clinical presentation of generalized anxiety

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• Generalized anxiety disorder

It's normal to feel anxious from time to time, especially if your life is stressful. However, excessive, ongoing anxiety and worry that are difficult to control and interfere with day-to-day activities may be a sign of generalized anxiety disorder.

It's possible to develop generalized anxiety disorder as a child or an adult. Generalized anxiety disorder has symptoms that are similar to panic disorder, obsessive-compulsive disorder and other types of anxiety, but they're all different conditions.

Living with generalized anxiety disorder can be a long-term challenge. In many cases, it occurs along with other anxiety or mood disorders. In most cases, generalized anxiety disorder improves with psychotherapy or medications. Making lifestyle changes, learning coping skills and using relaxation techniques also can help.

Generalized anxiety disorder care at Mayo Clinic

• Generalized anxiety disorder. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. Arlington, Va.: American Psychiatric Association; 2013. http://dsm.psychiatryonline.org. Accessed June 26, 2017.
• Gabbard GO, ed. Generalized anxiety disorder. In: Gabbard's Treatments of Psychiatric Disorders. 5th ed. Arlington, Va.: American Psychiatric Association; 2014. http://psychiatryonline.org/doi/book/10.1176/appi.books.9781585625048. Accessed June 26, 2017.
• Baldwin D. Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis. https//:www.uptodate.com/contents/search. Accessed June 26, 2017.
• Craske M, et al. Approach to treating generalized anxiety disorder in adults. https//:www.uptodate.com/contents/search. Accessed June 26, 2017.
• Craske M. Psychotherapy for generalized anxiety disorder in adults. https//:www.uptodate.com/contents/search. Accessed June 26, 2017.
• Bystritsky A. Pharmacotherapy for generalized anxiety disorder in adults. https//:www.uptodate.com/contents/search. Accessed June 26, 2017.
• Bystritsky A. Complementary and alternative treatments for anxiety symptoms and disorders: Herbs and medications. https//:www.uptodate.com/contents/search. Accessed June 20, 2017.
• Bystritsky A. Complementary and alternative treatments for anxiety symptoms and disorders: Physical, cognitive, and spiritual interventions. https//:www.uptodate.com/contents/search. Accessed June 20, 2017.
• Generalized anxiety disorder: When worry gets out of control. National Institute of Mental Health. https://www.nimh.nih.gov/health/publications/generalized-anxiety-disorder-gad/index.shtml. Accessed June 26, 2017.
• Natural medicines in the clinical management of anxiety. Natural Medicines. https://naturalmedicines.therapeuticresearch.com. Accessed June 20, 2017.
• Anxiety disorders. Natural Medicines. https://naturalmedicines.therapeuticresearch.com. Accessed June 20, 2017.
• AskMayoExpert. Anxiety disorders. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2017. Accessed June 20, 2017.
• Valerian. Natural Medicines. https://naturalmedicines.therapeuticresearch.com. Accessed June 26, 2017.
• Facts for families: The anxious child. American Academy of Child and Adolescent Psychiatry. http://www.aacap.org/AACAP/Families_and_Youth/Facts_for_Families/Facts_for_Families_Pages/The_Anxious_Child_47.aspx. Accessed June 26, 2017.
• Brown A. Allscripts EPSi. Mayo Clinic, Rochester, Minn. April 21, 2017.
• Kava. National Center for Complementary and Integrative Health. https://nccih.nih.gov/health/kava. Accessed July 21, 2017.
• Valerian. National Center for Complementary and Integrative Health. https://nccih.nih.gov/health/valerian. Accessed July 21, 2017.
• Passion flower. National Center for Complementary and Integrative Health. https://nccih.nih.gov/health/passionflower. Accessed July 21, 2017.
• Stein MB, et al. Treating anxiety in 2017: Optimizing care to improve outcomes. JAMA. 2017;318:236.
• Sawchuk CN (expert opinion). Mayo Clinic, Rochester, Minn. July 25, 2017.
• Anxiety and diet
• Herbal treatment for anxiety: Is it effective?
• Test anxiety: Can it be treated?

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Generalized Anxiety Disorder

• Henry White , M.D.

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Generalized anxiety disorder is by no means uncommon and often protean; it frequently appears as a complication of medical illness or in association with major depression and other mood disorders. With reported prevalence in the range of 2%–6%, patients with generalized anxiety disorder report levels of disability comparable to or greater than levels reported by patients with serious physical and mental disorders (including depression, arthritis, asthma, and diabetes) ( 1 ). Distinguishing generalized anxiety disorder from normal worry is a clinical challenge; patients tend not to self-identify. Given the importance of the disorder, there is certainly need for a simple, straightforward guide for both primary care providers as well as for early-career clinicians and other psychiatric practitioners.

This fact-filled monograph is part of the Oxford Psychiatry Library series. Written by two distinguished experts in the field, Michael Van Ameringen and Mark Pollack, it offers a thorough overview of the subject. Topics covered include diagnosis, neurobiology, clinical features, pharmaco- and psychotherapy, clinical management, and self-help resources. Its sleek, slim exterior, similar in size to a Zagat Survey and with color reminiscent of a Michelin Guide, promises an experience of a handy guide to a complex subject. Unfortunately, its interior is surprisingly difficult to navigate.

This volume does pack in a great deal of information (partly through the use of a petit 7-point typeface font). The chapter on diagnosis is a detailed discussion of the history of the classification of anxiety and the complex debates around DSM-5. Its summary of neurobiology contains an excellent overview of current imaging and neurochemical literature. The section on pharmacotherapy contains a comprehensive review of efficacy data, including the melatonergic agent agomelatine, not currently available in the United States. It features a six-page table listing many of the relevant randomized trials. The chapter on psychotherapy offers a summary description of three cognitive-behavioral therapy approaches and 15 different techniques. This book turns out to be a highly technical, academically oriented manual for practitioners already well versed in the field.

Where it falls short is being a “user-friendly overview” for the young professional or generalist, as its blurb promises. Its many clinical pearls are often buried in the midst of long paragraphs full of technical details. It includes an extensive discussion of the variety of treatment approaches without a clear set of recommendations for choosing between them. There is but one treatment algorithm, which lacks specificity (e.g., it does not provide a decision tool for choosing whether to begin treatment with psychotherapy, pharmacotherapy, or both).

There are three omissions of particular note. Although there is good evidence of the efficacy of the anticonvulsant pregabalin for generalized anxiety disorder, at present the Food and Drug Administration has not approved pregabalin for this indication. This fact is mentioned in passing in chapter 5 (titled “Pharmacotherapy”); however, in chapter 7 (titled “Clinical Management”), pregabalin is included in a list of “first-line treatments” with no mention of this proviso. The chapter on psychotherapy does not include any discussion of evidence-based psychodynamic approaches (although the book does acknowledge Freud as one of the first to describe the disorder). An appendix including several useful rating scales omits scoring instructions or norms for all but one. The authors are to be commended for fitting so much information into a small package, but this volume does not fulfill its promise of being a useful guide for those travelers with little prior knowledge of anxiety’s multifarious domain.

1 Kessler RC, Mickelson KD, Barber C, Wang P : The association between chronic medical conditions and work impairment , in Caring and Doing for Others: Social Responsibility in the Domains of Family, Work and Community . Edited by Rossi A . Chicago, University of Chicago, 2001 , pp 403–426 Google Scholar

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INTRODUCTION

This topic addresses the epidemiology, pathogenesis, clinical manifestations, and diagnosis of GAD. Pharmacotherapy for GAD, psychotherapy for GAD, and issues concerning treatment and assessment of comorbid disorders are discussed separately:

● (See "Generalized anxiety disorder in adults: Management" .)

● (See "Generalized anxiety disorder in adults: Cognitive-behavioral therapy and other psychotherapies" .)

● (See "Co-occurring substance use disorder and anxiety-related disorders in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" .)

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Generalized anxiety disorder

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Terminology

Complications and prognosis, screening and prevention, generalized anxiety disorder.

• Symptoms are present on most days for at least 6 months to confirm the diagnosis r1
• Psychiatric symptoms include excessive worrying, nervousness, restlessness, inability to relax, and fear of worst-case scenarios
• Associated physical signs and symptoms include tachycardia, dyspepsia, tremor, dizziness, hyperhidrosis, and cold extremities
• Patients with generalized anxiety disorder typically perceive impairments in their physical well-being, social relationships, occupation, and home and family life; they have an increased risk of alcohol and other drug use disorders, as well as suicide attempts
• DSM-5-TR criteria represent the gold standard for diagnosis r1
• Cognitive behavioral therapy is the preferred treatment at both initial diagnosis and relapse, along with patient education and recommendations for a healthy lifestyle
• Pharmacologic treatment typically consists of antidepressant therapy; supplemental medication (eg, antipsychotics) is added for refractory cases, usually under the care of a psychiatrist
• Benzodiazepines have immediate effect and may be used as short-term treatment; however, avoid routine use
• Most patients are prone to relapse 6 to 12 years after initial diagnosis, r2 with half in partial remission 5 years after initial diagnosis and treatment r3

Urgent Action

• Question all patients regarding active suicidal ideation; if discovered, immediately refer to psychiatrist r4
• Generalized anxiety disorder often coexists with major depressive disorder and panic disorder; maintain a high index of suspicion during diagnosis r5
• Consider possible suicidal ideation in patients presenting with generalized anxiety disorder r6

Clinical Clarification

• Anxiety and worry are accompanied by additional symptoms (eg, restlessness, fatigue, difficulty concentrating, irritability, muscle tension, disturbed sleep)
• Negatively affects patient's psychosocial functioning on a near-daily basis r1

Clinical Presentation

• Work or school responsibilities and interactions
• Family health and finances
• In children, worry about competence or quality of their performance
• Being nervous and unable to relax, with poor or disturbed sleep r1 c2 c3 c4 c5 c6 c7 c8 c9
• Worrying about trivial or minor matters, with no control over worrying
• Extreme restlessness and inability to concentrate r1 c10 c11
• Irritability c12 c13
• Fear of the worst happening and feeling scared in general
• Feeling that objects are unreal (derealization) or that the self is “not really here” (depersonalization) r7 c14 c15
• Sensation of losing control, “going crazy,” or passing out r7 c16 c17
• Fear of death r7 c18
• Muscle tension and fatigability are highly correlated with generalized anxiety disorder r1 c19 c20
• Palpitations c21 c22
• Dyspepsia or abdominal discomfort c23 c24
• Dizziness c25 c26
• Unsteady gait c27 c28
• Dyspnea c29 c30
• Feeling hot and/or experiencing diaphoresis, regardless of ambient temperature c31 c32
• Feeling faint, hands trembling, and face flushing c33 c34 c35
• Paresthesia marked by numbness and tingling c36 c37 c38
• Choking sensation c39
• Diarrhea c41
• Cold extremities c42
• Xerostomia c43
• Bruxism c44
• Headache c45
• Symptoms are typically more severe in younger adults r1

Physical examination

• Signs related to general emotional well-being include nervousness, irritability, and heightened vigilance r1 c46 c47 c48
• Visible tremor c49
• Cold hands c50
• Tachycardia c51
• Tachypnea c52

Causes and Risk Factors

• Includes loss of a close relative or long-term separation from a partner c55 c56
• Childhood adversity has a 32.4% association with anxiety disorders r11 c57

Risk factors and/or associations

• Onset of symptoms after the age of 35 years is suggestive of generalized anxiety disorder r12 c58
• Onset rarely occurs before adolescence; prevalence in the adolescent population is 0.9% in the United States r1 c59 c60
• Prevalence among adults (2.9% in the United States) is 3 times greater than in adolescents r12 c61
• Prevalence in adults 75 years and older is 2.8% to 3.1% r1
• Twice as common in female individuals as in male individuals r13 r14 c62 c63
• Twin studies have demonstrated that there is a moderate genetic risk of generalized anxiety disorder, estimated to be between 15% and 20%, r4 but may be as high as one-third r1 c64

Ethnicity/race

• White populations are more likely to be affected than those of African, Asian, or Hispanic ethnicity r15 c65 c66 c67 c68

Other risk factors/associations

• Generalized anxiety disorder contributes to increased use of alcohol and other drugs
• Cannabis use disorder is associated with an approximately three times increase in the risk of generalized anxiety disorder r16
• It is estimated that 35% of patients with generalized anxiety disorder use alcohol and/or other drugs to relieve symptoms r4
• Social phobia is the most prevalent (16%-59%), followed by phobias of other types (eg, specific places, situations, or objects; 16%-46%) c69 c70 c71
• Patients from developed countries are more likely to experience generalized anxiety disorder r1
• Behavioral inhibition and neuroticism are associated with generalized anxiety disorder r1 c72 c73

Diagnostic Procedures

Primary diagnostic tools.

• Excessive use of alcohol, caffeine, or other stimulants must be ruled out as a cause of symptoms
• GAD-7 assesses symptoms over the past 2 weeks instead of 6 months ( per DSM-5-TR r1 ) using 7 criteria, operating on the assumption that severe symptoms are typically chronic r8
• Beck Anxiety Inventory contains 21 items comprising somatic, affective, and cognitive symptoms related specifically to anxiety disorders r9
• Excessive anxiety and worry (apprehensive expectation) about various events or activities (eg, work or school performance), occurring more days than not, lasting 6 months or longer
• Patient has difficulty controlling this worry
• Restlessness
• Fatigability
• Compromised ability to concentrate
• Crankiness/irritability
• Increased muscle tension
• Poor sleep quality, including trouble falling asleep, difficulty staying asleep, or restlessness
• Patient's symptoms lead to clinical distress and engender negative effects on work, school, or everyday life
• Another medical condition or substance use disorder is not the cause
• Different mental disorder has not given rise to the patient's symptoms
• Maintain a high index of suspicion for medical conditions that could cause the symptoms; laboratory testing is generally deferred, but CBC, thyroid function tests, basic chemistry panel, urine drug screening, and ECG should be obtained as indicated by the clinical presentation and medical history r17

Functional testing

• Feeling nervous, anxious, or on edge
• Not being able to stop or control worrying
• Worrying too much about different things
• Trouble relaxing
• Being so restless that it is hard to sit still
• Becoming easily annoyed or irritable
• Feeling afraid as if something awful might happen
• Threshold score of 8 maximizes sensitivity and 15 maximizes specificity r8
• Threshold of 10 is optimal for high sensitivity and specificity r8
• 10: moderate anxiety
• 15: severe anxiety
• Numbness or tingling
• Feeling hot
• Wobbliness in legs
• Unable to relax
• Fear of the worst happening
• Dizzy or lightheaded
• Heart pounding or racing
• Feelings of choking
• Hands trembling
• Fear of losing control
• Difficulty breathing
• Fear of dying
• Indigestion or discomfort in abdomen
• Face flushed
• Sweating (not due to heat)
• Subjects are asked to rate how much each symptom has affected them over the past week on a 4-point scale ranging from 0 (not at all) to 3 (severely—I could barely stand it); total score ranges from 0 to 63
• 0 to 9: normal
• 10 to 18: mild to moderate anxiety
• 19 to 29: moderate to severe anxiety
• 30 to 63: severe anxiety

Procedures c77 c78

Differential diagnosis, most common.

• Characterized by unusually high r20 or low r21 levels of thyroxine due to dysfunction or removal of thyroid gland
• Anxiety and/or depression symptoms (eg, being more irritable, sad, emotionally sensitive, or anxious) r22
• Hypothyroidism can present with fatigue, dry skin, constipation, vocal changes, and prolonged ankle jerk reflex r23
• Hyperthyroidism can present with hypertension, tachycardia, warm and moist skin, and brisk ankle jerk reflex r20
• Evidence from history, physical examination, or laboratory findings that disturbance is not a direct pathophysiologic consequence of another medical condition
• Disturbance is not better explained by another mental disorder
• Disturbance does not occur exclusively during the course of a delirium
• Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning
• TSH level is elevated to more than 10 mIU/L in primary hypothyroidism r21 r24
• Low serum levels of total or free thyroxine r22
• TSH level is suppressed r20
• High serum levels of total or free thyroxine
• Preoccupation with the possibility of having or acquiring serious illness based on misinterpretations of benign or minor physical sensations; previously known as hypochondriasis
• Some psychological and physical symptoms of anxiety are also present
• Subject of anxiety differs, as the patient focuses mainly on their body and general health to the exclusion of work, finances, or family matters
• Preoccupation with having or acquiring a serious illness for at least 6 months
• Frequent visits to the clinic or maladaptive avoidance of medical attention
• Phobic anxiety disorder with concerns about social situations involving unfamiliar people or possible scrutiny
• Psychological and physical symptoms of anxiety are present in certain social situations
• Characterized by early onset; typically appears by age 11 years in 50% of patients and age 20 years in 80% of patients r27
• Extreme fear or anxiety related to meeting strangers, speaking in public, or being observed in social situations
• Social phobia must last for at least 6 months and cause clinically significant impairment in social interactions
• Marked by recurrent panic attacks or extreme but brief episodes of anxiety, at intervals ranging from 24 hours to several months; may coexist with generalized anxiety disorder
• Physical signs and symptoms of anxiety (eg, sweating, palpitations, dizziness, tachycardia) are present during a panic attack
• History of childhood trauma or abuse is more likely in patients with panic disorder than in those with generalized anxiety disorder
• Extreme panic or anxiety reaching its peak within minutes, manifesting more than 4 somatic symptoms of anxiety
• At least 1 panic attack preceded by more than 1 month of apprehensive expectation of a similar episode
• Sadness, lethargy, and apathy lasting at least 2 weeks, with reduced interest and pleasure in normal activities; may coexist with generalized anxiety disorder
• Irritability, fatigue, poor sleep, and digestive symptoms are typically present, as with generalized anxiety disorder
• Change in weight or appetite
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Feelings of worthlessness or inappropriate guilt
• Diminished ability to concentrate or indecisiveness
• Suicidal ideation or attempt
• Characterized by continually recurring thoughts or images (obsessions) that increase anxiety and repetitive or ritualistic actions (compulsions) performed to alleviate that anxiety
• Excessive worrying and some symptoms of anxiety can be present
• Anxiety relates more to imagined or fantastic events
• Obsessive thoughts and compulsive behaviors take up at least 1 hour of the day
• Patient suffers from clinically significant impairment in an occupational or social setting
• Psychological disturbance or anhedonic/dysphoric mental state caused by experiencing a serious traumatic event
• Heightened anxiety is typically present, along with its mental and physical symptoms
• Main distinguishing criterion is the association of anxiety with a specific event, not with normal daily functioning, and the presence of flashbacks, dreams, and dissociative states relating to that event
• Repeated exposure to circumstances surrounding such events, as with first responders or emergency department personnel
• Psychological disturbance lasting longer than 1 month, including invasive memories, dreams, flashbacks, avoidance of stimuli associated with such events, irritability, anxiety, and insomnia
• Witnessing traumatic events, especially those affecting a primary caregiver
• Constriction of play, social withdrawal, and emphasis on expression of negative emotions (eg, fear, guilt, shame)
• Initial symptoms and signs of withdrawal include heightened anxiety, as well as irritability, nausea, agitation, diaphoresis, and tachycardia from sedative or opioid use
• In case of withdrawal from benzodiazepines, signs and symptoms begin 2 to 10 days after last use r34
• Alcohol withdrawal may be accompanied by seizures and delirium; symptoms typically peak 72 hours after the last ingestion of alcohol (without medication) r34
• Opioid withdrawal is associated with anxiety and panic symptoms, with onset typically 4 to 6 hours after last use of a shorter-acting opioid (eg, heroin, oxycodone) or 1 to 2 days after last use of an opioid with a longer half-life (eg, methadone, buprenorphine) r35
• Diagnosis can be confirmed by patient history and observation
• Anxiety and panic may be present with intoxication from a variety of substances (eg, stimulants [including caffeine], alcohol, inhalants, cannabis, phencyclidine)
• Typical history would relate anxiety to intoxication with these substances, which would typically be absent with abstinence
• Diagnosis primarily made from patient history and clinical signs
• Alleviate anxiety in the short term and support normal day-to-day functioning
• Improve quality of life and prevent relapse in the long term

Disposition

Admission criteria.

• Admit patients reporting acute suicidal ideation or intent
• Consider admission in patients with comorbid conditions (eg, significant substance use disorder with toxicity or withdrawal of sedative-hypnotics [including alcohol])

Recommendations for specialist referral

• Refer patients to a psychiatrist, psychologist, or appropriately trained mental health therapist for psychotherapy
• Psychiatric referral is necessary for patients with suicidal ideation or complex coexisting illnesses
• Psychiatric evaluation, if not already accomplished, is recommended after 2 failed medication trials (ie, 2 different drugs with no response despite reaching target dose) r12

Treatment Options

Owing to the chronicity of generalized anxiety disorder, long-term therapy is anticipated r1

• Includes psychotherapy, drug therapy, and patient education (eg, self-help internet sites) regarding disease and healthy lifestyle recommendations
• Duration of treatment should be at least 12 months to reduce risk of relapse r36 r37

Psychotherapy is often recommended over drug treatment as initial therapy for patients with generalized anxiety disorder because relapse is common after therapeutic medications are withdrawn, lasting beyond the period of withdrawal symptoms after their discontinuation r7

• Best choice of treatment at diagnosis, at 6-month follow-up, and for relapse r7
• Group format may be preferred treatment in children and adolescents r41
• Pharmacologic treatment may be given in conjunction with psychotherapy r4

However, drug treatment is commonly prescribed in the primary care setting in the United States because of better resource availability r7 and patient preference r17

• Fewer adverse effects and lower risk of long-term dependence
• Take up to 4 weeks to act but significant improvement may be noted in as little as 2 weeks r7 r38
• Withdrawal effects may occur after drug regimen is complete; gradual dose tapering is recommended
• Do not use as monotherapy when depression is concurrent with anxiety r12
• Not recommended routinely owing to potential for misuse; if used, short-term use (3-6 months) is recommended r42 r43
• More likely to lead to requests for long-term prescription than antidepressants
• Stronger anxiolytic effect in the first 2 weeks of drug treatment r7
• May be used initially in combination with an antidepressant (eg, selective serotonin reuptake inhibitor), tapering off after several (4-5) weeks as the antidepressant becomes effective at reducing anxiety; benzodiazepine taper takes 2 to 4 weeks r7
• Drugs used in combination with antidepressants have included olanzapine, r44 risperidone, r7 trifluoperazine, and pregabalin r45
• Augmentation is typically initiated by a psychiatrist
• However, a systematic review of augmentation reported a small reduction in symptom severity, with no difference between medication and placebo on functional impairment r46

Drug therapy

• Escitalopram Oral solution; Children and Adolescents 7 to 17 years: 10 mg PO once daily, initially. May increase the dose to 20 mg/day as needed and tolerated after 2 weeks or more.
• Escitalopram Oral tablet; Adults: 10 mg PO once daily, initially. May increase the dose to 20 mg/day as needed and tolerated after 1 week or more.
• Escitalopram Oral tablet; Older Adults: 10 mg PO once daily.
• Paroxetine Hydrochloride Oral tablet; Adults: 20 mg PO once daily, initially. May increase the dose by 10 mg/day at weekly intervals as needed and tolerated. Usual Max: 20 mg/day. Max: 50 mg/day.
• Paroxetine Hydrochloride Oral tablet; Older Adults: 10 mg PO once daily, initially. May increase the dose by 10 mg/day at weekly intervals as needed and tolerated. Usual Max: 20 mg/day. Max: 40 mg/day.
• Sertraline Hydrochloride Oral solution; Children and Adolescents 7 to 17 years: 25 mg PO once daily, initially. May increase the dose gradually as needed. Max: 200 mg/day.
• Sertraline Hydrochloride Oral tablet; Adults: 25 mg PO once daily for 1 week, then 50 mg PO once daily for 1 week, and then may increase the dose by 50 mg/day at weekly intervals as needed. Max: 200 mg/day.
• Duloxetine Oral capsule, gastro-resistant pellets; Children and Adolescents 7 to 17 years: 30 mg PO once daily for 2 weeks, initially. May increase the dose by 30 mg/day as needed. Usual dose: 30 to 60 mg/day. Max: 120 mg/day.
• Duloxetine Oral capsule, gastro-resistant pellets; Adults: 60 mg PO once daily, or alternatively, 30 mg PO once daily for 1 week, then 60 mg PO once daily, initially. May increase the dose by 30 mg/day as needed. Usual dose: 60 mg/day. Max: 120 mg/day.
• Duloxetine Oral capsule, gastro-resistant pellets; Older Adults: 30 mg PO once daily for 2 weeks, initially. May increase the dose by 30 mg/day as needed. Usual dose: 60 mg/day. Max: 120 mg/day.
• Venlafaxine Hydrochloride Oral tablet, extended-release; Children† and Adolescents† 6 to 17 years weighing 25 to 39 kg: 37.5 mg PO once daily for 1 week, then 37.5 or 75 mg PO once daily for 1 week, and then may increase the dose by 37.5 mg/day every 2 weeks as needed. Max: 112.5 mg/day.
• Venlafaxine Hydrochloride Oral tablet, extended-release; Children† and Adolescents† 6 to 17 years weighing 40 to 49 kg: 37.5 mg PO once daily for 1 week, then 75 mg PO once daily for 1 week, and then may increase the dose by 37.5 mg/day every 2 weeks as needed. Max: 150 mg/day.
• Venlafaxine Hydrochloride Oral tablet, extended-release; Children† and Adolescents† 6 to 17 years weighing 50 kg or more: 37.5 mg PO once daily for 1 week, then 75 mg PO once daily for 1 week, and then may increase the dose by 75 mg/day every 2 weeks as needed. Max: 225 mg/day.
• Venlafaxine Hydrochloride Oral tablet, extended-release; Adults: 75 mg PO once daily, or alternatively, 37.5 mg PO once daily for 4 to 7 days, then 75 mg PO once daily, and then may increase the dose by 75 mg/day every 4 days or more as needed. Max: 225 mg/day.
• Alprazolam Oral tablet; Adults: 0.25 to 0.5 mg PO 3 times daily, initially. May increase the dose every 3 to 4 days as needed. Max: 4 mg/day. Use the lowest possible effective dose.
• Alprazolam Oral tablet; Older Adults: 0.25 mg PO 2 or 3 times daily, initially. May increase the dose gradually every 3 to 4 days as needed. Max: 4 mg/day. Use the lowest possible effective dose.
• Diazepam Oral solution; Infants, Children, and Adolescents 6 months to 17 years: 1 to 2.5 mg PO 3 to 4 times daily, initially. May increase the dose gradually as needed and tolerated. Adult Max: 40 mg/day.
• Diazepam Oral tablet; Adults: 2 to 10 mg PO 2 to 4 times daily.
• Diazepam Oral tablet; Older Adults: 2 to 2.5 mg PO 1 or 2 times daily, initially. May increase the dose gradually as needed and tolerated. Max: 40 mg/day.
• Lorazepam Oral solution; Children† 1 to 11 years: 0.025 to 0.05 mg/kg/dose PO up to every 4 hours as needed for anxiety. In older pediatric patients, the daily dosage for anxiety disorders is typically divided into 2 to 3 doses with a maximum of 10 mg/day.
• Lorazepam Oral tablet; Children and Adolescents 12 to 17 years: 2 to 3 mg/day PO in 2 to 3 divided doses, initially. May increase the dose gradually as needed. Usual dose: 2 to 6 mg/day. Max: 10 mg/day.
• Lorazepam Oral tablet; Adults: 2 to 3 mg/day PO in 2 to 3 divided doses, initially. May increase the dose gradually as needed. Usual dose: 2 to 6 mg/day. Max: 10 mg/day.
• Lorazepam Oral tablet; Older Adults: 1 to 2 mg/day PO in 2 to 3 divided doses, initially. May increase the dose gradually as needed. Usual dose: 2 to 6 mg/day. Max: 10 mg/day.
• Buspirone Hydrochloride Oral tablet; Children† 6 to 12 years: 2.5 to 5 mg PO twice daily, initially. May increase the dose by 5 mg/day every 3 to 7 days as needed. Usual dose: 10 to 15 mg/day. Max: 60 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
• Buspirone Hydrochloride Oral tablet; Adolescents†: 2.5 to 5 mg PO twice daily, initially. May increase the dose by 5 mg/day every 3 to 7 days as needed. Usual dose: 10 to 60 mg/day. Max: 60 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
• Buspirone Hydrochloride Oral tablet; Adults: 7.5 mg PO twice daily, initially. May increase the dose by 5 mg/day every 2 to 3 days as needed. Usual dose: 20 to 30 mg/day. Max: 60 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Nondrug and supportive care

• Improving quality and quantity of sleep c104
• Exercise has been shown to have significant ability to reduce anxiety symptoms and is encouraged r50 r51
• Minimizing caffeine and alcohol intake c106 c107
• Avoiding nicotine and other drugs c108 c109
• Multiple types of psychotherapy have been applied to the treatment of generalized anxiety disorder, with evidence strongest for the efficacy of cognitive behavioral therapy r4
• Recommended for all patients, although use may be guided by resource availability, patient finances, or patient preference
• Teaches patients to substitute positive thoughts for anxiety-provoking ones r7
• Present a cognitive model of anxiety to the patient and train in self-monitoring and identification of cues that contribute to interpretations of threat
• Inform patients that therapy focuses on learning different, less anxiety-provoking ways of viewing the self, the world, and the future
• Use standard cognitive therapy procedures (eg, outlining cognitive predictions, interpretations, beliefs, and assumptions that lead to threatening perceptions); emphasize Socratic method (ie, stimulate critical thinking by asking and answering questions)
• Focus discussions on multiple alternative perspectives for any given situation of daily living; homework emphasizes frequent applications of alternative perspectives and behavioral tasks
• Reduction in intolerance of uncertainty is an important predictor of outcome
• Therapy can be delivered in 6 to 12 sessions at weekly intervals r52

Comorbidities

• Occurs more often in female individuals than in male individuals r1
• Combination of these disorders is termed cothymia r7
• Antidepressants are the preferred drug treatment, in combination with cognitive behavioral therapy
• Occurs in 25% to 50% of patients with generalized anxiety disorder r5 r12
• Combination of buspirone with cognitive behavioral therapy is more effective than psychotherapy alone
• Separation anxiety disorder is often comorbid with generalized anxiety disorder in children r53

Special populations

• However, the combination of cognitive behavioral therapy and sertraline has demonstrated efficacy in children between the ages of 7 and 17 years r54
• Prescribe half the usual drug dose (typically buspirone) for pregnant patients. r12
• 1 of the goals of therapy in these patients is to prevent premature birth or miscarriage due to anxiety
• If medication is effective, continue course for 6 to 12 months and then slowly taper off r3
• Optional continued follow-up every 6 months for a period of 5 years or longer is recommended since rates of relapse are high r3

Complications

• Patients with anxiety disorders perceive impairments in their physical well-being, social relationships, occupation, and home and family life
• If untreated, generalized anxiety disorder can lead to alcohol and other drug use disorders, as patient self-medicates to control symptoms c115 c116
• Increased risk for suicidal ideation does not predict death by suicide r56
• Patients who improve the most initially also have the best long-term outcome r7
• Rate of full remission is 27% at 3 years and 38% at 5 years postdiagnosis r3
• Rates of partial remission are 37% at 3 years and 47% at 5 years postdiagnosis r3

Screening c119

Screening tests.

• Use clinical judgment to determine frequency of screening
• Beck Anxiety Inventory c120
• GAD-7 (Generalized Anxiety Disorder Scale) c121
• K-10 (Kessler Psychological Distress Scale) c122
• PHQ-9 (Patient Health Questionnaire) c123
• GAD-2, PHQ-2, K-6 (abbreviated versions of the above scales)
• SCARES (Screen for Child Anxiety Related Emotional disorders Scale) c124
• HADS (Hospital Anxiety and Depression Scale) c125
• Edinburgh Postnatal Depression Scale c126
• Bright Futures Pediatric Symptom Checklist–Youth Report in adolescent and young adult female patients c127

Prevention c128

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Nature of Generalized Anxiety Disorder

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Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) usually involves a persistent feeling of anxiety or dread, which can interfere with daily life. It is not the same as occasionally worrying about things or experiencing anxiety due to stressful life events. People living with GAD experience frequent anxiety for months, if not years. Learn more about generalized anxiety disorder .

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Clinical Markers of Panic and Generalized Anxiety Disorder: Overlapping Symptoms, Different Course and Outcome

Alice caldiroli.

1 Department of Mental Health and Addiction, Fondazione IRCCS San Gerardo dei Tintori, Via G.B. Pergolesi 33, 20900 Monza, Italy

Lia Colzani

2 Department of Medicine and Surgery, University of Milan Bicocca, Via Cadore 38, 20900 Monza, Italy

Enrico Capuzzi

Cecilia quitadamo, davide la tegola, teresa surace, stefania russo, mauro capetti.

3 Department of Medicine and Surgery, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy

Agnese Tringali

Matteo marcatili, francesco zanelli quarantini.

4 Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy

Fabrizia Colmegna

Antonios dakanalis, massimiliano buoli.

5 Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy

Massimo Clerici

Associated data.

Data sharing is not applicable to this article.

Generalized Anxiety Disorder (GAD) and Panic Disorder (PD) share underlying neurobiological mechanisms and several clinical features which, with medical comorbidities, may increase misdiagnosis and delay proper treatment. The aim of the study was to evaluate the association between clinical/socio-demographic markers and GAD/PD diagnosis. Outpatients (N = 290) with PD or GAD were identified in mental health services in Monza and Milan (Italy). Descriptive analyses and a binary logistic regression model were performed. Post-onset psychiatric ( p = 0.05) and medical ( p = 0.02) multiple co-morbidities were associated with GAD; treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with PD, while GAD diagnosis was associated with treatment with atypical antipsychotics or GABAergic drugs ( p = 0.03), as well as psychodynamic psychotherapy ( p < 0.01). Discontinuation of the last pharmacological treatment was associated with GAD diagnosis rather than the PD one ( p = 0.02). GAD patients may have a worse prognosis than PD patients because of more frequent multiple co-morbidities, relapses and poorer treatment compliance. The different treatment approaches were consistent with the available literature, while the association between GAD and psychodynamic psychotherapy is an original finding of our study. Further studies on larger samples are necessary to better characterize clinical factors associated with GAD or PD.

1. Introduction

According to epidemiological surveys, anxiety disorders affect roughly one-third of the global population [ 1 ] in their lifetime and are the most common mental illnesses worldwide [ 2 ]. From an economic point of view, anxiety disorders are associated with immense health care costs as a result of medical assistance and social impairment including workday loss [ 3 ]. For instance, some authors have demonstrated that the work loss days for these conditions are higher than for common somatic diseases such as diabetes [ 4 ]. Anxiety disorders are characterized by high chronicity, which significantly affects quality of life as well as familiar, social and occupational functioning [ 2 ].

The group of anxiety disorders includes generalized anxiety disorder (GAD), panic disorder (PD), phobic disorders and two disorders that are commonly confined to childhood (separation anxiety disorder and selective mutism). GAD and PD are prevalent conditions with a 12-month prevalence of about 4% for the first condition and 2% for the second [ 1 , 5 ]. The diagnostic criteria of GAD and PD first appeared in 1980 with the publication of the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), where the previously defined anxiety neurosis was split into these two disorders [ 6 ]. The question of the clinical differences between GAD and PD has always been a topic of interest in the literature, supporting the diagnostic separation of these two disorders. According to DSM-5 criteria, the hallmark of GAD is an excessive, out-of-control anxiety and worry (apprehensive expectation) whilst PD is characterized by recurrent and unexpected panic attacks [ 7 ]. However, even though core symptoms of these two conditions are clearly defined, the comorbidity with mood disorders [ 4 ], the co-occurrence of medical conditions mimicking anxiety symptoms (e.g., thyroid diseases) [ 8 ] or even the presence of patients affected by both GAD and PD hamper correct diagnosis and can delay the prescription of proper treatment [ 1 , 9 , 10 ]. On the other hand, biomarkers could be helpful in differentiating anxiety disorders and predicting the clinical path of patients affected by these conditions, but research on this topic is very limited with regard to GAD and PD [ 11 ].

As mentioned above, GAD shares clinical features with PD (e.g., somatic manifestations of anxiety) and the available literature indicates high rates of comorbidity between the two conditions. More than 20% of patients with GAD would also be affected by PD [ 12 , 13 , 14 , 15 ]. Regarding neurobiology, both GAD and PD may be the result of dysfunction of specific brain areas such as the amygdala, albeit each of these disorders is clearly the result of complex gene–environment interactions [ 16 ].

On the other hand, differences in clinical predictors of prognosis were identified in patients affected by GAD compared to those with PD [ 17 ]. Individuals with GAD were reported to be older, have an earlier age at onset, longer duration of illness and more psychiatric comorbidity than the patients affected by PD [ 17 , 18 ]. In contrast, individuals with PD seem to be more prone to show substance use disorders compared to patients affected by GAD [ 17 , 18 ]. Despite these preliminary findings, the studies regarding the differences in the clinical path of the two disorders are limited in number [ 19 ], even though these data would be useful for personalized medicine and proper management of patients [ 10 , 20 ]. This aspect is complicated by the fact that most available treatments are labelled for both the conditions, without clear evidence of efficacy in one or the other disorder; this is the case, for example, with antidepressants or cognitive behavioral therapy (CBT) [ 21 , 22 ].

In the light of these considerations, the purpose of this study was to identify clinical/socio-demographic differences between GAD and PD and evaluate the association between statistically significant variables and GAD/PD diagnosis. We hypothesize that the identification of potential clinical predictors for GAD or PD may favor an early diagnostic process and may promote personalized medicine.

2. Materials and Methods

2.1. sample and study design.

This is an observational retrospective study. Outpatients suffering from PD or GAD were identified from medical records in the pre-pandemic period (2016–2019) at two mental health services—Fondazione IRCCS San Gerardo dei Tintori (Monza) and Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico (Milan). Study procedures were reviewed and approved by the local accredited Medical Ethics Review Committee (Area 2 Ethic Committee) of Fondazione IRCCS San Gerardo dei Tintori (Monza). The research project conformed to the provisions of the Declaration of Helsinki regarding medical research in humans in line with good clinical practice requirements.

Inclusion criteria were (1) age 18–65 years; (2) ability and willing to give informed consent; (3) fluency in Italian; (4) diagnosis of GAD or PD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorder, 5th edition [ 7 ]. Exclusion criteria were (1) intellectual disability; (2) lack of clinical and socio-demographic information; (3) patients treated for less than three months in the outpatient clinics for the impossibility of a comprehensive collection of clinical variables. In the case of psychiatric comorbidity (e.g., with unipolar depression), GAD or PD was the disorder that affected patients for a longer time and/or was responsible for more current severe symptoms or disability.

The following variables were collected: age, gender, occupation and marital status, age at onset, duration of illness, duration of untreated illness (DUI), family history of psychiatric disorders, multiple family history of psychiatric disorders (yes/no), pre-onset psychiatric comorbidity, pre- and post-onset psychiatric multiple co-morbidities (yes/no), presence and type of personality disorder, pre- and post-onset substance misuse, pre- and post-onset poly-substance misuse (yes/no), pre- and post-onset medical comorbidity, pre- and post-onset medical multiple co-morbidities (yes/no), suicide attempts (yes/no), hospitalizations (yes/no), the presence and type of obstetric complications, main type of pharmacological treatment, duration of treatment, poly-therapy (yes/no), side effects, presence of poly-side effects (yes/no), reason for discontinuation of therapy (rather than for long-term treatment effectiveness), the presence of lifetime psychotherapy (yes/no) and type of psychotherapy.

In the case of multiple visits, the last one was taken into account for the collection of data. DUI was considered as the time between the onset of GAD/PD and the prescription of a proper pharmacological/psychological treatment (labelled antidepressants, pregabalin for GAD, CBT) [ 9 , 23 ]. Suicide attempt was defined as self-harm combined with the intent to die. Self-harm without intent was not taken into account [ 24 ].

2.2. Statistical Analyses

Descriptive analyses on the total sample were performed. Continuous and qualitative variables were compared between the groups identified according to the diagnosis (GAD or PD) by multivariate analyses of variance (MANOVAs) and χ 2 tests, respectively. In the case of co-presence of GAD and PD (25 subjects), a patient was assigned to a group according to the current most severe disorder. A binary logistic regression model was then performed considering statistically significant factors from univariate analyses as independent variables and the GAD/PD diagnosis as a dependent one. The goodness of fit of the model was assessed by Omnibus and Hosmer–Lemeshow tests. The significance was set at p ≤ 0.05, and confidence intervals at 95% for odds ratios were calculated where applicable.

Statistical Package for Social Sciences (SPSS) for Windows (version 26.0) was used as the statistical program.

3.1. Descriptive Analyses and Diagnostic Group Comparisons

The total sample of patients (N = 290) included 105 males and 185 females; in total, 131 (45.2%) patients were affected by GAD and 159 (54.8%) by PD. The mean age of patients was 45.10 years (±15.39). Demographic and clinical data of the total sample and groups of patients identified by a diagnosis of GAD or PD are summarized in Table 1 .

Descriptive and univariate analyses: comparison between GAD and PD in terms of sociodemographic and clinical variables.

Legend: * vortioxetine; ⁰ trazodone, agomelatine, mirtazapine; ■ valproic acid or lithium; ** tachycardia, dizziness, headache, constipation, diarrhea; ⌂ patients who discontinued for long-term treatment effectiveness are included in this group; ● patients who had previously another main diagnosis; AD, antidepressant; ADHD, attention deficit hyperactivity disorder; AMI, acute myocardial infarction; BD, bipolar disorder; CBT, cognitive behavioral therapy; DUI, duration of untreated illness; GAD, generalized anxiety disorder; MDMA, methylenedioxymethamphetamine; NOS, not otherwise specified; OCD, obsessive compulsive disorder; OR, odds ratio (GAD/PD); PD, panic disorder; PTSD, post-traumatic stress disorder; SGA, second generation antipsychotic; SKZ, schizophrenia; SLD, specific learning disorder; SNRI, serotonin and noradrenalin reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. Mean (±standard deviation) for quantitative variables; frequencies (percentage) for qualitative variables. In bold statistically significant differences ( p < 0.05).

The two groups of patients were statistically different for age (F = 10.37, p < 0.01) and age at onset (F = 5.92, p = 0.02). GAD patients were older ( p < 0.01) and had a higher age at onset ( p = 0.02) than PD ones. Moreover, the two groups of patients showed significant differences in terms of pre-onset medical multiple co-morbidities (χ 2 = 6.05, OR = 0.47, p = 0.01) and post-onset psychiatric (χ 2 = 5.55, OR = 0.38, p = 0.02) and medical (χ 2 = 12.01, OR = 0.36, p < 0.01) multiple co-morbidities (PD < GAD).

Regarding psychopharmacological treatment, PD patients were more frequently treated with selective serotonin reuptake inhibitors (SSRIs) while GAD patients with second generation antipsychotics (SGAs) and GABAergic drugs (χ 2 = 19.09, p = 0.01). Furthermore, patients in the GAD group discontinued treatment more frequently for poor compliance or relapse compared to PD patients (χ 2 = 10.10, p = 0.01). Finally, GAD patients had received lifetime dynamic psychotherapy more frequently than PD ones (χ 2 = 8.13, p = 0.04). No other statistically significant differences were found between the two diagnoses ( Table 1 ).

3.2. Binary Logistic Regression Analysis

The goodness-of-fit test (Hosmer and Lemeshow Test: χ 2 = 2.89, p = 0.94) showed that the model including age, age at onset, the presence of post-onset psychiatric multiple co-morbidities, the presence of pre- and post-onset medical multiple co-morbidities, type of main pharmacological treatment, type of psychotherapy and reason for treatment discontinuation (rather than for long-term effectiveness) as independent variables and GAD/PD diagnosis as a dependent one was reliable, allowing for a correct classification of 65.0% of the cases. In addition, the model was overall significant (Omnibus test: χ 2 = 38.30, p < 0.01).

Post-onset psychiatric multiple co-morbidities ( p = 0.05), post-onset medical multiple co-morbidities ( p = 0.02) and discontinuation of treatment (rather than for long-term effectiveness) ( p = 0.02) were associated with GAD diagnosis. Moreover, SSRIs were more frequently prescribed in PD while SGAs or GABAergic drugs ( p = 0.03) in GAD. Psychodynamic psychotherapy ( p < 0.01) was more frequently administered in GAD versus PD patients ( Table 2 ).

Association between significant variables and GAD/PD diagnosis: logistic regression model analysis.

Legend: B, regression coefficient; C.I., confidence interval; df, degrees of freedom; NA, not applicable; OR, odds ratio; S.E., standard error. In bold statistically significant differences ( p < 0.05).

4. Discussion

In this naturalistic retrospective study, we investigated potential clinical and socio-demographic differences between GAD and PD in a sample of 290 outpatients. The present research produced three main results.

The first interesting finding is that patients with GAD were older and had a higher age at onset than those suffering from PD. This result appears consistent with most literature, which reports a later onset of GAD as compared with other anxiety disorders [ 25 ]. This observation is supported by the fact that while PD is characterized by a substantial acute autonomic hyperactivity, GAD patients would present a milder and chronic autonomic nervous system dysregulation [ 26 , 27 ].

Second, post-onset psychiatric and medical multiple co-morbidities were associated with GAD diagnosis, while pre-onset medical multiple co-morbidities were more frequent in GAD patients than PD ones only in the univariate analyses. Many medical conditions can precede the onset of GAD for a number of reasons and patterns of comorbidity between GAD and PD have already been distinguished [ 26 ]. Underlying biological mechanisms such as inflammatory over-reactivity can be shared by medical diseases and anxiety disorders as in the case of cardiovascular diseases [ 8 ]. In this regard, some authors demonstrated that both GAD and PD patients presented higher interleukin (IL)-6 than healthy subjects and that PD patients had higher IL-6 plasma levels than GAD ones [ 28 ]. Moreover, while pre-treatment IL-6 levels negatively correlated with treatment response in PD in one study [ 29 ], other authors demonstrated that higher IL-6 levels were related to a better response to escitalopram treatment in PD [ 28 ]. In addition, worries linked to the prognosis of medical conditions (e.g., cancer) can favor the onset of GAD in biologically predisposed subjects [ 30 ]. Finally, sub-threshold somatic anxiety concerning a specific organ/system may trigger medical conditions as happens for example for atopic dermatitis [ 31 ] or irritable bowel syndrome [ 32 ]. Similarly, chronic dysfunction in different biological systems coupled with an unhealthy lifestyle (e.g., unbalanced diet or absence of physical activity) may increase the risk of different medical conditions in GAD patients [ 33 , 34 ]. On the other hand, the resistance of patients with GAD to seeking medical help, and the consequent progressive social deterioration and biological alterations shared by affective disorders predispose to the development of comorbid psychiatric disorders, particularly unipolar depression.

Third, regarding psychopharmacological treatment, we found that PD patients were largely treated with SSRIs, while GAD patients with SGAs (in particular quetiapine) and GABAergic drugs. These results are in line with available literature [ 35 , 36 , 37 ] and reflect the fact that only 50% of patients affected by GAD respond to a first-line treatment with SSRIs or selective serotonin-noradrenalin reuptake inhibitors (SNRIs) [ 22 ]. This aspect implies that most subjects affected by GAD are treated with second-line options or combined treatments [ 38 ]. Furthermore, we found that GAD patients discontinued treatment more frequently than those affected by PD as a result of poor compliance and re-exacerbations in line with literature about the path of GAD [ 17 , 39 , 40 , 41 , 42 ]. Patients affected by anxiety disorders and particularly GAD frequently report a fear of pharmacotherapy side effects; so, the choice of a specific compound should take into account its tolerability profile and speed of action. These are essential elements to obtain a good adherence to medical prescriptions [ 43 , 44 ].

Finally, patients affected by GAD were more frequently treated with psychodynamic psychotherapy than subjects suffering from PD. Psychodynamic psychotherapy is an insight-oriented form of therapy that aims to resolve unconscious conflicts linked to early-life relationships by using techniques such as clarifications, interpretations and confrontations [ 45 ]. This result is an original finding since most of the available literature highlights the efficacy of CBT for anxiety disorders [ 35 , 45 , 46 , 47 ], although evidence of the effectiveness of intensive short-term dynamic psychotherapy is emerging [ 48 , 49 ]. There are only a few studies comparing CBT and other techniques in the literature, suggesting more effectiveness of the first approach in GAD patients [ 50 , 51 , 52 , 53 ]. In addition, some reports showed that combining medication with psychotherapy may be more effective for patients with moderate to severe anxiety disorders with respect to pharmacotherapy alone [ 35 , 54 ]. In our sample, the patients with GAD might have been more preferentially referred to psychotherapy, as a result of less response to pharmacotherapy, in comparison with patients affected by PD. Alternatively, patients suffering from GAD may have simply preferred the psychodynamic psychotherapy approach of all the available therapeutic options. A review underlined how people with mental disorders who received their preferred treatment may have lower dropout rates and a higher therapeutic alliance [ 55 ], in line with the recent notion of a multi-disciplinary approach for the management of mental disorders, including a combination of pharmacologic and behavioral strategies [ 56 ]. Another plausible hypothesis is that there is a need to face and potentially solve problems related to an insecure attachment. Childhood trauma and neglect are early life stressors potentially underlying the increased risk of developing GAD or PD [ 57 , 58 , 59 ]. Moreover, insecure attachment, as a consequence of adverse childhood experiences, is also associated with anxiety disorders, especially GAD and emotional dysregulation [ 60 ]. While angry-dismissive style was associated only with GAD onset during adulthood and attachment style was unrelated to the development of PD [ 61 ], more recently it has been demonstrated that higher levels of subscales reflecting maternal insecure avoidant attachment (e.g., no memory of early childhood experiences and balancing/forgiving current state of mind) were more predictive of GAD relative to PD during adulthood [ 18 ].

The study presents several limitations. One main aspect is missing the psychosocial factors that may play a role in the enteropathogenesis of both anxiety disorders. Other limits related to the retrospective naturalistic design of the study are that (1) the sample size was relatively small; (2) the data were collected in two hospitals from the same geographic area so that the findings of the present article cannot be totally representative of other contexts; (3) diagnoses of anxiety disorders were made by a team of various psychiatrists; (4) no specific rating scales were used to assess symptom severity and side effects of pharmacological treatments. Moreover, no subjective questionnaires regarding satisfaction or quality of life were provided to patients, as reported by other studies [ 62 ]. Finally, a large part of the data are based on self-report, increasing the risk of recall bias and skewed self-presentation.

5. Conclusions

This study investigated the clinical differences between GAD and PD to optimize the management of patients with anxiety disorders in a framework of precision medicine. Our results seem to suggest a worse prognosis in GAD versus PD patients. More frequent multiple co-morbidities and relapses as well as poor compliance to treatment are aspects that seem to characterize patients affected by GAD, with respect to those suffering from PD. Further studies on larger samples are necessary to confirm our findings and shed light on the clinical differences between GAD and PD to ameliorate clinical practice and patients’ prognosis.

Funding Statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

Conceptualization, A.C. and M.B.; methodology, A.C. and M.B.; validation, F.C., A.D. and M.C. (Massimo Clerici); formal analysis, A.C.; investigation, L.C., S.R., M.C. (Mauro Capettiand), S.L., A.T. and F.Z.Q.; resources, D.L.T. and T.S.; data curation, E.C., C.Q. and M.M.; writing—original draft preparation, A.C., L.C. and C.Q.; writing—review and editing, A.C., E.C. and M.B.; visualization, A.D.; supervision, M.B. and M.C. (Massimo Clerici); project administration, M.B. and F.C. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Fondazione IRCCS San Gerardo dei Tintori (Monza) (protocol code 3955, 07/04/2022).

Informed Consent Statement

Informed consent was obtained from all patients involved in the study.

Data Availability Statement

Conflicts of interest.

The authors declare no conflict of interest.

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