European Neuropsychopharmacology 11 (Suppl.

4) (2001) S405–S413
www.elsevier.com / locate / euroneuro

Quetiapine: efficacy and tolerability in schizophrenia

*
Siegfried Kasper , Johannes Tauscher, Angela Heiden
Department of General Psychiatry, University of Vienna, Wahringer¨ Gurtel 18 –20, A-1090 Vienna, Austria

Abstract

Quetiapine, in common with clozapine, has a greater affinity for 5-HT 2 receptors than D 2 receptors and preclinical studies have
consistently predicted efficacy against schizophrenia, with a low potential for causing extrapyramidal symptoms (EPS). In clinical trials,
the efficacy of quetiapine was consistently superior to placebo and it was effective against both positive and negative symptoms.
Quetiapine was also at least as effective as chlorpromazine or haloperidol in improving the symptoms of acute schizophrenia and moreover
was associated with higher response rates. The consistent, placebo-level incidence of EPS associated with quetiapine in clinical trials was
not seen with haloperidol. Thus, the combination of efficacy comparable to other antipsychotic agents, with an acceptable side effect and
tolerability profile, provides support for the use of quetiapine as a first-line antipsychotic agent in the long-term treatment of schizophrenia.
2001 Elsevier Science B.V. All rights reserved.

Keywords: Quetiapine; Schizophrenia; Atypical antipsychotic; Serotonin antagonist

1. Introduction Clozapine, the first so-called ‘atypical’ antipsychotic to

The main goals in the treatment of schizophrenia are to
improve positive, negative, affective and cognitive symp-
toms as well as to enhance the patient’s quality of life and
minimise treatment-related side effects (Worrel et al.,
2000). Although moderate to substantial reductions in
positive symptoms are observed in most patients after
treatment with traditional antipsychotic drugs, about 30%
of patients do not respond to psychopharmacological
therapy (Remington and Chong, 1999; McGrath and
Emmerson, 1999). Traditional antipsychotic drugs are even
less effective in treating negative and cognitive symptoms
of schizophrenia (Jibson and Tandon, 1998; McGrath and
Emmerson, 1999) but, once remission has been achieved,
antipsychotic drugs can substantially reduce the risk of
relapse (McGrath and Emmerson, 1999). However, the
greatest limitation of traditional antipsychotic drugs is the
frequent occurrence of distressing and disabling side
effects, most notably treatment-emergent extrapyramidal
side effects (EPS), and anticholinergic effects, which may
lead to noncompliance and poor treatment outcome (Lind-
strom and Bingefors, 2000; McGrath and Emmerson,
1999).
*Corresponding author. Tel.: 143-1-40400-3568; fax: 143-1-40400-
3099.
E-mail address: sk@akh-wien.ac.at (S. Kasper).
be developed, is particularly effective against positive
symptoms in treatment-resistant patients and, because of its
low D 2 receptor occupancy, it produces few of the EPS
associated with traditional antipsychotic drugs (Horacek,
2000). After a few years of clinical use, clozapine was
withdrawn because of treatment-related agranulocytosis,
although it was subsequently re-introduced because of its
efficacy in treatment-resistant patients (Kane et al., 1988).
Newer atypical antipsychotic drugs that are not associ-
ated with agranulocytosis, and which are currently being
utilised in routine clinical practice, include risperidone,
olanzapine and quetiapine (‘Seroquel’) (Keks et al., 2000).
In comparison with traditional antipsychotic drugs, these
three agents are at least as effective in treating psychotic
symptoms, have greater efficacy against negative symp-
toms (Jibson and Tandon, 1998) and appear to be more
effective at improving cognitive function (Collaborative
Working Group on Clinical Trial Evaluations, 1998). While
these agents are associated with a lower risk of EPS,
tardive dyskinesia and hyperprolactinaemia than traditional
antipsychotics, they possess unique tolerability profiles
because of their different receptor binding properties
(Horacek, 2000). In particular, quetiapine is a diben-
zothiazepine derivative that, in common with clozapine,
has a greater affinity for serotonin 5-HT 2 receptors than
dopamine D 2 receptors, together with considerable activity
at histamine receptors and a-adrenoceptors (Saller and

0924-977X / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved.
PII: S0924-977X(01)00111-0
S406 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413
Salama, 1993). However, in comparison with clozapine,
quetiapine has low affinity for muscarinic receptors, in-
dicating minimal potential for anticholinergic activity, and
low affinity for benzodiazepine receptors (Goldstein,
1996). Preclinical studies with quetiapine have consistently
suggested efficacy in both the positive and negative
symptoms of schizophrenia with low potential for causing
EPS (Goldstein, 1996).
The aim of this review is to discuss the clinical efficacy
and tolerability data on quetiapine from randomised,
controlled trials, and from long-term open-label studies, in
order to explore its role as a first-line treatment option in
patients with schizophrenia.
2. Efficacy
2.1. Overall efficacy and effects on positive and negative
symptoms in comparison with placebo
The efficacy of quetiapine has been demonstrated in
three, 6-week, randomised, double-blind, controlled trials.
These studies involved 756 hospitalised patients with an
acute exacerbation of chronic or subchronic schizophrenia,
as defined by DSM-III-R criteria, who were randomised to
receive quetiapine or placebo, or haloperidol in one study.
Overall, the efficacy of quetiapine was consistently
superior to placebo and it was associated with clinically
meaningful improvements from baseline in the Brief
Psychiatric Rating Scale (BPRS) total score, and the
Clinical Global Impression (CGI) Severity of Illness score,
and it was effective against both positive and negative
symptoms of schizophrenia (Arvanitis and Miller, 1997;
Borison et al., 1996; Small et al., 1997).
The study conducted by Arvanitis and Miller (1997) was
a seven-arm comparative trial that involved randomisation
of 361 patients to placebo, five fixed doses of quetiapine
(75, 150, 300, 600 or 750 mg / day) or haloperidol 12 mg /
day. Borison et al. (1996) compared treatment with a
flexible dosage regimen of quetiapine (75–750 mg / day)
with placebo in 109 patients, and Small et al. (1997)
compared low-dose quetiapine (up to 250 mg / day) with
high-dose quetiapine (up to 750 mg / day) or placebo in
286 patients. In these studies, patients’ psychopathology
and overall function were rated weekly, using the BPRS
total score (primary measure of efficacy), CGI score and
Scale for the Assessment of Negative Symptoms (SANS).
Fig. 1a illustrates that, across these three studies, quetiapine
treat-ment was associated with a greater improvement than
placebo in the primary efficacy variable of improvement of
the BPRS score. The between-treatment differences in
mean improvement of BPRS score for quetiapine versus
placebo were statistically significant at the 150–750 mg /
day dose levels (P,0.05) in the study by Arvanitis and
Miller (1997), and in the high-dose group (mean dose 488
mg / day) (P,0.05) in the study by Small et al. (1997).
Additional examination of the BPRS positive symptoms
cluster in these studies confirmed these findings (Fig. 1b)
and the efficacy of quetiapine against negative symptoms
was demonstrated by significant improvements from
baseline in the SANS score compared with placebo (Fig.
1c) (Arvanitis and Miller, 1997; Borison et al., 1996; Small
et al., 1997).
2.2. Effects on hostility
The treatment of aggressive or hostile patients can be
problematic, as even traditional antipsychotics that have
sedative properties can compound problems of aggression
and hostility because of undesirable side effects such as
EPS (Drake and Ehrlich, 1985; Keck et al., 2000). A post-
hoc analysis of the dose-ranging study conducted by
Arvanitis and Miller (1997) has provided preliminary
evidence of the utility of quetiapine in this setting (Hel-
lewell et al., 1999a). Quetiapine significantly improved
scores on three indices of aggressive and hostile behaviour:
the BPRS hostility item, the hostility cluster and BPRS
Factor V.
Even after adjustment for improvement in positive
symptom score, the differences between quetiapine and
placebo remained statistically significant, which indicated
that the effect of quetiapine on hostility was not simply a
reflection of the general improvement of positive symp-
toms. In contrast, adjustment for improvement in positive
symptoms indicated that haloperidol, which has
traditionally been utilised in aggressive patients, was not
associated with significant benefit (Hellewell et al., 1999a).
In addi-tion, a meta-analysis of this trial and three other
placebo-controlled trials has also indicated that quetiapine
produced statistically significant improvements in BPRS
Factors I and V, hostility item and hostility cluster in
comparison with placebo (Data on file, AstraZeneca) (Fig.
2). Thus, there are indications that quetiapine may be
particularly useful in the management of disturbed and
aggressive patients.
2.3. Effects on depressive symptomatology
Encouraging preliminary evidence of the beneficial
effects of quetiapine on depressive symptomatology in
schizophrenia has been derived from placebo-controlled
studies in which quetiapine treatment led to significantly
greater improvements in scores on the BPRS mood cluster
than placebo (Hellewell et al., 1999a).
Beneficial effects of quetiapine on well established
measures of the severity of depression have also been
demonstrated in comparative studies with haloperidol and
the newer ‘atypical’ antipsychotic, risperidone. For exam-
ple, in a 6-month, double-blind study in 25 patients with
DSM-IV schizophrenia, quetiapine (300–600 mg / day), but
not haloperidol (10–20 mg / day), was associated with a
significant improvement (P,0.004) from baseline in the
 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413 S407

Fig. 1. Mean changes from baseline after 6 weeks of randomised treatment in three placebo-controlled trials of quetiapine in: (a) BPRS total score; (b) BPRS
positive symptom cluster score; and (c) SANS score (Arvanitis and Miller, 1997; Borison et al., 1996; Small et al., 1997).
S408 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413
Fig. 2. Mean changes from baseline to endpoint in symptoms of hostility in schizophrenic patients (last visit carried forward values) in a meta-analysis of
four placebo-controlled trials of quetiapine (Data on file, AstraZeneca).
Beck Depression Inventory (BDI) score (Purdon et al.,
2001). However, this study was too small in scale to allow
a direct comparison between quetiapine and haloperidol. In
contrast, the 4-month, open-label QUEST trial, in 728
patients with psychotic disorders, has demonstrated that
quetiapine (mean dose 317 mg / day) produced statistically
significantly greater improvement in Hamilton Rating Scale
for Depression (HAM-D) scores than risperidone (mean
dose 4.5 mg / day) (P50.028) (Reinstein et al., 1999).
2.4. Effects on cognitive symptoms
Cognitive impairment contributes to poor social function
and outcome in schizophrenia, and traditional an-
tipsychotics may exacerbate cognitive deficits (Bilder,
1997). A short-term study in 10 schizophrenic patients has
indicated that 2 months’ treatment with quetiapine (mean
dose 330 mg / day) produced significant improvements in
attentional function, as measured by the Continuous Per-
formance Test (CPT) (Sax et al., 1998). The small scale, 6-
month, double-blind study reported by Purdon et al. (2001)
has also demonstrated that quetiapine significantly
improved cognitive function from baseline in the domains
of verbal reasoning and fluency, immediate recall and
executive function, as well as overall cognitive function. In
comparison, haloperidol did not significantly improve
cognitive function, but the study was too small in scale to
demonstrate statistically significant differences between
treatments. In a cohort of 41 patients, included in a larger
randomised, double-blind study, it was found after 24
weeks of treatment that quetiapine-treated patients (600 mg
/ day) had improved overall cognitive function, while the
haloperidol-treated patients deteriorated, and that the
difference between treatments was statistically significant
(P,0.03) (Velligan et al., 1999). Such improvements in
cognitive function may confer important social and
economic benefits, as patients may be better able to look
after themselves and become more integrated into society.
2.5. Comparisons with traditional and atypical
antipsychotics
The efficacy of quetiapine is superior to traditional and
comparable with atypical antipsychotic agents. In 6-week,
randomised, double-blind, controlled trials, quetiapine was
as effective as chlorpromazine (Peuskens and Link, 1997)
and haloperidol (Arvanitis and Miller, 1997; Copolov et al.,
2000), as measured by improvements in the BPRS total
score, CGI Severity of Illness score and the Positive and
Negative Syndrome Scale (PANSS) total score.
In the study by Peuskens and Link (1997), which
included 201 hospitalised patients with acute exacerbation
of subchronic or chronic schizophrenia or schizophre-
niform disorder, quetiapine and chlorpromazine were both
administered flexibly at doses up to 750 mg / day (mean
doses 407 and 384 mg / day, respectively). Quetiapine was
at least as effective as chlorpromazine in improving the
symptoms of acute schizophrenia, as indicated by changes
in BPRS, PANSS negative symptom subscale and CGI
Severity of Illness Scores. However, the proportion of
patients who responded to treatment (.50% reduction in
BPRS total score) was significantly greater in the
quetiapine group than in the chlorpromazine group (65
versus 52%, respectively; P50.04).
A meta-analysis has been conducted on response rate
data from four randomised, double-blind, controlled trials
of quetiapine versus haloperidol in patients with acute
 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413
exacerbation of chronic or subchronic schizophrenia. In this
analysis, a clinically relevant response (improvement) was
defined as a $40% reduction from baseline to endpoint in
BPRS total score or derived PANSS score (using symptoms
that matched the BPRS). Response rates ranged from 19 to
47% for haloperidol and from 26 to 46% for quetiapine and
the response rate was higher for quetiapine than with
haloperidol in three out of four trials. Overall, it was
demonstrated that a significantly higher proportion of
patients with acute schizophrenia responded to quetiapine
than to haloperidol (odds ratio 1.32; 95% CI 1.04, 1.68;
P50.02) (Fig. 3), which indicated that quetiapine was
suitable for use as a first-line atypical antipsychotic
(Schulz, 2000).
The 4-month QUEST study has demonstrated that a
higher percentage of patients in the quetiapine group,
relative to the risperidone group, had ‘much’ or ‘very
much’ improvement in CGI score at each visit and that both
atypical antipsychotics were equally effective in reducing
positive and negative symptoms, as assessed by the PANSS
score (Reinstein et al., 1999). In addition, although no
direct comparison between quetiapine and olanzapine has
been performed, a meta-analysis of response rates has
shown that the highest dose of olan-zapine (15 mg / day)
and all doses of quetiapine (150–750 mg / day) produced
similar placebo-adjusted response rates (Data on file,
AstraZeneca; Kasper and Muller¨-Spahn, 2000).
Overall, the magnitude of the improvements in negative
symptoms in four quetiapine studies (Copolov et al., 2000;
Emsley et al., 2000; Peuskens and Link, 1997; Small et al.,
Fig. 3. Meta-analysis of responders in double-blind comparative trials of
quetiapine with haloperidol. Odds ratios .1 indicated a significantly higher
rate of response for quetiapine compared with placebo or halo-peridol. If
the lower limit of the 95% CI for the overview analysis was
.1, this indicated that across the studies, a significantly greater propor-tion
of patients responded to quetiapine, compared with placebo or haloperidol
(Schulz, 2000). Study 13, Arvanitis and Miller (1997); Study 14, Copolov
et al. (2000); Study 50, data on file, AstraZeneca; Study 52, Emsley et al.
(2000).
S409
1997) (209–600 mg / day) were similar to those reported in
trials with risperidone (Blin et al., 1996; Chouinard et al.,
1993; Marder and Meibach, 1994; Peuskens, 1995; Tran et
al., 1997) (4–12 mg / day) and olanzapine (Beasley et al.,
1996, 1997; Tollefson et al., 1997; Tran et al., 1997), as
determined by comparison of the mean change from
baseline in PANSS negative subscale (Kasper and Muller¨-
Spahn, 2000) (Fig. 4).
2.6. Efficacy in partial responders
The majority of patients with schizophrenia are treated
on an outpatient basis and about 30% of them do not
achieve a satisfactory level of symptom control with
traditional antipsychotic therapy. Such partial responders
are particularly difficult and expensive to treat and have not
been extensively studied previously (Emsley et al., 2000;
Lindstrom and Bingefors, 2000). However, the recently
completed Partial Responders International SchiZophrenia
Evaluation (PRIZE) study has suggested that quetiapine
may make a valuable contribution to the management of
patients with a history of partial response to traditional
antipsychotics (Emsley et al., 2000). This randomised,
double-blind study compared the efficacy and tolerability
of 8 weeks’ treatment with quetiapine
600 mg / day and haloperidol 20 mg / day in 288 patients
with a history of partial response to antipsychotics, who
displayed a partial or no response to 1 month of treatment
with fluphenazine 20 mg / day. Significantly more patients
on quetiapine (52.2%) than on haloperidol (38.0%; P5
0.043) showed a clinical response (a further reduction of
$20% or more in the PANSS total score) after 8 weeks of
treatment following initial treatment with fluphenazine.
Furthermore, there was a trend towards patients on
quetiapine having greater improvements in CGI scale
scores, PANSS total score, and BPRS scores (Emsley et al.,
2000).
2.7. Efficacy in maintenance therapy
The recurrent and chronic nature of schizophrenia means
that patients require effective long-term antipsychotic
treatment throughout their lives. An open-label extension
study of patients with chronic schizophrenia has demon-
strated that the initial clinical responses to quetiapine were
maintained on a mean daily dose of 478 mg / day for at
least 52 weeks. Patients who had responded to quetiapine in
short-term studies maintained the improvements in
symptoms of schizophrenia, as measured by further reduc-
tions in BPRS total score, CGI Severity of Illness scores
(Fig. 5) and SANS summary scores. Thus, quetiapine was
effective in reducing the positive and negative symptoms of
schizophrenia and in maintaining long-term clinical
responses in patients who were initial responders to
quetiapine (Rak and Raniwalla, 2000).
S410 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413

Fig. 4. Mean change from baseline in the PANSS negative subscale score in clinical trials of quetiapine, olanzapine and risperidone. Adapted from Kasper
and Muller¨-Spahn (2000) by permission of Ashley Publications.

3. Tolerability effects of antipsychotic therapy (Van Putten et al., 1984;

A favourable tolerability profile is an important consid-
eration in the selection of antipsychotic therapy, as schizo-
phrenia is a chronic condition that may require life-long
medication to prevent relapse. EPS (especially akathisia
and tardive dyskinesia) and prolactin elevation, which can
result in impotence, are the two particularly important side
Gerlach and Peacock, 1994; Finn et al., 1990).
3.1. Extrapyramidal side effects (EPS)
With the exception of clozapine, quetiapine is the only
atypical antipsychotic with a low propensity for induction
of EPS that also does not produce sustained elevations in

Fig. 5. Mean BPRS and CGI Severity of Illness scores during 52 weeks of open-label extension treatment with quetiapine in
patients who had previously responded to quetiapine in double-blind trials. Adapted from Rak and Raniwalla (2000).
 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413 S411

plasma prolactin levels across the full therapeutic dose
range (Arvanitis and Miller, 1997). Analysis of the data
from the quetiapine phase II and phase III clinical trial
programme has indicated that quetiapine produces an
incidence of EPS no greater than with placebo. The study
by Arvanitis and Miller (1997) was the pivotal trial in terms
of the tolerability profile of quetiapine and it indicated that
the percentage of quetiapine-treated patients who reported
an EPS event, or who required medication for EPS, was no
different from placebo and was lower than with
haloperidol, even at the highest dose of quetiapine (Fig. 6).
In addition, the low propensity for EPS with quetiapine in
relation to haloperidol in this study was also reflected in the
Simpson-Angus and Abnormal Involuntary Movement
scales that showed no evidence of any dose-related
increases in EPS with quetiapine (Arvanitis and Miller,
1997). This consistent placebo-level incidence of EPS with
quetiapine was not seen with other an-tipsychotics
including olanzapine (Eli Lilly & Co., 1999) and
risperidone (Owens, 1994) as well as haloperidol (Arvanitis
and Miller, 1997; Copolov et al., 2000). Further-more, the
incidence of EPS during long-term (1-year) treatment with
quetiapine was not higher than during short-term trials (Rak
and Gorman, 2000).
3.2. Effect on prolactin concentrations
Plasma prolactin concentrations in patients receiving
quetiapine or placebo in clinical trials have tended to
decrease during treatment, reflecting the presence of
abnormally high baseline concentrations of prolactin in
some patients due to previous antipsychotic therapy (Peus-
kens and Link, 1997). During double-blind treatment,
considerable decreases in prolactin have been observed
with quetiapine. At the end of a 6-week multicentre study,
the mean plasma prolactin decrease in patients who
received quetiapine compared with those who received
chlorpromazine was highly significant (P,0.0001; Peus-
kens and Link, 1997). In another multicentre, randomised
trial of quetiapine versus haloperidol (Emsley et al., 2000),
83% of quetiapine-treated patients had normal prolactin
levels at the end of treatment compared with only 21% of
haloperidol-treated patients. The reduction in serum
prolactin concentration from baseline (after fluphenazine
therapy) in the quetiapine group was marked and the
difference between the two treatments was highly signifi-
cant (P,0.001). The absence of an effect on plasma
prolactin is consistent with the low incidence of hormonal
and reproductive adverse events (1.8% of 2387 patients) in
clinical trials of quetiapine (Goldstein et al., 1997).
3.3. Effect on weight
Treatment with some atypical antipsychotics is associ-
ated with increased body weight. The extent of this weight
gain varies considerably and seems to be more pronounced
with clozapine and olanzapine than with risperidone or
quetiapine (Allison et al., 1999). However, it is in long-
term treatment that the real clinical significance of weight
gain is observed. Long-term weight changes, focusing on
body mass index (BMI), were analysed from 427 patients
with DSM-IV schizophrenia, involved in controlled and
open-label extension trials of long-term quetiapine mono-
therapy (mean dose 475 mg / day after 1 year). There were
no dose-related effects on weight, and only one person
withdrew due to an adverse event of weight gain. Any
weight changes with quetiapine showed no association with
dose or gender. Minimal overall weight change was

Fig. 6. Percentage of patients reporting an adverse event related to EPS, or requiring medication for EPS in a 6-week, double-blind, placebo-controlled trial
of five doses of quetiapine versus haloperidol. Adapted from Arvanitis and Miller, 1997 by permission of Elsevier Science, 1997 by the Society of Biological
Psychiatry; and from Kasper and Muller¨-Spahn (2000) by permission of Ashley Publications.
S412 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413
observed over 18 months of treatment with quetiapine, with
95% CI encompassing the zero change line. In fact, long-
term quetiapine monotherapy appeared to have a weight
neutral effect (Brecher et al., 2000).
3.4. Patient satisfaction
The issue of patient satisfaction with quetiapine therapy
has been investigated by Hellewell et al. (1999b) in an
open-label extension study in 129 patients with a range of
psychotic disorders who had been receiving quetiapine for
at least 6 months. The patients were asked to complete a
seven-item questionnaire concerning their subjective ex-
perience and satisfaction with treatment. Overall, more than
75% of respondents indicated that they were either ‘very’
or ‘extremely’ satisfied with their antipsychotic medication,
while 73.7% indicated that, over the previous month, their
medication had been ‘very’ or ‘extremely’ helpful. In
addition, the overwhelming majority of patients (114 / 118
patients (96.6%)) preferred quetiapine to previous
antipsychotic medications, primarily because of better
tolerability and greater efficacy. These high levels of
patient satisfaction and acceptance of treatment may help to
improve treatment compliance and consequently clinical
outcome of antipsychotic therapy (Hellewell et al., 1999b).
4. Conclusions
Quetiapine has a wide clinical dose range (150–750 mg /
day), although doses of 400 mg or above should be used in
patients who do not respond fully to lower doses of the
drug. Quetiapine is effective without producing sig-
nificantly more EPS than placebo across the full dose range
and, thus, offers an excellent benefit to risk profile amongst
antipsychotic agents. The combination of efficacy
comparable to other antipsychotic agents, with a favour-
able side effect and tolerability profile provides support for
the use of quetiapine as a first-line antipsychotic agent in
the long-term treatment of schizophrenia.
References
Allison, D.B., Mentore, J.L., Heo, M., Chandler, L.P., Cappelleri, J.C.,
Infante, M.C., Weiden, P.J., 1999. Antipsychotic-induced weight gain: a
comprehensive research synthesis. Am. J. Psychiatry 156, 1686– 1696.
Arvanitis, L.A., Miller, B.G., and the Seroquel Trial 13 Study Group,
1997. Multiple fixed doses of ‘Seroquel’ (Quetiapine) in patients with
acute exacerbation of schizophrenia: a comparison with haloperidol
and placebo. Biol. Psychiatry 42, 233–246.
Beasley, C.M., Sanger, T., Satterlee, W., Tollefson, G., Tran, P., Hamilton,
S., and the Olanzapine HGAP Study Group, 1996. Olanzapine versus
placebo: results of a double-blind, fixed-dose olanzapine trial. Psycho-
pharmacology 124, 159–167.
Beasley, C.M., Hamilton, S.H., Crawford, A.M., Dellva, M.A., Tollefson,
G.D., Tran, P.V., Blin, O., Beuzen, J.-N., 1997. Olanzapine versus
haloperidol: acute phase results of the international double-blind
olanzapine trial. Eur. Neuropsychopharmacol. 7, 125–137.
Bilder, R.M., 1997. Neurocognitive impairment in schizophrenia and how
it affects treatment options. Can. J. Psychiatry 42, 255–264.
Blin, O., Azorin, J.M., Bouhours, P., 1996. Antipsychotic and anxiolytic
properties of risperidone, haloperidol, and methotrimprazine in schizo-
phrenic patients. J. Clin. Psychopharmacol. 16, 38–44.
Borison, R.L., Arvanitis, L.A., Miller, B.G., and the US Seroquel Study
Group, 1996. ICI 204, 636, an atypical antipsychotic: efficacy and
safety in a multicenter, placebo-controlled trial in patients with
schizophrenia. J. Clin. Psychopharmacol. 16, 158–169.
Brecher, M., Rak, I.W., Westhead, E.K., Jones, A.M., 2000. The long-term
effect of quetiapine (‘Seroquel’) monotherapy on weight in patients
with schizophrenia. Int. J. Psychiatry Clin. Pract. 4, 287–292.
Chouinard, G., Jones, B., Remington, G., Bloom, D., Addington, D.,
MacEwan, G.W., Labelle, A., Beauclair, L., Arnott, W., 1993. A
Canadian multicenter placebo-controlled study of fixed doses of
risperidone and haloperidol in the treatment of chronic schizophrenic
patients. J. Clin. Psychopharmacol. 13, 25–40.
Collaborative Working Group on Clinical Trial Evaluations, 1998.
Evaluating the effects of antipsychotics on cognition in schizophrenia.
J. Clin. Psychiatry 59 (Suppl. 12), 35–40.
Copolov, D.L., Link, C.G.G., Kowalcyk, B., 2000. A multicentre, double-
blind, randomized comparison of quetiapine (ICI 204, 636, ‘Seroquel’)
and haloperidol in schizophrenia. Psychol. Med. 30, 95–105.
Drake, R.E., Ehrlich, J., 1985. Suicide attempts associated with akathisia.
Am. J. Psychiatry 142, 499–501.
Eli Lilly & Co. (1999) Olanzapine US prescribing information. Emsley,
R.A., Raniwalla, J., Bailey, P.J., Jones, A.M., on behalf of the
PRIZE Study Group, 2000. A comparison of the effects of quetiapine
(‘Seroquel’) and haloperidol in schizophrenic patients with a history of
and a demonstrated, partial response to conventional antipsychotic
treatment. Int. Clin. Psychopharmacol. 15, 121–131.
Finn, S.E., Bailey, J.M., Schultz, R.T., Faber, R., 1990. Subjective utility
ratings of neuroleptics in treating schizophrenia. Psychol. Med. 20,
843–848.
Gerlach, J., Peacock, L., 1994. Motor and mental side effects of clozapine.
J Clin Psychiatry 55 (Suppl. B), 107–109.
Goldstein, J.M., 1996. Preclinical profile of Seroquel (quetiapine): an
atypical antipsychotic with clozapine-like pharmacology. In: Holliday,
S.G., Ancill, R.J., MacEwan, G.W. (Eds.), Schizophrenia: Breaking
Down the Barriers. Wiley, Chichester, pp. 177–208.
Goldstein, J.M., Arvanitis, L.A., Cantillon, M., 1997. Low incidence of
reproductive / hormonal side effects with ‘Seroquel’ (quetiapine fuma-
rate) is supported by its lack of elevation of plasma prolactin
concentrations (Poster). 36th Annual Meeting of the American College
of Neuropsychology, Waikaloa, Hawaii, USA.
Hellewell, J., Cantillon, M., McKellar, M., Raniwalla, J., 1999a.
‘Seroquel’: efficacy in aggression, hostility and low mood schizophre-
nia. Int. J. Neuropsychopharmacol. 2 (Suppl. 1), S112.
Hellewell, J.S.E., Kalali, A.H., Langham, S.J., McKellar, J., Awad, A.G.,
1999b. Patient satisfaction and acceptability of long-term treatment
with quetiapine. Int. J. Psychiatry Clin. Pract. 3, 105–113.
Horacek, J., 2000. Novel antipsychotics and extrapyramidal side effects.
Theory and reality. Pharmacopsychiatry 33 (Suppl. 1), 34–42.
Jibson, M.D., Tandon, R., 1998. New atypical antipsychotic medications.
J. Psychiatr. Res. 32, 215–228.
Kane, J., Honigfeld, G., Singer, J., Meltzer, H., and the Clozaril
Collaborative Study Group, 1988. Clozapine for the treatment-resistant
schizophrenic: a double-blind comparison with chlorpromazine. Arch.
Gen. Psychiatry 45, 789–796.
Kasper, S., Muller¨-Spahn, F., 2000. Review of quetiapine and its clinical
applications in schizophrenia. Exp. Opin. Pharmacother. 1, 783–801.
Keck, Jr. P.E., Strakowski, S.M., McElroy, S.L., 2000. The efficacy of
atypical antipsychotics in the treatment of depressive symptoms,
hostility, and suicidality in patients with schizophrenia. J. Clin.
Psychiatry 61 (Suppl. 3), 4–9.
 S. Kasper et al. / European Neuropsychopharmacology 11 (Suppl. 4) (2001) S405 –S413
Keks, N., Mazumdar, P., Steele, K., 2000. The new antipsychotics. How
much better are they? Aust. Fam. Physician 29, 445–450.
Lindstrom, E., Bingefors, K., 2000. Patient compliance with drug therapy
in schizophrenia. Economic and clinical issues. Pharmacoeconomics
18, 106–124.
McGrath, J., Emmerson, W.B., 1999. Treatment of schizophrenia. Br.
Med. J. 519, 1045–1048.
Marder, S.R., Meibach, R.C., 1994. Risperidone in the treatment of
schizophrenia. Am. J. Psychiatry 151, 825–835.
Owens, D.G., 1994. Extrapyramidal side effects and tolerability of
risperidone: a review. J. Clin. Psychiatry 55 (Suppl.), 29–35.
Peuskens, J., Link, C.G.G., 1997. A comparison of quetiapine and
chlorpromazine in the treatment of schizophrenia. Acta Psychiatr.
Scand. 96, 265–273.
Peuskens, J., on behalf of the Risperidone Study Group, 1995. Ris-
peridone in the treatment of patients with chronic schizophrenia: a
multi-national, multi-centre, double-blind, parallel-group study versus
haloperidol. Br. J. Psychiatry 166, 712–726.
Purdon, S.E., Malla, A., Labelle, A., Litt, W., 2001. Neuropsychological
change in patients with schizophrenia after treatment with quetiapine or
haloperidol. J. Psychiatry Neurosci. 26, 137–149.
Rak, I.W., Gorman, A.P., 2000. Maintenance of long-term efficacy with
‘Seroquel’ (quetiapine). Int. J. Neuropsychopharmacol. 3 (Suppl. 1),
S149.
Rak, I.W., Raniwalla, J., 2000. Maintenance of long-term efficacy with
‘Seroquel’ (Poster). In: The Winter Workshop, Davos, Switzerland, 5–
11 February.
Reinstein, M., Bari, M., Ginsberg, L., Mullen, J., 1999. Quetiapine and
risperidone in outpatients with psychotic disorders: results of the
QUEST trial (Poster). The American Psychiatric Association Annual
Meeting, Washington, DC, 15–20 May.
Remington, G., Chong, S.A., 1999. Conventional versus novel an-
S413
tipsychotics: changing concepts and clinical implications. J. Psychiatry
Neurosci. 24, 431–441.
Saller, F., Salama, A.I., 1993. Seroquel: biochemical profile of a potential
atypical antipsychotic. Psychopharmacology 112, 285–292.
Sax, K.W., Strakowski, S.M., Keck, Jr. P.E., 1998. Attentional improve-
ment following quetiapine fumarate treatment in schizophrenia.
Schizophr. Res. 33, 151–155.
Schulz, S.C., 2000. Efficacy of quetiapine vs. haloperidol and placebo in
the short-term treatment of acute schizophrenia (Poster). The 13th
European Neuropsychopharmacology Congress, Munich, Germany, 9–
13 September.
Small, J.G., Hirsch, S.R., Arvanitis, L.A., Miller, B.G., Link, C.G.G., and
the Seroquel Study Group, 1997. Quetiapine in patients with schizo-
phrenia. A high- and low-dose double-blind comparison with placebo.
Arch. Gen. Psychiatry 54, 549–557.
Tollefson, G.D., Beasley, C.M., Tamura, R.N., Tran, P.V., Potvin, J.H.,
1997. Blind, controlled, long-term study of the comparative incidence
of treatment-emergent tardive dyskinesia with olanzapine or halo-
peridol. Am. J. Psychiatry 154, 1248–1254.
Tran, P.V., Hamilton, S.H., Kuntz, A.J., Potvin, J.H., Andersen, S.W.,
Beasley, C., Tollefson, G.D., 1997. Double-blind comparison of
olanzapine versus risperidone in the treatment of schizophrenia and
other psychotic disorders. J. Clin. Psychopharmacol. 17, 407–418.
Van Putten, T., May, P.R.A., Marder, S.R., 1984. Akathisia with
haloperidol and thiothixene. Arch. Gen. Psychiatry 41, 1036–1039.
Velligan, D.I., Newcomer, J., Pultz, J., Csernansky, J., Hoff, A.L.,
Mahurin, R., Miller, A., 1999. Changes in cognitive functioning with
quetiapine fumarate versus haloperidol (Poster). The American Psychi-
atric Association Annual Meeting, Washington, DC, 15–20 May.
Worrel, J.A., Marken, P.A., Beckham, S.E., Ruehter, V.L., 2000. Atypical
antipsychotic agents: a critical review. Am. J. Health Syst. Pharm. 57,
238–255.