Although panic attacks are an essential feature of panic disorder, other psychiatric symptoms, such as phobic avoidance, anxiety, depression and obsessions, may also be present in panic disorder. Most studies have focused on the frequency of panic attacks as the principle measure of the severity and outcome of panic disorder, despite growing consensus on the importance of focusing on a wider spectrum of symptoms. Because selective serotonin reuptake inhibitors (SSRIs) have significant antidepressant and anxiolytic actions, it is likely that they provide improved clinical outcomes by reducing the frequency of panic attacks and improving mood and phobic symptoms. Michelson and associates studied the effect of fluoxetine treatment in patients who were diagnosed with panic disorder.

A total of 243 patients were randomly assigned to daily treatment with either 10 mg or 20 mg of fluoxetine, or placebo. Primary outcomes measured were changes in the frequency of panic attacks and clinical symptoms associated with the disorder. Symptom change was assessed by clinician-rated Clinical Global Impression scores. The study included an initial single-blind, placebo lead-in phase, followed by a 10-week acute phase with randomization. Patients who completed the 10 weeks and showed improvement could enter a 24-week continuation phase of treatment with either fluoxetine or placebo. The primary outcome measured in this phase was relapse rate.

Overall response to treatment as assessed by clinical parameters was significantly greater in patients treated with 20 mg (but not 10 mg) per day of fluoxetine than in those treated with placebo. The comparison of placebo and combined fluoxetine treatment also favored fluoxetine. Patients treated with either dosage of fluoxetine experienced a significant reduction in the total frequency of panic attacks compared with the placebo group. The three groups did not differ significantly in the number of patients who were completely panic-free at the last visit of the acute phase.

Anxiety was significantly reduced in the patients treated with 20 mg (but not 10 mg) per day of fluoxetine compared with the patients treated with placebo. Likewise, depressive symptoms were significantly reduced in both fluoxetine groups compared with the placebo group. Phobic avoidance was similarly reduced in either group taking fluoxetine. Patient-rated overall improvement of symptoms was significantly greater in the group taking 20 mg per day of fluoxetine than the group taking placebo.

In addition, repeated analysis of symptom relief in the continuation phase of the trial demonstrated that more patients treated with fluoxetine experienced improvement than those treated with placebo. In the two phases of the trial, both dosages of fluoxetine were well tolerated. Discontinuation rates were similar in the fluoxetine and placebo groups.

Results of this study suggest that fluoxetine is safe and effective in the acute and continuation treatment phases of panic disorder. Treatment with either 10 mg or 20 mg per day of fluoxetine was associated with significantly greater reduction in the total number of panic attacks than treatment with placebo. In addition, treatment with the higher dosage (20 mg per day) of fluoxetine was also associated with a significant reduction in anxiety, phobia and depression.

The authors conclude that a reduction in the frequency of panic attacks does not adequately reflect improvement as a primary measure of psychiatric disease. Clinical improvement in panic disorder is better reflected by a multidimensional approach to symptom control. Better outcomes are achieved if a broader focus on symptom relief is maintained by the treating physician.