To the Editor: Panic disorder usually responds favorably to therapy with selective serotonin reuptake inhibitors, tricyclics, or benzodiazepines (1). However, there are a number of patients whose disorders are refractory to standard treatment and whose management represents a challenge. We present the cases of two patients with treatment-resistant panic disorder who responded to treatment with olanzapine.
Mr. A, a 32-year-old man without comorbid disorders, was seen for a panic disorder of 4 months’ duration. His panic attacks were initially nocturnal but later appeared at any time of the day. Mr. A was treated consecutively with 40 mg/day of paroxetine for 2 months, 200–300 mg/day of fluvoxamine for 6 months, and 150 mg/day of clomipramine for 2 months. He also received concomitant alprazolam, 2–4 mg/day, during this 10-month period. Mr. A was later hospitalized for suicidal thoughts and discharged 1 month later on a regimen of 2 mg/day of clonazepam, 15 mg/day of perphenazine, 30 mg/day of ketazolam, and 150 mg/day of venlafaxine. Five days after his discharge, his perphenazine dose was replaced with olanzapine, 7.5 mg at bedtime.
Two weeks later Mr. A was much calmer and sleeping well, but he had mild morning anxiety. His olanzapine dose was increased to 12.5 mg/day, and his venlafaxine was replaced with nefazodone, up to 600 mg/day. Mr. A improved progressively during the following weeks, and clonazepam and ketazolam were discontinued. After 4 months Mr. A was free from panic attacks, left his house alone, and enjoyed leisure activities.
Ms. B was a 40-year-old woman who was seen for panic attacks with agoraphobia that had lasted for 2 years. She had intense somatic worries and was away from work on sick leave. She had no comorbid conditions. She received treatment with 40 mg/day of paroxetine plus 2–3 mg/day of alprazolam for 6 months. She then received 400 mg/day of nefazodone, plus 10 mg/day of diazepam, 50 mg/day of sulpiride, and 1 mg/day of alprazolam for 6 months with no improvement. Then a combination of 12 mg/day of perphenazine, 75 mg/day of amitriptyline, and 10 mg/day of diazepam was tried. After 5 months, 10 mg/day of olanzapine was begun, while maintaining her doses of amitriptyline (75 mg/day) and diazepam (10 mg/day). After 15 days Ms. B was feeling calmer and in a better mood. After 2.5 months Ms. B was being treated with 10 mg/day of olanzapine, 50 mg/day of amitriptyline, and 2.5 mg/day of diazepam; she had had no crises since she began olanzapine treatment and had started going out alone.
The American Psychiatric Association’s practice guideline for panic disorder (1) states that there is no evidence to support the use of typical antipsychotics for anxiety disorders and that the neurological risks outweigh the potential benefits. There are reports of olanzapine’s efficacy in bipolar disorder and depression (2), but we believe this is the first report in the literature suggesting a favorable response in panic disorder. The mechanism of action could be through serotonin type 2 receptors. Given the benign side effect profile of olanzapine compared to that of conventional neuroleptics, we believe that its use could be justified in cases of panic disorder that are refractory to conventional treatment.