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CNS Spectr. 2000 Sep;5(9):29-43.

Social anxiety and premorbid personality disorders in paranoid schizophrenic patients treated with clozapine.

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Institute of Neurosciences at the University of Florence Medical School, Italy.


The concept of anxiety as a distinct comorbid disorder in schizophrenia has recently been rediscovered after having been neglected for a long period of time due to both theoretical and clinical approaches adopted from the appearance of the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1950. This rediscovery was accentuated by the fact that the concept of comorbidity in various psychiatric disorders has recently won widespread favor within the scientific community, and that the use of atypical neuroleptic medication to treat patients with schizophrenia has been reported to lead to the emergence of anxiety symptoms. Of the atypical neuroleptic medications used to treat schizophrenia, clozapine has most frequently been reported to induce anxiety symptoms. In this paper, 12 cases of patients with paranoid schizophrenia who developed social phobia during clozapine treatment are reported, and their response to fluoxetine augmentation is assessed. Premorbid personality disorders were also investigated; patients were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). In addition, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Liebowitz Social Anxiety Scale (LSAS), the Frankfurt Beschwerde Fragebogen (Frankfurt Questionnaire of Complaints), and the Brief Psychiatric Rating Scale were used to rate clinical symptomatology. All patients were reevaluated after 12 weeks of cotreatment with clozapine and fluoxetine. In 8 (66.6%) of the 12 cases, symptoms responded (>/=35% LSAS score reduction) to an adjunctive regimen of fluoxetine. Furthermore, in 7 (58.3%) of the 12 cases, an anxious personality disorder (avoidant=33.3%; dependent=25%) was identified, but no significant differences in the prevalence of comorbid personality disorders emerged in comparison with a group of 16 patients with paranoid schizophrenia treated with clozapine who did not show symptoms of social phobia. The clinical relevance of the assessment and treatment of anxiety disorders is discussed in light of a clinical therapeutic approach that overcomes the implicit hierarchy of classification. Considering that the onset of anxiety-spectrum disorders (such as social phobia) can occur during the remission of psychotic symptoms in clozapine-treated patients with schizophrenia, a comprehensive approach to pharmacological therapy for patients with schizophrenia (or, at least for those treated with clozapine) should be adopted.


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