Antipanic agents

Benzodiazepines are highly effective anxiolytics and sedatives. They also have muscle relaxant, amnestic, and anticonvulsant properties. Benzodiazepines effectively treat both acute and chronic generalized anxiety and panic disorder. The high-potency benzodiazepines alprazolam and clonazepam have received more attention as antipanic agents, but double-blind studies also have confirmed the efficacy of diazepam and lorazepam in the treatment of panic disorder. Although only a few benzodiazepines are specifically approved by the... 

In 1962, Klein and Fink (88) reported that imipramine blocked panic attacks but had only a minor effect on phobic avoidance or anticipatory anxiety. This clinical observation has been validated by approximately 15 double-blind studies, and TCAs have since been studied for their antipanic efficacy. Although many TCAs are effective antipanic agents, they differ in safety and efficacy, a fact that mandates fitting the drug to the individual patient based on the known advantages and potential adverse effects of each TCA (Table 13-4). 

Imipramine has been the most widely studied TCA for the treatment of PD and agoraphobia, with excellent data to show that it is an effective antipanic agent ( 89, 90). Other TCAs reported to have therapeutic efficacy in PD include the following ... 

Although clinical experience indicates tranylcypromine may be an effective antipanic agent, there are no controlled trials confirming this observation. Phenelzine, however, has been found to be very effective in both open and controlled designs ( 21, 116, 117). Onset of action is similar to that of other antidepressants, and although adverse effects tend to be less troublesome than with tricyclics, dietary restrictions may limit the usefulness of MAOIs in some patients. Unfortunately, the relapse rate may be comparable to that seen with BZDs and TCAs. For example, Kelly et al., in a follow-up of 246 patients, found that 50% who had discontinued MAOIs relapsed within 1 year (118). 

Novel serotonergic agents The same agents in testing as antidepressants and discussed in the section Other antidepressants in clinical trials, in Chapter 7, may also be promising antipanic agents. Such compounds tend to be tested first as... 

Reversible inhibitors of monoamine oxidase A Clinical experience with RIMAs in those countries where these agents are approved for marketing or testing suggests potential utility as antipanic agents. Further research is required to determine the relative advantages and relative efficacy of these compounds as compared with available antipanic agents. 

Xanax Alprazolam (Xanax) is an antianxiety and antipanic agent. Several of the side effects include episodes of violent and aggressive behavior, seizures, delirium, and other withdrawal reactions. 

BZs are second-line agents except when rapid response is essential. They should not be used as monotherapy in panic disorder patients with a history of depression or alcohol or drug abuse. BZs are often used concomitantly with antidepressants in the first weeks to offset the delay in onset of antipanic effects. 

Until the 1980s, the BZDs were considered ineffective in the treatment of PD. Early controlled studies with the triazolobenzodiazepine alprazolam, however, demonstrated its antipanic properties. To achieve this benefit, this agent must often be given in higher doses (4 to 10 mg per day) than when given as an anxiolytic. Although alprazolam usually produces its therapeutic effect during the first week, antidepressants may take several weeks. 

All SSRIs have an antipanic effect. Their advantages are limited adverse effects and lack of toxicity. Because of more acceptable adverse effect profiles, the SSRIs are usually the drugs of choice. Several studies consistently indicate that SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, as well as agents such as clomipramine and trazodone, all possess antipanic efficacy, although the last may be less effective than imipramine ( 24, 105, 106, 107, 108 and 109). 

It is well-established that the MAOIs available in the United States (e.g., phenelzine, tranylcypromine) are effective antipanic and antiphobic agents. Of these, phenelzine has been the most extensively studied. As with the other nonselective MAOIs, however, it also carries the risk of hypertensive and hyperpyrexic reactions (see also Chapter 5). 

Cholecystokinin (CCK) The tetrapeptide CCK causes more panic attacks when infused into patients with panic disorder than it does in normal volunteers, which suggests increased sensitivity of the brain type of CCK receptor, known as CCK-B. Unfortunately, in early investigations CCK-B antagonists did not appear to be effective for panic disorder. Nevertheless, agents with novel pharmacological mechanisms of action are sometimes evaluated for their potential antipanic actions by testing whether they can block CCK-induced panic attacks. 

Patients taking alprazolam, clonazepam, or imipramine for up to 8 months maintained antipanic efficacy without dosage increases, suggesting that tolerance does not develop to the antipanic effects of these agents. The most important determinant of compliance with... 

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