Carbon dioxide induction of panic anxiety in schizophrenia with auditory hallucinations

Panic is commonly co-morbid with schizophrenia. Panic may emerge prodromally, contribute to specific psychotic symptoms, and predict medication response. Panic is often missed due to agitation, impaired cognition, psychotic symptom overlap and limited clinician awareness. Carbon dioxide exposure has been used reliably to induce panic in non-psychotic panic subjects, but has not been systematically studied in schizophrenia. Eight inpatients with schizophrenia, recent auditory hallucinations, none preselected for panic, all on antipsychotic medication, received a structured Panic and Schizophrenia Interview (PaSI), assessing DSM-IV panic symptoms concurrent with paroxysmal auditory hallucinations. On that interview, all eight subjects reported panic concurrent with auditory hallucinations. At one sitting, subjects were exposed, in random order, to 35% carbon dioxide and to placebo room air, blinded to condition. All subjects experienced panic to carbon dioxide, one with limited symptoms. Only one subject panicked to placebo. One subject (one of only two without antipanic medication) had paroxysmal voices concurrent with induced panic. With added adjunctive clonazepam, that patient had marked clinical improvement and no response to carbon dioxide re-challenge. This first systematic examination offers preliminary evidence that carbon dioxide safely induces panic symptoms in schizophrenia. Panic may be prevalent and pathophysiologically significant in schizophrenia with auditory hallucinations.