{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:26:06Z","timestamp":1762323966679,"version":"3.41.0"},"reference-count":93,"publisher":"Cambridge University Press (CUP)","issue":"9","license":[{"start":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T00:00:00Z","timestamp":1415318400000},"content-version":"unspecified","delay-in-days":5180,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS spectr."],"published-print":{"date-parts":[[2000,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>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<\/jats:italic>Diagnostic and Statistical Manual of Mental Disorders<jats:italic>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<\/jats:italic>DSM-III-R\u2014<jats:italic>Patient Version and the Structured Clinical Interview for<\/jats:italic>DSM-IV<jats:italic>Axis II Personality Disorders<\/jats:italic>(DSM-III-R=Diagnostic and Statistical Manual of Mental Disorders,<jats:italic>Third Edition Revised;<\/jats:italic>DSM-IV=Diagnostic and Statistical Manual of Mental Disorders,<jats:italic>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 (\u226535% 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<\/jats:italic>.<\/jats:p>","DOI":"10.1017\/s1092852900021635","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T03:14:29Z","timestamp":1470107669000},"page":"29-43","source":"Crossref","is-referenced-by-count":18,"title":["Social Anxiety and Premorbid Personality Disorders in Paranoid Schizophrenic Patients Treated With Clozapine"],"prefix":"10.1017","volume":"5","author":[{"given":"Stefano","family":"Pallanti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Quercioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo","family":"Pazzagli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2014,11,7]]},"reference":[{"key":"S1092852900021635_ref045","doi-asserted-by":"publisher","DOI":"10.2466\/pr0.1962.10.3.799"},{"key":"S1092852900021635_ref043","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n1203"},{"key":"S1092852900021635_ref084","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1992.01820010037005"},{"key":"S1092852900021635_ref040","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(99)00033-5"},{"key":"S1092852900021635_ref059","first-page":"1092","article-title":"Schizophrenia: manifestations, incidence and course in different cultures: a World Health Organization ten-country study [published correction appears","volume":"22","author":"Jablensky","year":"1992","journal-title":"Psychol Med Monogr"},{"key":"S1092852900021635_ref038","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700028488"},{"volume-title":"Schizofrenia. Scale per la valutazione dei Sintomi Positivi e Negativi","year":"1987","author":"Andreasen","key":"S1092852900021635_ref046"},{"key":"S1092852900021635_ref039","doi-asserted-by":"publisher","DOI":"10.1177\/070674379303801018"},{"key":"S1092852900021635_ref036","first-page":"32","volume-title":"Quando vince l'ombra. Problemi di psicopatologia clinica","author":"Callieri","year":"1982"},{"first-page":"10","volume-title":"La schizofrenia","year":"1998","key":"S1092852900021635_ref028"},{"first-page":"105","volume-title":"Psicopatologia Generale","year":"1964","key":"S1092852900021635_ref026"},{"key":"S1092852900021635_ref029","doi-asserted-by":"publisher","DOI":"10.1159\/000148659"},{"key":"S1092852900021635_ref024","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1192\/S0007125000296876","article-title":"The importance of serotonin-dopamine interactions in the action of clozapine","volume":"160","author":"Meltzer","year":"1992","journal-title":"Br J Psychiatry"},{"key":"S1092852900021635_ref023","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199619040-00003"},{"key":"S1092852900021635_ref044","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1176\/ajp.154.6.792","article-title":"Relapse in young schizophrenic patients: a prospective study of stressful life events, P300 measures, and coping","volume":"154","author":"Pallanti","year":"1997","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref017","doi-asserted-by":"publisher","DOI":"10.1016\/0010-440X(75)90019-X"},{"key":"S1092852900021635_ref010","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(70)90054-8"},{"key":"S1092852900021635_ref058","doi-asserted-by":"publisher","DOI":"10.1080\/00332747.1999.11024850"},{"key":"S1092852900021635_ref052","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1983.01790010017002"},{"key":"S1092852900021635_ref008","doi-asserted-by":"publisher","DOI":"10.2466\/pr0.1962.10.3.799"},{"first-page":"84","volume-title":"La teoria organodinamica della malattia mentale","year":"1977","key":"S1092852900021635_ref033"},{"key":"S1092852900021635_ref007","first-page":"39","article-title":"The psychopathology of the psychoses: a proposed revision","volume":"50","author":"Arlow","year":"1969","journal-title":"Int J Psychoanal"},{"key":"S1092852900021635_ref004","first-page":"490","volume-title":"Allgemeine Psychopathologie","author":"Jaspers","year":"1913"},{"key":"S1092852900021635_ref003","first-page":"21","volume-title":"Themes and Variations in European Psychiatry: an anthology","author":"Kretschmer","year":"1974"},{"key":"S1092852900021635_ref019","first-page":"439","article-title":"Emergence of obsessive compulsive symptoms during treatment with clozapine","volume":"53","author":"Baker","year":"1992","journal-title":"J Clin Psychiatry"},{"key":"S1092852900021635_ref022","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1176\/ajp.151.7.1096b","article-title":"Treatment of clozapine-induced obsessive-compulsive symptoms with sertraline","volume":"151","author":"Allen","year":"1994","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref011","doi-asserted-by":"publisher","DOI":"10.1037\/h0041029"},{"key":"S1092852900021635_ref030","first-page":"30","volume-title":"Schizophrenie","author":"Binswanger","year":"1957"},{"volume-title":"Des id\u00e8es de Jackson \u00e0 un mod\u00e8le organodynamique en psychiatrie","year":"1975","author":"Ey","key":"S1092852900021635_ref032"},{"key":"S1092852900021635_ref035","first-page":"176","volume-title":"Disturbi schizofrenici","author":"Cortina","year":"1984"},{"key":"S1092852900021635_ref031","first-page":"25","volume-title":"The Schizophrenic Reactions","author":"Arieti","year":"1970"},{"volume-title":"La schizophr\u00e9nie","year":"1927","author":"Minkowsky","key":"S1092852900021635_ref027"},{"key":"S1092852900021635_ref073","first-page":"27","article-title":"Fluoxetine efficacy in social phobia","volume":"54","author":"Van Ameringen","year":"1993","journal-title":"J Clin Psychiatry"},{"key":"S1092852900021635_ref016","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1819.1999.00477.x"},{"key":"S1092852900021635_ref093","first-page":"313","article-title":"The continuity of personality in schizophrenia","volume":"3","author":"Selzer","year":"1994","journal-title":"J Psychother Pract Res"},{"key":"S1092852900021635_ref074","first-page":"224","article-title":"Neurobiology of social phobia","volume":"54","author":"Tancer","year":"1993","journal-title":"J Clin Psychiatry"},{"key":"S1092852900021635_ref014","doi-asserted-by":"publisher","DOI":"10.3109\/00048679809062708"},{"volume-title":"Allgemeine Psychopathologie","year":"1913","author":"Jaspers","key":"S1092852900021635_ref025"},{"key":"S1092852900021635_ref089","first-page":"454","article-title":"Lack of effect of fluoxetine on plasma clozapine concentrations","volume":"55","author":"Eggert","year":"1994","journal-title":"J Clin Psychiatry"},{"key":"S1092852900021635_ref047","first-page":"141","volume-title":"Modern Problems in Pharmacopsychiatry: Anxiety","author":"Liebowitz","year":"1987"},{"key":"S1092852900021635_ref057","first-page":"111","volume-title":"Schizoph Res","volume":"16","author":"Baum","year":"1994"},{"key":"S1092852900021635_ref077","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1176\/ajp.156.5.799","article-title":"Olanzapine-induced obsessive-compulsive disorder","volume":"156","author":"Mottard","year":"1999","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref082","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199903000-00006"},{"key":"S1092852900021635_ref001","first-page":"16","volume-title":"Die beginnende Schizophrenie","author":"Conrad","year":"1958"},{"key":"S1092852900021635_ref013","doi-asserted-by":"publisher","DOI":"10.1159\/000284607"},{"key":"S1092852900021635_ref002","first-page":"20","volume-title":"Der verlust der nat\u00fcrlichen selbstverst\u00e4ndlichkeit. Ein beitrag zur psychopathologie symptomarmen schizophrenien","author":"Blankenburg","year":"1971"},{"volume-title":"Schizophrenic disorders","year":"1979","author":"Pao","key":"S1092852900021635_ref034"},{"key":"S1092852900021635_ref078","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199904000-00021"},{"key":"S1092852900021635_ref076","doi-asserted-by":"publisher","DOI":"10.1089\/cap.1999.9.277"},{"key":"S1092852900021635_ref015","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v59n0204"},{"key":"S1092852900021635_ref009","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1965.01730040056009"},{"key":"S1092852900021635_ref012","doi-asserted-by":"publisher","DOI":"10.3928\/0048-5713-19930701-05"},{"key":"S1092852900021635_ref006","first-page":"99","article-title":"Notes on some schizoid mechanisms","volume":"27","author":"Klein","year":"1946","journal-title":"Int J Psycho-anal"},{"key":"S1092852900021635_ref018","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1176\/ajp.149.2.272a","article-title":"Development of transient obsessive-compulsive symptoms during treatment with clozapine","volume":"149","author":"Patil","year":"1992","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref064","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1176\/ajp.154.2.239","article-title":"Dopamine reuptake site densities in patients with social phobia","volume":"154","author":"Tiihonen","year":"1997","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref085","doi-asserted-by":"publisher","DOI":"10.1016\/0920-9964(94)90022-1"},{"key":"S1092852900021635_ref048","first-page":"1","volume-title":"Questionario dei Sintomi-Base","author":"S\u00fcllwold","year":"1991"},{"key":"S1092852900021635_ref050","first-page":"147","volume-title":"Scand J Psychol","volume":"40","author":"Torgalsboen","year":"1999"},{"key":"S1092852900021635_ref051","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1982.04290060020005"},{"key":"S1092852900021635_ref053","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/11.4.554"},{"volume-title":"Psychiatrie","year":"1904","author":"Kraepelin","key":"S1092852900021635_ref054"},{"first-page":"145","volume-title":"Trattato di Psichiatria","year":"1907","key":"S1092852900021635_ref055"},{"key":"S1092852900021635_ref041","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1996.01830110060007"},{"key":"S1092852900021635_ref061","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.164.4.487"},{"key":"S1092852900021635_ref049","first-page":"51","volume-title":"Psychiatry Q","volume":"67","author":"Smith","year":"1996"},{"key":"S1092852900021635_ref056","first-page":"197","volume-title":"Dementia praecox o il gruppo delle schizofrenie","author":"Bleuler","year":"1985"},{"first-page":"1","volume-title":"Psychol Med Monogr","year":"1992","key":"S1092852900021635_ref060"},{"key":"S1092852900021635_ref062","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(99)00203-0"},{"key":"S1092852900021635_ref063","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(92)90020-F"},{"key":"S1092852900021635_ref021","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199503000-00005"},{"key":"S1092852900021635_ref065","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(94)90118-X"},{"key":"S1092852900021635_ref067","first-page":"274","article-title":"Anxiety disorders in familial parkinsonism","volume":"148","author":"Lauterbach","year":"1987","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref069","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1176\/ajp.138.12.1572","article-title":"School avoidance and social phobia triggered by haloperidol in patients with Tourette's disorder","volume":"138","author":"Mikkelsen","year":"1981","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref091","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1176\/ajp.150.11.1661","article-title":"True schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands","volume":"150","author":"Torgersen","year":"1993","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref070","first-page":"237","volume-title":"The Paradox of Anxiety Syndromes Comorbid With Bipolar Illnesses in Bipolar Disorder: clinical course and outcome","author":"Himmelhoch","year":"1999"},{"key":"S1092852900021635_ref071","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1987.01800180093014"},{"key":"S1092852900021635_ref072","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-81"},{"key":"S1092852900021635_ref079","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-198710000-00009"},{"key":"S1092852900021635_ref037","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n1105"},{"key":"S1092852900021635_ref075","doi-asserted-by":"publisher","DOI":"10.1176\/ps.49.4.526"},{"key":"S1092852900021635_ref080","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1176\/ajp.145.6.742","article-title":"Adjunctive alprazolam for chizophrenia with panic anxiety: clinical observation and pathogenetic implications","volume":"145","author":"Kahn","year":"1988","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref081","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.156.6.973a"},{"key":"S1092852900021635_ref083","first-page":"402","article-title":"Panic attacks with psychotic features","volume":"57","author":"Galynker","year":"1996","journal-title":"J Clin Psychiatry"},{"key":"S1092852900021635_ref086","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-199208000-00022"},{"key":"S1092852900021635_ref087","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1176\/ajp.153.6.820","article-title":"Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors","volume":"153","author":"Centorrino","year":"1996","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref088","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199805000-00009"},{"key":"S1092852900021635_ref066","first-page":"19","article-title":"Magnetic resonance spectroscopy in social phobia","volume":"54","author":"Davidson","year":"1993","journal-title":"J Clin Psychiatry"},{"key":"S1092852900021635_ref090","unstructured":"Stern RG , Meiraj H , Ballou S , et al. High social phobia scale scores in schizophrenia do not correlate with psychosis symptom severity scores. Presented at: American Psychiatric Association 152nd Annual Meeting; May 15-20, 1999; Washington DC; abstract book:66."},{"key":"S1092852900021635_ref092","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1995.03950160046009"},{"key":"S1092852900021635_ref005","first-page":"135","article-title":"The onset of schizophrenia","volume":"151","year":"1927","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref068","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1176\/ajp.147.2.217","article-title":"Anxiety disorders in patients with Parkinson's disease","volume":"147","author":"Stein","year":"1990","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref020","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1176\/ajp.150.5.836a","article-title":"Development of obsessive compulsive symptoms during clozapine treatment","volume":"150","author":"Patel","year":"1993","journal-title":"Am J Psychiatry"},{"key":"S1092852900021635_ref042","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1176\/ajp.152.10.1444","article-title":"D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients","volume":"152","author":"Nordstr\u00f6m","year":"1995","journal-title":"Am J Psychiatry"}],"container-title":["CNS Spectrums"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S1092852900021635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T10:55:49Z","timestamp":1749034549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S1092852900021635\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9]]},"references-count":93,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2000,9]]}},"alternative-id":["S1092852900021635"],"URL":"https:\/\/doi.org\/10.1017\/s1092852900021635","relation":{},"ISSN":["1092-8529","2165-6509"],"issn-type":[{"type":"print","value":"1092-8529"},{"type":"electronic","value":"2165-6509"}],"subject":[],"published":{"date-parts":[[2000,9]]}}}