The aim of our study was to evaluate the effectivenessof clozapine and olanzapine in the treatment of schizophrenicpatients. Either clozapine or olanzapine signifcantly ameliorated positive symptoms, but only clozapine was effective in reducinganxiety and hallucinations, while olanzapine was more effective in reducing negative symptoms, such as mannerism and posturing, blunted affect and emotional withdrawal. Olanzapine-treated patients obtained significantly higher GAF scores than clozapine-treated patients and more frequently participated in rehabilitative programmes. In conclusio, olanzapine therapy has surprisingly been shown to be more effective than clozapine in improving social and working skills

G. Tondelli

GENEDANI, Susanna

R. Di Lorenzo

English

Rosaria Di Lorenzo

Grazia Tondelli

Susanna Genedani

Crossref

The International Journal of Neuropsychopharmacology

Effectiveness of clozapine and olanzapine: a comparison in severe, psychotically ill patients

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

LETTER TOTHE EDITORInternational Journal of Neuropsychopharmacology (2001), 4, 135–137. Copyright # 2001 CINPEffectiveness of clozapine and olanzapine : acomparison in severe, psychotically ill patientsReceived 26 July 2000 ; Reviewed 20 November 2000 ; Revised 24 January 2001 ; Accepted 7 February 2001New atypical antipsychotics have opened a new era in thetreatment of schizophrenia owing to their effectivenessboth on positive, but especially negative, symptoms,without extrapyramidal side-effects (Tandon et al., 1999).The archetypal atypical antipsychotic is clozapine, whosemain side-effect is agranulocytosis. Recently, other newatypical antipsychotics have been developed, such asolanzapine (Stephenson and Pilowsky, 1999), which donot produce any adverse haematological effects (Beasleyet al., 1997). Clozapine and olanzapine share lower D2and D3 receptor affinity in the basal ganglia and nigro-striatal system, and higher affinity to muscarinic (M) andhistaminergic (H) receptors than haloperidol. Moreover,clozapine has higher affinity to adrenergic (a1 and a2)receptors, while olanzapine has higher affinity to D2, D3,D4 and serotonergic (5-HT-2A) receptors (ratio 5-HT-2A}D2" 2) (Coward, 1992). The pharmacologicalprofile can explain the efficacy of these drugs not only onthe positive, but also especially on the negativesymptoms, representing the originality of new anti-psychotic treatment. The improvement of primary nega-tive symptoms (Crow, 1980) and the absence of secondarysymptoms (produced by extrapyramidal side-effects)result in an increased compliance (Marder, 1998) andimprovement of cognitive functions (insight capacity,self-awareness, judgement) (Meyer-Lindenberg et al.,1997).The aim of our study was to evaluate the effectivenessof clozapine and olanzapine in the treatment of schizo-phrenic patients in our psychiatric department. This isconstituted by hospital wards connected to communityservices (outpatient care, semi-residential and residentialcentres for rehabilitative social programmes).Subjects and clinical assessmentsAll patients admitted to our psychiatric wards (PresidioPsichiatrico di Diagnosi e Cura 1) with schizophreniadiagnosis and schizoid personality disorders (according toDSM-IV) (American Psychiatric Association, 1994), andtreated with clozapine and olanzapine from SeptemberAddress for correspondence : Dr R. Di Lorenzo, Department ofMental Health, Presidio Psichiatrico di Diagnosi e Cura 1, PoliclinicoVia del Pozzo 71, I41100 Modena, Italy.Tel. : 0039-59-422232-951 Fax : 0039-59-422589 or 0039-59-2055376E-mail : genedani!unimo.it1995 to September 1998 were selected. Previously thesepatients had never been treated with these drugs, onlywith traditional neuroleptics. The sample consisted of 25patients : 12 treated with clozapine and 13 witholanzapine. In the clozapine group 10 patients wereaffected by paranoid and 2 by disorganized schizophrenia ;in the olanzapine group 4 patients were affected byparanoid, 3 by disorganized, 3 by catatonic, 1 byundifferentiated schizophrenia and 2 by schizoid per-sonality disorder, according to DSM-IV criteria. Thesample size was conditioned by the difficulty in selectingpatients whose clinical features were similar enough to becompared.The atypical neuroleptic treatments were evaluated fora whole period of 482–08‡29–42 d for the clozapinegroup and 207–30‡30–26 d for the olanzapine group(patients treated for a period less than 30 d were excludedfrom our study) composed of a period of in-patient care(overlapped for the two groups : 43–3‡4–49 d forclozapine, 44–23‡4–45 d for olanzapine) and the fol-lowing outpatient care. The therapeutic dose ranges were :from 250 to 600 mg}d for clozapine and from 10 to30 mg}d for olanzapine. Clozapine (Leponex, NovartisFarma SpA, Origgio Varese, Italy) and olanzapine(Ziprexa, Eli Lilly, Nieuwegein, The Netherlands) wereused. The procedures followed were in accordancewith the ethical standards of the Institutional EthicalCommittee on human experimentation.The following clinical features of the sample wereanalysed : age, diagnosis, previous illness duration, rate ofhospitalization and previous neuroleptical treatment(effectiveness, compliance, tolerance and side-effects).Clinical symptoms were assessed by means of BriefPsychiatric Rating Scale (BPRS) (Overall and Gorham,1962) at admission and discharge. Social functioning wasevaluated by means of the Global Assessment ofFunctioning (GAF) scale (Spitzer et al., 1979) at admissionand at the end of the follow-up period. The rate of therehospitalization under atypical neuroleptics treatmentwas evaluated. Moreover, patients’ compliance withrehabilitative outdoor programmes under clozapine andolanzapine treatment was assessed at the end of follow-upperiod. Data were analysed by means of ANOVA, Fishertest and Kruskal–Wallis test, and expressed as mean‡s.e.(Statistica, Version 5, ’97 Edition, Statsoft, Italy).The two groups were significantly different for meanage (40–75‡6–27 yr in clozapine-treated patients,Downloaded from https://academic.oup.com/ijnp/article-abstract/4/2/135/794934 by Ombretta Malavasi user on 19 February 2020136 R. Di Lorenzo et al.Table 1. Influence of clozapine and olanzapine treatments on BPRS scoreBPRS score itemsClozapine OlanzapineAdmission Discharge Admission DischargeUnusual thought content 6–54 4–91* 6–07 4–07*Suspiciousness 6–00 3–36* 5–54 2–76*Conceptual disorganization 5–00 2–64* 4–69 2–61*Distractibility 5–00 2–36* 3–00 1–46*Bizarre behaviour 5–91 3–91* 6–46 3–23*Self-neglect 4–82 2–18* 5–31 2–46*Hostility 5–54 2–55* 5–93 2–46*Tension 6–18 2–82* 5–38 3–00*Anxiety 5–55 3–00* 4–23 2–31Hallucinations 6–27 4–36* 4–38 3–00Mannerism and posturing 5–00 3–64 5–15 3–00*Emotional withdrawal 3–73 2–27 5–38 2–38*Blunted affect 3–91 2–45 5–15 3–00** p! 0–05 (at least) vs. admission of clozapine and olanzapine group respectively. p! 0–009 vs. discharge of clozapine group. Kruskal–Wallis test.33–15‡8–45 yr in olanzapine-treated patients) and pre-vious illness duration (18–58‡8–16 yr in the clozapinegroup, 9–92‡8–78 yr in the olanzapine group), butboth groups presented the same rate of previoushospitalization, quantified in number of admission}illnessdays (4–41‡4–38 d in the clozapine group, 3–43‡2–92 din the olanzapine group) and similar compliance, effective-ness and side-effects with previous neuroleptical treat-ments (7 patients in the clozapine group and 9 in theolanzapine group had rarely and irregularly taken theprevious therapy ; 8 patients under clozapine therapy and6 under olanzapine therapy did not present any sympto-matic improvement, while all others presented only amild improvement ; 9 patients in each group were notaffected by important side-effects). Further, at admission,the score of BPRS items was similar for the two groups aswell as the GAF scale score.Our results have shown that at discharge, bothclozapine and olanzapine treatments significantly de-creased the BPRS score of the following items (Table 1) :unusual thought content, suspiciousness, conceptualdisorganization, distractibility, bizarre behaviour, self-neglect, hostility, tension.The score of anxiety and hallucinations was sig-nificantly decreased by clozapine therapy, while man-nerism and posturing, emotional withdrawal, bluntedaffect score were significantly ameliorated by olanzapinetherapy (Table 1). Only the score of distractibilty wassignificantly reduced by olanzapine in comparison withthe clozapine group (Table 1).Both drugs significantly reduced the rate ofhospitalization during the treatment evaluated as percentof admissions before and under treatment (from 100 to25% in clozapine group ; from 100 to 23% in theolanzapine group, pfl 0–0002 and pfl 0–0001, respect-ively, Fisher test). At the end of the follow-up period, theGAF score of both groups was significantly increased(from 26–66‡2–84 to 37–08‡1–89 in the clozapinegroup ; from 25–00‡3–15 to 46–53‡4–09 in olanzapinegroup, at least p! 0–005 ANOVA) but the GAF scoreof the olanzapine group was significantly higher thanthat of the clozapine group, in spite of a shorter periodof treatment (p! 0–05, ANOVA). Moreover, bothatypical neuroleptics facilitated the patients’ participationin psychosocial rehabilitative programs : 7 olanzapine-treated patients began a semi-residential centre activityand 2 patients again started competitive work ; 2clozapine-treated patients were admitted to residentialcentres and 2 patients began a social training programme.DiscussionOur sample was constituted by ‘non-responsive ’ patients,who were affected by a severe psychotic disturbance, asdemonstrated by long period of illness, high rate ofhospitalization and low GAF score at admission. Eitherclozapine or olanzapine significantly ameliorated positivesymptoms, but only clozapine was effective in reducinganxiety and hallucinations, while olanzapine was moreeffective in reducing negative symptoms, such as man-nerism and posturing, blunted affect and emotionalwithdrawal. Olanzapine-treated patients obtained signifi-Downloaded from https://academic.oup.com/ijnp/article-abstract/4/2/135/794934 by Ombretta Malavasi user on 19 February 2020137Clozapine and olanzapine : a clinical comparisoncantly higher GAF scores than clozapine-treated patientsand more frequently participated in rehabilitative pro-grammes (9 olanzapine-treated patients vs. 4 clozapine-treated patients). This result could be due to the differenceof age and previous illness period between the twogroups : clozapine-treated patients were 7.5 yr older andfell ill 9 yr earlier than olanzapine-treated patients. But thetwo groups were not significantly different in otherclinical features (the rate of previous hospitalization, GAFscale and score of BPRS items) which might have affectedthe therapeutic efficacy. Finally, the clozapine treatmentperiod was longer than olanzapine treatment but, in anycase, we compared clozapine- to olanzapine-treatedpatients, because we observed an early and dramaticimprovement of psychotic symptoms with olanzapinetreatment.In conclusion, even though the two groups were smalland not completely comparable, the data suggest that theimprovement of negative and positive symptoms,associated with a more tolerable side-effects profile,enhances therapeutic compliance and permits regulartherapy that, consequently, prevents relapses. Moreover,olanzapine therapy has surprisingly been shown to bemore effective than clozapine in improving social andworking skills.ReferencesAmerican Psychiatric Association (1994). Diagnostic andStatistical Manual of Mental Disorders (4th edn)Washington, DC: American Psychiatric Association.Beasley CM, Tollefson GD, Tran PV (1997). Safety ofolanzapine. Journal of Clinical Psychiatry 58 (Suppl. 10),13–17.Coward DM (1992). General pharmacology of clozapine.British Journal of Psychiatry 160 (Suppl. 17), 5–11.Crow TJ (1980). Molecular pathology of schizophrenia : morethan one disease process? British Medical Journal 280,66–68.Marder SR (1998). Facilitating compliance with antipsychoticmedication. Journal of Clinical Psychiatry 59 (Suppl. 3),21–25.Meyer-Lindenberg A, Grupe H, Bauer U, Lis S, Krieger S,Gallhofer B (1997). Improvement of cognitive function inschizophrenic patients receiving clozapine or zotepine :result from a double-blind study. Pharmacopsychiatry 30,35–42.Overall JE, Gorham DR (1962). The Brief Psychiatric RatingScale. Psychological Reports 10, 799–812.Spitzer RL, Gibbon M, Endicott J (1979). Global AssessmentScale. New York : New York State Psychiatric Institute.Stephenson CME, Pilowsky LS (1999). Psychopharmacologyof olanzapine. British Journal of Psychiatry 174 (Suppl. 38),52–58.Tandon R, Milner K, Jibson MD (1999). Antipsychotics fromtheory to practice : integrating clinical and basic data.Journal of Clinical Psychiatry 60 (Suppl. 8), 21–28.Rosaria Di Lorenzo", PhD, Grazia Tondelli", PhD andSusanna Genedani#, ScD"Department of Mental Health, ‘Presidio Psichiatrico diDiagnosi e Cura 1 ’, Policlinico, Via del Pozzo 71, Modena,Italy#Department of Biomedical Sciences, Section of Pharmacology,University of Modena and Reggio Emilia, Via Campi, 287,I41100 Modena, ItalyDownloaded from https://academic.oup.com/ijnp/article-abstract/4/2/135/794934 by Ombretta Malavasi user on 19 February 2020

https://iris.unimore.it/bitstream/11380/303581/1/4-2-135.pdf

Effectiveness of clozapine and olanzapine: a comparison in severe, psychotically ill patients

Abstract

Similar works

Full text

Available Versions

Crossref

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia