Panic disorder is characterized by the occurrence of panic attacks--sudden, unexpected periods of intense fear or discomfort. About 15% of the general population experiences panic attacks; 1.6-3.2% of women and 0.4%-1.7% of men have panic disorder.
DSM-IV Criteria for panic attack
A discrete period of intense fear or discomfort in which four or more of the following symptoms developed abruptly and reached a peak within 10 minutes.
Chest pain or discomfort Choking
Depersonalization or derealization Dizziness, faintness, or unsteadiness Fear of "going crazy" or being out of control Fear of dying
Flushes or chills
Nausea or gastrointestinal distress Palpitations or tachycardia Paresthesias
Shortness of breath (or feelings of smothering) Sweating
Trembling or shaking
Diagnostic criteria for panic disorder without ago- raphobia
Recurrent, unexpected panic attacks
And
At least one attack has been followed by at least 1 month of one (or more) of the following:
Persistent concern about experiencing more attacks Worry about the meaning of the attack or its consequences (fear of losing control, having a heart attack, or "going crazy") A significant behavioral change related to the attacks
And
Absence of agoraphobia
And
Direct physiological effects of a substance (drug abuse or medication) or general medical condition has been ruled out as a cause of the attacks
And
The panic attacks cannot be better accounted for by another mental disorder
I.Clinical evaluation
A.Panic attacks are manifested by the sudden onset of an overwhelming fear, accompanied by feelings of impending doom, for no apparent reason.
B.The essential criterion for panic attack is the presence of 4 of 13 cardiac, neurologic, gastrointestinal, or respira- tory symptoms that develop abruptly and reach a peak within 10 minutes. The physical symptoms include short- ness of breath, dizziness or faintness, palpitations, accelerated heart rate, and sweating. Trembling, choking, nausea, numbness, flushes, chills, or chest discomfort are also common, as are cognitive symptoms such as fear of dying or losing control.
C.One third of patients develop agoraphobia, or a fear of places where escape may be difficult, such as bridges, trains, buses, or crowded areas. Medications, substance abuse, and general medical conditions such as hyperthyroidism must be ruled out as a cause of the patient's symptoms.
D.The history should include details of the panic attack, its onset and course, history of panic, and any treatment. Questioning about a family history of panic disorder, agoraphobia, hypochondriasis, or depression is important. Because panic disorder may be triggered by marijuana or stimulants such as cocaine, a history of substance abuse must be identified. A medication history, including prescrip- tion, over-the-counter, and herbal preparations, is essential. E.The patient should be asked about stressful life events or problems in daily life that may have preceded onset of the disorder. The extent of any avoidance behavior that has developed or suicidal ideation, self-medication, or exacer- bation of an existing medical disorder should be assessed. II.Management
A.Patients should reduce or eliminate caffeine consump- tion, including coffee and tea, cold medications, analgesics, and beverages with added caffeine. Alcohol use is a particularly insidious problem because patients may use drinking to alleviate the panic.
Pharmacologic treatment of panic disorder
Dosage range (mg/d)
Drug Initial Therapeutic
SSRIs Fluoxetine (Prozac) Fluvoxamine (LuVox) Paroxetine (Paxil) Sertraline (Zoloft) Citalopram (Celexa) 5-10 25-50 10-20 25-50 10-20 mg qd 10-60 25-300 20-50 50-200 20-40 Benzodiazepines Alprazolam (Xanax) Alprazolam XR (Xanax XR) Clonazepam (Klonopin) Diazepam (Valium) Lorazepam (Ativan) 0.5 In divided doses, tid-qid 0.5 to 1 mg/day given once in the morning. 0.5 In divided doses, bid-tid 2.0 In divided doses, bid-tid 0.5 In divided doses, bid-tid 1-4 In divided doses, tid-qid 3-6 mg qAM 1-4 In divided doses, bid-tid 2-20 In divided doses, bid 1-4 In divided doses, bid-tid TCAs Amitriptyline (Elavil) Clomipramine (Anafranil) Desipramine (Norpramin) Imipramine (Tofranil) Nortriptyline (Pamelor) 10 25 10 10 10 10-300 25-300 10-300 10-300 10-300 MAOIs Phenelzine (Nardil) Tranylcypromine (Parnate) 1510 15-90 10-30
B.Selective serotonin reuptake inhibitors (SSRIs) are an effective, well-tolerated alternative to benzodiazepines and TCAs. SSRIs are superior to either imipramine or alprazolam. They lack the cardiac toxicity and anticholinergic effects of TCAs. Fluoxetine (Prozac), fluvoxamine (LuVox), paroxetine (Paxil), sertraline (Zoloft), and citalopram (Celexa) have shown efficacy for the treatment of panic disorder.
C.Tricyclic antidepressants (TCAs) have demonstrated efficacy in treating panic. They are, however, associated with a delayed onset of action and side effects--particu- larly orthostatic hypotension, anticholinergic effects, weight gain, and cardiac toxicity.
D.Benzodiazepines
1.Clonazepam (Klonopin), alprazolam (Xanax), and lorazepam (Ativan), are effective in blocking panic attacks. Advantages include a rapid onset of therapeu- tic effect and a safe, favorable, side-effect profile. Among the drawbacks are the potential for abuse and dependency, worsening of depressive symptoms, withdrawal symptoms on abrupt discontinuation, anterograde amnesia, early relapse on discontinua- tion, and inter-dose rebound anxiety.
2.Benzodiazepines are an appropriate first-line treatment only when rapid symptom relief is needed. The most common use for benzodiazepines is to stabilize severe initial symptoms until another treat- ment (eg, an SSRI or cognitive behavioral therapy) becomes effective.
3.The starting dose of alprazolam is 0.5 mg bid. Approximately 70% of patients will experience a discontinuance reaction characterized by increased anxiety, agitation, and insomnia when alprazolam is tapered. Clonazepam's long duration of effect dimin- ishes the need for multiple daily dosing. Initial symp- toms of sedation and ataxia are usually transient. E.Monoamine oxidase inhibitors (MAOIs). MAOIs such phenelzine sulfate (Nardil) may be the most effective agents for blocking panic attacks and for relieving the depression and concomitant social anxiety of panic disorder. Recommended doses range from 45-90 mg/d. MAOI use is limited by adverse effects such as orthostatic hypotension, weight gain, insomnia, risk of hypertensive crisis, and the need for dietary monitoring. MAOIs are often reserved for patients who do not respond to safer drugs.
F.Beta-blockers are useful in moderating heart rate and decreasing dry mouth and tremor; they are less effective in relieving subjective anxiety.
Insomnia
Insomnia is the perception by patients that their sleep is inadequate or abnormal. Insomnia may affect as many as 69% of adult primary care patients. The incidence of sleep problems increases with age. Younger persons are apt to have trouble falling asleep, whereas older persons tend to have prolonged awakenings during the night.
I.Causes of insomnia
A.Situational stress concerning job loss or problems often disrupt sleep. Patients under stress may experience interference with sleep onset and early morning awakening. Attempting to sleep in a new place, changes in time zones, or changing bedtimes due to shift work may interfere with sleep.
B.Drugs associated with insomnia include antihypertensives, caffeine, diuretics, oral contraceptives, phenytoin, selective serotonin reuptake inhibitors, protrip- tyline, corticosteroids, stimulants, theophylline, and thyroid hormone.
C.Psychiatric disorders. Depression is a common cause of poor sleep, often characterized by early morning awak- ening. Associated findings include hopelessness, sadness, loss of appetite, and reduced enjoyment of formerly pleasurable activities. Anxiety disorders and substance abuse may cause insomnia.
D.Medical disorders. Prostatism, peptic ulcer, congestive heart failure, and chronic obstructive pulmonary disease may cause insomnia. Pain, nausea, dyspnea, cough, and gastroesophageal reflux may interfere with sleep. E.Obstructive sleep apnea syndrome
1.This sleep disorder occurs in 5-15% of adults. It is characterized by recurrent discontinuation of breathing during sleep for at least 10 seconds. Abnormal oxygen saturation and sleep patterns result in excessive daytime fatigue and drowsiness. Loud snoring is typical. Overweight, middle-aged men are particularly predis- posed. Weight loss can be helpful in obese patients. 2.Diagnosis is by polysomnography. Use of hypnotic agents is contraindicated since they increase the frequency and the severity of apneic episodes. II.Clinical evaluation of insomnia
A.Acute personal and medical problems should be sought, and the duration and pattern of symptoms and use of any psychoactive agents should be investigated. Substance abuse, leg movements, sleep apnea, loud snoring, nocturia, and daytime napping or fatigue should be sought. B.Consumption of caffeinated beverages, prescribed drugs, over-the-counter medications, and illegal substances should be sought.
III.Pharmacologic management
A.Hypnotics are the primary drugs used in the management of insomnia. These drugs include the benzodiazepines and the benzodiazepine receptor agonists in the imidazopyridine or pyrazolopyrimidine classes.
Recommended dosages of hypnotic medications (elderly dosages are in parentheses)
Benzodiaz- epine hypnotics Recom- mended dose, mg Tmax Elimi- nation half- life Re- cepto r se- lectiv ity Benzodiazepine receptor agonists
Zolpidem (Ambien) 5-10 (5) 1.6 2.6 Yes Zaleplon (So- nata) 5-10 (5) 1 1 Yes Hypnotic Medications Estazolam (ProSom) 1-2 (0.5-1) 2.7 17.1 No Flurazepam (Dalmane) 15-30 (15) 1 47.0- 100 No Triazolam (Halcion) 0.250 (0.125) 1.2 2.6 No Temazepam (Restoril) 7.5-60 (7.5-20) 0.8 8.4 No Quazepam (Doral) 7.5-15.0 (7.5) 2 73 No
B.Zolpidem (Ambien) and zaleplon (Sonata) have the advantage of achieving hypnotic effects with less tolerance and fewer adverse effects.
C.The safety profile of these benzodiazepines and benzodiazepine receptor agonists is good; lethal
overdose is rare, except when benzodiazepines are taken with alcohol. Sedative effects may be enhanced when benzodiazepines are used in conjunction with other central nervous system depressants.
D.Zolpidem (Ambien) is a benzodiazepine agonist with a short elimination half-life that is effective in inducing sleep onset and promoting sleep maintenance. Zolpidem may be associated with greater residual impairment in memory and psychomotor performance than zaleplon. E.Zaleplon (Sonata) is a benzodiazepine receptor agonist that is rapidly absorbed (TMAX = 1 hour) and has a short elimination half-life of 1 hour. Zaleplon does not impair memory or psychomotor functioning at as early as 2 hours after administration, or on morning awakening. Zaleplon does not cause residual impairment when the drug is given in the middle of the night. Zaleplon can be used at bedtime or after the patient has tried to fall asleep naturally.
F.Benzodiazepines with long half-lives, such as flurazepam (Dalmane), may be effective in promoting sleep onset and sustaining sleep. These drugs may have effects that extend beyond the desired sleep period, however, resulting in daytime sedation or functional impairment. Patients with daytime anxiety may benefit from the residual anxiolytic effect of a long-acting benzodiazepine administered a t b e dtime. Benzodiazepines with intermediate half-lives, such as temazepam (Restoril), facilitate sleep onset and mainte- nance with less risk of daytime residual effects. G.Benzodiazepines with short half-lives, such as triazolam (Halcion), are effective in promoting the initiation of sleep but may not contribute to sleep mainte- nance.
H.Sedating antidepressants are sometimes used as an alternative to benzodiazepines or benzodiazepine receptor agonists. Amitriptyline (Elavil), 25-50 mg at bedtime, or trazodone (Desyrel), 50-100 mg, are common choices.
References: See page 255.