Generalized anxiety disorder differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2] Irfan Dotani

Overview

The differential diagnosis in generalized anxiety disorder is similar to that of panic disorder. It is important to rule out drug-induced conditions. The mental status examination should take in consideration the possibility of schizophrenia, obsessive-compulsive disorder, major depressive disorder, and both specific and social phobias.

Differential Diagnosis

• Adjustment disorder
• Anxiety disorder due to another medical condition

• Pheochromocytoma
• Hyperthyroidism

• Bipolar disorder
• Panic disorder- anxiety is only in regards to having a panic attack
• Post-traumatic stress disorder- presence of flashbacks, hyper-arousal, and hyper-vigilance
• Social phobia- anxiety only occurs in regards to social situations
• Obsessive-compulsive disorder- presence of obsessions and compulsions
• Separation anxiety disorder- anxiety occurs in response to being away from home or family
• Anorexia nervosa- anxiety occurs in response to potentially gaining weight
• Somatization disorder- multiple physical complaints
• Hypochondriasis- anxiety in regards to developing a specific disease
• Schizophrenia- presence of psychotic symptoms such as hallucinations and delusions
• Major depressive disorder- criteria requires two weeks of specific symptoms
• Medications- in particular stimulants such as methylphenidate, pseudoephedrine, and other decongestants or appetite suppressants
• Drug abuse- particularly stimulants and hallucinogenics such as cocaine, caffeine, amphetamines, and PCP
• Drug withdrawal- particularly alcohol withdrawal, benzodiazepine withdrawal, and opiate withdrawal.
• Hyperthyroidism- presence of an elevated TSH on laboratory findings

Differentiating generalized anxiety disorder from other diseases

Disease	Prominent clinical features	Investigations
Hyperthyroidism	The main symptoms include: Palpitations Insomnia Anxiety Weight loss Heat intolerance Diarrhea Depending on the underlying diagnosis, the patient might have exophthalmus or goiter	The patient usually has elevated T3 and T4 TSH might be increased or decreased depending on the underlying cause Thyroid stimulating antibodies (TSI) might be increased in cases of Graves’ disease
Essential hypertension	Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below: Headache Blurry vision Dyspnea Epistaxis Tinnitus Fatigue Drowsiness	JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension: 12-Lead electrocardiogram (ECG) Urinalysis, including urinary albumin excretion or albumin/creatinine ratio Blood glucose Blood hematocrit Serum electrolytes, especially potassium Serum calcium Lipid profile: Total cholesterol, LDL, HDL, triglycerides Creatinine or estimated GFR
Generalized anxiety disorder	According to DSM V, the following criteria should be present to fit the diagnosis of generalized anxiety disorder: The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months Difficulty to control the apprehension Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations) The anxiety or the physical manifestations must affect the social and the daily life of the patient Exclusion of another medical condition or the effect of another administered substance Exclusion of another mental disorder causing the symptoms	-
Menopause	The perimenopausal symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of estrogens, progestin, and testosterone. Some of these symptoms such as formication etc may be associated with the hormone withdrawal process. Vasomotor instability in the form of hot flushes, including night sweats and sleep disturbances Urogenital atrophy causing itching, dryness, bleeding, watery discharge, urinary frequency, urinary urgency and urinary incontinence Skeletal symptoms in the form of osteoporosis (gradually developing over time), artharlgia, myalgia and back pain Psychological manifestations such as mood disturbance, irritability, fatigue, memory loss and depression Sexual disorders: decreased libido, vaginal dryness, problems reaching orgasm and dyspareunia	B-HCG should always be done first to rule out pregnancy especially in women under the age of 45 years FSH can be measured but it can be falsely normal or low TSH, T3 and T4 to rule out thyroid abnormalities Prolactin can be measured to rule out prolactinoma as a cause of menopause
Opioid withdrawal disorder	According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal: Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an opioid antagonist after a period of opioid use. Development of three or more of the following criteria minutes to days after cessation of drug use: dysphoric mood, nausea or vomiting, muscle aches, Lacrimation or rhinorrhea, pupillary dilation, piloerection, or sweating, diarrhea, yawning, fever, and insomnia. The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient. The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.	Urine drug screen to rule out any other associated drug abuse Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
Pheochromocytoma	The hallmark symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include: Palpitations especially in epinephrine producing tumors. Anxiety often resembling that of a panic attack Sweating Headaches occur in 90 % of patients. Paroxysmal attacks of hypertension but some patients have normal blood pressure. It may be asymptomatic and discovered by incidence screening especially MEN patients. Please note that not all patients with pheochromocytoma experience all classical symptoms.	Diagnostic lab findings associated with pheochromocytoma include: Elevated plasma and urinary catecholamines and metanephrines Elevated urinary vanillyl mandelic acid
Social phobia	The main symptoms include: Anxiety or persistent fear is limited to social situations and fear of social scrutiny or embarrassment. Avoidance behavior commonly present.	No differentiating tests exist.
OCD	The main symptoms include: Anxiety is directly related to compulsions or obsessions.	No differentiating tests exist.
PTSD	The main symptoms include: Anxiety is directly related to exposure to reminders of past trauma; patients re-experience symptoms (through flashbacks, nightmares).	No differentiating tests exist.
Somatoform disorders	The main symptoms include: Anxiety is directly related to specific physical complaints. Thorough medical evaluation shows no basis for physical complaints.	No differentiating tests exist.
Depression	The main symptoms include: Inability to feel pleasure with an overall sad or irritable mood.	No differentiating tests exist.
Substance-or drug-induced anxiety disorder	The main symptoms include: 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. A history of illicit drug and alcohol use should also be obtained.	Urine drug screen may identify substance abuse, 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.
CNS-depressant withdrawal	The main symptoms include: 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), and, if delirium is present, mental confusion. Typical signs are tachypnea, tachycardia, and disorientation.	Monitoring of vital signs is essential to detect autonomic instability and sometimes delirium.
Anorexia nervosa	The main symptoms include: Anxiety is directly related to a fear of gaining weight. Body weight <85% of ideal.	No differentiating tests exist.