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International Clinical Psychopharmacology 2002, 17:41–44 Relationship between neuroleptic dosage andsubjective cognitive dysfunction in schizophrenicpatients treated with either conventional oratypical neuroleptic medication S. Moritza,b,c, T.S. Woodwarda,c, PERSIST Study Groupb, M. Krauszband D. Naberb aUniversity of British Columbia, Department of Psychology, Vancouver, BC, Canada, bUniversity Hospital Hamburg-Eppendorf, Hospital for Psychiatry and Psychotherapy,Hamburg, Germany and cDepartment of Medicine and Research, Riverview Hospital, PortCoquitlam, BC, Canada Correspondence to Ste¡en Moritz, University of British Columbia, Department ofPsychology, West Mall 2136, V6T 1Z4 Vancouver, BC, CanadaTel: +604 822 2755; fax: +604 822 6923; e-mail: smoritz@cortex.psych.ubc.ca Received 21 August 2001; accepted 13 November 2001 Previous research has suggested that high doses of conventional neuroleptics may induce neurocognitive deficits when assessed withstandard tasks. However, little is known about the effects of high doses of neuroleptics (conventional or atypical) on subjectivecognitive dysfunction. Recent research stresses the putative importance of self-reported cognitive deficits for both symptomaticoutcome and medication compliance. The aim of the present study was to investigate the impact of neuroleptic medication onsubjective cognition in patients treated with either conventional or atypical agents (clozapine, risperidone, olanzapine). Patients wereasked to endorse the items of a questionnaire entitled ‘Subjective Well-Being under Neuroleptic Treatment’ prior to discharge.
Subjective impairment, as assessed with the subscale ‘mental functioning’, was significantly correlated with greater conventionalneuroleptic dosage after controlling for psychopathology (Po0.05). The difference between patients medicated with higher doses ofconventional neuroleptics and those with lower doses was highly significant (Po0.001). In contrast, higher atypical neurolepticdoses were not associated with impairment. Int Clin Psychopharmacol 17:41–44 r 2002 Lippincott Williams & Wilkins Keywords: antipsychotics, atypical, dosage, neurocognition, neuroleptics, side-effects, well-being neurocognition in schizophrenia research refers tosubjective assessment. Recent research suggests that Since the early work of Kraepelin and Bleuler, the assessment of subjective deficits bears special neurocognitive deficits have been considered of major potential importance for predicting symptomatic out- pathogenetic importance for the emergence of schizo- come and medication compliance. Moritz et al. (2000) phrenia. However, while an extensive body of research report that subjective cognitive dysfunction, as as- indicates that schizophrenic patients are impaired on a sessed by the Frankfurt Complaint Questionnaire wide range of cognitive functions, no deficit pattern (FCQ), predicted symptomatic outcome in first-epi- specific to schizophrenic psychopathology has yet been sode schizophrenic patients. Furthermore, it has been suggested that subjective cognitive dysfunction under Neurocognitive deficits are most often indexed using neuroleptics may have a negative impact on medication so-called objective measures (e.g. the Wisconsin compliance (Moritz et al., 1999). For example, Naber card sorting test). A somewhat neglected aspect of (1995) found that high scores in a scale measuring 0268-1315 r 2002 Lippincott Williams & Wilkins International Clinical Psychopharmacology 2002, Vol 17 No 1 subjective cognitive, physical and other side-effects patients met DSM-IV criteria for schizophrenia or under neuroleptic treatment were correlated with later schizophreniform disorder. Diagnoses were determined by experienced clinicians. Psychopathology was further The finding that atypical agents, such as olanzapine, assessed using the Positive and Negative Syndrome risperidone and clozapine, ameliorate some primary Scale (PANSS) following a semi-structured interview objective cognitive deficits is frequently reported (for (SCI-PANSS). Patients with severe neurological illness, review, see Keefe et al., 1999; Moritz et al., 2001b).
other axis 1 diagnoses and substance abuse were There is some evidence that this effect may also excluded from the samples. For the purpose of this transfer to subjective cognitive deficits. It should be study, doctors-in-charge were not recommended any noted in this context that the cognitive dysfunction dose ranges. No concomitant drugs were prescribed perceived by schizophrenic patients themselves has except for the occasional application of benzodiaze- been shown to be correlated with objective neurocog- pines in the groups treated with atypicals. Socio- nitive measures (Cuesta et al., 1996). Naber et al.
demographic and psychopathological characteristics of (2001) found that patients treated with olanzapine showed greater improvement than those either takingrisperidone or clozapine over the course of inpatient treatment. In addition, Morgner (1992) has shown that Patients were administered the short form of a clozapine is superior to haloperidol across several questionnaire entitled ‘Subjective Well-Being under subjective cognitive and motor aspects.
Neuroleptic Treatment’ (SWN-S; Naber, 1995; Naber Another issue related to neuroleptic treatment, et al., 2001). The SWN-S is a 20-item scale that has which is the topic of the present study, deals with the been designed to assess subjective antipsychotic side- impact of neuroleptic dosage on neurocognition.
effects. It has been translated into several languages Sweeney et al. (1991) demonstrated that conventional and is widely used in clinical trials to assess various neuroleptic dosage and benztropine dosage were domains of side-effects. Its five subscales index the significantly correlated with several aspects of objective following functions: mental functioning, self-control, neurocognitive functioning; see also Spohn et al.
emotional regulation, physical functioning and social (1985). Our group (Krausz et al., 2000) has reported integration. Items are to be endorsed on a six-point evidence that conventional neuroleptic dosage was Likert scale. For the present analysis, only items from significantly correlated with subjective cognitive defi- the subscale ‘mental functioning’ were submitted for analysis (example: ‘my thinking is difficult and slow’).
The aim of the present study was to investigate Higher scores in the SWN correspond to greater well- whether atypical (clozapine, risperidone, olanzapine) and conventional agents have similar dose-relatedeffects on self-report neurocognitive functioning. It ishypothesized that patients receiving higher doses ofconventional antipsychotics display decreased neuro- Table 1 displays the sociodemographic and psycho-pathological background variables of the four samples.
Since no admission scores were determined for patients and groups largely differed regarding several back- ground variables (Table 1), SWN-differences at dis- A total of 207 schizophrenic patients were enrolled in charge do not allow for differential interpretation.
the study. Recruitment was carried out in two different clinical settings. Patients on risperidone (n=26) and Po0.001), no other psychopathological or sociodemo- olanzapine (n=40) took part in a medication study graphic variable (e.g. gender, age, length of illness) with random medication assignment following a wash- correlated with the SWN subscale ‘mental function- out period of at least 3 days, whereas patients on Partial correlations controlling for psychopathology (n=106; predominantly haloperidole and flupenthix- (overall PANSS symptoms) revealed a significant ole) were assessed in a naturalistic clinical design.
negative correlation between dosage of conventional Informed consent was obtained from all patients.
Patients were naive to the hypotheses of the study.
P=0.038). No significant relationships emerged for Data was collected shortly before discharge. All clozapine (r=0.22) and olanzapine (r=À0.10). In the 42 International Clinical Psychopharmacology 2002, Vol 17 No 1 NEUROLEPTIC DOSAGE AND SUBJECTIVE COGNITIVE DYSFUNCTION Table 1. Sociodemographic and psychopathological characteristics of the samplesa Sociodemographic variablesAge (SD) (years) (atypical agents) orchlorpromazine equivalentdosesLength of current hospitalization (days)Length of illness (years) aDue to di¡erences in the clinical setting, no group comparisons were conducted.
case of risperidone, a significant positive partial emerged. For risperidone and clozapine, positive correlation was detected (r=0.49, P=0.015).
correlations were measured. However, no group Since the primary aim of the study was to investigate differences occurred after division into low and high the impact of higher doses of neuroleptics on subjective cognitive functioning, samples were split into high and The present results indicate that when high neuro- low dosage groups. The high dosage groups were leptic doses are clinically necessary, atypical rather defined as typical agents: at least 400 mg chlorproma- than conventional neuroleptics should be prescribed zine; equivalent doses: risperidone, at least 6 mg; because medication-induced deficits are more likely to clozapine, at least 400 mg; olanzapine, at least 15 mg.
appear under conventional agents. It is also important No significant differences between low and high dosage to note that anti-Parkinson by-medication, which is patients emerged for atypical agents (all P40.2).
more often prescribed in conventional than atypical Patients receiving high typical doses (n=21) showed neuroleptics, has also been found to induce objective 13.28 (SD 4.5) points on the SWN-subscale relative to and subjective deficits (Sweeney et al., 1991; Krausz 16.91 (SD 4.5) in the low dosage group (n=81; t=3.31: Po0.001). The difference remained highly significant More research is needed to confirm the present after controlling for overall PANSS symptoms in a results before any definite conclusions can be drawn.
First, only a restricted set of cognitive functions wasassessed that may best be referred to as subjective‘mental fluency’. Second, the dose range in patients medicated with atypical agents was rather narrow. Itcannot be entirely ruled out that higher doses of The focus of the present study was to explore the atypical neuroleptics may lead to different results.
impact of neuroleptic dosage on subjective cognitive Therefore, our conclusions are limited to the dose deficits as indexed with the SWN subscale ‘mental ranges investigated. Subsequent research should in- functioning’. The findings replicate and extend pre- vestigate if the present findings hold true for objective vious studies reporting cognitive decline under higher tasks, other atypical agents, wider dose ranges and doses of conventional neuroleptics (Krausz et al., 2000; subjective rating scales that cover a greater number of Sweeney et al., 1991). Small but significant inverse correlations emerged between conventional neurolepticdosage and cognitive dysfunction as assessed with theSWN. When the sample treated with conventional neuroleptics was divided into high and low dosage The authors would like to thank V. Aderholt, R.
patients, a highly significant between-group difference Basdekis, P. Briken, E. Gottwalz, C. Haasen, A.
was obtained regarding SWN scores. With respect to Karow, M. Lambert, C. Perro, L. Nika, I. Scha¨fer and O. Yagdiran (PERSIST Study Group).
International Clinical Psychopharmacology 2002, Vol 17 No 1 baseline predicts symptomatic one-year outcome in first-episode schizophrenics. Psychopathology 33:48–51.
Cuesta MJ (1996) Abnormal subjective experiences in Moritz S, Kloss M, Jahn H, Hand I, Haasen C, Krausz M schizophrenia: its relationships with neuropsychological (2001a) Executive functioning in obsessive-compulsive disturbances and frontal signs. Eur Arch Psychiatry Clin disorder, unipolar depression and schizophrenia. Arch Keefe RSE, Silva SG, Perkins DO, Lieberman JA (1999) The effects of atypical antipsychotic drugs on neurocog- Moritz S, Naber D, Lambert M (2001b) Neurocognition nitive impairment in schizophrenia: a review and meta- under atypical and conventional neuroleptics. In: Atypi- analysis. Schizophr Bull 25:201–222.
cal Neuroleptics (Naber D, Lambert M, Krausz M, eds), Krausz M, Moritz SH, Naber D, Lambert M, Andresen B (1999) Neuroleptic-induced extrapyramidal symptoms Naber D (1995) A self-rating to measure subjective effects are accompanied by cognitive dysfunction in schizophre- of neuroleptic drugs, relationships to objective psycho- pathology, quality of life, compliance and other clinical Krausz M, Moritz S, Lambert M, Naber D (2000) Dosage variables. Int Clin Psychopharmacol 10 (Suppl. 3):133– of conventional neuroleptic medication and subjectivecognitive functioning in schizophrenia. Int Clin Psycho- Naber D, Moritz S, Lambert M, Pajonk F, Holzbach R, Morgner J (1992) Die Therapie schizophrener Ziel- und Mass R, Andresen B (2001) Improvement of schizo- Basissymptome mit Clozapin (Leponexs). In: Clozapin.
phrenic patients’ subjective well-being under atypical Pharmakologie undKlinik eines atypischen Neurolepti- antipsychotic drugs. Schizophr Res 50:81–90.
kums: Eine kritische Bestandsaufnahme (Naber D, Mu¨l- Spohn HE, Coyne L, Lacoursiere R, Mazur D, Hayes K ler-Spahn F, eds), Stuttgart: Schattauer, pp. 43–50.
(1985) Relation of neuroleptic dose and tardive dyskine- Moritz S, Naber D, Krausz M, Lambert M, Andresen B sia to attention, information-processing, and psychophy- (1999) Neurokognitive Vera¨nderungen in der Behan- siology in medicated schizophrenics. Arch Gen Psychiatry dlung schizophrener Patienten mit Clozapin. In: Cloza-pin.
Sweeney JA, Keilp JG, Haas GL, Hill J, Weiden PJ (1991) Neuroleptikums (Naber D, Mu¨ller-Spahn F, eds), Berlin:Springer, pp. 90–108.
Relationships between medication treatments and neu- Moritz S, Krausz M, Gottwalz E, Lambert M, Perro C, ropsychological test performance in schizophrenia. Psy- Ganzer S, Naber D (2000) Cognitive dysfunction at 44 International Clinical Psychopharmacology 2002, Vol 17 No 1

Source: http://www.cnoslab.com/pdfs/Relationship-between-neuroleptic-dosage.pdf

Doi:10.1016/s0001-6918(02)00150-6

cognitive processes: effects on perseverationDimitri van der Linden a,b,*, Michael Frese a,1,a Work and Organizational Psychology, University of Amsterdam, Roetersstraat 15,b Work and Organizational Psychology, University of Nijmegen, Montessorilaan 3,c Experimental and Work Psychology, University of Groningen, Grote Kruisstraat 2/1,Received 4 June 2002; received in revised form 19 November

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