Panic Disorder Associated With Clozapine

Ms. A, a 34-year-old woman, was first seen for psychiatric treatment at age 30 after experiencing 2 months of psychotic symptoms. She described hearing threatening voices saying that they wanted to cut her fingers. She suspected that her mother’s doctors had formed an organization to harm her and that these doctors could hear her thoughts by means of a “neurotransmitter” installed inside her head. Treatment with two typical antipsychotics (haloperidol, 30 mg/day, and trifluoperazine, 40 mg/day) and one atypical antipsychotic (risperidone, 8 mg/day) resulted in no significant improvement in her symptoms. After 8 months of unsuccessful treatment, including two hospital admissions, the diagnosis of treatment-resistant paranoid schizophrenia (per DSM-IV) was confirmed, and Ms. A was treated with clozapine. Clozapine monotherapy (400 mg/day) led to a marked improvement in positive symptoms, but Ms. A remained a bit withdrawn. In the 20th week of clozapine treatment, Ms. A developed clozapine-induced sinus tachycardia and the fear of dying of a heart attack. She was effectively medicated with a β blocker (atenolol, 100 mg/day). Despite a normal ECG and the exclusion of other organic causes, Ms. A experienced recurrent attacks of sudden chest compression, dizziness, fear of dying, and intense anxiety. She often went to emergency clinics, where her symptoms were treated with benzodiazepines. Her panic symptoms occurred daily, and she developed agoraphobic symptoms that confined her to the house and compromised her rehabilitation.

When assessed by a blind rater with the Structured Clinical Interview for DSM-IV, Ms. A fulfilled the DSM-IV criteria for paranoid schizophrenia and panic disorder with agoraphobia. The temporal relationship between clozapine treatment and the development of panic attacks suggested that clozapine could have been inducing the panic symptoms. Reduction of clozapine therapy to 250 mg/day led to a modest improvement in Ms. A’s anxiety symptoms but some worsening of her psychotic symptoms. Olanzapine (10 mg/day) was then substituted for clozapine without recurrence of the psychotic symptoms. Her panic symptoms progressively improved, and 2 months after switching antipsychotics, Ms. A patient was stable, with some negative symptoms but no panic or agoraphobic symptoms.