Psychiatry · Anxiety Disorders
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Defined by excessive, hard-to-control worry about multiple domains present more days than not for >= 6 months.
DSM-5 requires the worry plus at least three of six somatic symptoms: restlessness, fatigue, poor concentration, irritability, muscle tension, and sleep disturbance.
SSRIs (or SNRIs/buspirone) are first-line pharmacotherapy.
Avoid chronic benzodiazepines given sedation, dependence, and abuse potential; reserve them for short-term bridging only.
Always rule out organic mimics: check TSH for hyperthyroidism, assess caffeine/stimulant intake, and obtain a urine drug screen.
It is twice as common in women and often described as present as long as the patient can remember.
Distinguish from panic disorder, which features discrete attacks peaking within minutes rather than chronic pervasive worry.
Vignette unlocked
A 34-year-old woman reports nearly a year of persistent, uncontrollable worry about her finances, her job, and the health of her healthy parents. She feels restless and fatigued, has difficulty concentrating, complains of muscle tension, and sleeps poorly. She denies discrete episodes of sudden panic. TSH is normal and a urine drug screen is negative.
Which of the following is the most appropriate first-line treatment?
An SSRI (e.g., escitalopram or sertraline).
Chronic, pervasive worry for more than 6 months with at least three somatic symptoms and no organic cause meets DSM-5 criteria for generalized anxiety disorder. SSRIs (or SNRIs/buspirone) are first-line, whereas chronic benzodiazepines are avoided because of dependence and abuse potential.
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Etiology / Epidemiology
Chronic, excessive worry about multiple domains; twice as common in women and often present "as long as the patient can remember."
Clinical Manifestations
Worry out of proportion to events plus fatigue, poor concentration, sleep problems, muscle tension, and restlessness.
Diagnosis
Clinical DSM-5 diagnosis requiring >=6 months of uncontrollable worry; rule out hyperthyroidism, caffeine, and substance use.
Treatment
SSRIs (or SNRIs/buspirone) are first-line; avoid chronic benzodiazepines given abuse potential.
Prognosis
Chronic and relapsing but highly treatable; commonly comorbid with depression.
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Epidemiology & Etiology
Generalized anxiety disorder (GAD) is among the most common psychiatric disorders, affecting women roughly twice as often as men, and patients frequently report feeling anxious "as long as they can remember." Onset is typically gradual in early adulthood, and a strong family history and high comorbidity with major depression and other anxiety disorders are characteristic. In men, anxiety symptoms are most commonly substance-induced, so a thorough history and urine drug screen are essential. Caffeine, stimulants, and hyperthyroidism can mimic or exacerbate symptoms.
Pertinent Anatomy
Pathologic anxiety reflects dysregulation of the amygdala (the fear-processing center) and its connections to the prefrontal cortex, which normally exerts top-down inhibitory control. Neurochemically, anxiety disorders involve deficient GABA-ergic inhibitory tone and dysregulated serotonin and norepinephrine signaling. The hypothalamic-pituitary-adrenal (HPA) axis is chronically activated, producing the autonomic and somatic symptoms that dominate the clinical picture.
Pathophysiology
GAD is conceptualized as a failure of fear circuitry, in which an overactive amygdala drives sustained autonomic arousal that the prefrontal cortex fails to dampen. Reduced inhibitory GABA transmission and altered serotonergic and noradrenergic modulation lower the threshold for chronic apprehension. This produces persistent activation of the sympathetic nervous system and HPA axis, manifesting as muscle tension, restlessness, insomnia, and fatigue rather than discrete panic surges. The benefit of SSRIs/SNRIs supports the central role of monoamine dysregulation.
Clinical Manifestations
Patients describe excessive, hard-to-control worry about numerous everyday matters (finances, health of loved ones, work) that is clearly out of proportion to actual circumstances. The DSM-5 requires the worry plus at least three of six somatic symptoms: restlessness, fatigue, difficulty concentrating, irritability, muscle tension, and sleep disturbance. A classic vignette is a woman with chronic palpitations, dizziness, and sweating who has seen many physicians, cannot relax, and worries about healthy parents and secure finances. Unlike panic disorder, there are no discrete attacks; symptoms are persistent and pervasive.
Diagnosis
GAD is a clinical diagnosis. Per DSM-5, symptoms of excessive anxiety and worry must be present more days than not for at least 6 months and cause functional impairment, with at least three associated somatic symptoms. Before assigning the diagnosis, always rule out organic causes and substance use: check TSH for hyperthyroidism, assess caffeine and stimulant intake, and obtain a urine drug screen. The distinction from panic disorder hinges on chronic pervasive worry versus recurrent discrete attacks of autonomic hyperactivity.
Treatment
SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram) are first-line. Venlafaxine (an SNRI) and buspirone are also effective and non-addictive. Cognitive-behavioral therapy is beneficial but generally adjunctive rather than first-line monotherapy. Benzodiazepines provide rapid relief but are reserved for short-term bridging because of sedation, dependence, and abuse potential; buspirone is a useful non-sedating alternative when an anxiolytic is desired. Patient education and treating any comorbid depression improve outcomes.
Prognosis
GAD is typically chronic and relapsing, with a waxing-and-waning course over years, but it responds well to a combination of SSRIs/SNRIs and CBT. Prognosis worsens with untreated comorbid major depression or substance use disorder, both of which must be screened for and addressed. With adherence to pharmacotherapy and psychotherapy, most patients achieve meaningful symptom control and functional improvement.
Differential Diagnosis
Panic Disorder: recurrent discrete attacks of intense autonomic hyperactivity peaking within minutes, rather than chronic persistent worry; treat panic disorder with SSRIs.
Hyperthyroidism: anxiety with weight loss, heat intolerance, tremor, and tachycardia; suppressed TSH confirms it and must be excluded before diagnosing GAD.
Major Depressive Disorder: anxiety can accompany depression, but MDD is dominated by depressed mood/anhedonia for >=2 weeks with neurovegetative symptoms.
Substance/Caffeine-induced anxiety: stimulant, caffeine, or withdrawal states reproduce anxiety; urine drug screen and history clarify, and it is the most common cause in men.
Social Anxiety Disorder: anxiety is situation-specific (fear of embarrassment in social settings) rather than free-floating worry about many domains.