Hostname: page-component-745bb68f8f-kw2vx Total loading time: 0 Render date: 2025-01-07T08:57:58.419Z Has data issue: false hasContentIssue false
  • English
  • Français

Antiserotonergic antipsychotics are associated with obsessive–compulsive symptoms in schizophrenia

Published online by Cambridge University Press:  05 April 2011

F. Schirmbeck ,
C. Esslinger ,
F. Rausch ,
S. Englisch ,
A. Meyer-Lindenberg  and
M. Zink
F. Schirmbeck
Affiliation:
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany
C. Esslinger
Affiliation:
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany
F. Rausch
Affiliation:
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany
S. Englisch
Affiliation:
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany
A. Meyer-Lindenberg
Affiliation:
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany
M. Zink*
Affiliation:
Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Mannheim, Germany
*
*Address for correspondence: M. Zink, M.D., Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, PO Box 12 21 20, D-68072 Mannheim, Germany. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Epidemiological investigations show that up to 30% of schizophrenic patients suffer from obsessive–compulsive symptoms (OCS) associated with negative impact on the general prognosis. It has been proposed that antiserotonergic second-generation antipsychotics (SGAs) might induce OCS, but investigations of large samples integrating psychopathology, neuropsychology and psychopharmacology are missing.

Method

We stratified 70 patients with schizophrenia according to their mode of antipsychotic treatment: clozapine and olanzapine (group I) compared with aripiprazole and amisulpride (group II). The groups were matched according to age, sex, educational levels and severity of the psychotic disorder (Positive and Negative Syndrome Scale). As the primary endpoint, we evaluated OCS severity (Yale–Brown Obsessive–Compulsive Scale).

Results

OCS were significantly more prevalent and severe in group I, in which OCS severity correlated with dosage of clozapine and duration of treatment. Pronounced cognitive deficits in group I were found in visuospatial perception and visual memory (Wechsler Adult Intelligence Scale-Revised block design, Rey–Osterrieth Complex Figure Test), impulse inhibition (go/no-go test), higher perseveration scores (Wisconsin Card Sorting Test) and reduced set-shift abilities (Trail Making Test Part B, Set-shift Task). These cognitive domains correlated with OCS severity.

Conclusions

OCS in schizophrenia are associated with antiserotonergic SGA treatment, but longitudinal studies have to prove causality. Before starting treatment with antiserotonergic SGAs, specific neurocognitive domains should be evaluated, as visuospatial learning and impulse inhibition performance might allow early detection of OCS secondary to antipsychotic treatment in schizophrenia.

Keywords

Antipsychoticclozapinecompulsiveobsessiveschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 11 , November 2011 , pp. 2361 - 2373
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Beckmann, H, Bartsch, AJ, Neumärker, K-J, Pfuhlmann, B, Verdaguer, MF, Franzek, E (2000). Schizophrenias in the Wernicke–Kleist–Leonhard school. American Journal of Psychiatry 157, 1024–1025.CrossRefGoogle ScholarPubMed
Berman, I, Merson, A, Viegner, B, Losonczy, MF, Pappas, D, Green, AI (1998). Obsessions and compulsions as a distinct cluster of symptoms in schizophrenia: a neuropsychological study. Journal of Nervous and Mental Disease 186, 150–156.CrossRefGoogle ScholarPubMed
Bottas, A, Cooke, RG, Richter, MA (2005). Comorbidity and pathophysiology of obsessive–compulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia? Journal of Psychiatry and Neuroscience 30, 187–193.Google ScholarPubMed
Buckley, PF, Miller, BJ, Lehrer, DS, Castle, DJ (2009). Psychiatric comorbidities and schizophrenia. Schizophrenia Bulletin 35, 383–402.CrossRefGoogle ScholarPubMed
Bymaster, FP, Rasmussen, K, Calligaro, DO, Nelson, DL, DeLapp, NW, Wong, DT, Moore, NA (1997). In vitro and in vivo biochemistry of olanzapine: a novel, atypical antipsychotic drug. Journal of Clinical Psychiatry 58 (Suppl. 10), 28–36.Google ScholarPubMed
Catapano, F, Perris, F, Fabrazzo, M, Cioffi, V, Giacco, D, De Santis, V, Maj, M (2010). Obsessive–compulsive disorder with poor insight: a three-year prospective study. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, 323–330.CrossRefGoogle ScholarPubMed
Chang, JS, Ahn, YM, Park, HJ, Lee, KY, Kim, SH, Kang, UG, Kim, YS (2008). Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychiatry 69, 720–731.CrossRefGoogle ScholarPubMed
Connor, KM, Payne, VM, Gadde, KM, Zhang, W, Davidson, JR, Connor, KM, Payne, VM, Gadde, KM, Zhang, W, Davidson, JRT (2005). The use of aripiprazole in obsessive–compulsive disorder: preliminary observations in 8 patients. Journal of Clinical Psychiatry 66, 49–51.CrossRefGoogle ScholarPubMed
Coward, DM (1992). General pharmacology of clozapine. British Journal of Psychiatry Supplementum 17, 5–11.CrossRefGoogle Scholar
Cunill, R, Castells, X, Simeon, D (2009). Relationships between obsessive–compulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis. Journal of Clinical Psychiatry 70, 70–82.CrossRefGoogle ScholarPubMed
de Haan, L, Beuk, N, Hoogenboom, B, Dingemans, P, Linszen, D (2002). Obsessive–compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders. Journal of Clinical Psychiatry 63, 104–107.CrossRefGoogle ScholarPubMed
de Haan, L, Dudek-Hodge, C, Verhoeven, Y, Denys, D (2009). Prevalence of psychotic disorders in patients with obsessive–compulsive disorder. CNS Spectrums 14, 415–417.CrossRefGoogle ScholarPubMed
de Haan, L, Hoogeboom, B, Beuk, N, Wouters, L, Dingemans, PM, Linszen, DH (2006). Reliability and validity of the Yale–Brown Obsessive–Compulsive Scale in schizophrenia patients. Psychopharmacology Bulletin 39, 25–30.Google ScholarPubMed
de Haan, L, Linszen, DH, Gorsira, R (1999). Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders. Journal of Clinical Psychiatry 60, 364–365.CrossRefGoogle ScholarPubMed
de Haan, L, Oekeneva, A, van Amelsvoort, T, Linszen, D (2004). Obsessive–compulsive disorder and treatment with clozapine in 200 patients with recent-onset schizophrenia or related disorders. European Psychiatry: the Journal of the Association of European Psychiatrists 19, 524.CrossRefGoogle ScholarPubMed
Englisch, S, Esslinger, C, Inta, D, Weinbrenner, A, Peus, V, Gutschalk, A, Schirmbeck, F, Zink, M (2009). Clozapine-induced obsessive compulsive syndromes improve in combination with aripiprazole. Clinical Neuropharmacology 32, 227–229.CrossRefGoogle ScholarPubMed
Englisch, S, Zink, M (2008). Combined antipsychotic treatment involving clozapine and aripiprazole. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32, 1386–1392.CrossRefGoogle ScholarPubMed
Erbfelder, E, Faul, F, Buchner, A (1996). GPOWER: a general power analysis program. Behavior Research Methods, Instruments, Computers 28, 1–11.CrossRefGoogle Scholar
Fink, M, Taylor, MA (2001). The many varieties of catatonia. European Archives of Psychiatry and Clinical Neuroscience 251 (Suppl. 1), I8–I13.CrossRefGoogle ScholarPubMed
Green, MF, Nuechterlein, KH, Kern, RS, Baade, LE, Fenton, WS, Gold, JM, Keefe, RS, Mesholam-Gately, R, Seidman, LJ, Stover, E, Marder, SR (2008). Functional co-primary measures for clinical trials in schizophrenia: results from the MATRICS Psychometric and Standardization Study. American Journal of Psychiatry 165, 221–228.CrossRefGoogle ScholarPubMed
Guillem, F, Satterthwaite, J, Pampoulova, T, Stip, E (2009). Relationship between psychotic and obsessive compulsive symptoms in schizophrenia. Schizophrenia Research 115, 358–362.CrossRefGoogle ScholarPubMed
Hwang, MY, Kim, SW, Yum, SY, Opler, LA (2009). Management of schizophrenia with obsessive–compulsive features. Psychiatric Clinics of North America 32, 835–851.CrossRefGoogle ScholarPubMed
Hwang, MY, Morgan, JE, Losconzcy, MF (2000). Clinical and neuropsychological profiles of obsessive–compulsive schizophrenia: a pilot study. Journal of Neuropsychiatry and Clinical Neurosciences 12, 91–94.CrossRefGoogle ScholarPubMed
Kern, RS, Nuechterlein, KH, Green, MF, Baade, LE, Fenton, WS, Gold, JM, Keefe, RS, Mesholam-Gately, R, Mintz, J, Seidman, LJ, Stover, E, Marder, SR (2008). The MATRICS Consensus Cognitive Battery, part 2: co-norming and standardization. American Journal of Psychiatry 165, 214–220.CrossRefGoogle ScholarPubMed
Kim, SW, Shin, IS, Kim, JM, Yang, SJ, Hwang, MY, Yoon, JS (2008). Amisulpride improves obsessive–compulsive symptoms in schizophrenia patients taking atypical antipsychotics: an open-label switch study. Journal of Clinical Psychopharmacology 28, 349–352.CrossRefGoogle ScholarPubMed
Klepsch, R, Zaworka, W, Hand, I, Luenenschloss, K, Jauernig, G (1993). Hamburger Zwangsinventar – Kurzform (HZI-K). Manual [Hamburg Obsessive-Compulsive Inventory – short form (HZI-K)]. Goettingen: Beltz Test GmbH.Google Scholar
Kuelz, AK, Hohagen, F, Voderholzer, U (2004). Neuropsychological performance in obsessive–compulsive disorder: a critical review. Biological Psychology 65, 185–236.CrossRefGoogle ScholarPubMed
Kumbhani, SR, Roth, RM, Kruck, CL, Flashman, LA, McAllister, TW (2010). Nonclinical obsessive–compulsive symptoms and executive functions in schizophrenia. Journal of Neuropsychiatry and Clinical Neurosciences 22, 304–312.CrossRefGoogle ScholarPubMed
Kwon, JS, Joo, YH, Nam, HJ, Lim, M, Cho, EY, Jung, MH, Choi, JS, Kim, B, Kang, DH, Oh, S, Park, T, Hong, KS (2009). Association of the glutamate transporter gene SLC1A1 with atypical antipsychotics-induced obsessive–compulsive symptoms. Archives of General Psychiatry 66, 1233–1241.CrossRefGoogle ScholarPubMed
Lim, M, Park, DY, Kwon, JS, Joo, YH, Hong, KS (2007). Prevalence and clinical characteristics of obsessive–compulsive symptoms associated with atypical antipsychotics. Journal of Clinical Psychopharmacology 27, 712–713.CrossRefGoogle ScholarPubMed
Lin, SK, Su, SF, Pan, CH (2006). Higher plasma drug concentration in clozapine-treated schizophrenic patients with side effects of obsessive/compulsive symptoms. Therapeutic Drug Monitoring 28, 303–307.CrossRefGoogle ScholarPubMed
Linden, DE (2006). How psychotherapy changes the brain – the contribution of functional neuroimaging. Molecular Psychiatry 11, 528–538.CrossRefGoogle ScholarPubMed
Lopez-Gil, X, Artigas, F, Adell, A (2010). Unraveling monoamine receptors involved in the action of typical and atypical antipsychotics on glutamatergic and serotonergic transmission in prefrontal cortex. Current Pharmaceutical Design 16, 502–515.CrossRefGoogle ScholarPubMed
Lykouras, L, Alevizos, B, Michalopoulou, P, Rabavilas, A (2003). Obsessive–compulsive symptoms induced by atypical antipsychotics. A review of the reported cases. Progress in Neuro-Psychopharmacology and Biological Psychiatry 27, 333–346.CrossRefGoogle ScholarPubMed
Lysaker, PH, Bryson, GJ, Marks, KA, Greig, TC, Bell, MD (2002). Association of obsessions and compulsions in schizophrenia with neurocognition and negative symptoms. Journal of Neuropsychiatry and Clinical Neurosciences 14, 449–453.CrossRefGoogle ScholarPubMed
Lysaker, PH, Lancaster, RS, Nees, MA, Davis, LW (2004). Patterns of obsessive–compulsive symptoms and social function in schizophrenia. Psychiatry Research 125, 139–146.CrossRefGoogle ScholarPubMed
Lysaker, PH, Whitney, KA (2009). Obsessive–compulsive symptoms in schizophrenia: prevalence, correlates and treatment. Expert Review of Neurotherapeutics 9, 99–107.CrossRefGoogle ScholarPubMed
McCreary, AC, Jones, CA (2010). Antipsychotic medication: the potential role of 5-HT1A receptor agonism. Current Pharmaceutical Design 16, 516–521.CrossRefGoogle Scholar
Meltzer, HY (1994). An overview of the mechanism of action of clozapine. Journal of Clinical Psychiatry 55 (Suppl. B), 47–52.Google ScholarPubMed
Meltzer, HY (1995). Role of serotonin in the action of atypical antipsychotic drugs. Clinical Neuroscience 3, 64–75.Google ScholarPubMed
Meltzer, HY, Huang, M (2008). In vivo actions of atypical antipsychotic drug on serotonergic and dopaminergic systems. Progress in Brain Research 172, 177–197.CrossRefGoogle ScholarPubMed
Meltzer, HY, Li, Z, Kaneda, Y, Ichikawa, J (2003). Serotonin receptors: their key role in drugs to treat schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 27, 1159–1172.CrossRefGoogle ScholarPubMed
Meltzer, HY, Sumiyoshi, T (2008). Does stimulation of 5-HT1A receptors improve cognition in schizophrenia? Behavioural Brain Research 195, 98–102.CrossRefGoogle ScholarPubMed
Mukhopadhaya, K, Krishnaiah, R, Taye, T, Nigam, A, Bailey, AJ, Sivakumaran, T, Fineberg, NA (2009). Obsessive–compulsive disorder in UK clozapine-treated schizophrenia and schizoaffective disorder: a cause for clinical concern. Journal of Psychopharmacology 23, 6–13.CrossRefGoogle ScholarPubMed
Newman-Tancredi, A (2010). The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. Current Opinion in Investigational Drugs 11, 802–812.Google Scholar
Niendam, TA, Berzak, J, Cannon, TD, Bearden, CE (2009). Obsessive compulsive symptoms in the psychosis prodrome: correlates of clinical and functional outcome. Schizophrenia Research 108, 170–175.CrossRefGoogle ScholarPubMed
Nuechterlein, KH, Green, MF, Kern, RS, Baade, LE, Barch, DM, Cohen, JD, Essock, S, Fenton, WS, Frese, FJ III, Gold, JM, Goldberg, T, Heaton, RK, Keefe, RS, Kraemer, H, Mesholam-Gately, R, Seidman, LJ, Stover, E, Weinberger, DR, Young, AS, Zalcman, S, Marder, SR (2008). The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. American Journal of Psychiatry 165, 203–213.CrossRefGoogle ScholarPubMed
Öngür, D, Goff, DC (2005). Obsessive–compulsive symptoms in schizophrenia: associated clinical features, cognitive function and medication status. Schizophrenia Research 75, 349–362.CrossRefGoogle ScholarPubMed
Patel, DD, Laws, KR, Padhi, A, Farrow, JM, Mukhopadhaya, K, Krishnaiah, R, Fineberg, NA (2010). The neuropsychology of the schizo-obsessive subtype of schizophrenia: a new analysis. Psychological Medicine 40, 921–933.CrossRefGoogle ScholarPubMed
Pogarell, O, Hamann, C, Poepperl, G, Juckel, G, Chouker, M, Zaudig, M, Riedel, M, Moeller, HJ, Hegerl, U, Tatsch, K (2003). Elevated brain serotonin transporter availability in patients with obsessive–compulsive disorder. Biological Psychiatry 54, 1406–1413.CrossRefGoogle ScholarPubMed
Poyurovsky, M, Faragian, S, Pashinian, A, Heidrach, L, Fuchs, C, Weizman, R, Koran, L (2008). Clinical characteristics of schizotypal-related obsessive–compulsive disorder. Psychiatry Research 159, 254–258.CrossRefGoogle ScholarPubMed
Poyurovsky, M, Glick, I, Koran, LM (2010). Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive–compulsive symptoms. Journal of Psychopharmacology 24, 861–866.CrossRefGoogle ScholarPubMed
Poyurovsky, M, Koran, LM (2005). Obsessive–compulsive disorder (OCD) with schizotypy vs. schizophrenia with OCD: diagnostic dilemmas and therapeutic implications. Journal of Psychiatric Research 39, 399–408.CrossRefGoogle ScholarPubMed
Poyurovsky, M, Weizman, A, Weizman, R (2004). Obsessive–compulsive disorder in schizophrenia: clinical characteristics and treatment. CNS Drugs 18, 989–1010.CrossRefGoogle ScholarPubMed
Rajkumar, RP, Reddy, YC, Kandavel, T (2008). Clinical profile of ‘schizo-obsessive’ disorder: a comparative study. Comprehensive Psychiatry 49, 262–268.CrossRefGoogle ScholarPubMed
Remington, G (2008). Alterations of dopamine and serotonin transmission in schizophrenia. Progress in Brain Research 172, 117–140.CrossRefGoogle ScholarPubMed
Reznik, I, Kotler, M, Weizman, A (2005). Obsessive and compulsive symptoms in schizophrenia patients – from neuropsychology to clinical typology and classification. Journal of Neuropsychiatry and Clinical Neurosciences 17, 254–255.CrossRefGoogle ScholarPubMed
Reznik, I, Yavin, I, Stryjer, R, Spivak, B, Gonen, N, Strous, R, Mester, R, Weizman, A, Kotler, M (2004). Clozapine in the treatment of obsessive–compulsive symptoms in schizophrenia patients: a case series study. Pharmacopsychiatry 37, 52–56.Google ScholarPubMed
Rocha, FL, Hara, C (2006). Benefits of combining aripiprazole to clozapine: three case reports. Progress in Neuro-Psychopharmacology and Biological Psychiatry 30, 1167–1169.CrossRefGoogle ScholarPubMed
Saxena, S, Gorbis, E, O'Neill, J, Baker, SK, Mandelkern, MA, Maidment, KM, Chang, S, Salamon, N, Brody, AL, Schwartz, JM, London, ED (2009). Rapid effects of brief intensive cognitive–behavioral therapy on brain glucose metabolism in obsessive–compulsive disorder. Molecular Psychiatry 14, 197.CrossRefGoogle ScholarPubMed
Scatton, B, Claustre, Y, Cudennec, A, Oblin, A, Perrault, G, Sanger, DJ, Schoemaker, H (1997). Amisulpride: from animal pharmacology to therapeutic action. International Clinical Psychopharmacology 12 (Suppl. 2), S29–S36.CrossRefGoogle ScholarPubMed
Sevincok, L, Akoglu, A, Arslantas, H (2006). Schizo-obsessive and obsessive–compulsive disorder: comparison of clinical characteristics and neurological soft signs. Psychiatry Research 145, 241–248.CrossRefGoogle ScholarPubMed
Shapiro, DA, Renock, S, Arrington, E, Chiodo, LA, Liu, LX, Sibley, DR, Roth, BL, Mailman, R (2003). Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 28, 1400–1411.CrossRefGoogle ScholarPubMed
Sliman, EB (2007). Differential neurocognitive deficits in obsessive-compulsive patients according to their clinical pathology and symptom intensity, compared to patients with schizophrenia and healthy controls [in German]. Ph.D. Dissertation, Ruhr University Bochum, Germany.Google Scholar
Sparshatt, A, Taylor, D, Patel, MX, Kapur, S (2010). A systematic review of aripiprazole – dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. Journal of Clinical Psychiatry 71, 1447–1456.CrossRefGoogle ScholarPubMed
Tiryaki, A, Ozkorumak, E (2010). Do the obsessive–compulsive symptoms have an effect in schizophrenia? Comprehensive Psychiatry 51, 357–362.CrossRefGoogle ScholarPubMed
Tumkaya, S, Karadag, F, Oguzhanoglu, NK, Tekkanat, C, Varma, G, Ozdel, O, Atesci, F (2009). Schizophrenia with obsessive–compulsive disorder and obsessive–compulsive disorder with poor insight: a neuropsychological comparison. Psychiatry Research 165, 38–46.CrossRefGoogle ScholarPubMed
van Nimwegen, L, de Haan, L, van Beveren, N, Laan, W, van den Brink, W, Linszen, D (2008). Obsessive–compulsive symptoms in a randomized, double-blind study with olanzapine or risperidone in young patients with early psychosis. Journal of Clinical Psychopharmacology 28, 214–218.CrossRefGoogle ScholarPubMed
Woody, SR, Steketee, G, Chambless, DL (1995). Reliability and validity of the Yale–Brown Obsessive–Compulsive Scale. Behaviour Research and Therapy 33, 597–605.CrossRefGoogle ScholarPubMed
Zink, M, Englisch, S, Dressing, H (2008). Neurobiology confirms psychopathology: on the antagonism of psychosis and obsessive–compulsive syndromes. Psychopathology 41, 279–285.CrossRefGoogle ScholarPubMed
Zink, M, Englisch, S, Knopf, U, Kuwilsky, A, Dressing, H (2007). Augmentation of clozapine with valproic acid for clozapine-induced obsessive compulsive symptoms. Pharmacopsychiatry 40, 202–203.CrossRefGoogle ScholarPubMed
Zink, M, Englisch, S, Meyer-Lindenberg, A (2010). Polypharmacy in schizophrenia. Current Opinion in Psychiatry 23, 103–111.CrossRefGoogle ScholarPubMed
Zink, M, Knopf, U, Kuwilsky, A (2006). Management of clozapine-induced obsessive compulsive symptoms in a man with schizophrenia. Australian and New Zealand Journal of Psychiatry 41, 293–294.CrossRefGoogle Scholar