Definition and etiology

Anxiety is a natural response and a necessary warning adaptation in humans. Anxiety can become a pathologic disorder when it is excessive and uncontrollable, requires no specific external stimulus, and manifests with a wide range of physical and affective symptoms as well as changes in behavior and cognition. As outlined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR), anxiety disorders include generalized anxiety disorder (GAD), social anxiety disorder (also known as social phobia), specific phobia, panic disorder with and without agoraphobia, obsessivecompulsive disorder (OCD), posttraumatic stress disorder (PTSD), anxiety secondary to medical condition, acute stress disorder (ASD), and substance-induced anxiety disorder. Back to Top

Prevalence and risk factors

Anxiety is one of the most prevalent of all psychiatric disorders in the general population. Simple phobia is the most common anxiety disorder, with up to 49% of people reporting an unreasonably strong fear and 25% of those people meeting criteria for simple phobia. Social anxiety disorder is the next most common disorder of anxiety, with roughly 13% of people reporting symptoms that meet the DSM criteria. PTSD, which is often unrecognized, afflicts approximately 7.8% of the overall population and 12% of women, in whom it is significantly more common. In victims of war trauma, PTSD prevalence reaches 20%. Surprisingly, disorders that are more commonly recognized have lower lifetime prevalence rates; GAD and panic disorder, for example, have lifetime prevalence rates of roughly 5% and 3.5%, respectively. Of the panic sufferers, up to 40% also meet criteria for agoraphobia. Another often underdiagnosed disorder, OCD, is found in 2.5% of the population. Interestingly, a recent study found very little change in the prevalence of mental disorders, including specific anxiety disorders, since 1990. 3 Genetic risk factors are being studied, and researchers have found genetic predisposition for two broad groups of anxiety disorders: a panic-generalized anxiety-agoraphobia group and a specific phobias group. 4 More clinically important risk factors include comorbid substance abuse and family history. One 20-year study of the offspring of depressed parents found a threefold increase in anxiety disorders, including greater substance abuse, younger onset, and more significant physical health concerns. 5 Back to Top

Pathophysiology

Definitive pathophysiologic mechanisms have not yet been determined, but anxiety symptoms and the resulting disorders are believed to be due to disrupted modulation within the central nervous system. Physical and emotional manifestations of this dysregulation are the result of heightened sympathetic arousal of varying degrees. Several neurotransmitter systems have been implicated in one or several of the modulatory steps involved. The most commonly considered are the serotoninergic and noradrenergic neurotransmitter systems. In very general terms, it is believed that an underactivation of the serotoninergic system and an overactivation of the noradrenergic system are involved. These systems regulate and are regulated by other pathways and neuronal circuits in various regions of the brain, including the locus caeruleus and limbic structures, resulting in dysregulation of physiologic arousal and the emotional experience of this arousal. Disruption of the gamma-aminobutyric acid (GABA) system has also been implicated because of the response of many of the anxiety-spectrum disorders to treatment with benzodiazepines. There has also been some interest in the role of corticosteroid regulation and its relation to symptoms of fear and anxiety. Corticosteroids might increase or decrease the activity of certain neural pathways, affecting not only behavior under stress but also the brain's processing of fear-inducing stimuli. Although a genetic predisposition to developing an anxiety disorder is likely, 4 environmental stressors clearly play a role in varying degrees. All of the disorders are affected in some way by external cues and how they are processed and reacted to. Research has also shown that patients suffering from anxiety are generally more sensitive to physiologic changes than nonanxious patients, and panic disorder sufferers are even more sensitive to these than GAD patients. Objective testing, however, reveals that physiologic changes between anxious and nonanxious patients are comparable. This heightened sensitivity leads to diminished autonomic flexibility, which may be the result of faulty central information processing in anxiety-prone persons.6 Back to Top

Signs and symptoms

A subjective experience of distress with accompanying disturbances of sleep, concentration, and social or occupational functioning are common symptoms in many of the anxiety disorders. Despite their similarities, these disorders often differ in presentation, course, and treatment. Patients often present with complaints of poor physical health as their primary concern. This can temporarily distract from the underlying anxiety symptoms. This is particularly common in panic attacks (Box 1), which are characterized by a short period of intense fear

and a sense of impending doom, with accompanying physical symptoms, such as chest pain, dizziness, and shortness of breath. Very often, these patients first present to an emergency department. When panic disorder is complicated by agoraphobia, the person fears having a panic attack in a place from which escape is perceived to be difficult. The patient then avoids such situations, with subsequent disturbances in functioning. Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.

GAD rarely occurs without a comorbid psychiatric disorder, and the patient experiences consistent worry over multiple areas of his or her life for at least 6 months. Social anxiety disorder describes fear and anxiety in social situations leading to avoidance of social interaction. Specific phobia is characterized by similar symptoms and behavior, but it is triggered by a specific object or situation, such as a fear of certain animals or heights. Acute stress disorder and PTSD occur after a patient experiences a traumatic event with subsequent physiologic arousal in the face of stimuli that trigger memories of the event, avoidance of such stimuli, and a sense of re-experiencing the event. Acute stress disorder occurs at the time of and shortly after the event, and PTSD is the chronic version of the disorder. OCD is characterized by repeated actions (compulsions) that serve to reduce anxiety connected to unwanted, intrusive thoughts (obsessions). Commonly seen behaviors are cleaning or washing in response to concerns about contamination or repeatedly checking to see if a stove is turned off in response to concerns over a fire starting. Some people repeatedly check work or seek excessive reassurance due to obsessive self-doubt. Back to Top

Diagnosis
An anxiety disorder can only be diagnosed in a patient who meets DSM IV-TR criteria. Diagnosis is often complicated by other psychiatric disorders. Up to 60% of sufferers of GAD (Box 2) have a comorbid condition; panic disorder and major depressive disorder are the most common. Panic disorder (Box 3) is often comorbid with alcohol abuse, with an increased risk for suicidality. Agoraphobia (Box 4) is commonly connected to panic disorder, and comorbidity rates approach 40%. Many of these disorders have overlapping signs and symptoms, requiring the clinician to explore several lines of questioning to clarify the primary diagnosis.
Box 2: DSM IV-TR Criteria for Generalized Anxiety Disorder Excessive anxiety about a number of events or activities, occurring more days than not, for at least 6 months. The person finds it difficult to control the worry.

The anxiety and worry are associated with at least three of the following six symptoms (with at least some symptoms present for more days than not, for the past 6 months): Restlessness or feeling keyed up or on edge Being easily fatigued Difficulty concentrating or mind going blank Irritability Muscle tension Sleep disturbance The focus of the anxiety and worry is not confined to features of an Axis I disorder, being embarrassed in public (as in social phobia), being contaminated (as in obsessive-compulsive disorder), being away from home or close relatives (as in separation anxiety disorder), gaining weight (as in anorexia nervosa), having multiple physical complaints (as in somatization disorder), or having a serious illness (as in hypochondriasis), and the anxiety and worry do not occur exclusively during posttraumatic stress disorder. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social or occupational functioning. The disturbance does not occur exclusively during a mood disorder, a psychotic disorder, pervasive developmental disorder, substance use, or general medical condition.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.
Box 4: DSM IV-TR Criteria for Agoraphobia Fear of being in places or situations from which escape might be difficult (or embarrassing) or in which help might not be available in the event of having unexpected panic-like symptoms. The situations are typically avoided or require the presence of a companion. The condition is not better accounted for by another mental disorder.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.

Important in the diagnosis of PTSD (Box 5) is identifying a history of trauma and being sure to ask questions related to avoidance, re-experiencing, and physiologic arousal in the face of triggering stimuli. The most common trauma associated with the disorder is rape. The symptoms of PTSD may be mistaken for depression, other anxiety disorders, or dysfunctional personality traits. Patients might not be able to identify a connection between the symptoms and the trauma history, requiring that the clinician be sensitive to the possibility that a trauma history exists. If the patient presents with complaints within 4 weeks of the trauma (with resolution within 4 weeks of symptom onset) then acute stress disorder (Box 6) should be the diagnosis.
Box 5: DSM IV-TR Criteria for Posttraumatic Stress Disorder

The person has been exposed to a traumatic event in which both of the following were present: The person experienced, witnessed, or was confronted with an event that involved actual or threatened death or serious injury or a threat to the physical integrity of others. The person's response involved intense fear, helplessness, or horror. The traumatic event is persistently re-experienced in at least one of the following ways: Recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions. Recurrent distressing dreams of the event. Acting or feeling as if the traumatic event were recurring, including a sense of reliving the experience, illusions, hallucinations, and flashback episodes. Intense psychological distress at exposure to cues that symbolize an aspect of the traumatic event. Physiologic reactivity on exposure to cues that symbolize or resemble an aspect of the traumatic event. The person persistently avoids stimuli associated with the trauma and has numbing of general responsiveness including at least three of the following: Efforts to avoid thoughts, feelings, or conversations associated with the trauma Efforts to avoid activities, places, or people that arouse recollections of the trauma Inability to recall an important aspect of the trauma Markedly diminished interest or participation in significant activities Feeling of detachment or estrangement from others Restricted range of affect Persistent symptoms of increased arousal are indicated by at least two of the following: Difficulty falling or staying asleep Irritability or outbursts of anger Difficulty concentrating Hypervigilance Exaggerated startle response Duration of the disturbance is more than 1 month. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.
Box 6: DSM IV-TR Criteria for Acute Stress Disorder The person has been exposed to a traumatic event in which both of the following were present: The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury. The person's response involved intense fear, helplessness, or horror. Either while experiencing or after experiencing the distressing event, the person has at least three of the following: A subjective sense of numbing, detachment, or absence of emotional responsiveness A reduction in awareness of his or her surroundings Derealization Depersonalization Dissociative amnesia

The traumatic event is re-experienced in at least one of the following ways: recurrent images, thoughts, dreams, illusions, flashback episodes, or a sense of reliving the experience; or distress on exposure to reminders of the traumatic event. The patient avoids the stimuli that arouse recollections of the trauma. The patient has marked symptoms of anxiety or increased arousal. The disturbance causes clinically significant distress or impairment in social or occupational areas of functioning, or it impairs the person's ability to pursue some necessary task. The disturbance lasts for a minimum of 2 days and a maximum of 4 weeks and occurs within 4 weeks of the traumatic event. The disturbance is not better accounted for by brief psychotic disorder and is not merely an exacerbation of a preexisting Axis I or Axis II disorder, substance or general medical condition.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.

Patients with OCD (Box 7) are often secretive regarding their symptoms. These are secondary to feelings of shame and a sense of isolation. Many are not aware that others suffer from the same constellation of thoughts and behavior. Questions should explore whether certain routines are related to specific phobias (Box 8), thoughts, or images. OCD is often comorbid with major depressive disorder (in two thirds of patients over their lifetime) and panic attacks, with rates of up to 60%. One must also distinguish between OCD and obsessive-compulsive personality disorder (OCPD). Although up to 25% of patients suffering from OCD also suffer from the personality disorder, the two disorders can manifest very differently. Patients with obsessive-compulsive personality disorder have idealized standards often rewarded by others, whereas patients with OCD experience significant distress due to true obsessions and compulsions. If the source of compulsive behavior is kept secret, a patient with OCD can sometimes appear to be suffering from psychosis. The treatment strategy for psychosis differs markedly, making it very important to distinguish between the two when presented with bizarre behavior. Questions should differentiate between voices and intrusive thoughts. The patient suffering from OCD knows his or her thoughts and actions are irrational.
Box 7: DSM IV-TR Criteria for Obsessive-Compulsive Disorder Obsessions Recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate, causing anxiety or distress. The thoughts, impulses, or images are not simply excessive worries about real-life problems. The person attempts to ignore or suppress such thoughts, impulses, or images or to neutralize them with some other thought or action. The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind. Compulsions Repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession or according to rules that must be applied rigidly. The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation. These behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent, or they are clearly excessive.

Obsessive-Compulsive Disorder At some point during the course of the disorder, the person has recognized that the obsessions or compulsions are excessive or unreasonable. The obsessions or compulsions cause marked distress, take up more than 1 hour a day, or significantly interfere with the person's normal routine, occupation, or usual social activities. If another Axis I disorder, substance use, or general medical condition is present, the content of the obsessions or compulsions is not restricted to it.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.
Box 8: DSM IV-TR Criteria for Specific Phobia Persistent fear that is excessive or unreasonable, cued by the presence or anticipation of a specific object or situation. Exposure provokes immediate anxiety, which can take the form of a situationally predisposed panic attack. Patients recognize that the fear is excessive or unreasonable. Patients avoid the phobic situation or else endure it with intense anxiety or distress. The distress in the feared situation interferes significantly with the person's normal routine, occupational functioning, or social activities or relationships. In persons younger than 18 years, the duration is at least 6 months. The fear is not better accounted for by another mental disorder.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.

The symptoms of social anxiety disorder (Box 9) can also be confused with psychosis. One must distinguish between paranoia and the fear of being evaluated. Those suffering from social anxiety disorder desire social interaction, but they avoid it to reduce anxiety. When diagnosing specific phobia, the clinician should remember that most patients who meet the criteria have more than one fear-inducing object or situation.
Box 9: DSM IV-TR Criteria for Social Phobia A fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others and feels he or she will act in an embarrassing manner. Exposure to the feared social situation provokes anxiety, which can take the form of a panic attack. The person recognizes that the fear is excessive or unreasonable. The feared social or performance situations are avoided or are endured with distress. The avoidance, anxious anticipation, or distress in the feared situation interferes significantly with the person's normal routine, occupational functioning, or social activities or relationships. The condition is not better accounted for by another mental disorder, substance use, or general medical condition If a general medical condition or another mental disorder is present, the fear is unrelated to it. The phobia may be considered generalized if fears include most social situations.

Data from American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text rev. Washington, DC, American Psychiatric Association, 2000.

Central to the diagnosis of any of the anxiety disorders is a good history, often requiring collateral from friends and family. Often overlooked is the patient's subjective quality of life.7 When polled, 59% of PTSD sufferers have an overall quality of life significantly lower than that of the general population, and acknowledging this can increase effective patient care. It is important to perform a thorough medical workup when initially assessing the patient with anxiety symptoms. The differential diagnosis can include several organic causes, such as endocrine dysfunction, intoxication or withdrawal, hypoxia, metabolic abnormalities, and neurologic disorders. It is also important to rule out other comorbid psychiatric disorders. Severe depression, bipolar disorder, prodromal schizophrenia, delusional disorder, and adjustment disorder can all mimic the signs and symptoms of anxiety. Many organic causes can be ruled out by a thorough history and basic laboratory work, including thyroid-stimulating hormone, urine toxicology, electrocardiogram, complete blood count, and metabolic panel. Anxiety disorders are common, however, and finding an underlying medical cause is unusual. Back to Top

Summary
Thorough screening history to ensure the patient meets DSM IV-TR criteria for an anxiety disorder. Relevant medical examination and laboratory work to rule out organic causes and substance abuse or withdrawal. Proper screening of comorbid psychiatric conditions that can mimic or exacerbate anxiety disorders. Back to Top

Treatment
An important part of any intervention with a patient with an anxiety disorder is education. The practice guidelines for panic disorder recommend education of the family as well. Many people are confused by the symptoms and behavior and are reassured to know they are not alone and that there are effective interventions. The patient should receive an appropriate medical workup, such as a physical examination, and studies (e.g., electrocardiogram, thyroid-stimulating hormone) when indicated. After ruling out a medical condition, developing a working alliance with the patient provides a basis for ongoing management and prevents further inappropriate use of the medical system. A combination of psychotherapy and medication management is recommended in all of the anxiety disorders. Cognitive-behavioral therapy (CBT) has the strongest support of all the psychotherapies, but it requires commitment to treatment on the part of the patient. Its

efficacy is also contingent on the ability of the therapist and the length of therapy, with a 78% response rate in panic disorder patients who have committed to 12 to 15 weeks of therapy. Studies show that when compared with patients undergoing treatment as usual, patients treated with a combination of CBT and medication experience nearly twice the remission rate, even when the CBT was administered by someone with minimal to no CBT experience.8 The selective serotonin reuptake inhibitors (SSRIs) have been shown to be the besttolerated medications, and response rates are significantly higher than placebo for panic disorder, OCD, PTSD, social anxiety disorder, and GAD. This class of medication includes fluoxetine (Prozac), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), and sertraline (Zoloft). Some improvement should be noted within 3 or 4 weeks, and the dose should be increased if no improvement is seen. In OCD, symptoms can take 8 to 12 weeks to respond to treatment. These patients often require doses at the higher end of the dosage range, so one should not be hesitant to make increases. It is also rare to achieve absolute resolution of symptoms in OCD, and partial reduction is the typical response. In all of the anxiety disorders, SSRIs should be started at low doses and gradually titrated up to therapeutic levels to avoid an initial exacerbation of anxiety. Benzodiazepines, which have been used commonly in the past to treat anxiety disorders, continue to be useful in the short-term management of symptoms until acceptable reduction of symptoms is achieved with an SSRI or CBT. The tolerability and lack of addiction potential make the SSRIs more desirable for long-term management, but the delay in response makes short-term symptom relief with a benzodiazepine desirable for those with the greatest impairment. Because of the risk for rebound anxiety when withdrawing from benzodiazepines with short half-lives, such as alprazolam (Xanax), many psychiatrists prefer the longer-acting benzodiazepines, such as clonazepam (Klonopin). If the patient does not respond to the combination of CBT and medication, a re-evaluation of symptoms might reveal a comorbid disorder missed on the first examination. Comorbid psychiatric disorders significantly lower the likelihood of recovery from anxiety and increase recurrence rates. 9 Many clinicians try switching between SSRIs before considering the next step in treatment. A referral to a psychiatrist for further evaluation and management may be necessary if none of these strategies works. Treatment-refractory anxiety can be extremely frustrating for both the patient and clinician. This can lead to increased dependence on benzodiazepines and an escalation of doses required for the same effect. When approaching the start of therapy, the clinician should reassure the patient that effective treatment is available, but that patience may be necessary until the right combination of modalities is found. Although all of the anxiety disorders display a significant amount of chronicity, most patients have an improved outcome with

appropriate treatment. Response rates improve when comorbidity is low. Patients with an earlier onset of symptoms (childhood or adolescence) can generally expect a more chronic course and may by more difficult to treat. In some of the disorders (PTSD, panic disorder), patients sometimes have spontaneous remission or can function despite the symptoms. However, time to resolution of symptoms is shortened and overall functioning can improve with treatment. Pharmacotherapy often helps to prevent relapse, and rates are improved when effective treatment is continued for 12 months. When considering the terminating pharmacologic treatment, the risk for relapse in all of the disorders should be discussed with the patient. When discontinuing the SSRIs, a slow taper is recommended, with close monitoring for rebound symptoms (headache, gastrointestinal upset, restlessness). If relapse occurs, reinstituting treatment is indicated, and many patients opt for indefinite treatment to maintain remission of symptoms. Lifelong management with pharmacotherapy or psychotherapy, or both, is not unusual for many patients. For many, a maximum reduction of symptoms, rather than a full remission, is an acceptable outcome. Back to Top

Summary
Educate the patient and family members about realistic treatment expectations and reassure them of the absence of medical causes. First-line treatment is with a selective serotonin reuptake inhibitor, starting at low doses with careful titration so as not to exacerbate anxiety symptoms. Initiate cognitive-behavioral therapy along with medication to significantly increase response rates. Consider short-term benzodiazepines in more severe cases. Use medications with longer half-lives to minimize withdrawal effects. Refer to a mental health professional in difficult cases or for patients with a less-thanexpected response to treatment. Back to Top

Prevention and screening

No biologic markers are specific enough at this time to detect anxiety early, and no research shows that current medications prove efficacious in preventing these disorders. It is therefore important to screen for specific risk factors, such as strong family psychiatric history and concurrent substance abuse. Efforts since the 1990s have improved the diagnosis of these disorders, but the overall quality of care provided to patients remains substandard and CBT continues to be underused.10 Given the morbidity and mortality due to comorbid conditions, suicide, and higher rates of medical illness, it is essential to complete a comprehensive psychiatric, medical, and substance use history and to treat this

disease early and aggressively. Back to Top

Considerations in special populations

Physicians must take precautions when treating certain populations of anxious patients, including patients with substance dependence, chronic obstructive pulmonary disease (COPD) or other respiratory illness, and pregnant or elderly patients. Benzodiazepines are the chief concern in all of these patients. This class of medication can decrease the respiratory rate in many illnesses in which the rate is already compromised (COPD) and can increase the likelihood of delirium in both the elderly and medically ill. Benzodiazepines are also considered generally unsafe for use during pregnancy and have the potential for abuse in patients with substance dependence. In these populations the combined treatment of an SSRI with CBT therapy is preferred. If benzodiazepines are necessary, it is important to start at a low dose, titrate slowly, and plan for only short-term use. Back to Top

References
1. Sadock B, Sadock V. Synopsis of Psychiatry. 10th ed. Philadelphia: Lippincott Williams & Wilkins, 2007, pp 579-633 2. In: Stern TA, Herman JB (eds): Massachusetts General Hospital Psychiatry Update and Board Preparation. 2nd ed. New York: McGraw-Hill, 2004, pp 121-126. 3. Kessler R, Demier O, Frank R, et al: Prevalence and treatment of mental disorders 1990-2003. N Engl J Med. 2005, 352: 2515-2523. 4. Hettema J, Prescott C, Meyers J, et al: The structure of genetic and environmental risk factors for anxiety disorders in men and women. Arch Gen Psychiatry. 2005, 62: 182189. 5. Weissman M, Wickramaratne P, Nomura Y, et al: Offspring of depressed parents: 20 years later. Am J Psychiatry. 2006, 163: 1001-1008. 6. Hoehn-Sark R, McLeod D, Funderburk F, et al: Somatic symptoms and physiologic responses in generalized anxiety disorder and panic disorder. Arch Gen Psychiatry. 2004, 61: 913-921. 7. Rapaport M, Clary C, Fayyad R, Endicott J. Quality of life impairment in depressive and anxiety disorders. Am J Psychiatry. 2005, 162: 1171-1178. 8. Roy-Byrne P, Craske M, Stein M, et al: A randomized effectiveness trial of cognitive behavioral therapy and medication for primary care panic disorder. Arch Gen Psychiatry. 2005, 62: 290-298. 9. Bruce S, Yonkers K, Otto M, et al: Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: A 12 year prospective study. Am J Psychiatry. 2005, 162: 1179-1187.

10. Stein M, Sherbourne C, Craske M, et al: Quality of care for primary care patients with anxiety disorder. Am J Psychiatry. 2004, 161: 2230-2237. 11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association, 2000. Back to Top

Suggested Readings
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association, 2000. Bruce S, Yonkers K, Otto M, et al: Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: A 12 year prospective study. Am J Psychiatry. 2005, 162: 1179-1187. Hettema J, Prescott C, Meyers J, et al: The structure of genetic and environmental risk factors for anxiety disorders in men and women. Arch Gen Psychiatry. 2005, 62: 182189. Hoehn-Sark R, McLeod D, Funderburk F, et al: Somatic symptoms and physiologic responses in generalized anxiety disorder and panic disorder. Arch Gen Psychiatry. 2004, 61: 913-921. Kessler R, Demier O, Frank R, et al: Prevalence and treatment of mental disorders 1990-2003. N Engl J Med. 2005, 352: 2515-2523. Rapaport M, Clary C, Fayyad R, Endicott J. Quality of life impairment in depressive and anxiety disorders. Am J Psychiatry. 2005, 162: 1171-1178. Roy-Byrne P, Craske M, Stein M, et al: A randomized effectiveness trial of cognitive behavioral therapy and medication for primary care panic disorder. Arch Gen Psychiatry. 2005, 62: 290-298. Sadock B, Sadock V. Synopsis of Psychiatry. 10th ed. Philadelphia: Lippincott Williams & Wilkins, 2007, pp 579-633 Stein M, Sherbourne C, Craske M, et al: Quality of care for primary care patients with anxiety disorder. Am J Psychiatry. 2004, 161: 2230-2237. In: Stern TA, Herman JB (eds): Massachusetts General Hospital Psychiatry Update and Board Preparation. 2nd ed. New York: McGraw-Hill, 2004, pp 121-126. Weissman M, Wickramaratne P, Nomura Y, et al: Offspring of depressed parents: 20 years later. Am J Psychiatry. 2006, 163: 1001-1008.