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Chapter 66: Anxiety Disorders

INTRODUCTION

  • Anxiety disorders (eg, generalized anxiety disorder [GAD] and panic disorder [PD]) have prominent features of anxiety and avoidance that are irrational or that impair functioning. In posttraumatic stress disorder (PTSD), there is previous exposure to trauma and intrusive, avoidant, and hyperarousal symptoms.

ETIOLOGY

  • Evaluation of anxiety requires a physical and mental status examination; complete psychiatric diagnostic exam; appropriate laboratory tests.

  • Anxiety symptoms may be associated with medical illnesses (Table 66-1) or medications (Table 66-2), and they may be present in several major psychiatric illnesses (eg, mood disorders, schizophrenia, organic mental syndromes, and substance withdrawal).

TABLE 66-1Common Medical Illnesses Associated with Anxiety Symptoms
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TABLE 66-1 Common Medical Illnesses Associated with Anxiety Symptoms

  • Cardiovascular: Angina, arrhythmias, cardiomyopathy, congestive heart failure, hypertension, ischemic heart disease, mitral valve prolapse, myocardial infarction

  • Endocrine and metabolic: Cushing disease, diabetes, hyperparathyroidism, hyperthyroidism, hypothyroidism, hypoglycemia, hyponatremia, hyperkalemia, pheochromocytoma, vitamin B12 or folate deficiencies

  • Gastrointestinal: Crohn disease, irritable bowel syndrome, ulcerative colitis, peptic ulcer disease

  • Neurologic: Migraine, seizures, stroke, neoplasms, poor pain control

  • Respiratory system: Asthma, chronic obstructive pulmonary disease, pulmonary embolism, pneumonia

  • Others: Anemias, cancer, systemic lupus erythematosus, vestibular dysfunction
TABLE 66-2Drugs Associated with Anxiety Symptoms
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TABLE 66-2 Drugs Associated with Anxiety Symptoms

  • Anticonvulsants: carbamazepine, phenytoin

  • Antidepressants: bupropion, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors

  • Antihypertensives: clonidine, felodipine

  • Antibiotics: quinolones, isoniazid

  • Bronchodilators: albuterol, theophylline

  • Corticosteroids: prednisone

  • Dopamine agonists: amantadine, levodopa

  • Herbals: ma huang, ginseng, ephedra

  • Illicit substances: ecstasy, marijuana

  • Nonsteroidal anti-inflammatory drugs: ibuprofen, indomethacin

  • Stimulants: amphetamines, caffeine, cocaine, methylphenidate, nicotine

  • Sympathomimetics: pseudoephedrine, phenylephrine

  • Thyroid hormones: levothyroxine

  • Toxicity: anticholinergics, antihistamines, digoxin

PATHOPHYSIOLOGY

  • Noradrenergic model. The autonomic nervous system of anxious patients is hypersensitive and overreacts to various stimuli. The locus ceruleus (LC) may have a role in regulating anxiety, because it activates norepinephrine release and stimulates the sympathetic and parasympathetic nervous systems. Chronic noradrenergic overactivity downregulates α2-adrenoreceptors in patients with GAD and PTSD, while this receptor is hypersensitive in PD. Drugs with anxiolytic or antipanic effects (eg, benzodiazepines and antidepressants) inhibit LC firing, decrease noradrenergic activity, and block the effects of anxiogenic drugs.

  • γ-Aminobutyric acid (GABA) receptor model. GABA is the major inhibitory neurotransmitter in the central nervous system (CNS). Benzodiazepines enhance the inhibitory effects of GABA, which regulates or inhibits serotonin (5-hydroxytryptamine; 5-HT), norepinephrine, and dopamine activity. The number of GABAA receptors can change with alterations in the environment, and GABA receptor subunit expression can be altered by hormonal changes. Abnormal functioning of several neurotransmitter systems, including norepinephrine, GABA, glutamate, dopamine, and 5-HT, may affect manifestations of anxiety disorders.

  • 5-HT model. Abnormalities in serotonergic functioning may play a role. Preclinical models suggest that greater 5-HT function facilitates avoidance behavior; but primate studies show that ...

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