serotonin reuptake inhibitors are currently the only medications that have consistently shown efficacy in treatment of anxiety disorders in children and adolescents. Despite proven efficacy, the availability of CBT in the community is limited. Current research is focusing on early identification of anxiety disorders in community settings, increasing the availability of evidence-based interventions, and modification of interventions for specific populations.     

Incomplete remission in depression: role of psychiatric and somatic comorbidity

Depression is one of the most pressing public health issues, because of its high lifetime prevalence and because it is associated with substantial disability. In depressed patients, psychiatric and medical comorbidity is the rule rather than the exception. About 60% to 70% of depressed patients have at least one, while 30% to 40% have two or more, concurrent psychiatric disorders. Among these, anxiety disorders and substance use disorders are the most common axis I comorbidities. Furthermore, two thirds of depressed patients have at least one comorbid medical illness. Among depressed patients, those with a current comorbid psychiatric condition (in particular an anxiety or substance use disorder) or medical illness seem to have an impaired response and remission rate during treatment compared with those patients without comorbidity. However, in depressed patients who all have the same comorbid condition, the relative benefit of an antidepressant compared with placebo appears to be equal to those effects achieved in depressed patients without comorbidity. These findings raise important research and treatment issues regarding the generalizability from randomized controlled trials that tend to exclude patients with comorbidity.