Generalized Anxiety Disorder

Terminology

Clinical Clarification

• Generalized anxiety disorder is a common illness characterized by excessive anxiety and worry about a number of events or activities, which is out of proportion in intensity, duration, or frequency to the actual likelihood or impact of the anticipated event ^[1][7]

  • 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 ^[1]

Diagnosis

Clinical Presentation

History

• Hallmark of generalized anxiety disorder is excessive worrying and apprehensive expectation of a wide range of normal events and activities, such as: ^[1]

  • Work or school responsibilities and interactions

  • Family health and finances

  • In children, worry about competence or quality of their performance

• Common psychological symptoms related to generalized anxiety disorder include: ^[8]

  • Being nervous and unable to relax, with poor or disturbed sleep ^[1]

  • Worrying about trivial or minor matters, with no control over worrying

  • Extreme restlessness and inability to concentrate ^[1]

  • Irritability

  • 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) ^[7]

  • Sensation of losing control, “going crazy,” or passing out ^[7]

  • Fear of death ^[7]

• Muscle tension and fatigability are highly correlated with generalized anxiety disorder ^[1]

• Common physical symptoms related to anxiety include the following, ranked in order of clinical significance: ^[9]

  • Palpitations

  • Dyspepsia or abdominal discomfort

  • Dizziness

  • Unsteady gait

  • Dyspnea

  • Feeling hot and/or experiencing diaphoresis, regardless of ambient temperature

  • Feeling faint, hands trembling, and face flushing

  • Paresthesia marked by numbness and tingling

  • Choking sensation

• Other common physical symptoms include: ^[1]

  • Nausea

  • Diarrhea

  • Cold extremities

  • Xerostomia

  • Bruxism

  • Headache

• Symptoms are typically more severe in younger adults ^[1]

Physical examination

• Signs related to general emotional well-being include nervousness, irritability, and heightened vigilance ^[1]

• Physical signs include: ^[1]

  • Visible tremor

  • Cold hands

  • Tachycardia

  • Tachypnea

Causes and Risk Factors

Causes

• Exact cause is unknown

  • Onset of pure generalized anxiety disorder is often associated with stress arising from emotional loss and dangerous situations ^[10]

    • Includes loss of a close relative or long-term separation from a partner

  • Childhood adversity has a 32.4% association with anxiety disorders ^[11]

Risk factors and/or associations

Age

• Increasing prevalence with age, peaking in middle age ^[1]

  • Onset of symptoms after the age of 35 years is suggestive of generalized anxiety disorder ^[12]

  • Onset rarely occurs before adolescence; prevalence in the adolescent population is 0.9% in the United States ^[1]

  • Prevalence among adults (2.9% in the United States) is 3 times greater than in adolescents ^[12]

  • Prevalence in adults 75 years and older is 2.8% to 3.1% ^[1]

Sex

• Twice as common in female individuals as in male individuals ^[13][14]

Genetics

• Twin studies have demonstrated that there is a moderate genetic risk of generalized anxiety disorder, estimated to be between 15% and 20%, but may be as high as one-third ^[4][1]

Ethnicity/race

• White populations are more likely to be affected than those of African, Asian, or Hispanic ethnicity ^[15]

Other risk factors/associations

• Substance use disorders

  • 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 ^[16]

  • It is estimated that 35% of patients with generalized anxiety disorder use alcohol and/or other drugs to relieve symptoms ^[4]

• Coexisting anxiety disorders ^[5]

  • Social phobia is the most prevalent (16%-59%), followed by phobias of other types (eg, specific places, situations, or objects; 16%-46%)

• Patients from developed countries are more likely to experience generalized anxiety disorder ^[1]

• Behavioral inhibition and neuroticism are associated with generalized anxiety disorder ^[1]

Diagnostic Procedures

Primary diagnostic tools

• Diagnosis is based on patient history and physical examination findings; DSM-5-TR criteria must be met for a diagnosis of generalized anxiety disorder ^[1]

  • Excessive use of alcohol, caffeine, or other stimulants must be ruled out as a cause of symptoms

• GAD-7 scale and Beck Anxiety Inventory are useful screening instruments that can aid clinicians in achieving a diagnosis^[8][9]

  • GAD-7 assesses symptoms over the past 2 weeks instead of 6 months (per DSM-5-TR ) using 7 criteria, operating on the assumption that severe symptoms are typically chronic ^[1][8]

  • Beck Anxiety Inventory contains 21 items comprising somatic, affective, and cognitive symptoms related specifically to anxiety disorders ^[9]

Functional testing

• GAD-7 ^[8]

  • Consists of 7 criteria, namely:

    • 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

  • Subjects rate how often they have been bothered by each symptom in the last 2 weeks, with responses being 0 (not at all), 1 (several days), 2 (more than half the days), and 3 (nearly every day); total score ranges from 0 to 21

    • Threshold score of 8 maximizes sensitivity and 15 maximizes specificity ^[8]

    • Threshold of 10 is optimal for high sensitivity and specificity ^[8]

  • Interpretation ^[18]

    • 10: moderate anxiety

    • 15: severe anxiety

• Beck Anxiety Inventory ^[9]

  • Comprises 21 criteria, specifically:

    • Numbness or tingling

    • Feeling hot

    • Wobbliness in legs

    • Unable to relax

    • Fear of the worst happening

    • Dizzy or lightheaded

    • Heart pounding or racing

    • Unsteady

    • Terrified

    • Nervous

    • Feelings of choking

    • Hands trembling

    • Shaky

    • Fear of losing control

    • Difficulty breathing

    • Fear of dying

    • Scared

    • Indigestion or discomfort in abdomen

    • Faint

    • 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

  • Interpretation ^[19]

    • 0 to 9: normal

    • 10 to 18: mild to moderate anxiety

    • 19 to 29: moderate to severe anxiety

    • 30 to 63: severe anxiety

Procedures

Differential Diagnosis

Most common

• Anxiety due to thyroid disorder

  • Characterized by unusually high or low levels of thyroxine due to dysfunction or removal of thyroid gland^[20][21]

  • Anxiety and/or depression symptoms (eg, being more irritable, sad, emotionally sensitive, or anxious) ^[22]

  • Differentiating features are as follows: ^[23]

    • Hypothyroidism can present with fatigue, dry skin, constipation, vocal changes, and prolonged ankle jerk reflex ^[23]

    • Hyperthyroidism can present with hypertension, tachycardia, warm and moist skin, and brisk ankle jerk reflex ^[20]

  • DSM-5- TR diagnostic criteria:

    • 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

  • Diagnosis can be confirmed by the following laboratory findings:

    • Hypothyroidism

      • TSH level is elevated to more than 10 mIU/L in primary hypothyroidism ^[21][24]

      • Low serum levels of total or free thyroxine ^[22]

    • Hyperthyroidism

      • TSH level is suppressed ^[20]

      • High serum levels of total or free thyroxine

• Illness anxiety disorder ^[25][26]

  • 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

  • Diagnosis can be confirmed by DSM-5-TR criteria:

    • Preoccupation with having or acquiring a serious illness for at least 6 months

    • Frequent visits to the clinic or maladaptive avoidance of medical attention

• Social anxiety disorder (social phobia) ^[27][28]

  • 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

  • Anxiety is specific to social situations

    • Characterized by early onset; typically appears by age 11 years in 50% of patients and age 20 years in 80% of patients ^[27]

  • Diagnosis can be confirmed by DSM-5-TR criteria:

    • 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

• Panic disorder ^[29]

  • 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

  • Intense fear or discomfort of an attack reaches its peak within minutes, unlike the constantly elevated anxiety of generalized anxiety disorder

    • History of childhood trauma or abuse is more likely in patients with panic disorder than in those with generalized anxiety disorder

  • Diagnosis can be confirmed by DSM-5-TR criteria:

    • 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

• Major depressive disorder ^[30][31]

  • 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

  • Diagnosis can be confirmed by DSM-5-TR criteria:

    • Depressed mood for most days over 2 weeks along with at least 2 characteristic symptoms

      • Anhedonia

      • Change in weight or appetite

      • Insomnia or hypersomnia

      • Psychomotor agitation or retardation

      • Fatigue

      • Feelings of worthlessness or inappropriate guilt

      • Diminished ability to concentrate or indecisiveness

      • Suicidal ideation or attempt

• Obsessive-compulsive disorder ^[32]

  • 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

  • Differentiated by repetitive rituals and behaviors (eg, hand-washing, mental acts of ordering or checking) performed to alleviate anxiety

    • Anxiety relates more to imagined or fantastic events

  • Diagnosis can be confirmed by DSM-5-TR criteria:

    • 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

• Posttraumatic stress disorder ^[33]

  • 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

  • Diagnosis can be confirmed by DSM-5-TR criteria:

    • Adults and children older than 6 years

      • Traumatic experience (eg, grave injury, sexual violence, threat of death) or such an event affecting a close friend or relative

        • 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

      • Patient suffers from clinically significant impairment in an occupational or social setting

    • Children younger than 6 years, specific criteria include:

      • 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)

• Drug withdrawal ^[34]

  • Withdrawal symptoms caused by cessation of sedative use (eg, alcohol, benzodiazepines) or opioid use

    • Initial symptoms and signs of withdrawal include heightened anxiety, as well as irritability, nausea, agitation, diaphoresis, and tachycardia from sedative or opioid use

  • Short-term episodic nature of anxiety symptoms, compared to the chronic nature of generalized anxiety disorder symptoms

    • In case of withdrawal from benzodiazepines, signs and symptoms begin 2 to 10 days after last use ^[34]

    • Alcohol withdrawal may be accompanied by seizures and delirium; symptoms typically peak 72 hours after the last ingestion of alcohol (without medication) ^[34]

    • 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) ^[35]

  • Diagnosis can be confirmed by patient history and observation

• Substance intoxication ^[1]

  • 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

Treatment

Goals

• 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) ^[12]

Treatment Options

Owing to the chronicity of generalized anxiety disorder, long-term therapy is anticipated ^[1]

• 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 ^[36][37]

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 ^[7]

• Cognitive behavioral therapy is the treatment of choice, with proven efficacy in reducing anxiety symptoms in the short term ^[38][39][40]

  • Best choice of treatment at diagnosis, at 6-month follow-up, and for relapse ^[7]

  • Group format may be preferred treatment in children and adolescents ^[41]

• Pharmacologic treatment may be given in conjunction with psychotherapy ^[4]

However, drug treatment is commonly prescribed in the primary care setting in the United States because of better resource availability and patient preference ^[7][17]

• Antidepressants (selective serotonin reuptake inhibitors [eg, paroxetine, escitalopram, sertraline]; serotonin-norepinephrine reuptake inhibitors [eg, venlafaxine, duloxetine]) are considered first line agents for adults and children ^[42]

  • 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 ^[7][38]

  • Withdrawal effects may occur after drug regimen is complete; gradual dose tapering is recommended

• Second line agents in adults include buspirone, second-generation antipsychotics (eg, quetiapine), benzodiazepines, and anticonvulsants (eg, pregabalin) ^[42]

  • Buspirone typically acts within 72 hours, followed by a mild dysphoric adverse effect; does not lead to dependence ^[7]

    • Do not use as monotherapy when depression is concurrent with anxiety ^[12]

  • Benzodiazepines (eg, diazepam, lorazepam) alleviate anxiety symptoms in the short term, and have a noticeable effect in 15 to 60 minutes, although they are associated with a greater risk of dependence after long-term use ^[7]

    • Not recommended routinely owing to potential for misuse; if used, short-term use (3-6 months) is recommended ^[42][43]

    • More likely to lead to requests for long-term prescription than antidepressants

    • Stronger anxiolytic effect in the first 2 weeks of drug treatment ^[7]

    • 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 ^[7]

• In refractory cases that do not significantly improve with first line drugs, augmentation with other drugs has demonstrated some success ^[7]

  • Drugs used in combination with antidepressants have included olanzapine, risperidone, trifluoperazine, and pregabalin ^[44][7][45]

  • 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 ^[46]

Drug therapy

• Selective serotonin reuptake inhibitors

  • Escitalopram ^[7]

    • 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

    • 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

    • 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.

• Serotonin-norepinephrine reuptake inhibitors

  • Duloxetine

    • 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 ^[7]

    • 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.

• Benzodiazepines ^[7]

  • Alprazolam

    • 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

    • 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

    • 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.

• Azapirones

  • Buspirone ^[47]

    • 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

• Direct all patients and their families to self-help internet sites for education on generalized anxiety disorder (eg, Anxiety and Depression Association of America ) ^[49][48]

  • Educate patients on lifestyle changes that may help reduce symptoms

    • Improving quality and quantity of sleep

    • Regular exercise

      • Exercise has been shown to have significant ability to reduce anxiety symptoms and is encouraged ^[50][51]

    • Minimizing caffeine and alcohol intake

    • Avoiding nicotine and other drugs

• Psychotherapy

  • Cognitive behavioral therapy

    • Multiple types of psychotherapy have been applied to the treatment of generalized anxiety disorder, with evidence strongest for the efficacy of cognitive behavioral therapy ^[4]

    • 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 ^[7]

    • Brief description: ^[52]

      • 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 ^[52]

Comorbidities

• Major depressive disorder is the most common coexisting psychiatric illness in patients with generalized anxiety disorder, coexisting in nearly two-thirds of cases ^[12]

  • Occurs more often in female individuals than in male individuals ^[1]

  • Combination of these disorders is termed cothymia ^[7]

  • Antidepressants are the preferred drug treatment, in combination with cognitive behavioral therapy

• Panic disorder ^[7]

  • Occurs in 25% to 50% of patients with generalized anxiety disorder ^[5][12]

  • 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 ^[53]

Special populations

• Children

  • Preferably, treat with cognitive behavioral therapy; medications such as antidepressants are often avoided over concern for adverse effects ^[7]

    • However, the combination of cognitive behavioral therapy and sertraline has demonstrated efficacy in children between the ages of 7 and 17 years ^[54]

• Pregnant patients

  • In the perinatal period, generalized anxiety may be exacerbated, requiring pharmacotherapy in addition to psychotherapy ^[12]

    • Prescribe half the usual drug dose (typically buspirone) for pregnant patients. ^[12]

    • 1 of the goals of therapy in these patients is to prevent premature birth or miscarriage due to anxiety

Monitoring

• When initiating drug therapy, see patients every 2 to 4 weeks; frequency is decreased to every 3 to 4 months during maintenance therapy ^[12]

  • If medication is effective, continue course for 6 to 12 months and then slowly taper off ^[3]

• After taper, 6-month follow-up is necessary ^[7]

  • Optional continued follow-up every 6 months for a period of 5 years or longer is recommended since rates of relapse are high ^[3]

Complications and Prognosis

Complications

• Generalized anxiety disorder affects quality of life ^[55]

  • 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

• Patients have increased odds of 2.32 for suicidal ideation and an odds ratio of 3.64 for suicide attempts, as demonstrated by longitudinal analysis ^[6]

  • Increased risk for suicidal ideation does not predict death by suicide ^[56]

Prognosis

• Most patients are susceptible to a relapse 6 to 12 years after initial diagnosis ^[2]

  • Patients who improve the most initially also have the best long-term outcome ^[7]

• Rate of full remission is 27% at 3 years and 38% at 5 years postdiagnosis ^[3]

• Rates of partial remission are 37% at 3 years and 47% at 5 years postdiagnosis ^[3]

Screening and Prevention

Screening

Screening tests

• Women's Preventive Services Initiative guidelines recommend screening for anxiety in adult and adolescent female patients aged 13 years or older, including pregnant and postpartum patients ^[57][58]

  • Use clinical judgment to determine frequency of screening

• Appropriate screening instruments include: ^[58][59]

  • Beck Anxiety Inventory

  • GAD-7 (Generalized Anxiety Disorder Scale)

  • K-10 (Kessler Psychological Distress Scale)

  • PHQ-9 (Patient Health Questionnaire)

  • GAD-2, PHQ-2, K-6 (abbreviated versions of the above scales)

  • SCARES (Screen for Child Anxiety Related Emotional disorders Scale)

  • HADS (Hospital Anxiety and Depression Scale)

  • Edinburgh Postnatal Depression Scale

  • Bright Futures Pediatric Symptom Checklist–Youth Report in adolescent and young adult female patients