Resident Editor: Saundra Nguyen, M.D.

Faculty Editor: Emma Samelson-Jones, M.D.

BOTTOM LINE ✔ Psychiatric comorbidity is common in anxiety disorders. ✔ Psychotherapy combined with medications is the standard of care for most anxiety disorders ✔ Always rule out drugs (including caffeine) and medical issues as cause. ✔ Refer to psychiatry if: Suicidal or homicidal ideation; refractory symptoms; diagnostic uncertainty; need for multidisciplinary approach.

Background

• Anxiety is a normal and natural reaction to environmental stimuli (“fight or flight” response).
• Anxiety disorders occur when symptoms become excessive, persistent, and functionally impairing.
• Anxiety disorders are common. They are associated with worsened quality of life and loss of productivity as well as higher health care utilization and cost.

Signs and Symptoms:

• Typically manifest as 3 categories of symptoms: emotional (e.g., nervousness, fear), cognitive (e.g., worry, derealization), and physical (e.g., insomnia, tachycardia, muscle tension)
• See signs and symptoms of individual anxiety disorders below

Differential Diagnosis

• Substance use (caffeine, stimulant pills like Ritalin, cocaine, amphetamines) or withdrawal (alcohol, opiods, benzodiazepines)
• Medication Effects: including, but not limited to, corticosteroids, sympathomimetics, herbal medications
• Cardiopulmonary Disorders: ischemic heart disease, arrhythmias, CHF, asthma, COPD
• Endocrine Disorders: hyperthyroidism, hypocalcemia, pheochromocytoma, carcinoid, diabetes
• Other: anemia, menopausal or premenstrual symptoms, seizure disorders
• Psychiatric Disorders: depression, dysthymia, bipolar disorder, adjustment disorder, PTSD, OCD

Evaluation and Treatment

• Anxiety-related disorders can manifest in many different ways and include generalized anxiety disorder, panic disorder, specific phobias, agoraphobia, and social anxiety disorder. Trauma and Stressor-Related Disorders (e.g. PTSD, adjustment disorder) and Obsessive-Compulsive Disorders, which were previously categorized under anxiety disorders in DSM IV, now have their own separate classifications in DSM V.
• Specific screening/monitoring tools for anxiety-related disorders include the GAD-7 for generalized anxiety disorder, the 4-item primary care PTSD screen (PC-PSTD), the Panic Disorder Severity Scale (PDSS), and the Mini-Social Phobia Inventory for social anxiety disorder. Please see the corresponding sections below for more information.
• In general, anxiety disorders are marked by excessive fear and anxiety and are often associated with related behavioral disturbances (e.g. avoidance) and physical symptoms.
• Other key questions: How much does this get in the way of your life? What kinds of things do you avoid?
• Evaluate for co-morbid psychiatric conditions (e.g. depression). Screen for suicidality.
• Ask about alcohol and substance use.
• Assess physical symptoms and work up medical causes as appropriate
• Diagnosis of individual disorders is based on criteria list below.
• It is important to diagnose individual disorders as treatment and prognosis vary.

When to Refer

• Suicidal or homicidal thoughts
• Refractory symptoms or severe impairment
• Diagnostic uncertainty 
• Comorbid psychiatric disorders or substance abuse
• Need for multidisciplinary approach or specialized therapy (e.g., cognitive-behavioral therapy or desensitization therapy)

Generalized anxiety disorder (GAD)

A.  Signs and Symptoms:

Lifetime prevalence is about 5.7%. Prevalence in the primary care population is 7.6%. There is a 2:1 female predominance with onset frequently in adolescence/early adulthood, though GAD is common in late life. Tends to have a chronic, fluctuating course and often worsens under stress. Co-morbid psychiatric disorders, particularly depression, are common. Approximately 35% of people with GAD self-medicate with alcohol to reduce anxiety symptoms.

• The DSM-5 criteria for diagnosis of generalized anxiety disorder (GAD) are:
  • Excessive anxiety and worry occurring more days than not for at least 6 months about a number of events/activities.
  • The individual finds it difficult to control the worry
  • Anxiety and worry are associated with 3 or more of the following six symptoms:

Restlessness or feeling “keyed up” or “on edge”	Irritability
Easily fatigued	Muscle tension
Difficulty concentrating or going blank	Sleep disturbance

• Anxiety and worry causes significant distress and functional impairment (social life, work).
• Not due to direct effects of a drug or medical condition
• Not better explained by another psychiatric disorder, including:
  • Health anxiety disorder (formerly known as hypochondriasis): anxiety is tied to preoccupation of illness and disease
  • Obsessive-compulsive disorder: anxiety is tied to irrational beliefs (e.g. contamination) and associated with compulsions
  • Social anxiety: anxiety is tied to social situations and fear of judgment by others or embarrassment
  • Panic disorder: anxiety occurs in abrupt and transient episodes of fear and physical symptoms
  • PTSD: history of life-threatening trauma precedes onset of anxiety which is related to reminders of the traumatic event

B. Screening/Monitoring: The GAD-7 is a validated screening tool for generalized anxiety disorder in the primary care setting and can also be used to monitor disease severity over time. A score of 10+ has good sensitivity and specificity.

• Over the last two weeks, how often have you been bothered by the following problems?

1. Feeling nervous, anxious, or on edge
2. Not being able to stop or control worrying
3. Worrying too much about different things
4. Trouble relaxing
5. Being so restless that it is hard to sit still
6. Becoming easily annoyed or irritable
7. Feeling afraid as if something awful might happen

• Scoring 0-not at all, 1-several days, 2-more than half the days, 3-nearly every day. Add up the total score: 5 to 9 = mild anxiety; 10 to 14 = moderate anxiety; 15 to 21 = severe anxiety.

C. Treatment: Effective treatment of GAD utilizes medications, psychotherapy, or both, with insufficient evidence for one modality over another. Selection should depend on availability, patient preference, and severity. For patients who have no or partial response to initial treatment, practice guidelines recommend the combination of medications and psychotherapy.

• Medications
  • SSRIs and SNRIs are generally prescribed as first line treatments with response rates of 30-50%. No single agent has been shown to be superior to another and selection is based on patient preference, prior response, and side effect profile.
    • Similar to depression, start at low dose, uptitrate after 2-4 weeks. Try a second agent if no response within 6-8 weeks. If still no response, refer.
    • Continue for at least 12 months.
  • Pregabalin and buspirone can be used as second-line or adjunctive medications. Buspirone is nonsedating, but has only moderate efficacy compared to the SSRIs and does not have antidepressant properties. Buspirone also has slow onset of action similar to SSRIs.
  • Due to the potential for misuse, benzodiazepine use, if needed, should be short term to help stabilize patient (i.e., while awaiting effects of SSRI), then tapered off. A 4-week trial followed by 2-4 week taper is reasonable. For GAD, long-acting benzodiazepines (e.g. clonazepam) are more effective and prevent withdrawal anxiety compared to benzodiazepines with shorter half-lives. Long-term benzodiazepine use can be considered in treatment-resistant cases.
• Psychotherapy
  • First-line therapy is cognitive behavioral therapy (CBT), which usually consists of 12-20 weekly sessions involving education, exposure therapy, relaxation, and problem-solving techniques.
  • Other options include psychodynamic therapy, mindfulness-based therapy, and supportive therapy.  Self-help books or internet resources can be helpful.
• Lifestyle Modifications
  • Good sleep-hygiene practices

Panic Attacks and Panic Disorder 

A. Signs and Symptoms:

A panic attack is a discrete period of intense fear or discomfort with 4 or more symptoms (see below) peaking in minutes, with or without an identified trigger. About 12-15% of the population will have a panic attack in their lifetime.

Symptoms of a panic attack can include: tachycardia or palpitations, sweating, trembling or shaking, choking, SOB, chest pain or discomfort, nausea or abdominal pain, feeling dizzy, chills, hot flushes, paresthesias, feeling as if floating or detached, fear of losing control or “going crazy,” fear of dying.

• Most panic attacks resolve in 1 hour, sometimes with 1-2 residual symptoms lasting a day.
• Frequency and severity of symptoms vary, and panic attacks can be expected or unexpected.
• Having a panic attack does not necessarily equate with panic disorder, as attacks can occur in other anxiety disorders (specific phobia, PTSD, OCD) and even some medical conditions.
• They rarely occur in isolation (screen for psychiatric disorders and psychosocial stressors).
• Since somatic symptoms are common, patients often present to primary care and have high utilization.
• They can be triggered by somatic sensations associated with certain medical issues (cardiac, pulmonary, thyroid). Having a panic attack does not necessarily preclude a concurrent medical issue.

Panic disorder is when panic attacks lead to fear of future attacks. Prevalence is 2-4% in the general population, 6.8% in the primary care population; average onset age 25 years. DSM-5 defines panic disorder as recurrent unexpected panic attacks and at least 1 month of one or both of the following features:

• Persistent worry about additional panic attacks or their consequences (“going crazy”, “having a heart attack” “losing control”)
• Significant maladaptive change in behavior following the attacks (avoiding certain places or situations, changing behavior to prevent attacks)

B. Screening/Monitoring: The provider-administered Panic Disorder Severity Scale (PDSS) can be used to monitor treatment outcome and includes the questions below. The PDSS-SR version (self-report) can be used for screening.

• How many panic attacks did you have during the week?
• How distressing were they while they were happening?
• How much have you worried about when your next panic attack would occur?
• Were there any places or situations you avoided or felt afraid of because of the fear of having a panic attack?
• Were there any activities you avoided or felt afraid of because they might trigger or cause similar physical sensations that you feel during panic attacks?
• How did these symptoms interfere with your ability to carry out responsibilities at: a) home? b) your social life?

C. Treatment: Effective treatment for panic disorder combines medication and psychotherapy. Medications and CBT have similar effectiveness, although CBT may have a more durable response. Studies have shown a combination of medications and psychotherapy has a slight advantage over either modality alone.

• Cognitive behavioral therapy (CBT) is first-line and involves
  • Improving self-care (sleep hygiene, stress reduction)
  • Learning techniques to cope with panic (relaxation techniques, changing distorted thinking)
  • Exposure therapy to ultimately reduce panic response to external or somatic triggers

If resources are limited, group therapy or book- or internet-based CBT are accessible and effective. 

• Medications
  • 1st line medications are selective serotonin reuptake inhibitors. There is also evidence for venlafaxine.
  • Titration to initial target doses of SSRIs should be slow because these patients are sensitive to side effects (e.g., start with sertraline 12.5-25 mg, escitalopram 2.5-5 mg, increase incrementally q1-2weeks).
  • Benzodiazepine use, if needed, should be short term (to help stabilize patient while awaiting effects of SSRI, then tapered off) and used secondarily to coping methods (breathing into paper bag, relaxation techniques). Consider clonazepam (long-acting; use if able to anticipate situations that induce panic) 0.25 to 0.5 mg 1-2x/day or lorazepam (short-acting; use as rescue therapy during severe attacks) 0.5 mg 1-3x/day.

Specific Phobias and Social Anxiety Disorder

A. Signs and Symptoms:

Specific Phobia refers to an excessive fear of a specific situation or object that is out of proportion to the actual danger or threat. About 5-10% of the population have a specific phobia. Features are relationship of trigger to a marked fear response (including panic attacks), avoidance of triggers, functional impairment, and duration of 6 months or more.

• Common simple phobias include: animal type (ex: fear of spiders), situational type (ex: fear of bridges, airplanes), natural environment (ex: fear of heights, storms), blood-injection-injury type (often accompanied by vasovagal response). Agoraphobia (fear of situations where escape is difficult or embarrassing) is its own separate classification.
• Social Anxiety Disorder (previously social phobia) is defined in the DSM-V as a marked fear or anxiety about one or more social situations (e.g. having a conversation, being observed, performing) in which the person is exposed to possible scrutiny, embarrassment, or humiliation. The fear is out of proportion to the actual threat posed, and leads to anxiety about and avoidance of provoking situations. Typically lasts 6 months or more for diagnosis.
  • Under-recognized and under-treated, only 35% of people with social anxiety disorder receive treatment
  • Often mistaken for shyness – however, social anxiety disorder involves significant impairment in social, occupational, or other areas of functioning
  • Can be fear of many different kinds of social situations (generalized) or specific to speaking or performing in public only (specific or performance anxiety)
  • Prevalence in the U.S. population is up to 13%
  • Often have co-existing anxiety disorders, depression, substance-use, and mood disorders

B. Screening: The following questions can be used to screen for social anxiety disorder.

• Do you find yourself avoiding social situations or activities where you are the center of attention?
• Are you fearful or embarrassed in social situations?

C. Treatment

• For social anxiety disorder, either psychotherapy or medications are useful, with similar efficacy for short-term treatment. Treatment strategy is similar to GAD, with SSRIs or SNRIs and CBT as the first line pharmacologic and psychotherapy choices, respectively. ­
  • Pregabalin has also been shown to be superior to placebo though with response rates of only 30-43% compared to 20-22% for placebo.
• For predictable performance anxiety (e.g., public speaking, airplane ride), beta-blockers (propranolol 10-40 mg) 30 minutes to an hour prior to event can reduce autonomic symptoms (e.g. tachycardia, tremor, sweating) that contribute to anxiety.
  • Cautious use of benzodiazepines is also reasonable for very occasional use though they may cause sedation.
• For other simple phobias: First-line treatment is exposure therapy where patient is desensitized to the fear stimulus. If the stimulus is encountered frequently, can treat similarly to generalized social anxiety disorder as above with SSRI/SNRI.

Trauma- and Stressor-Related Disorders

A. Signs and Symptoms:

In DSM-5, trauma and stressor-related disorder is a category of illness that includes acute stress disorder, adjustment disorders, and posttraumatic stress disorder (PTSD). For acute stress disorder and PTSD, the qualifying traumatic event may be experienced directly, witnessed, or experienced indirectly.

Although 50-60% of people experience trauma in a lifetime, the prevalence of PTSD in the U.S. is around 6.7%. The probability that PTSD will develop depends on the sex of the patient and the type of trauma: 65% of men and 45% of women after rape, 2% of men and 22% of women after physical assault, 6% of men and 9% of women after an accident.

Substance abuse, sleep disturbance, mood disorders, anxiety, dissociated states, and depression often co-occur.

•  DSM-5 defines PTSD according to criteria that must all be present for ≥1 month:
  • Exposure to actual or threatened death, serious injury, or sexual violence
  • Avoidance of stimuli associated with the traumatic event
  • Persistent negative changes to mood and cognition, including numbing
  • Alterations in arousal and reactivity, including symptoms such as anxiety, hypervigilence, restless sleep, irritable or aggressive behavior, or self-destructive behavior
  • Intrusive thoughts of the traumatic event, such as nightmares or re-experiencing of the event.

B. Screening/Monitoring: The 5-item Primary Care PTSD Screen (PC-PTSD-5) is a DSM-V update to the validated PC-PTSD, which can be used for screening for PTSD (questions listed below). The 17-item PTSD Checklist (PCL5) can be used to quantify severity and monitor response to treatment.

• In the past month, have you…
  • Had nightmares or thoughts about the events when you did not want to?
  • Tried hard not to think about events or went out of your way to avoid situations that reminded you of the event?
  • Been constantly on guard, watchful, or easily startled?
  • Felt numb or detached from people, activities, or your surroundings?
  • Felt guilty or unable to stop blaming yourself or others from the event(s) or any problems the events may have caused?
• A positive screen is considered if the patient responds yes to at least 3 of the 5 questions.

C. Treatment: A combination of psychotherapy, medication, and psychosocial intervention is the standard.

• Trauma-focused CBT or exposure therapy is recommended as first-line treatment. Group therapy for PTSD from similar traumas (e.g., sexual assault, combat-related) or couples CBT have also been shown to work.
• Refer for long-term psychiatric care with multidisciplinary approach, including psychiatrist, social worker, psychologist, etc. Encourage military veterans to seek VA care.
• Choose medications to target and manage anxiety, depression, and insomnia. First-line medication for PTSD is SSRI (sertraline and paroxetine are FDA-approved). Prazosin (start at 1 mg, increase in 1 mg increments until efficacious or side effects limit further titration) can be very effective for PTSD-related nightmares and nighttime hyperarousal.

Obsessive-Compulsive and Related Disorders

A. Signs and Symptoms:

In DSM-5, obsessive-compulsive and related disorders are a category of illness that includes OCD, hoarding disorder, excoriation (skin-picking) disorder, trichotillomania (hair-picking), and body dysmorphic disorder.

Definition: obsessions (intrusive thoughts or urges, worries, anxiety-provoking fears, superstitions) and/or compulsions (rituals or repetitive behavior or mental acts, e.g. handwashing, repeated checking, hoarding) that take up at least 1 hour each day, cause marked distress or functional impairment.

• The person’s insight into their symptoms as excessive or unrealistic can range from good/fair to poor to absent insight/delusional.
• It is commonly misdiagnosed as anxiety or depression which can delay appropriate therapy.
• Only 1/3 of patients with OCD receive appropriate pharmacotherapy and <10% receive evidence-based psychotherapy.

B. Screening Questions

• Some people are bothered by intrusive thoughts that keep repeating over and over. For example, that a loved one has been seriously hurt or they are contaminated by germs. Have you experienced anything like this?
• Some people are bothered by doing certain rituals over and over, like washing their hands or checking locks or the stove or counting things excessively. Has anything like that been a problem for you?

C. Treatment: First-line treatments include exposure-and-response-prevention therapy (exposure to fear-eliciting stimuli in a progressive manner with abstinence from compulsive behaviors) or cognitive therapy combined with SSRIs. SSRIs are often at higher doses than those used to treat anxiety or depression (e.g. sertraline 200-400 mg) and a longer time needed for response (8-12 weeks). If no response, then switch SSRI or to clomipramine (a TCA, which is equally as efficacious but has more side effects). Medications should be continued for at least 1-2 years followed by taper. However, relapse rates are high and medications are generally restarted and continued indefinitely.

Self-help workbooks/bibliotherapy

Anxiety and Phobia Workbook, by E. Bourne

Stop Obsessing, by E. Foa

Overcoming Panic Disorder and Agoraphobia-Client Manual, by McKay & Zuercher-White

Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness, by Jon Kabat-Zinn

Reinventing Your Life: The Breakthrough Program to End Negative Behavior…and Feel Great Again, by Jeffrey E. Young, PhD and Janet S. Klosko, PhD

Mastery of Your Anxiety and Worry: Workbook (Treatments that Work), by Michelle G. Crasky and David H. Barlowe

Websites

Anxiety Disorders Association of America http://www.adaa.org/

The Anxiety and Phobia Internet Resource (TAPIR) http://www.algy.com/anxiety/

eCouch http://ecouch.anu.edu.au/new_users/welcome01 This site is related to MoodGym

References

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Cole ., Christensen JF, Cole MR et al.. Depression. Behavioral Medicine: A guide for clinical practice. Feldman MD, Christensen JF, ed. McGraw-Hill. 2008. 199-226

Grant JE. Clinical practice: obsessive-compulsive disorder. N Engl J Med. 2014;371(7):646-653.

Kroenke K et al.  Anxiety Disorders in Primary care: Prevalence, Impairment, Comorbidity, and Detection. Ann Intern Med. 2007;146:317-325.

Leichsenring, F., & Leweke, F. (2017). Social anxiety disorder. New England Journal of Medicine, 376, 2255–2264.

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