The American Psychiatric Association Practice Guideline for the Treatment of Patients With Panic Disorder: Recommendations and Controversies

Fredric N. Busch, MD and Barbara L. Milrod, MD

In This Article


Four classes of medications have been found to be effective in the treatment of panic disorder: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), benzodiazepines, and monoamine oxidase inhibitors (MAOIs). As these medications are of roughly equal efficacy, treatment decisions should be based on adverse effects, the patient's preferences, and other aspects of the clinical situation.

Despite side effects related to sexual function, SSRIs are generally felt to present the best balance between effectiveness and adverse effects. TCAs are associated with a greater risk because of cardiovascular and anticholinergic side effects. Benzodiazepines are helpful in rapid control of symptoms but are potentially addictive. MAOIs, because of the risk of hypertensive crises, are generally reserved for patients unresponsive to other agents and treatments.

On SSRIs patients may experience an initial feeling of increased anxiety, jitteriness, shakiness, and agitation. Therefore, it is recommended that patients begin on a lower dose of medication than is typically used for depression. Response frequently does not occur for at least 4 weeks. As with other medication, the guideline notes that the optimum time period on SSRIs is not known. When the medication is discontinued, the taper should occur over several weeks.

Side effects of TCAs include anticholinergic effects, sleep disturbance, orthostatic hypotension, weight gain, sexual dysfunction, and cognitive disturbance. These drugs should not be used for patients with acute narrow angle glaucoma or prostatic hypertrophy. Patients may suffer severe cardiac toxicity and fatality if they have preexisting cardiac conduction abnormalities or if they overdose on tricyclics. As with the SSRIs, patients can have a stimulant response that includes anxiety, agitation, and insomnia, and panic patients need to be started on substantially lower doses than those used in treatment of depression. As with other medications, there are few long-term outcome studies. Evidence suggests that maintenance treatment is of value for at least a year after the patient has responded to the medication.[25,26] The exact relapse rate after stopping the medication is unknown.

Alprazolam in the 5- to 6-mg/day range has been found to be effective in treating a wide range of symptoms in panic patients. Alprazolam has been demonstrated to have an earlier onset of action than imipramine. Side effects of benzodiazepines include "sedation, fatigue, ataxia, slurred speech, memory impairment, and weakness" (p 15). Although alprazolam should be avoided in patients with a history of substance abuse, there are no data demonstrating that long-term use frequently leads to an increased dose or abuse. At times the medications may be avoided inappropriately due to fear of addiction. Evidence suggests that patients can have significant difficulties tapering off alprazolam and may suffer from withdrawal symptoms and rebound anxiety.[27] It is recommended that tapering proceed slowly, with a maximum decrease of 10% of the dose per week. As with other treatments, there are few data indicating optimum length of treatment for responders. Some studies suggest that imipramine may be a better medication for panic over the long term.[28,29]


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