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2 0 13 VOLUME 2, ISSUE 3 V O L U M E 1 , I S S U EV O L U M E 1, ISSUE 1 CURRENT CLINICAL TOPICS FROM LEADING RA SPECIALISTS ACROSS CANADA AND AROUND THE AWPHYSICIAN O R L D I N V I TLEARNING E D B Y T H RESOURCE E R E B E C C A FROM M A C D THE O N A LCANADIAN D C E N T R E NETWORK F O R A R T HFOR R I T IMOOD S A N D AND A U T ANXIETY O I M M U N ETREATMENTS DISEASE Anxiety Disorders in the DSM-5: New Rules on Diagnosis and Treatment By Cara Katz, BSc, Murray B. Stein, MD, FRCPC, and Jitender Sareen, MD, FRCPC Anxiety disorders are among the most common mental disorders, with a lifetime prevalence of 16%–29%.1,2 In addition to provoking substantial disability, anxiety disorders are highly comorbid with other mental and physical disorders, thus complicating the treatment of both types of disorders. This issue of Mood and Anxiety Disorders Rounds highlights changes to the diagnostic category of anxiety disorders reflected in the recently published fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and outlines evidence-based treatments for individuals with anxiety disorders. Anxiety disorders are common in clinical practice and are highly comorbid and disabling.3 Among the anxiety disorders, specific phobia and social anxiety disorder are the most common, with lifetime prevalence rates of 18.4% and 13.0%, respectively.4 Panic disorder, generalized anxiety disorder (GAD), agoraphobia, and separation anxiety disorder each have lifetime prevalence rates of 2%–7%. While all anxiety disorders share the core features of excessive fear, anxiety, and avoidance, they differ in the specific object or situation of concern.5 They also differ from normal fear or anxiety in terms of duration; symptoms related to an anxiety disorder typically persist for >6 months. Anxiety disorders can only be diagnosed when the physiological effects of substances, other medications, or other medical diagnoses have been ruled out or when the symptoms cannot be better explained by the diagnosis of another mental disorder.5 Thus, thorough patient assessment should include a review of systems, medication history (including over-the-counter medications), substance use, a complete evaluation of anxiety symptoms, a focused physical examination of symptomatic areas, and a functional assessment. Inquiries about substance use should include questions about illicit drugs (particularly stimulants), alcohol, and caffeine. Further investigations should follow based on the results of the initial assessment (Table 1).6 What’s New in the DSM-5 for Anxiety Disorders? Several important changes were made to the diagnostic category of Anxiety Disorders in the fifth edition of the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5), including “cleaving” certain disorders into multiple new chapters, regrouping, adding new conditions, and refining criteria for some disorders. For example, obsessive compulsive disorder (OCD) has moved into its own chapter that includes the new entity of “hoarding disorder,” while posttraumatic stress disorder (PTSD) has shifted into a new chapter that includes acute stress and adjustment disorders. Anxiety disorders in childhood are no longer in a separate chapter. Within Anxiety Disorders, panic disorder and agoraphobia have been declared separate disorders since each can occur alone. In order to distinguish the diagnosis of agoraphobia from that of specific phobia, the criteria for the former require the endorsement of fears from ≥2 agoraphobic situations. Additionally, a panic attack specifier has been added to the DSM-5 that can be applied across all mental disorders. Panic attacks outside of panic disorder – but associated with other disorders – are frequently noted and may have value in predicting psychopathology, severity, and outcome.7 Regarding agoraphobia, specific phobia, and social anxiety disorder, the criteria no longer include age >18 years in order to recognize that patients’ anxiety is excessive or unreasonable; the rationale is that individuals typically overestimate their risk in “phobic” situations. In addition, Available online at www.moodandanxietyrounds.ca CANMAT Advisory Board Executive Sagar V. Parikh, MD, FRCPC Education Chair, Toronto Editor, Mood and Anxiety Disorders Rounds [email protected] Raymond W. Lam, MD, FRCPC Executive Chair, Vancouver Sidney H. Kennedy, MD, FRCPC Depression Group Chair, Toronto Lakshmi N. Yatham, MBBS, FRCPC, MRCPsych (UK) Bipolar Group Chair, Vancouver Jitender Sareen, MD, FRCPC Anxiety Group Chair, Winnipeg Roger S. McIntyre, MD, FRCPC Business & Research Development Chair, Toronto Roumen Milev, MD, PhD, FRCPsych, FRCPC International Conference Chair, Kingston CANMAT Board of Directors Serge Beaulieu, MD, PhD, FRCPC Montréal Glenda MacQueen, MD, PhD, FRCPC Calgary Diane McIntosh, MD, FRCPC Vancouver Arun V. Ravindran, MB, PhD, FRCPC Toronto Canadian Network for Mood and Anxiety Treatments Education Office Room 9M-329, Toronto Western Hospital 399 Bathurst St, Toronto, On CANADA M5T 2S8 CANMAT – or the Canadian Network for Mood and Anxiety Treatments – is a federally incorporated academically based not-for-profit research organization with representation from multiple Canadian universities. The ultimate goal of CANMAT is to improve the quality of life of persons suffering from mood and anxiety disorders, through conduct of innovative research projects and registries, development of evidence based and best practice educational programs and guideline/policy development. Table 1: Baseline investigations in patients with anxiety disorders6 • Complete blood count • Fasting glucose • Fasting lipid profile (total, LDL, very LDL, and HDL cholesterol, and triglycerides) • Electrolytes • Liver enzymes • Serum bilirubin • Serum creatinine • Urinalysis • Urine toxicology for substance use • 24-hour creatinine clearance (if history of renal disease) • Thyroid-stimulating hormone • Electrocardiogram (if age >40 years or if indicated) • Pregnancy test (if relevant) • Prolactin LDL = low-density lipoprotein; HDL = high-density lipoprotein Reproduced with permission from Canadian Psychiatric Association Clinical Practice Guidelines. Management of anxiety disorders. Can J Psychiatry 2006;51(8 Suppl 2):9S-91S. Copyright © 2006, Canadian Psychiatric Association. older adults tend to incorrectly attribute their phobia to aging and may, therefore, not report it. While there is evidence to support this change, the boundary between “routine” and “excessive” anxiety may still require clarification.8,9 According to the DSM-5, it is primarily the clinician who can determine whether the anxiety is excessive, taking into account the patient’s report of his symptoms and cultural factors. Additionally, the criterion of a 6-month duration of symptoms is now extended to all ages. Another controversial change in the diagnosis of social anxiety disorder is that the “generalized” specifier has been removed and replaced with a “performance only” specifier, noting that this group tends to be distinct in etiology, age of onset, and physiological and treatment response.5 However, a study by Kearns et al10 called this new criterion into question, as none of a sample of 204 anxious youth exhibited a discrete “performance” fear without fear in other social circumstances. Clinical and research experience with this new DSM-5 specifier will, in the coming year, determine whether this change was well founded. Separation anxiety disorder, previously considered in the Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence section, is now listed under Anxiety Disorders, consistent with evidence that the disorder may persist from childhood into adulthood and, in some instances (although this remains controversial), may have onset in adulthood.11 Selective mutism has likewise been added to the Anxiety Disorders category. A summary of these changes by disorder can be found in Table 2. OCD, PTSD, and acute stress disorder are no longer included in the Anxiety Disorders chapter, but are now included in the OCD and Related Disorders and Trauma- and Stressor-related Disorders chapters, respectively.5 These category changes are controversial in that they emphasize how these disorders differ from one another in terms of biological mechanism and treatment approach. On the other hand, these changes may underemphasize the similarities in these conditions.12 Furthermore, it is unclear if these individuals require a separate or different treatment than what was previously provided. The decision to create a distinct category for OCD is based on research showing that OCD is related to both anxiety and other disorders, including Cluster C, tic, somatoform, grooming, and mood disorders.13 Additionally, hoarding – previously categorized within the diagnosis of OCD – has become its own disorder. Similarly, evidence suggests that PTSD and acute stress disorder be classified as a distinct category, recognizing their common etiology of trauma.14 A new “anxious distressed” specifier has also been added to the Depressive Disorders and Bipolar and Related Disorders categories in the DSM-5. The anxious-distressed feature has been noted to be a major feature of bipolar and major depressive disorder, and high levels of anxiety are associated with increased suicidality and burden of illness. Therefore, identifying this specifier can help with treatment and management. This specifier is applied to individuals with ≥2 anxious symptoms as specified in the DSM-5.5 This new criterion, however, does not come with a clause indicating not to diagnose if there is a comorbid anxiety disorder. This has the potential for individuals with a comorbid mood and anxiety disorder to be labeled with the “anxious-distressed” specifier, rather than a separate (comorbid) anxiety disorder, which may lead to undertreatment of the anxiety disorder. One of the major implications of the DSM-5 may be its impact on research, particularly in terms of childhood anxiety disorders. For example, these changes have encouraged the development of child-specific assessment tools (eg, Picture Anxiety Tests)15 and disorder-specific treatment (eg, the TAFF program for Separation Anxiety Disorder).16 Currently, the DSM-5 changes to the Anxiety Disorders category can be considered a necessary step towards increased evidence-based diagnosis, assessment, and treatment of childhood anxiety disorders that, to this date, has been lacking.17 However, in the authors’ opinion, these changes will have a less immediate impact on clinical practice. CASE STUDY 18 A 35-year-old Asian-Canadian woman was referred to a psychiatrist for assessment of anxiety and avoidance. Two years earlier, she was awakened one night by chest pain that she believed was due to a heart attack. Accompanying symptoms were shortness of breath, rapid pulse, sweating, and dizziness. Her family took her to the Emergency Department, where a thorough medical work-up ruled out any cardiac problems. After this event, however, she stopped driving and was unable to attend her children’s sports events, go on buses, or to her church for fear of recurrence of the chest pain. Although she could not define a specific stressor prior to the onset, a number of stressful life events had occurred, including the death of a close friend from cancer and her husband losing his job. There was no prior history of emotional problems; however, she had a history of asthma. As well, when the patient was 12 years old, her father had suddenly died of a heart attack. When considering treatment for the patient in this case, an algorithm (Figure 1) can be helpful. She presented with physiological symptoms of panic attacks and subsequent avoidance of situations that she believed were the cause of her Table 2: Highlights of DSM-5 Changes DSM-5 anxiety disorder Panic Disorder (PD) DSM-IV diagnosis PD with or without Agoraphobia Panic Attack – Specifier (can be added to any of the DSM-5 disorders) Changes in diagnosis • Requires presence of recurrent panic attacks AND worry about possibility of future attacks, development of phobic avoidance OR other change in behaviour due to attacks • Decoupled from agoraphobia • Types of panic attacks described as “unexpected” versus “expected” Social Anxiety Disorder (SAD) Social Phobia • Removal of “generalized social phobia” • Newly defined “performance only” specifier • No longer a requirement for individuals aged >18 years to recognize fear as excessive; instead, anxiety must be out of proportion to actual danger or threat in the situation, after taking cultural context into accounta • 6-month duration extended to all ages (not just to those aged <18 years) Agoraphobia Agoraphobia without a history of panic disorder • Decoupled from PD • No longer a requirement for individuals aged >18 years to recognize fear as excessive (Instead, anxiety must be out of proportion to actual danger or threat in the situation after taking cultural context into account)a • 6-month duration extended to all ages (not just to those aged <18 years) • Endorsement of fears from ≥2 agoraphobia situations required (in order to distinguish it from specific phobia) Specific Phobia No change • Includes specifiers for different types of situations or objects involved (ie., animal, natural environment, blood-injection-injury, situational, and others) • No longer a requirement for individuals aged >18 years to recognize fear as excessive (Instead, anxiety must be out of proportion to actual danger or threat in the situation, after taking cultural context into account)a • 6-month duration extended to all ages (not just to those aged <18 years) Generalized Anxiety Disorder (GAD) No change No change • Now considered an anxiety disorder, (formerly in the Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence category) • No longer specifies that age of onset must be before age 18 years • Duration criterion of ≥6 months added Separation Anxiety Disorder Selective Mutism No change • Now considered an anxiety disorder (formerly in the Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence category a Also new in DSM-5, this judgment of fear or anxiety being excessive is made by the clinician DSM = Diagnostic and Statistical Manual of Mental Disorders episodes. In keeping with the algorithm, medical causes were ruled out in the Emergency Room. After a complete assessment, this patient would likely be diagnosed with panic disorder. General treatment options for anxiety disorders are presented in the following section and an update to this case report is presented later in this issue.18 access to evidence-based psychotherapies is important. Measuring symptoms using panic or “worry” diaries or the use of self-reported standardized scales (eg, the Overall Anxiety Severity and Interference Scale [OASIS])22 can help both patients and therapists track the course and severity of anxiety problems and are indisputable aids to treatment. Evidence-based Treatment of Anxiety Disorders The impact of comorbidity Treatments are derived from studies using DSM-IV criteria and so may need adjustment in view of DSM-5 changes. The presence of a current comorbidity with a mental disorder (ie, mood, substance use, or a personality disorder) significantly affects management. If an individual is severely depressed, treatment of the depression – usually with a combination of medication(s) and therapy, and attention to anxiety symptoms – is a priority. If a bipolar disorder is comorbid with an anxiety disorder(s), it may affect the type of medications used (eg, choice of a mood stabilizer or gabapentin). Self-medication with alcohol and drugs to reduce tension and anxiety is common and is associated with an increased risk of substance-use disorders.23 It is important for both patients and clinicians to understand that a vicious cycle can develop when anxiety symptoms lead to self- General approach The treatment of anxiety disorders can be extremely gratifying for clinicians because patients tend to respond well to psychological and pharmacological therapies. Several practice guidelines can be referenced for the treatment of anxiety disorders, specifically, panic disorder and social anxiety disorder.6,19-21 A careful, comprehensive assessment of anxiety symptoms, disabilities, the presence of comorbid mental and physical conditions, patient preferences for treatment, and Figure 1: Algorithm for the Treatment and Management of Anxiety Disorders Identify Anxiety Symptoms 1. Assess impact on function 2. Assess suicide risk Differential Diagnosis 1. Rule out medical or substance induced anxiety 2. Consider comorbidity with another medical or psychiatric condition 3. Conduct physical and laboratory examinations Comorbid Medical Condition 1. Consider risks and benefits of medication for anxiety disorder and consider impact of untreated anxiety Identify Specific Anxiety Disorder Specific phobia, social anxiety disorder, panic disorder, generalized anxiety disorder, agoraphobia, separation anxiety disorder Treatment 1. Consider patient preference 2. Provide psychoeducation to patient and family 3. Consider comorbid mental and physical disorder(s) in management of the anxiety disorder Comorbid Mental Disorder 1. If substance abuse: prescribe benzodiazepines with caution 2. If another anxiety disorder: use therapies that are first-line for both disorders 3. If mood disorder: use therapies that are effective for both disorders Treatment by Disorder Type Specific Phobia 1. Cognitive behaviour therapy (CBT) 2. Benzodiazepines PRN Social anxiety disorder, panic disorder, generalized anxiety disorder, agoraphobia, separation anxiety disorder 1. CBT 2. Antidepressants 3. Consider addition of benzodiazepines, atypical antipsychotics Adapted from Canadian Psychiatric Association Clinical Practice Guidelines. Management of anxiety disorders. Can J Psychiatry 2006;51(8 Suppl 2):9S-91S, and Stein MB, Sareen J. Anxiety disorders. In: Hales R, Yudofsky S, Gabbard G, eds. The American Psychiatric Publishing Textbook of Psychiatry. 6th ed. In press. medication with alcohol and drugs, resulting in rebound anxiety. Past recommendations insisted on abstinence before treating comorbid anxiety and substance use disorders; however, current thinking favours concurrent treatment of both disorders whenever feasible. Most patients prefer treating anxiety with psychotherapy alone or in combination with medication.24 However, evidence-based psychotherapy may not be readily accessible to all patients. Thus, medication often becomes the de facto treatment of anxiety disorders. Even in such circumstances, it should be possible to optimize patient care with appropriate educational, motivational, and behavioural instructions and resources. Psychotherapy Among the interventions for anxiety disorders, cognitive behavioural therapy (CBT) has the most robust evi- dence for efficacy.19,21,24 It can be delivered via a variety of formats, including individual, group, bibliotherapy, telephone, and the computer. Although there have been few changes in the treatment of anxiety disorders since the Canadian Psychiatric Association’s 2006 clinical practice guidelines,6 Internet-based CBT (iCBT) has become a well-established treatment for depression, panic disorder, and social anxiety disorder, with the potential to reduce comorbidity.25,26 Mobile CBT applications are increasingly available but have not been evaluated. CBT for the various anxiety disorders differ somewhat in focus and content, but are similar in underlying principles and approaches.27 Core components include psychoeducation, relaxation training, cognitive restructuring, and exposure therapy. Over the course of CBT, patients slowly face their anxiety-provoking situations and learn that if they stay in the situation long enough, their anxiety resolves. While other psychotherapies – eg, psychodynamic psychotherapy, acceptance and commitment therapy, mindfulness-based stress reduction, or other therapies that target emotion regulation – are promising, further research is necessary to establish both efficacy and linkage to patient preferences. Acceptability and response to CBT for anxiety disorders is high; however, there is ample room for new treatments to meet the needs of patients who fail standard therapies. Pharmacotherapy Pharmacotherapy is an important option for many patients with anxiety disorders, either in combination with CBT or as stand-alone treatment.28 Pharmacotherapy should never be prescribed without additional educational materials. These can be provided at low or no cost online by accessing unbiased sources of high-quality information, including the National Institutes of Health, the Anxiety and Depression Association of America (ADAA), UpToDateTM (written expressly for consumers), or anxieties.com. Several classes of medications are indicated by Health Canada and similar regulatory agencies in other countries for the treatment of specific anxiety disorders. Although adherence to approved medications guarantees that a certain level of evidence has been attained in granting their approval, any licensed practitioner can choose to prescribe off-label, provided the marketed medication has a base of solid, peer-reviewed, published evidence for efficacy and safety in the particular clinical condition and specific to patient circumstances. The classes of medications with the best evidence of safety (when used appropriately) and efficacy for the treatment of anxiety disorders (with the exception of specific phobias) are the antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and the benzodiazepine anxiolytics. TCAs and MAOIs have been rarely used since the advent of the SSRIs because they are less well-tolerated. Some experts, however, believe that MAOIs may be efficacious for patients whose symptoms do not respond to other treatments, particularly in the treatment of social anxiety disorder. There is also evidence that several nonbenzodiazepine anxiolytics (eg, buspirone and pregabalin) can play a role and, for refractory anxiety, possibly the atypical antipsychotics can help. SSRIs and SNRIs. There are currently 6 SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram) and 3 SNRIs (extended-release venlafaxine, desvenlafaxine, and duloxetine) available in Canada. Although the SSRIs have different indications for particular anxiety disorders, clinicians tend to treat them as having equal efficacy since there is no evidence to the contrary. As a class, the SSRIs are considered first-line agents for each of the anxiety disorders (with the notable exception of specific phobia) due to their overall levels of efficacy, safety, and tolerability.6 It is recommended to begin a treatment trial with the lowest available dose of an SSRI. Follow-up should occur after the first week to assess medication tolerability and patient compliance. The dose is then gradually increased until a therapeutic dose is reached. An initial response is typically seen in 4–6 weeks and an optimal response achieved in 12–16 weeks. Follow-up should occur biweekly for the first 6 weeks and then monthly thereafter. There is a misconception that patients with anxiety disorders respond to lower doses of antidepressants than patients with depression. In fact, average doses for treating anxiety disorders are as high or higher than for depression.6,18 In addition, many patients presenting with anxiety also have major depression, necessitating the use of a full antidepressant dose. Clinicians may take an extra 1–2 weeks to reach these doses in patients with anxiety disorders, comorbid or otherwise. Progress can be measured at each appointment with clinician-rated tools (eg, the Clinical Global Impression scale) or self-report scales (eg, the Depression Anxiety Stress scale).6 In patients who fail to respond to an SSRI, the next step is to try a different SSRI or to switch to an SNRI. Patients who experience a partial response to an SSRI or SNRI may be considered for adjunctive treatment with a benzodiazepine or another anti-anxiety agent. Pharmacotherapy may be needed for 1–2 years, or longer. Benzodiazepines are among the best tolerated and most efficacious of all the anti-anxiety agents, with broadspectrum efficacy across the anxiety disorders, including specific phobia. They can be used as first-line agents for treating anxiety and are the best-established pharmacotherapy for treating anxiety that is predictable and limited to particular situations (eg, a specific phobia such as flying or social phobia such as public speaking) as they can be prescribed on an as-needed (prn) basis.29 However, benzodiazepines need to be prescribed with caution due to the potential for abuse. They should only be prescribed with great care and strict supervision to patients with a history of alcohol or other substance abuse. Prescription of prn benzodiazepines for unpredictable anxieties (eg, panic disorder) or chronic anxiety (eg, GAD) is not recommended. Benzodiazepines should generally be prescribed for anxiety on a regular schedule (ie, 1–4 times daily depending on the pharmacokinetic and pharmacodynamic properties of the particular benzodiazepine), with prn use for occasionally recurring, predictable specific phobias. Nonbenzodiazepine anxiolytics. Buspirone is a nonbenzodiazepine anxiolytic with efficacy limited to the treatment of GAD. Gabapentin and pregabalin have limited evidence for efficacy in treating anxiety disorders, although they are sometimes used as an alternative to the benzodiazepines, often as an adjunct to antidepressants. Atypical antipsychotics. There is very limited evidence that ayptical antipsychotics may be efficacious as monotherapy or as an adjunct to antidepressants for treatment-resistant anxiety disorders.30 Combining psychotherapy and pharmacotherapy Several studies suggest, albeit with few data, that combining CBT and pharmacotherapy for anxiety disorders is superior to either one alone, particularly in children.31,32 However, the efficacy of either treatment modality is sufficiently high that clinicians may choose one or the other as initial therapy, based primarily on patient preference, and subsequently add the other option in patients who fail to respond adequately to a therapeutic trial. CASE STUDY (cont.) Our patient, after being diagnosed with panic disorder, was taught about the panic model. The therapist asked her to keep a diary of her panic attacks, including details such as where the attack occurred, her symptoms during the attack, and what she did to manage her anxiety. During treatment sessions, she learned how to identify the “hot” thoughts that increased her anxiety and ways to challenge this thinking by considering the evidence for and against her fear of having a heart attack. Along with CBT, she was offered a trial of an SSRI. She started on 50 mg/day of sertraline that was titrated up until an optimal therapeutic dose was achieved. After 6 weeks, the patient did not demonstrate a meaningful clinical response and the panic attacks continued. The treating physician then decided to switch her to paroxetine, another SSRI. After 6 weeks, the patient reported benefit with the paroxetine, and was maintained on this medication. Conclusion Anxiety disorders are highly prevalent and frequently disabling conditions that often begin in childhood and persist into adulthood. They are generally very responsive to CBT and/or pharmacotherapy. All patients should receive education regarding their anxiety disorder, options for treatment, prognosis, triggering factors, and signs of relapse. Ms. Katz is a graduate student in the Department of Psychiatry and member of the Manitoba Population Mental Health Research Group, University of Manitoba, Winnipeg, Manitoba. Dr. Stein is a Professor of Psychiatry and Family & Preventive Medicine, University of California San Diego. Dr. Sareen is a Professor of Psychiatry, Psychology and Community Health Sciences, and Group Leader of the Manitoba Population Mental Health Research Group, University of Manitoba, Winnipeg, Manitoba. References 1. Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) Surveys. Epidemiol Psichiatr Soc. 2009;18(1):23-33. 2. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593-602. 3. Sareen J, Jacobi F, Cox BJ, Belik SL, Clara I, Stein MB. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med. 2006;166(19):2109-2116. 4. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21(3):169-184. 5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington (VA): American Psychiatric Publishing; 2013. 6. Canadian Psychiatric Association. Clinical practice guidelines. Management of anxiety disorders. Can J Psychiatry 2006;51(8 Suppl 2):9S-91S. 7. Batelaan NM, Rhebergen D, de Graaf R, Spijker J, Beekman AT, Penninx BW. Panic attacks as a dimension of psychopathology: evidence for associations with onset and course of mental disorders and level of functioning. J Clin Psychiatry. 2012;73(9):1195-1202. 8. Zimmerman M, Dalrymple K, Chelminski I, Young D, Galione JN. Recognition of irrationality of fear and the diagnosis of social anxiety disorder and specific phobia in adults: implications for criteria revision in DSM-5. Depress Anxiety. 2010;27(11):1044-1049. 9. Frances AJ, Nardo JM. ICD-11 should not repeat the mistakes made by DSM-5. Br J Psychiatry. 2013;203(1):1-2. 10. Kerns CE, Comer JS, Pincus DB, Hofmann SG. Evaluation of the proposed social anxiety disorder specifier change for DSM-5 in a treatment-seeking sample of anxious youth. Depress Anxiety. 2013;30(8):709-715. 11. Bogels SM, Knappe S, Clark LA. Adult separation anxiety disorder in DSM-5. Clin Psychol Rev. 2013;33(5):663-674. 12. Stein DJ, Craske MG, Friedman MJ, Phillips KA. Meta-structure issues for the DSM-5: how do anxiety disorders, obsessive-compulsive and related disorders, post-traumatic disorders, and dissociative disorders fit together? Curr Psychiatry Rep. 2011;13(4):248-250. 13. Bienvenu OJ, Samuels JF, Wuyek LA, et al. Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med. 2012;42(1):1-13. 14. Friedman MJ, Resick PA, Bryant RA, Strain J, Horowitz M, Spiegel D. Classification of trauma and stressor-related disorders in DSM-5. Depress Anxiety. 2011;28(9):737-749. 15. Dubi K, Schneider S. The Picture Anxiety Test (PAT): a new pictorial assessment of anxiety symptoms in young children. J Anxiety Disord. 2009;23(8):1148-1157. 16. Schneider S, Blatter-Meunier J, Herren C, et al. The efficacy of a family-based cognitivebehavioral treatment for separation anxiety disorder in children aged 8-13: a randomized comparison with a general anxiety program. J Consult Clin Psychol. 2013 Apr 22. [Epub ahead of print] 17. Mohr C, Schneider S. Anxiety disorders. Eur Child Adolesc Psychiatry. 2013;22 Suppl 1:S17-S22. 18. Stein MB, Sareen J. Anxiety disorders. In: Hales R, Yudofsky S, Gabbard G, eds. The American Psychiatric Publishing Textbook of Psychiatry. 6th ed. (In press). 19. American Psychiatric Association. Practice Guidelines for the Treatment of Patients with Panic Disorder. 2nd ed. Washington (DC): American Psychiatric Publishing; 2009. 20. Roy-Byrne P, Stein M, Bystrisky A, Katon W. Pharmacotherapy of panic disorder: proposed guidelines for the family physician. J Am Board Fam Pract. 1998;11(4):282-290. 21. Stein MB, Stein DJ. Social anxiety disorder. Lancet. 2008;371(9618):1115-1125. 22. Campbell-Sills L, Norman SB, Craske MG, et al. Validation of a brief measure of anxiety-related severity and impairment: the Overall Anxiety Severity and Impairment Scale (OASIS). J Affect Disord. 2009;112(1-3):92-101. 23. Robinson J, Sareen J, Cox BJ, Bolton JM. Role of self-medication in the development of comorbid anxiety and substance use disorders: a longitudinal investigation. Arch Gen Psychiatry. 2011;68(8):800-807. 24. Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010;303(19):1921-1928. 25. Hedman E, Ljotsson B, Lindefors N. Cognitive behavior therapy via the Internet: a systematic review of applications, clinical efficacy and cost-effectiveness. Expert Rev Pharmacoecon Outcomes Res. 2012;12(6):745-764. 26. Johnston L, Titov N, Andrews G, Dear BF, Spence J. Comorbidity and internet-delivered transdiagnostic cognitive behavioural therapy for anxiety disorders. Cogn Behav Ther. 2013;42(3):180-192. 27. Craske MG, Stein MB, Sullivan G, et al. Disorder-specific impact of coordinated anxiety learning and management treatment for anxiety disorders in primary care. Arch Gen Psychiatry. 2011;68(4):378-388. 28. Ravindran LN, Stein MB. The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry. 2010;71(7):839-854. 29. el-Guebaly N, Sareen J, Stein MB. Are there guidelines for the responsible prescription of benzodiazepines? Can J Psychiatry. 2010;55(11):709-714. 30. Depping AM, Komossa K, Kissling W, Leucht S. Second-generation antipsychotics for anxiety disorders. Cochrane Database Syst Rev. 2010;12:CD008120. 31. Blanco C, Heimberg RG, Schneier FR, et al. A placebo-controlled trial of phenelzine, cognitive behavioral group therapy, and their combination for social anxiety disorder. Arch Gen Psychiatry. 2010;67(3):286-295. 32. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008;359(26):2753-2766. The authors stated that they have no disclosures to report in association with the contents of this issue. 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