BACKGROUND: The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. METHODS: In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. RESULTS: Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. CONCLUSION: Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration

AJ Mitchell

Andreas Schreiner

Dieter Naber

G Bondolfi

HJ Möller

JE Rojo

JG Small

Klaus Wiedemann

MO Huttunen

O Agid

S Kapur

S Leucht

Thomas J Raedler

TJ Raedler

English

PubMed

Crossref

Early onset of treatment effects with oral risperidone

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BioMed CentralBMC Psychiatry
ssOpen AcceResearch article
Early onset of treatment effects with oral risperidone
Thomas J Raedler*1, Andreas Schreiner2, Dieter Naber1 and 
Klaus Wiedemann1
Address: 1Department of Psychiatry, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany and 2Department 
of Medical & Scientific Affairs, Janssen-Cilag, Raiffeisenstr. 8, 41470 Neuss, Germany
Email: Thomas J Raedler* - traedler@uke.uni-hamburg.de; Andreas Schreiner - aschrein@jacde.jnj.com; Dieter Naber - naber@uke.uni-
hamburg.de; Klaus Wiedemann - wiedemann@uke.uni-hamburg.de
* Corresponding author    
Abstract
Background: The dogma of a delayed onset of antipsychotic treatment effects has been
maintained over the past decades. However, recent studies have challenged this concept. We
therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of
acutely decompensated patients with schizophrenia.
Methods: In this observational study, 48 inpatients with acutely decompensated schizophrenia
were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day
0, day 1, day 3, day 7 and day 14.
Results: Significant effects of treatment were already present on day 1 and continued throughout
the study. The PANSS positive subscore and the PANSS total score improved significantly more
than the PANSS negative subscore.
Conclusion: Our results are consistent with the growing number of studies suggesting an early
onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also
need to be taken into consideration.
Background
Since their introduction half a century ago, antipsychotics
have constituted the backbone of pharmacological treat-
ment of psychosis. In accordance with other groups of
psychotropic agents (e.g. antidepressants), a substantial
time-lag has been postulated between the initiation of
antipsychotic treatment and the onset of the antipsychotic
effect. However, this concept of a delayed onset of action
has been challenged recently and an earlier onset of antip-
sychotic treatment effects has been proposed [1,2].
Our group has recently shown that the atypical antipsy-
chotic risperidone is effective in the treatment of acutely
decompensated patients with schizophrenia [3]. In this
manuscript we present an analysis of the time-course of
treatment effects in acutely decompensated patients with
schizophrenia, who remained in treatment.
Methods
A detailed description of the study-design was previously
published [3]. In brief, acutely decompensated subjects
with schizophrenia were offered treatment with oral risp-
eridone (daily dose 4 – 8 mg given in two doses) upon
admission to the secure unit of the Dept. of Psychiatry of
the University Medical Center Hamburg-Eppendorf. This
unit serves a catchment-area of approximately 250.000
Published: 19 January 2007
BMC Psychiatry 2007, 7:4 doi:10.1186/1471-244X-7-4
Received: 08 November 2006
Accepted: 19 January 2007
This article is available from: http://www.biomedcentral.com/1471-244X/7/4
© 2007 Raedler et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
BMC Psychiatry 2007, 7:4 http://www.biomedcentral.com/1471-244X/7/4inhabitants of the city of Hamburg, Germany. Benzodi-
azepines (diazepam 5 – 60 mg/d and lorazepam 0.5 – 10
mg/d) as well as anticholinergics (biperiden 2 – 8 mg/d)
were added as clinically indicated. The demographic
information of the treatment-group is listed in Table 1.
Subjects were rated with the PANSS and CGI on day 0
(baseline), day 1, day 3, day 7 and day 14. For the PANSS,
we analysed the total score as well as the positive, negative
and general psychopathology scales. Due to weekends
and holidays, four subjects were not rated on day 1. All
other ratings were performed as scheduled. For easier
comparison, all ratings were expressed as percentage of
the baseline-values (day 0 = 100%).
Statistical Analysis
We performed an observed cases analysis for the first two
weeks of treatment. Wilcoxon's matched pairs test was
used for comparison of symptom-ratings with baseline-
ratings. Friedman's two-way analysis of variance was used
to assess statistical differences between the different
PANSS-subscores for each day.
Results
48 subjects participated in this open-label observational
study. Subjects were diagnosed with schizophrenia (n =
40), schizoaffective disorder (n = 5) or schizophreniform
disorder (n = 3) according to DSM-IV-TR.
Data are available for 43 patients on day 1 (89.6%), 37
patients on day 3 (77.1%), 32 patients on day 7 (66.7%)
and 25 patients on day 14 (52.1%). The reasons for dis-
continuation of risperidone are shown in Table 2.
All PANSS ratings showed a significant improvement with
antipsychotic treatment. Table 3 lists the PANSS total
scores as well as the different PANSS subscores for each
time-point.
On day 1, the PANSS total score as well as the PANSS neg-
ative subscale and the PANSS general psychopathology
subscale decreased significantly compared to baseline (n
= 43; all Z > 2.92; all p < 0.01). The positive symptoms
subscale of the PANSS on day 1 showed no significant dif-
ference when compared to baseline (n = 43; Z = 1.46; p <
0.15).
On day 3, the positive symptom subscale of the PANSS
was significantly lower than the baseline-rating. The
PANSS total score as well the PANSS negative subscale and
the PANSS general psychopathology subscale also
decreased further. All scores were significantly lower than
the baseline-scores on day 3 (n = 37; all Z > 3.61; all p <
0.001). On day 7 and day 14, a highly significant decrease
in the ratings of total PANSS and all PANSS subscales was
observed compared to baseline (all Z > 3.29; all p <
0.001).
Comparing the changes between the subscales of the
PANSS, significant differences were found on day 7 (X2 =
23.7; p < 0.001) and day 14 (X2 = 15.1; p < 0.01). While
all ratings improved, the decrease in symptom severity
was most pronounced on the PANSS positive subscale. In
contrast, the ratings on the PANSS negative subscale
showed the smallest decrease over time. Further analysis
revealed that the decrease in symptom rating was signifi-
cantly higher on the positive subscale (Z = 3.80; p <
0.001) and the PANSS total score (Z = 2.59; p < 0.01) than
on the PANSS negative subscale on day 7. Similar differ-
ences were found on day 14 with a significantly stronger
improvement in the PANSS positive subscore (Z = 2.62; p
< 0.01) and a trend towards significance for the PANSS
total score (Z = 1.92; p = 0.05) compared to the PANSS
negative subscale.
Discussion
Over the past decades, the concept of a delayed onset of
antipsychotic effects on symptoms of acute schizophrenia
has been generally accepted. This concept included the
understanding that first effects after the initiation of antip-
sychotic treatment were not seen until after several weeks
of treatment.
The dogma of a delayed onset of action has only recently
been challenged for antipsychotic treatment [1,2] as well
as for antidepressant treatment [4,5]. Our data provide
additional support for the concept of an early onset of
action of antipsychotic treatment in acutely decompen-
sated patients with schizophrenia. Our results suggest that
in severely ill subjects who remained in treatment, first
effects of treatment can be demonstrated as early as after
one day of treatment. Over the course of the next two
weeks, symptom ratings for positive, negative and general
Table 1: Demographic information
Number of participants: 48 (25 males/23 females)
Age: 36.9 ± 13.4 years (range 18 – 68 years)
PANSS at admission: 110.9 ± 20.4 (range 72 – 158)
CGI at admission: 5.9 ± 0.6 (range 5 – 7)
Duration of treatment: 13.4 ± 9.7 days (range 1 – 31 days)
Maximum dose of risperidone: 6.1 ± 1.4 mg/d (range 4 – 8 mg/d)Page 2 of 4
(page number not for citation purposes)
BMC Psychiatry 2007, 7:4 http://www.biomedcentral.com/1471-244X/7/4symptoms of schizophrenia decreased further. While pos-
itive symptoms responded even better to antipsychotic
treatment, we still saw a significant improvement in neg-
ative symptoms during the first two weeks of treatment.
The observational nature of this study without a placebo-
group precludes definite statements on the time-course of
antipsychotic treatment effects. Still, our data are consist-
ent with previously published studies. Looking at the
effects of intramuscular medications, both intramuscular
haloperidol and olanzapine led to an improvement in
symptoms of schizophrenia within the first 24 hours of
treatment [6]. In a large meta-analysis of antipsychotic
response, a decrease in psychotic symptom ratings (e.g.
PANSS and BPRS) of 13.8% was seen during the first week
of treatment. The second week of treatment led to an addi-
tional decrease in symptom-ratings of 8.1% [1]. Similar
acute treatment effects were seen with the atypical antip-
sychotic amisulpride with the largest improvement in psy-
chotic symptoms occurring within the first two weeks of
treatment [2]. Both studies found a larger symptom reduc-
tion during the first two weeks of treatment than during
consecutive weeks. An onset of action during the first
week of treatment across a broad range of symptoms was
also described for the second generation antipsychotic
quetiapine [7]. The atypical antipsychotic risperidone has
been associated with an earlier onset of action than
haloperidol [8], clozapine [9] and zuclopenthixol [10] in
the treatment of schizophrenia. While the rate of improve-
ment of symptoms in our study exceeds some of these
studies [e.g. [1,2]], it should be kept in mind that subjects
who discontinued treatment were excluded from further
analysis.
Potential effects of non-pharmacological interventions
should be taken into consideration when assessing the
results of this study. We studied a group of patients with
schizophrenia who were admitted to a secure unit with
acute psychotic decompensation. All subjects were treated
with oral risperidone in a daily dose between 4 and 8 mg
as well as benzodiazepines as needed. In addition to the
pharmacological intervention, all subjects received skilled
nursing-care in the setting of an acute treatment ward.
Non-pharmacological interventions included a safe, struc-
tured and quiet environment, the normalization of food-
and fluid-intake as well as adequate opportunity to rest.
Concomitant alcohol- and substance-use, which may
have contributed to the exacerbation of psychosis, also
came to an end with the admission. In addition, precipi-
tating events were addressed during the in-patient treat-
ment. These non-pharmacological factors need to be
taken into consideration when assessing the effects of
acute treatment. However, in clinical practice, a substan-
tial number of patients with schizophrenia refuse antipsy-
chotic treatment and fail to stabilize despite being placed
in a quiet and safe environment. The lack of improvement
in patients who refuse antipsychotic treatment points to a
specific role of the pharmacological treatment in the sta-
bilization of acutely decompensated patients with schizo-
phrenia.
Conclusion
Our data add to the growing number of studies showing
an early onset of antipsychotic effects in subjects with
acutely exacerbated schizophrenia. While full benefits of
antipsychotic treatment may take several weeks to
months, first effects of antipsychotic treatment can be
seen as early as after one day of treatment. However, non-
pharmacological effects also need to be taken into consid-
eration.
List of abbreviations
BPRS: Brief Psychiatric Rating Scale
Table 3: Total PANSS-scores and PANSS-subscores. For easier comparison, ratings on day 1, day 3, day 7 and day 14 are expressed as 
percentage of base-line (day 0 = 100%)
PANSS Total PANSS Positive PANSS Negative PANSS Gen. Psychopath.
Day 0 (n = 48) 100% 100% 100% 100%
Mean ± SD 110.9 ± 20.4 30.4 ± 5.2 25.3 ± 7.3 55.1 ± 11.8
Day 1 (n = 43) 96.7% ± 6.7% 97.7% ± 9.3% 96.8% ± 9.7% 96.3% ± 6.7%
Day 3 (n = 37) 87.3% ± 12.9% 85.1% ± 14.3% 91.1% ± 19.5% 88.0% ± 14.3%
Day 7 (n = 32) 76.6% ± 17.5% 69.6% ± 21.8% 83.6% ± 25.8% 79.0% ± 17.5%
Day 14 (n = 25) 68.0% ± 19.0% 62.6% ± 25.2% 72.4% ± 19.6% 69.9% ± 18.1%
Table 2: Reasons for discontinuation of risperidone
n
Discharge against medical advice 7
Regular discharge 2
Intramuscular injection 8
Switch to another antipsychotic 4
Noncompliance 2Page 3 of 4
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CGI: Clinical Global Impression scale
PANSS: Positive and Negative Syndrome Scale
Competing interests
Dr. Raedler, Prof. Naber and Prof. Wiedemann have
received honoraria, grant-support and/or travel funds
from Janssen Pharmaceuticals. Dr. Schreiner is an
employee of Janssen-Cilag Germany.
Authors' contributions
TJR conceived of the study, participated in the design and
coordination and drafted the manuscript.
AS participated in the design and coordination, helped
with the statistical analysis and drafted the manuscript
DN participated in the design and coordination of the
study
KW conceived of the study and participated in the design
and coordination.
All authors read and approved the final manuscript
Acknowledgements
This study was supported by an unrestricted grant from Janssen Pharma-
ceuticals.
We thank Dr. Alexander Reiprich, Medical Project Coordination, Janssen-
Cilag Germany, for his assistance with the statistical analysis
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Abstract Background The dogma of a delayed onset of antipsychotic treatment effects has been maintained over the past decades. However, recent studies have challenged this concept. We therefore performed an analysis of the onset of antipsychotic treatment effects in a sample of acutely decompensated patients with schizophrenia. Methods In this observational study, 48 inpatients with acutely decompensated schizophrenia were offered antipsychotic treatment with oral risperidone. PANSS-ratings were obtained on day 0, day 1, day 3, day 7 and day 14. Results Significant effects of treatment were already present on day 1 and continued throughout the study. The PANSS positive subscore and the PANSS total score improved significantly more than the PANSS negative subscore. Conclusion Our results are consistent with the growing number of studies suggesting an early onset of antipsychotic treatment effects. However, non-pharmacological effects of treatment also need to be taken into consideration.</p

Naber Dieter

Schreiner Andreas

Raedler Thomas J

Wiedemann Klaus

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