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Social Anxiety and Premorbid Personality Disorders in Paranoid Schizophrenic Patients Treated With Clozapine

Published online by Cambridge University Press:  07 November 2014

Stefano Pallanti ,
Leonardo Quercioli  and
Adolfo Pazzagli
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Abstract

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.

Type
Feature Articles
Information
CNS Spectrums , Volume 5 , Issue 9: The Anxiety-Psychosis Spectrum , September 2000 , pp. 29 - 43
Copyright
Copyright © Cambridge University Press 2000

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References

1.Conrad, K. Die beginnende Schizophrenie. Thieme, G, ed. Stuttgart; 1958:16–26.Google Scholar
2.Blankenburg, W. Der verlust der natürlichen selbstverständlichkeit. Ein beitrag zur psychopathologie symptomarmen schizophrenien. Enke, , ed. Stuttgart; 1971:20–39.Google Scholar
3.Kretschmer, E. Der sensitive beziehungwahn. In: SR, Hirsch, Shepherd, M, eds. Themes and Variations in European Psychiatry: an anthology. Bristol, England: Wright; 1974:21–36.Google Scholar
4.Jaspers, K (1913). Allgemeine Psychopathologie. Springer, Berlin. Italian transl: Psicopatologia Generale. Ed: Il pensiero scientifico Roma; 1964:490.Google Scholar
5.The American Journal of Psychiatry. The onset of schizophrenia 1927. Am J Psychiatry. 1994;151(suppl 6):135–139.Google Scholar
6.Klein, M. Notes on some schizoid mechanisms. Int J Psycho-anal. 1946;27:99–110.Google ScholarPubMed
7.Arlow, J, Brenner, C. The psychopathology of the psychoses: a proposed revision. Int J Psychoanal. 1969;50:5–14. 39.Google ScholarPubMed
Overall, JE, Gorham, DR. The Brief Psychiatric Rating Scale. Psychol Rep. 1962;10:799–812.CrossRefGoogle Scholar
8.Burnham, DL. Separation anxiety: a factor in the object relations of schizophrenic patients. Arch Gen Psychiatry. 1965;13(4):346–358.CrossRefGoogle ScholarPubMed
9.Feinstein, AR. The pre-therapeutic classification of comorbidity in chronic disease. J Chronic Disease. 1970;23:455–468CrossRefGoogle ScholarPubMed
10.Meehl, PE. Schizotaxia, schizotypy, schizophrenia. Am Psychol. 1962;17:827–838.CrossRefGoogle Scholar
11.Hollander, E. Obsessive-compulsive spectrum disorders: an overview. Psychiatr Ann. 1993;23:355–358CrossRefGoogle Scholar
12.Akiskal, HS, Cassano, GB, Musetti, L, et al.Psychopathology, temperament, and past course in primary major depressions: review of evidence for a bipolar spectrum. Psychopathology. 1989;22:268–277.CrossRefGoogle ScholarPubMed
13.Cosoff, SJ, Hafner, RJ. The prevalence of comorbid anxiety in schizophrenia, schizoaffective disorder and bipolar disorder. Aust NZ J Psychiatry. 1998;32(1):67–72.CrossRefGoogle ScholarPubMed
14.Cassano, GB, Pini, S, Saettoni, M, et al.Occurrence and clinical correlates of psychiatric comorbidity in patients with psychotic disorders. J Clin Psychiatry. 1998;59(2):60–68.CrossRefGoogle ScholarPubMed
15.Higuchi, H, Kamata, M, Yoshimoto, M, et al.Panic attacks in patients with chronic schizophrenia: a complication of long-term neuroleptic treatment. Psychiatry Clin Neurosci. 1999;53(1):91–94.CrossRefGoogle ScholarPubMed
16.Van Putten, T. The many faces of akathisia. Compr Psychiatry. 1975;16:43–47.CrossRefGoogle ScholarPubMed
17.Patil, VJ. Development of transient obsessive-compulsive symptoms during treatment with clozapine. Am J Psychiatry. 1992;149(letter):272.Google ScholarPubMed
18.Baker, RW, Chengappa, KNR, Baird, JW, et al.Emergence of obsessive compulsive symptoms during treatment with clozapine. J Clin Psychiatry. 1992;53:439–442.Google ScholarPubMed
19.Patel, B, Tandon, R. Development of obsessive compulsive symptoms during clozapine treatment. Am J Psychiatry. 1993;150:836.Google ScholarPubMed
20.Levkovitch, Y, Kronnenberg, Y, Gaoni, B. Can Clozapine trigger OCD? J Am Acad Child Adolesc Psychiatry. 1995;34(3):263.CrossRefGoogle ScholarPubMed
21.Allen, L, Tejera, C. Treatment of clozapine-induced obsessive-compulsive symptoms with sertraline. Am J Psychiatry. 1994;151(letter):1096–1097.Google ScholarPubMed
22.Poyourovsky, M, Hermesh, H, Weizman, A. Fluvoxamine treatment in clozapine-induced obsessive-compulsive symptoms in schizophrenic patients. Clin Neuropharmacol. 1996;19(4):305–313.CrossRefGoogle Scholar
23.Meltzer, HY. The importance of serotonin-dopamine interactions in the action of clozapine. Br J Psychiatry. 1992;160(suppl 17):22–29.CrossRefGoogle Scholar
24.Jaspers, K (1913). Allgemeine Psychopathologie. Springer, Berlin.Google Scholar
Italian transl: Psicopatologia Generale. Ed: Ilpensiero scientifico Roma; 1964:105–107.Google Scholar
25.Minkowsky, E (1927). La schizophrénie. Payot, ParisGoogle Scholar
Italian transl: La schizofrenia. Einaudi, Torino, 1998:10–13.Google Scholar
26.Von Gebsattel, VE. Die welt des zwangskranken. Monatschr Psychiatr Neurol. 1938;99:10–74.CrossRefGoogle Scholar
27.Binswanger, L. Schizophrenie. Neske Verlag, Pfullingen; 1957:30–36.Google Scholar
28.Arieti, S. The concept of schizophrenia. In: Cancro, R, ed. The Schizophrenic Reactions. New York, NY: Brunner/Mazel; 1970:25–40Google Scholar
29.Ey, H. (1975) Des idèes de Jackson à un modèle organodynamique en psychiatrie. Edouard Privat: Toulouse.Google Scholar
Italian transl: La teoria organodinamica della malattia mentale. Roma: Astrolabio-Ubaldini Editore; 1977:84–88.Google Scholar
30.Pao, PN. (1979) Schizophrenic disorders. Int Univ. Press, Inc., New York.Google Scholar
Italian transl: Disturbi schizofrenici. Cortina, , ed. Milano; 1984:176–181.Google Scholar
31.Callieri, B. Quando vince l'ombra. Problemi di psicopatologia clinica. Nuova, Città, ed. Roma; 1982:32–38.Google Scholar
32.Emsley, RA, Oosthuizen, PP, Joubert, AF, et al.Depressive and anxiety symptoms in patients with schizophrenia and schizophreniform disorder. J Clin Psychiatry. 1999;60:747–751.CrossRefGoogle ScholarPubMed
33.Birchwood, M, Mason, R, Macmillan, F, et al.Depression, demoralisation and control over psychotic illness: a comparison of depressed and non-depressed patients with a chronic psychosis. Psychol Med. 1993;23:387–395.CrossRefGoogle ScholarPubMed
34.Roy, A. Anxiety and suicide. Can J Psychiatry. 1993;38(10 letter):694–695.CrossRefGoogle ScholarPubMed
35.Pallanti, S, Quercioli, L, Pazzagli, A. Effects of clozapine on awareness of illness and cognition in schizophrenia. Psychiatry Res. 1999;86:239–249.CrossRefGoogle ScholarPubMed
36.Kendler, KS, Gallagher, TJ, Abelson, JM, et al.Lifetime prevalence, demographic risk factors, and diagnostic validity of nonaffective psychosis as assessed in a US community sample: the national comorbidity survey. Arch Gen Psychiatry. 1996;53:1022–1031.CrossRefGoogle Scholar
37.Nordström, AL, Farde, L, Nyberg, S, et al.D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry. 1995;152:1444–1449.Google ScholarPubMed
38.Pallanti, S, Quercioli, L, Rossi, A, et al.The emergence of social phobia during clozapine treatment and its response to fluoxetine augmentation. J Clin Psychiatry. 1999;60(12):819–823.CrossRefGoogle ScholarPubMed
39.Pallanti, S, Quercioli, L, Pazzagli, A. Relapse in young schizophrenic patients: a prospective study of stressful life events, P300 measures, and coping. Am J Psychiatry. 1997;154:792–798.Google ScholarPubMed
40.Overall, JE, Gorham, DR. The Brief Psychiatric Rating Scale. Psychol Rep. 1962;10:799–812.CrossRefGoogle Scholar
41.Andreasen, NC. Schizofrenia. Scale per la valutazione dei Sintomi Positivi e Negativi. Moscarelli, M, Maffei, C, eds. Milano, Italy: Cortina; 1987.Google Scholar
42.Liebowitz, MR. Social phobia. In: Klein, DF, ed. Modern Problems in Pharmacopsychiatry: Anxiety. Basel, Switzerland: Karger; 1987:141–173.Google Scholar
43.Süllwold, L. FBF. In: Stanghellini, G, Strik, WK, Cabras, PL, eds. Questionario dei Sintomi-Base. Florence, Italy: Organizzazioni Speciali; 1991:1–20.Google Scholar
44.Smith, TE, Grabstein, E, Kentros, M, et al.Axis II diagnoses and treatment refractoriness in schizophrenia. Psychiatry Q. 1996;67(1):51–64.Google Scholar
45.Torgalsboen, AK. Comorbidity in schizophrenia: a prognostic study of personality disorders in recovered and non-recovered schizophrenia patients. Scand J Psychol. 1999;40(2):147–152.Google Scholar
46.Parnas, J, Schulsinger, F, Schulsinger, H. Behavioral precursors of schizophrenia spectrum: a prospective study. Arch Gen Psychiatry. 1982;39:658–664.CrossRefGoogle ScholarPubMed
47.Gunderson, JG, Siever, LJ, Spaulding, E. The search for a schizotype: crossing the border again. Arch Gen Psychiatry. 1983;40:15–22.CrossRefGoogle Scholar
48.Torgersen, S. Relationship of schizotypal personality disorder to schizophrenia: genetics. Schizophr Bull. 1985;11:554–563.CrossRefGoogle ScholarPubMed
49.Kraepelin, E (1904). Psychiatrie. VII Ed. Leipzig: Berth.Google Scholar
Italian transl: Trattato di Psichiatria. Milano: Vallardi; 1907:145–147.Google Scholar
50.Bleuler, E. Dementia praecox oder gruppe der schizophrenien. F, Deuticke, Leipzig, trans-eds. Dementia praecox o il gruppo delle schizofrenie. Roma: La Nuova Italia Scientifica; 1985:197–203.Google Scholar
51.Baum, KM, Walker, EF. Childhood behavioral precursors of adult symptom dimensions in schizophrenia. Schizoph Res. 1994;16:111–120.Google Scholar
52.Lysaker, PH, Bell, MD, Kaplan, E, et al.Personality and psychopathology in schizophrenia: the association between personality traits and symptoms. Psychiatry. 1999;62(1):36–48.CrossRefGoogle ScholarPubMed
53.Jablensky, A, Sartorius, N, Ernberg, G, et al.Schizophrenia: manifestations, incidence and course in different cultures: a World Health Organization ten-country study [published correction appears in Psychol Med Monogr. 1992;22:1092].Google Scholar
Psychol Med Monogr. 1992;(suppl 20):1–97.Google Scholar
54.Malla, AK, Norman, RM. Prodromal symptoms in schizophrenia. Br J Psychiatry. 1994;164(4):487–493.CrossRefGoogle ScholarPubMed
55.Solano, RJJ, Gonzalez De Chavez, M. Premorbid personality disorders in schizophrenia. Schizoph Res. 2000;44:137–144.CrossRefGoogle Scholar
56.Potts, NLS, Davidson, JRT. Social phobia: biological aspects and pharmacotherapy. Prog Neuropsychopharmacol Biol Psychiatry. 1992;16:635–646.CrossRefGoogle ScholarPubMed
57.Tiihonen, J, Kuikka, J, Bergstrom, K, et al.Dopamine reuptake site densities in patients with social phobia. Am J Psychiatry. 1997;154(2):239–242.Google ScholarPubMed
58.Potts, NLS, Davidson, JRT, Krishnan, KR, et al.Magnetic resonance imaging in patients with social phobia. Psychiatry Res. 1994;52:35–42.CrossRefGoogle ScholarPubMed
59.Davidson, JRT, Boyko, O, Charles, HC. Magnetic resonance spectroscopy in social phobia. J Clin Psychiatry. 1993;54(suppl 12):19–25.Google ScholarPubMed
60.Lauterbach, EC, Duvoisin, RC. Anxiety disorders in familial parkinsonism. Am J Psychiatry. 1987;148(letter):274.Google Scholar
61.Stein, MB, Heuser, IJ, Juncos, JL, et al.Anxiety disorders in patients with Parkinson's disease. Am J Psychiatry. 1990;147:217–220.Google ScholarPubMed
62.Mikkelsen, EJ, Detlor, J, Cohen, DJ. School avoidance and social phobia triggered by haloperidol in patients with Tourette's disorder. Am J Psychiatry. 1981;138(12):1572–1576.Google ScholarPubMed
63.Himmelhoch, JM. The Paradox of Anxiety Syndromes Comorbid With Bipolar Illnesses in Bipolar Disorder: clinical course and outcome. Goldberg, JF, Harrow, eds. Washington DC: American Psychiatric Association; 1999:237–258.Google Scholar
64.Cloninger, RC. A systematic method for clinical description and classification of personality variants. Arch Gen Psychiatry. 1987;44:573–588.CrossRefGoogle ScholarPubMed
65.Benjamin, J, Patterson, C, Greenberg, BD, Murphy, DL, Hamer, DH. Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genet. 1996;12:81–84.CrossRefGoogle ScholarPubMed
66.Van Ameringen, M, Mancini, C, Streiner, DL. Fluoxetine efficacy in social phobia. J Clin Psychiatry. 1993;54:27–33.Google ScholarPubMed
67.Tancer, ME. Neurobiology of social phobia. J Clin Psychiatry. 1993;54(suppl 12):224–228.Google ScholarPubMed
68.Ashleigh, EA, Larsen, PD. A syndrome of increased affect in response to risperidone among patients with schizophrenia. Psychiatr Serv. 1998;49(4):526–528.CrossRefGoogle ScholarPubMed
69.Hanna, GL, Fluent, TE, Fischer, DJ. Separation anxiety in children and adolescents treated with risperidone. J Child Adolesc Psychopharmacol. 1999;9(4):277–283.CrossRefGoogle ScholarPubMed
70.Mottard, JP, de la Sablonnière, JF. Olanzapine-induced obsessive-compulsive disorder. Am J Psychiatry. 1999;156(5 letter):799–800.CrossRefGoogle ScholarPubMed
71.Mandalos, GE, Szarek, BL. New-onset panic attacks in a patient treated with olanzapine. J Clin Psychopharmacol. 1999;19(2):191.CrossRefGoogle Scholar
72.Sandberg, L, Siris, SG. Panic disorder in schizophrenia. J Nerv Ment Dis. 1987;175(10):627–628.CrossRefGoogle ScholarPubMed
73.Kahn, JP, Puertollano, MA, Schane, MD, et al.Adjunctive alprazolam for chizophrenia with panic anxiety: clinical observation and pathogenetic implications. Am J Psychiatry. 1988;145(6):742–744.Google Scholar
74.Strous, RD, Patel, JK, Zimmet, S, et al.Clozapine and paroxetine in the treatment of schizophrenia with obsessive-compulsive features. Am J Psychiatry. 1999;156(6 letter):973–974.CrossRefGoogle ScholarPubMed
75.Poyourovsky, M, Isakov, V, Hromnikov, S, et al.Fluvoxamine treatment of obsessive-compulsive symptoms in schizophrenic patients: an add-on open study. Int Clin Psychopharmacol. 1999;14(2):95–100.CrossRefGoogle Scholar
76.Galynker, I, Ieronimo, C, Perez-Acquino, A, et al.Panic attacks with psychotic features. J Clin Psychiatry. 1996;57(9):402–406.Google ScholarPubMed
77.Tien, AY, Eaton, WW. Psychopathologic precursors and sociodemographic risk factors for the schizophrenia syndrome. Arch Gen Psychiatry. 1992;49(1):37–46.CrossRefGoogle ScholarPubMed
78.Penn, DL, Hope, DA, Spaulding, W, et al.Social anxiety in schizophrenia. Schizoph Res. 1994;11:277–284.CrossRefGoogle ScholarPubMed
79.Black, B, Uhde, TW, Tancer, ME. Fluoxetine for the treatment of social phobia. J Clin Psychopharmacol. 1992;12:293–295.CrossRefGoogle ScholarPubMed
80.Centorrino, F, Baldessarini, RJ, Frankenburg, FR, et al.Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors. Am J Psychiatry. 1996;153:820–822.Google ScholarPubMed
81.Spina, E, Avenoso, A, Facciolà, G, et al.Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolities in patients with schizophrenia. Int Clin Psychopharmacol. 1998;13(3):141–145.CrossRefGoogle ScholarPubMed
82.Eggert, AE, Crismon, ML, Dorson, PG. Lack of effect of fluoxetine on plasma clozapine concentrations. J Clin Psychiatry. 1994;55(letter):454–455.Google ScholarPubMed
83.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.Google Scholar
84.Torgersen, S, Onstad, S, Skre, I, et al.True schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands. Am J Psychiatry. 1993;150:1661–1667.Google ScholarPubMed
85.Kendler, KS, McGuire, M, Gruenberg, AM, et al.Schizotypal symptoms and signs in the Roscommon Family Study: their factor structure and familial relationship with psychotic and affective disorders. Arch Gen Psychiatry. 1995;52:296–303.CrossRefGoogle ScholarPubMed
86.Selzer, MA, Schwartz, F. The continuity of personality in schizophrenia. J Psychother Pract Res. 1994;3:313–324.Google ScholarPubMed