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: [email protected]
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).
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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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