Differentials
Panic disorder
SIGNS / SYMPTOMS
Characterized by recurrent unexpected panic attacks over a 1-month period. People with panic disorder are persistently concerned about having another panic attack, and/or about the consequences of this (e.g., having a heart attack or losing control). People with panic disorder may also change their behavior in an attempt to avoid having more panic attacks (e.g., avoiding situations that may trigger the panic sensations; engaging in various safety-related behaviors). In panic disorder, the autonomic complaints are experienced simultaneously during an acute attack without the predominant picture of multi-themed worry.[1]
Panic attacks are not necessarily pathognomonic of panic disorder, and may occur in association with other mental health disorders, including GAD. Panic disorder may also co-exist with GAD.
INVESTIGATIONS
Meets Diagnostic and Statistical Manual of mental disorders, fifth edition, text revision (DSM-5-TR) or International Classification of Diseases 11th Revision (ICD-11) criteria for panic disorder.
Social anxiety disorder
Obsessive-compulsive disorder
SIGNS / SYMPTOMS
Anxiety is directly related to compulsions or obsessions.
INVESTIGATIONS
Meets DSM-5-TR or ICD-11 criteria for obsessive-compulsive disorder.
Post-traumatic stress disorder
SIGNS / SYMPTOMS
Anxiety is directly related to exposure to reminders of past trauma; patients re-experience symptoms (through flashbacks, nightmares).
At times this is very hard to differentiate, and GAD is best considered as a co-occurring problem.
INVESTIGATIONS
Meets DSM-5-TR or ICD-11 criteria for PTSD.
Somatic symptom and related disorders
SIGNS / SYMPTOMS
Patients may experience distressing physical symptoms associated with maladaptive thoughts, feelings, and behaviors in response to these symptoms. Examples include functional neurologic disorder (FND) and somatic symptom disorder. Medical evaluation shows no basis for physical complaints in somatic symptom disorder. FND can be diagnosed on the basis of positive "rule in" features on neurologic examination, confirming a functional cause of symptoms. Some patients will have had adverse life events, but, importantly, these are neither necessary nor sufficient for the diagnosis.[60] Psychological comorbidities - especially anxiety, panic, and depression - are common, affecting over 50% of patients with FND.[61]
INVESTIGATIONS
Meets DSM-5-TR criteria for somatic symptom and related disorders, or ICD-11 criteria for bodily distress disorder.
Depression
SIGNS / SYMPTOMS
Inability to feel pleasure with an overall sad or irritable mood.[1][52] Major depressive disorder is frequently accompanied by anxiety symptoms. This dual presentation may reflect true comorbidity (i.e., co-occurrence of depression with GAD) or may occur in depression with anxious distress (sometimes termed "anxious depression").[1]
INVESTIGATIONS
Meets DSM-5-TR or ICD-11 criteria for a depressive disorder.
Substance- or drug-induced anxiety disorder
SIGNS / SYMPTOMS
Anxiety is directly related to substance (e.g., caffeine, toxin, alcohol, illicit drug), drug (e.g., albuterol, theophylline, corticosteroid, antidepressant), or herbal medicine (e.g., ma huang, St. John's wort, ginseng, guarana, belladonna) exposure.
Thorough history of prescribed and over-the-counter medications and herbal medicines should be obtained.[52]
A history of illicit drug use, herbal supplement use, caffeine use, and alcohol use should also be obtained.
INVESTIGATIONS
Urine and/or plasma drug screening may be indicated and may identify substance misuse, such as intoxication with stimulants or withdrawal from alcohol or benzodiazepines. May miss cocaine, which is rapidly metabolized and excreted.
Urine drug screen for antidepressants may detect prescribed medications or those taken in overdose.
Serum theophylline level may be elevated above the therapeutic range.
No differentiating tests exist for other substances or drugs.
Central nervous system-depressant withdrawal
SIGNS / SYMPTOMS
Anxiety may occur during withdrawal of a substance (e.g., alcohol, opioids, sedative-hypnotics), with characteristic symptoms such as shakiness (i.e., rapid heart rate, fluctuating blood pressure).
Typical signs are tachypnea, tachycardia, and disorientation.
INVESTIGATIONS
Monitoring of vital signs is essential to detect autonomic instability and sometimes delirium
Situational anxiety (nonpathologic)
SIGNS / SYMPTOMS
Anxiety is more controllable and less pervasive (limited to one situation or context, such as an upcoming examination).
Situational worries are less likely to be accompanied by physical symptoms.[1]
Restlessness, fatigue, and other physical symptoms are rarely present.
INVESTIGATIONS
No differentiating tests exist.
Adjustment disorder
SIGNS / SYMPTOMS
Anxiety occurs temporarily in response to a life stressor and does not persist for more than 6 months after the stressor ends.
INVESTIGATIONS
Meets DSM-5-TR or ICD-11 criteria for adjustment disorder. Full criteria for GAD are not met.
Cardiac disease
SIGNS / SYMPTOMS
Anxiety symptoms are predominantly cardiac in nature (i.e., palpitations, sensation of rapid heartbeat or skipped heartbeat, dizziness, dyspnea on exertion, chest pain, and numbness).
Chest pain is typically exertional.
Cardiac risk factors may be present.
Physical examination may be normal or show hypertension, hypotension, tachycardia or bradycardia, or S3 or S4 gallops.
INVESTIGATIONS
Imaging studies such as angiogram, echocardiogram, exercise stress test, or ECG ± cardiac markers rule out cardiac disease.
Pulmonary conditions
SIGNS / SYMPTOMS
There may be a history of pulmonary disease such as asthma or COPD, or signs/symptoms such as wheezing, cough, respiratory distress, or sputum production.
Patients may specifically have a feeling of suffocation accompanied by physical signs.
INVESTIGATIONS
Pulmonary function tests (or less commonly bronchoscopy) rule out primary lung pathology.
Pulse oximetry shows low oxygen saturation.
Hyperthyroidism
SIGNS / SYMPTOMS
Often accompanied by anxiety symptoms. Differentiating features include weight loss, warm moist skin, heat intolerance, ophthalmopathy, or goiter.
INVESTIGATIONS
Thyroid function tests (increased thyroxine, decreased thyroid-stimulating hormone) can identify primary hyperthyroidism or use of excessive thyroid hormone.
Infections
SIGNS / SYMPTOMS
Anxiety limited to the time period of the infection.
Other symptoms include fever, night sweats, or cough.
INVESTIGATIONS
Viral antibody titers, blood cultures, and acid-fast bacillus test of sputum can assess possible infectious causes.
Successful treatment of infection should result in resolution of symptoms.
Peptic ulcer disease
SIGNS / SYMPTOMS
Typically, burning epigastric pain that occurs hours after meals or with hunger, relieved by food or antacids.
It may be difficult to distinguish gastrointestinal symptoms as a cause versus a result of anxiety.
INVESTIGATIONS
Upper gastrointestinal endoscopy detects peptic ulcer and possibly presence of Helicobacter pylori.
Crohn disease
SIGNS / SYMPTOMS
Chronic diarrhea, weight loss, and right lower quadrant abdominal pain mimicking acute appendicitis.
Perianal lesions including skin tags, fistulae, abscesses, scarring, or sinuses.
It may be difficult to distinguish gastrointestinal symptoms as a cause versus a result of anxiety.
INVESTIGATIONS
Colonoscopy shows aphthous ulcers, hyperemia, edema, cobblestoning, or skip lesions.
Irritable bowel syndrome
SIGNS / SYMPTOMS
Alteration of bowel habits associated with pain, and abdominal discomfort, bloating, or distention.
It may be difficult to distinguish gastrointestinal symptoms as a cause versus a result of anxiety.
INVESTIGATIONS
No differentiating tests. Diagnosis is clinical and investigations are only performed to exclude other causes.
Pheochromocytoma
SIGNS / SYMPTOMS
Diaphoresis, headache, pallor, palpitations, and paroxysmal hypertension may accompany anxiety. Episodes resemble panic attacks. May be family history of pheochromocytoma.
This condition is very rare and should only be considered if there is demonstrable hypertension.
INVESTIGATIONS
Diagnosed by increased levels of urine and serum catecholamines, metanephrines, and normetanephrines.
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