Asian Journal of Psychiatry 24 (2016) 1722

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Asian Journal of Psychiatry

journal homepage: www.elsevier.com/locate/ajp

Dimensions of schizophrenia and their time course of response to a

second generation antipsychotic olanzapineA clinical study
Badari Birur, MD, Assistant Professora,* , Jagadisha Thirthalli, MDb ,
N. Janakiramaiah, MDb , Richard C. Shelton, MDa , Bangalore N. Gangadhar, MDb
a
Department of Psychiatry, University of Alabama Birmingham (UAB), Birmingham, AL, United States
b
National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India

A R T I C L E I N F O A B S T R A C T

Article history: Background: The pattern of symptom response to second generation antipsychotics (SGAs) has not been
Received 26 February 2016 studied extensively. Understanding the time course of symptom response would help to rationally
Received in revised form 13 July 2016 monitor patient progress.
Accepted 17 August 2016
Objective: To determine the short-term differential time course of response of symptom dimensions of
Available online xxx
rst episode schizophrenia viz., negative, positive symptoms and 5 factors of anergia, thought
disturbance, activation, paranoid-belligerence and depression to treatment with SGA olanzapine.
Keywords:
Methods: 57 drug naive patients with schizophrenia were treated for 4 weeks with olanzapine 10 mg/day,
Dimensions
First episode schizophrenia
increased to 20 mg/day in 1 week. Weight was recorded and ratings with the Positive and Negative
Drug nave Syndrome scale (PANSS), the Simpson Angus Scale (SAS) were performed weekly.
Second generation antipsychotic olanzapine Results: 43 patients completed 4 weeks of assessment. Scores on all of the dimensions improved. By the
end of week 1, only positive syndrome, thought disturbance and paranoid-belligerence dimensions
improved. Maximum improvement was seen with paranoid-belligerence by week 1, followed by positive
syndrome in week 2, and depression at week 3. The percentage improvement in positive syndrome was
signicantly greater than negative. Over 4 weeks there was a mean weight gain of 2 kg and there were
signicant extrapyramidal symptoms.
Conclusions: Olanzapine produced reduction in all dimensions, but the pace of responding of individual
dimensions differed. Longer-term studies comparing SGAs with rst generation antipsychotics are
needed.
2016 Elsevier B.V. All rights reserved.

1. Introduction and hallucinations. Improvement in negative symptoms, if at all,

Antipsychotics are the mainstay of treatment of schizophrenia.
The rst generation antipsychotics (FGAs) like chlorpromazine,
haloperidol, etc., though effective in a large majority of patients
with schizophrenia, are fraught with distressing and sometimes
disabling neurological side effects. With the advent of a number of
second generation antipsychotics (SGAs), these concerns have
taken a back seat and their use as the rst line antipsychotics in the
treatment of schizophrenia has become increasingly common.
When a FGA is administered to a psychotic patient, it has
traditionally been recognized that the improvement is seen rst in
biological functions like sleep and appetite, followed by improve-
ment in excitement and then in positive symptoms like delusions
* Corresponding author at: Department of Psychiatry, University of Alabama,
Birmingham, 1713 6th Avenue South, Birmingham, Alabama 35210, United States.
E-mail address: bbirur@uabmc.edu (B. Birur).
would occur the last. The pattern of symptom response to SGAs has
not been studied systematically. Second generation antipsychotics
(SGAs) are claimed to decrease negative symptoms as well as
positive symptoms. As these agents are more commonly used
nowadays, it is useful to have an empirically established time
frame of reference to enable the clinician to rationally monitor
patient progress.
The importance of exploring symptom dimensions of schizo-
phrenia beyond the positive and negative symptom dichotomy
cannot be overemphasized. Symptoms and signs of schizophrenia
are myriad. Several attempts have been made to group these
symptoms along meaningful dimensions. The earliest comprehen-
sive discussion of positive and negative symptoms was presented
by Hughlings-Jackson, a nineteenth century neurologist, although
Reynolds had made an earlier but less extensive presentation
(Berrios, 1991). Subsequently, a three-dimensional approach was
proposed (Andreasen et al., 1995; Liddle, 1987). Liddle proposed

http://dx.doi.org/10.1016/j.ajp.2016.08.007
1876-2018/ 2016 Elsevier B.V. All rights reserved.
18 B. Birur et al. / Asian Journal of PsychiatryAJP 24 (2016) 1722
disorganization, psychomotor poverty and reality distortion in
chronic schizophrenia patients by using factor analysis and
Andreasen proposed: psychosis, disorganization dimension and
negative symptoms.
Later studies (Lindenmayer et al., 1995; von Knorring and
Lindstrom, 1995; White et al., 1997; Lancon et al., 2000) have
consistently found the presence of at least ve factors: negative,
positive, disorganized, excited and depression/anxiety factors into
which most of the symptoms and signs of schizophrenia can be
grouped. Using factor analysis, the above ve factor solutions of
Positive and Negative Syndrome Scale (PANSS) have been
consistently pinpointed across schizophrenia patients (Citrome
et al., 2011; Davis and Chen, 2001; Kim et al., 2012; Lindenmayer
et al., 1994; Marder et al., 1997; van der Gaag et al., 2006; Wallwork
et al., 2012). Reecting the progress in our conceptualization of
schizophrenia as heterogeneous illness, DSM-V places emphasis on
six symptom dimensions that include: positive symptoms
(delusions, hallucinations), negative symptoms, disorganization,
cognitive impairment, motor symptoms (catatonia) and mood
symptoms (depression, mania) (Heckers et al., 2013). The relative
severities of these 6 symptom dimensions are each rated on a scale
of 04, with anchor points guiding the ratings (American
Psychiatric Association, 2013).
Our study was undertaken to examine the short-term
differential time course of response of symptom dimensions of
schizophrenia viz., negative symptoms, positive symptoms and
ve factors of anergia, thought disturbance, activation, paranoid-
belligerence, and depression to treatment with the SGA olanza-
pine. This prospective open label study was unique that it
examined differential time course of response of symptom
dimensions in drug nave rst episode schizophrenia patients to
olanzapine.
2. Materials and methods
2.1. Subjects
The subjects for the study consisted of 57 never-treated patients
with schizophrenia in the age group of 1850 years. The subjects
fullling the following inclusion and exclusion criteria were
consecutively recruited from screening block of National Institute
of Mental Health and Neuro Science (NIMHANS), Bangalore, India.
2.2. Inclusion criteria
a)Age between 18 and 50 years b) Diagnosis of schizophrenia
according to DSM-IV (Association, 1994)[American Psychiatric
Association, 1994] c) Never treated with any psychotropic drugs d)
Total duration of illness 5 years or shorter e)Informed consent from
patient and or family member
2.3. Exclusion criteria
a)Any medical or neurological disorder that may complicate the
diagnosis or may interfere with olanzapine treatment b) Pregnant,
lactating or postpartum women c) Co morbid alcohol use disorders
(screened by Alcohol Use Disorders Identication Test, AUDIT)
(Babor et al., 1992) d) Intellectual disability (examined by clinical
evaluation) e) History of use of any psychotropic drugs
2.4. Tools
The following tools were used:
 The Positive and Negative Syndrome Scale (PANSS); (Kay et al.,
1987).
The researcher was trained in administering PANSS and good
inter-rater reliability was established with other senior psychia-
trists.
 Simpson Angus Scale (SAS); (Simpson and Angus, 1970).
Correlation between 2 raters on total scales ranged from 0.71 to
0.96 in the original study
 Alcohol Use Disorders Identication Test (AUDIT); (Babor et al.,
1992).
 Structured Clinical Interview for DSM-IV; (First et al., 1996).
2.5. Procedure
Subjects meeting inclusion and exclusion criteria were
recruited. The Structured Clinical Interview for DSM-IV Axis I
Disorders (SCID) was applied to establish a diagnosis of
schizophrenia. The diagnosis was conrmed by an independent
clinical interview by an experienced clinician. Subjects were rated
on Positive and Negative Syndrome Scale (PANSS), Simpson Angus
Scale (SAS), and their weight was recorded before starting treating
(baseline assessment). Patients were then started on olanzapine
10 mg/day, which was increased to 20 mg/day within the end of the
rst week. This dose was maintained till the end of 4-week period.
Family member stayed with hospitalized patient 24  7 for 4 weeks
to ensure compliance. Assessment on PANSS and SAS were
repeated at weekly intervals for four weeks. Weight was also
recorded at weekly intervals. The study was approved by ethics
committee at NIMHANS, Bangalore.
3. Results
3.1. Sample characteristics
Of the 57 patients 43 patients completed four weeks of
assessment. The 14 patients who dropped out did not differ from
the other 43 patients on the variables including age, age at onset,
duration of illness, positive syndrome score, negative syndrome
score, general psychopathology score and the ve factor scores
(i.e., anergia, thought disturbance, activation, paranoid-belliger-
ence, and depression) as shown in Table 1. Per protocol analysis
was carried out on 43 patients who completed four-week follow
up.
3.2. Response to olanzapine treatment
The total score of positive syndrome, negative syndrome and
the ve factors of each of the ve assessments of PANSS were
computed. Table 2 shows the results of paired t-tests between the
scores at baseline and the scores at the 4th weeks assessment.
There was signicant reduction of scores on each of the
dimensions: positive syndrome, negative syndrome and the ve
factors.
3.3. Pattern of response
To know the pattern of response to olanzapine, percentage
improvement in the symptom dimensions was calculated for each
of the symptom dimensions using the formula (Vanelle, 1994).
 
Baseline score nth week score
 100
Baseline score
 B. Birur et al. / Asian Journal of PsychiatryAJP 24 (2016) 1722 19

Table 1
Comparison of clinical characteristics of participants included in this analysis and those who dropped out of the study.

Variables Included (Mean  SD)n = 43 Dropout (Mean  SD)n = 14 t-value/x2 p value

Age (years) 30.49  7.92 30.29  8.89 0.08 0.94
Age at onset (years) 28.54  8.06 26.25  8.02 0.93 0.36
Sex (M:F) 23:20 6: 8 0.48 0.50
Education (years) 7.16  4.42 8.14  6.15 0.65 0.52
Duration (months) 23.16  16.84 49.28  66.68 1.45 0.18
Positive syndrome 25.09  6.65 23.78  7.06 0.63 0.53
Negative syndrome 24.58  6.23 24.78  7.15 0.11 0.92
Gen.psychopathology 43.55  9.28 42.57  7.59 0.37 0.72
Thought factor 12.55  3.01 12.50  3.08 0.07 0.95
Paranoid factor 10.32  3.06 9.71  3.26 0.64 0.53
Depression factor 9.81  3.64 8.71  2.23 1.07 0.29
Anergia factor 11.53  3.17 12.14  3.03 0.63 0.53
Activation factor 6.86  1.98 6.50  1.95 0.59 0.56

Table 2
Mean scores of baseline and 4th week assessment of symptom dimensions.

Variable Baseline (Mean  SD) 4th week (Mean  SD) t value p value(<)
Positive syndrome score 25.09  6.65 16.20  7.33 9.64 0.001
Negative syndrome score 24.58  6.23 19.20  6.58 6.30 0.001
Thought disturbance score 12.55  3.01 9.02  3.77 8.99 0.001
Paranoid-Belligerence score 10.32  3.06 6.95  3.19 7.24 0.001
Depression score 9.81  3.64 7.83  3.13 3.72 0.001
Anergia score 11.53  3.17 8.90  3.12 6.43 0.001
Activation score 6.86  1.98 5.13  1.83 5.99 0.001

Median percent improvement in different dimension for each
week is shown in Fig. 1. Improvement in positive syndrome,
thought disturbance and paranoid/belligerence dimensions oc-
curred by the end of rst week. All symptom dimensions started
showing improvement by the end of 2nd week. Improvement in all
symptom dimensions continued till the 4th week except in
depression symptom, where it plateaued, by the 3rd week. By the
4th week maximum improvement is seen with positive symptoms
followed by activation, paranoid- belligerence, thought distur-
bance, anergia, depression, with negative symptoms showing the
least change. The rst dimension to show maximum percentage
improvement by rst week is paranoid-belligerence followed by
positive syndrome and thought disorder. By 2nd week the
maximum improvement is seen with positive syndrome; this
trend continued till the 4th week (Table 3).
3.4. Improvement in Positive/Negative symptoms
To examine relative effect of treatment on positive and negative
symptoms a ratio of two scores was computed for each week and
this was subjected to repeated measure analysis of variance
(RMANOVA). Week 0: 1.07 0.36; Week 1: 0.96 0.34; Week 2:
0.91 0.32; Week 3: 0.91 0.31; Week 4: 0.86 0.31; df = (4,39)
p= < 0.001, F = 11.539. With four weeks of treatment reduction
occurred signicantly in positive and negative symptoms. Positive/
Negative ratio was close to 1.1 at baseline; with four weeks of
treatment with olanzapine the ratio progressively dropped close to
0.9 and this drop was signicant. The percentage improvement in
positive and negative symptoms was compared using paired t-test
for each of the four weeks. Signicance level was xed at p< 0.05.
Table 4 below shows the scores of percentage improvement.
Percentage improvement in positive syndrome score was signi-
cantly more than negative syndrome scores at all four weeks
(Fig. 2). There was reduction in positive and negative symptoms.
Fig. 3 shows the change in median PANSS scores over four weeks.
At baseline median positive and negative syndrome scores were
comparable. Over four weeks there was greater reduction in
positive symptoms when than in negative symptoms.
3.5. Weight gain
Over four weeks of treatment with olanzapine there was a
signicant weight gain, which was signicant using RMANOVA.
Week 0: 48.56  11.10; Week 1: 49.33  11.26; Week 2:
49.87  11.29; Week 3: 50.40  11.23, Week 4: 50.88  11.21;
df = (4,39); F = 30.25; p = < 0.001. The mean weight gain was 2 kg.
Maximum weight gain seen was 8 kg; one patient lost 2 kg of
weight after four weeks of treatment with olanzapine.
3.6. Extra pyramidal side effects
On four weeks of treatment with olanzapine there was a
statistically signicant extra pyramidal symptoms, analyzed using
RMANOVA. Week 0: 0.55  0.77; Week 1: 1.07  1.18; Week 2:
1.11 1.10; Week 3: 1.10  1.01; Week 4: 1.32  1.12; df = (4, 39);
F = 6.02; p = < 0.001. The mean difference (SD) from baseline was:
0.77 (0.36) and the mean maximum score on the SAS was
1.32  1.12. The most common extra pyramidal symptom was
tremor and the maximum score they showed was 2 on a 4-point
severity scale. Only one patient developed akathisia, who
improved on propranolol and another patient developed dystonia
who dropped out earlier in the study. Seven patients required
anticholinergic medications to relieve EPS.
4. Discussion
The current study was undertaken to examine the short-term
differential pattern of response of symptom dimensions of
schizophrenia in never-treated subjects to treatment with
olanzapine. Forty-three subjects with DSM-IV diagnosis of
schizophrenia were treated with olanzapine (20 mg/day) for four
weeks and their psychopathology was assessed weekly using
PANSS.
The important ndings of this study are rstly that the entire
symptom dimensions, positive symptoms, negative symptoms,
and the ve factors (thought disturbance, paranoid-belligerence,
depression, anergia and activation symptoms), improved with
20 B. Birur et al. / Asian Journal of PsychiatryAJP 24 (2016) 1722

Fig. 1. Patterns of dimension responses by week.

response of these patients may be different from those who have

Table 3
already been exposed to medications. This study, by recruiting
Median percentage improvement in symptom dimension scores by week.
never-treated rst episode psychotic patients could answer some
Symptom dimension Median percent improvement of the questions on pattern of symptom response to a SGA.
1st week 2nd week 3rd week 4th week Very few studies have examined the effect of antipsychotics on
Positive 6.45 22.22 25.00 31.03 symptom dimensions other than positive and negative symptoms
Negative 0 11.76 14.28 16.66 and even fewer focused exclusively on treatment nave patients
Thought disturbance 6.25 11.76 23.52 26.66 (Pelayo-Teran et al., 2014). Symptom dimensions like anergia,
Paranoid-Belligerence 6.66 20.00 25.00 27.27 paranoid/belligerence, depression, activation and thought distur-
Depression 0 16.66 20.00 20.00
Anergia 0 12.50 15.36 23.07
bance are important features of schizophrenia, which have not
Activation 0 12.50 25.00 28.57 received due attention in studies evaluating the effect of
antipsychotics on patients with schizophrenia. The present study
All results were signicant for time effect at p < 0.01 with repeated measures
ANOVA. showed that with olanzapine there was improvement in all
symptom dimensions. Similar ndings of signicant improvement
olanzapine. Paranoid/belligerence and positive symptoms were in all symptom dimensions of schizophrenia have been found in
the rst to show improvement, whereas depression and anergia two prior meta-analyses involving risperidone and olanzapine
improved later and also improved the least. The positive symptoms (Marder et al., 1997), (Davis and Chen, 2001). However, they
continued to improve relative to negative symptoms throughout reported differences in improvement in individual symptom
the 4-week period. This study was unique in that it included dimensions. The meta-analysis on studies involving risperidone
exclusively treatment nave rst episode schizophrenia patients. (Marder et al., 1997) reported that improvement in negative
Most of the studies on symptom dimensions of schizophrenia symptoms, disorganized thought, excitement and hostility was
have been done on medicated and chronically ill subjects (Davis seen only until the 3rd week and then it plateaued, whereas
and Chen, 2001; Marder et al., 1997). There are very few studies improvement in positive symptoms and anxiety/depression
that have examined pattern of response in never-treated continued until the end of 8 weeks. The meta-analysis on studies
schizophrenia subjects (Levine and Rabinowitz, 2010; Levine involving olanzapine (Davis and Chen, 2001) reported improve-
et al., 2010). Drug-nave patients with schizophrenia are different ment in all symptom dimensions throughout the study period,
from the patients who are already have been exposed to several starting from the second week. This is similar to the present study,
antipsychotics and other psychotropic medications. The pattern of which also examined the effect of olanzapine all symptom

Table 4
Comparison of percent improvement in positive and negative symptoms at each week.

Weeks Percent improvement in positive syndrome score (Mean  SD) Percent improvement in negative syndrome score (Mean  SD) t p(<)
Week1 11.79  19.93 2.80  10.90 3.37 0.001
Week2 22.18  21.97 10.26  14.83 4.03 0.001
Week3 30.79  22.37 17.88  19.77 4.93 0.001
Week4 35.07  23.85 20.89  21.40 5.21 0.001

40
Mean Scores
30 30.8
22.2
20
17.9
10 11.8 10.3
2.9
0
Week1 Week2 Week3 Week4
Assessment
Fig. 2. Percentage improvement in positive and negative symptom scores.
dimensions showed continued improvement (except depression,
which plateaued off by the third week).
The ndings of these studies suggest that with olanzapine there
is improvement in all symptom dimensions, whereas with
risperidone improvement in several symptom dimensions starts
tapering off by the 2nd/3rd week. However, this inference is only
tentative and only head-to-head comparison of these drugs can
clarify this matter. Both these SGAs seem to be better than
haloperidol, with which there is plateauing and even worsening of
negative symptoms, impulsivity/hostility and thought disorgani-
zation after the initial 12 weeks (Marder et al., 1997). A review by
Davis and Chen (Davis and Chen, 2001) also stresses the point that
in each of the symptom dimensions of schizophrenia SGAs
risperidone and olanzapine are superior to haloperidol. Thus SGAs
seem to be more comprehensive treatment options for schizo-
phrenia than FGAs. In other words, they seem to be rather anti-
schizophrenic and not just antipsychotics.
A pooled analysis of short-term randomized, double- blind,
placebo-controlled 6- week study demonstrated efcacy of
lurasidone across all ve symptom dimensions (positive, negative,
disorganized thought, hostility/excitement and depression/anxi-
ety) for patients with an acute exacerbation of chronic schizo-
phrenia. For positive symptoms, disorganized thought and
hostility/excitement, separation from placebo happened at week
1 and at week 2 for the other two factors (Loebel et al., 2015).
PANSS factor analyses have been reported for other SGAs namely
risperidone (Marder et al., 1997), aripiprazole (Janicak et al., 2009),
olanzapine (Davis and Chen, 2001) and asenapine (Kane et al.,
2010). Risperidone and aripiprazole showed similar results as
above while olanzapine showed no difference in regards to
depression/anxiety factor and asenapine showed no difference on
negative symptoms or hostility/excitement when compared to
placebo (Davis and Chen, 2001; Janicak et al., 2009; Marder et al.,
1997).
One major difference between the reports cited above and the
present study is in the symptom dimensions examined. The studies
cited above used factor analysis derived symptom dimensions
from PANSS (negative symptoms, positive symptoms, disorganized
30
26
25
Median scores
25 23
22 21
20
18
16
10
0 representation of different subtypes of schizophrenia is very small,
0week 1week 2week 3week 4week
Assessment
Fig. 3. Change in PANSS scores, positive and negative subscales.
B. Birur et al. / Asian Journal of PsychiatryAJP 24 (2016) 1722 21
thought, hostility/excitement and depression/anxiety) (citations in
35.1 Lurasidone article page 1). However in our study we used the 5
factor-derived symptom dimensions (anergia, thought distur-
bance, activation, paranoid-belligerence, and depression) of BPRS
20.9
Positive (Guy, 1976), which were included in PANSS (Kay et al., 1987). It can
be noted, however, that some dimensions were measured in
Negative
common, though not identical to the ones used in the above
reports, and thus the results are comparable.
Our study is different and unique from the above studies that,
we examined dimensions of schizophrenia and their pattern of
response in drug nave rst episode schizophrenia patients to
olanzapine. The studies mentioned above examined dimensions of
schizophrenia and their response in chronic patients and
compared risperidone and olanzapine versus haloperidol and
compared different SGAs versus placebo
Our ndings suggest that olanzapine was more effective on
positive symptoms than on negative symptoms throughout the 4-
week period. Other studies using atypical antipsychotics (Dab-
kowska, 2002) have shown that positive symptoms scores are
better than the negative symptoms scores at the end of 6 weeks.
This study demonstrates that as far as relative efcacy of
olanzapine on positive symptoms versus on the negative
symptoms is concerned, it is similar to typical antipsychotics,
which also have better effect on positive symptoms than on the
negative symptoms (Tandon et al., 1993).
However several caveats need to be considered here. This study
did not compare olanzapine with a FGA. Hence, the question
whether one would nd similar or different relative efcacy on
positive and negative symptoms with FGA remains unanswered.
Moreover, this study was conducted only for duration of 4 weeks.
Hence the issue of whether negative symptoms would show
improvement to the tune of improvement in positive symptoms
over a longer period time also remains open. Such a possibility is
suggested by the fact that the negative symptoms showed a steady
improvement from week 2 till week 4 and did not plateau off. The
modest inference that we can draw from this study is that at least
in the rst four weeks of treatment with olanzapine, patients with
schizophrenia would show improvement in all dimensions and
greater improvement in positive symptoms than negative symp-
toms. A limitation in the design of this study is we did not
distinguish primary from negative symptoms as improvement in
negative symptoms may be secondary to improvement in positive
symptoms (Tandon et al., 1993). Random designed study compar-
ing olanzapine with a classical antipsychotic would have been able
to demonstrate the difference between a classical and an atypical
antipsychotic. However, this could not be done in view of ethical,
administrative and funding difculties. Observation period of more
than 6-weeks could have shown a more complete picture,
especially since most symptom dimensions had not plateaued
and were continuing to improve. However because of time
constraints and as per study protocol we could follow up these
subjects for only four weeks. Although fty-seven subjects were
recruited, only 43 subjects completed four weeks of assessment.
Per protocol we analyzed data on 43 patients who completed four
weeks and did not utilize intent to treat analyses for the entire 57
subjects. This could have affected the results of the study. However,
19
the 14 subjects who dropped out were not different from the other
16
43 in any of the socio-demographic and baseline clinical variables.
Hence we can consider that the 43 subjects were representative of
Positive
Negative the entire sample. Subtypes of schizophrenia could have had
differential outcome to olanzapine. Since in a sample of 43 the
we could not examine this aspect. Studies of similar nature using
larger samples to accommodate sufcient number of patients
belonging to the different schizophrenic subtypes would be able to
22 B. Birur et al. / Asian Journal of PsychiatryAJP 24 (2016) 1722
answer the question as to whether the ndings of this study are
applicable to all subtypes of schizophrenia.
The ndings of this study is useful in treating rst episode
psychotic patients as it provides vital information to the clinician
about patterns of response and thereby monitors the progress of
patients and eventually helps determine if the patient is
responding by following this trajectory in symptom dimension
response.
5. Conclusions
In summary, Olanzapine produced reduction in positive,
negative syndrome scores and ve factor scores (thought
disturbance, anergia, activation, paranoid-belligerence and de-
pression), which was statistically signicant. The rst symptom
dimension to show improvement was paranoid-belligerence and
positive symptoms followed by thought disturbance and activa-
tion. The last symptom dimension to show improvement was
negative symptoms and responded the least. There was statisti-
cally signicant weight gain of 2 kg over four weeks of treatment
with olanzapine. Also EPS was statistically signicant but minimal.
Longer-term studies comparing with FGAs are needed to elucidate
its relative performance on symptom dimensions of schizophrenia.
Disclosure of interest
Each author has materially participated in the research and/or
article preparation. All authors have approved the above manu-
script and none of them have any conict of interest to declare.
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