Tension, irritability, apprehension, and mild distractibility are common (particularly in medical and psychiatric patients), often related to environmental factors, and treated with supportive and reality-oriented therapy. Medications are of little value over the long term, and iatrogenic addiction is a serious problem. Environmentally induced, short-lived, mild anxiety (ADJUSTMENT DISORDER WITH ANXIETY p. 679, 309.24) usually resolves with the disappearance of the stress.

A diagnosis of GENERALIZED ANXIETY DISORDER (p. 472, 300.02) is made with more severe, chronic anxiety (longer than 6 months; usually years, but waxing and waning) and including symptoms such as autonomic responses (palpitations, diarrhea, cold clammy extremities, sweating, urinary frequency), insomnia, poor concentration, fatigue, sighing, trembling, hypervigilance, marked apprehension, or a combination of these. It tends to run in families, has a moderate genetic component, prevalence of 3% and lifetime prevalence of 5%, and is associated with simple and social phobias and with major depression (50%⁺ of patients at some time; elevated risk for suicide) (1). Usually no convincing etiologic stress is found, but look anyway.

Consider both medication and psychotherapy. The antidepressant, venlafaxine, seems to be particularly effective and safe for treating generalized anxiety disorder (GAD) (2). Also consider selective serotonin reuptake inhibitors (SSRIs) as a first-line treatment. Use benzodiazepines sparingly (diazepam, 5 mg, p.o., t.i.d.—q.i.d., or 10 mg hs) and for short periods (weeks to several months); allow medication use to follow the fluctuating course of the illness. Consider buspirone for a first medication or for long-term use (20 to 30 mg/day; divided doses); a patient may not find it effective after the “instant relief” of a benzodiazepine. Tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) are useful in selected patients (particularly those who have depressive symptoms), whereas some patients with autonomic symptoms improve with β-blockers (e.g., propranolol, 80 to 160 mg/day).

Encourage self-reliance, maintenance of productive activity, and reality-based cognitions. Train the patient in relaxation techniques (e.g., biofeedback, meditation, self-hypnosis). More than 50% of patients become asymptomatic with time (months, years), but the rest retain a significant degree of impairment. It is common in old age. Help the patient understand the chronic nature of the illness and the likelihood of having to live with some symptoms (3).

A PANIC DISORDER WITHOUT AGORAPHOBIA (p. 433, 300.01) has dramatic, acute symptoms lasting minutes to hours, is self-limited, and occurs in patients with or without chronic
anxiety. Symptoms often are perceived by the patient as medical and are characteristic of strong autonomic discharge—hyperventilation, heart pounding, chest pains, trembling, choking, abdominal pain, sweating, dizziness—as well as disorganization, confusion, dread, and often a sense of impending doom, terror, or death. Attacks may come “out of the blue,” usually in young adults, or may be initiated by crowds, stressful situations, or anticipation (“anticipatory anxiety”). They may be repeated several times daily, weekly, or monthly, and wax and wane, often disappearing for months at a time (but may become chronic; 20% of patients). A typical panic attack can be produced in 50% to 75% of patients with panic disorder (but not in normal patients) by the intravenous infusion of sodium lactate or by breathing CO2. (Panic patients seem to be hypersensitive to a sense of breathlessness, whether chemically or environmentally produced.)

Like other anxiety conditions, it runs in families (15%⁺ of first-degree relatives; 30%⁺ of monozygotic twins), is probably genetic, but no linkage to a particular gene has been found. It is comorbid with major depression (50%), suicide, social and specific phobias, and alcoholism (however, family members are at risk only for panic disorder and social phobia). It occurs in women more frequently than in men (2:1), particularly in those who have had a disturbed childhood and early difficulty separating from their parents (separation anxiety disorder). In its milder forms, panic disorder tends to grade into the GAD clinically, although it appears to be a distinct disorder. Etiology is unclear, but an overactive locus coeruleus with excessive norepinephrine (NE) in panic attacks is often involved. In addition, the majority of patients with panic also have agoraphobia (PANIC DISORDER WITH AGORAPHOBIA, p. 433, 300.21; see later): combined, these conditions afflict about 3% of the population. Patients often receive the “million dollar workup” for angina, thyrotoxicosis, or abdominal complaints. Hyper- and hypothyroidism and stimulant drug abuse may initiate a first panic attack. Effective treatment exists.

Phobias are fears that are persistent and intense, are out of proportion to the stimulus, make little sense even to the sufferer, lead to avoidance of the feared object or situation, and when sufficiently distressful or disabling are termed a phobic disorder. Common, mild, frequently transient fears (of the dark, heights, snakes) receive no diagnosis. Phobias may wax and wane over months or years and may disappear spontaneously, but serious cases may continue for decades and gradually take the form of a depressive disorder. The fears may generalize during their developing stages (e.g., fear of a store generalizes to the street in front of the store and then to the entire shopping area).

More than 12% of the population may have a phobic disorder in some circumstances, yet in fewer than 1% is it significantly disabling. Many begin suddenly in women (F/M, 2:1) from stable families and of ages 15 to 30 years. Anxiety with ruminations may dominate the day-to-day picture, or anxiety may occur only when the phobic object is encountered directly. Relief occurs with escape, thus reinforcing the avoidance pattern—a vicious cycle.
Phobics are at risk to abuse alcohol and drugs as self-medication. Three subtypes have been identified, all of which have a moderate genetic component: