Alprazolam (Xanax, Xanor, Tafil) and clonazepam (Klonopin, Rivotril) for treatment of panic disorder

The introduction of the benzodiazepines represented a significant advance in the treatment of panic disorder. In contrast to MAOIs and TCAs, the benzodiazepines begin to provide relief the very first day of treatment, and many patients experience a complete response by the end of the second week of therapy. All benzodiazepines should theoretically alleviate the symptoms of a panic attack at comparable doses, but the benzodiazepines of choice are alprazolam (Xanax, Xanor, Tafil Xanax XR) and clonazepam (Klonopin, Rivotril). It likely is not coincidental that these two are among the highest potency benzodiazepines. However, they differ considerably from a pharmacokinetic standpoint. If clonazepam is the tortoise of benzodiazepines, then alprazolam is the hare.

Alprazolam has an especially rapid onset of action and can therefore provide rapid relief when a panic attack is impending. In addition to its rapid onset, alprazolam also has a brief duration of action. Thus, it’s often necessary to administer alprazolam several times per day, and patients are more likely to complain of breakthrough anxiety in between doses. Without careful discussion prior to initiating
alprazolam, this breakthrough anxiety can lead to a rapid escalation in dose. This problem, however, can be minimized by a newly available sustained-release preparation of alprazolam. Alprazolam should be started at 0.25–0.50 mg given three times daily. The dose can be increased every 5–7 days as necessary. The typical daily dose is 2–4 mg per day given in three to fi  ve divided doses. A long-acting preparation (Xanax XR) is now available that can be administered one to three times daily. Xanax XR is typically started at a dose of 0.5–1 mg/day and gradually increased to a therapeutic dose of 3–6 mg/day.

In contrast to alprazolam, clonazepam has a gradual onset of action and a relatively longer duration of action. Whereas clonazepam is less effective than alprazolam at providing rapid relief when a panic attack is underway, it provides more consistent symptom relief during the course of the day with less potential for interdose breakthrough anxiety. Clonazepam should be started at 0.5–1.0 mg/day and
increased every 3–5 days as needed to a maximum dose of 4 mg/day. Due to its long duration of action, clonazepam can be administered two to three times per day and provide adequate symptom control throughout the day for patients with panic disorder. A clonazepam wafer that is rapidly dissolving is believed to provide a more rapid onset of action than the usual oral preparation.

As noted earlier, the principal advantage of the benzodiazepines is that they provide faster relief than the MAOIs, TCAs, and SSRIs (which were introduced later). They are also considerably safer than the MAOIs, TCAs, and barbiturates.  However, there are disadvantages to benzodiazepines. They produce sedation and can impair short-term memory and coordination (psychomotor function such as
driving). They can magnify the effects of alcohol and are subject to abuse and withdrawal syndromes. Refer to Section 5.1 for a more extended discussion of benzodiazepines.