Schizophrenia Research 76 (2005) 127 – 129
www.elsevier.com/locate/schres
Letter to the Editors
Efficacy of clozapine, olanzapine, risperidone, and
haloperidol in schizophrenia and schizoaffective
disorder assessed with nurses observation scale for
inpatient evaluation
Dear Editors,
Studies to determine the efficacy of antipsychotics
have relied primarily on scales assessing psychotic
symptoms, e.g. the Positive and Negative Syndrome
Scale (PANSS) (Kay et al., 1987). These ratings are
typically completed by highly trained professional
researchers whose contact with the patient may be
limited.
However, treatment outcome includes not only
reductions in symptoms, but also changes in func-
tional ability. The Nurses Observational Scale for
Inpatient Evaluation (NOSIE) (Honigfeld, 1974) is a
ward behavior rating scale complementing the more
widely used psychiatric scales, and is easier to
administer and score than instruments such as the
PANSS. We implemented a study that used both
PANSS (the primary measure of efficacy) and NOSIE
(a secondary outcome measure). The PANSS results
have been published (Volavka et al., 2002). In this
letter we report the NOSIE results and compare them
with the PANSS.
The subjects were 157 treatment-resistant patients
diagnosed with schizophrenia or schizoaffective dis-
order. The patients were randomly assigned to treat-
ment with clozapine, olanzapine, risperidone, or
haloperidol in a 14-week, double-blind prospective
study. Written informed consent and institutional
review board approvals were obtained. The interrater
reliability, estimated by intraclass correlation coeffi-
cient (ICC) for the PANSS total score for paired
ratings ranged between 0.93 and 0.98 (Volavka et al.,
2002).
0920-9964/$ - see front matter D 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.schres.2004.11.007
The NOSIE version we used consists of 30 items,
each rated according to its frequency of occurrence: (0)
never; (1) occasionally; (2) sometimes; (3) often, and
(4) always. The items cluster into six factors: Social
competence, Social interest, Personal neatness, Irrita-
bility, Manifest psychosis, and Retardation (Honigfeld,
1974).
In our study, the NOSIE was usually administered
by a research nurse who read the NOSIE items and the
choice of answers to the ward nurse or the therapy
aide who knew the patient well and observed his or
her behavior. The behavior that was captured by the
NOSIE was limited to the three days preceding the
interview. Minimal training was provided in the
administration of the NOSIE. The PANSS was usually
administered on the same day as the NOSIE. The
NOSIE and the PANSS were not administered by the
same people. The results of the NOSIE were not
known by the person administering the PANSS, and
vice versa. Statistical analyses were analogous to
those described elsewhere (Volavka et al., 2002).
The results are summarized in Table 1. Statistically
significant improvements in comparison with baseline
were detected for clozapine and olanzapine for the
NOSIE total score as well as for three subscales (Social
competence, Social interest, and Manifest psychosis).
Clozapine was the only treatment that was associated
with a significant improvement of Irritability. Neither
risperidone nor haloperidol were associated with a
significant improvement on any NOSIE measure.
Clozapine and olanzapine showed significant supe-
riority over haloperidol on NOSIE total score and
manifest psychosis; clozapine was also superior to
haloperidol on social interest. Risperidone was not
significantly superior to haloperidol on any measure.
Clozapine, olanzapine, and risperidone showed no
significant differences from each other on pairwise
tests. The correlation coefficients between the total
scores of the NOSIE and the PANSS at baseline and at
128 Letter to the Editors

Table 1
NOSIE baseline scores (expressed as points per item) and analyses of change with clozapine, olanzapine, risperidone, and haloperidol treatment
NOSIE measure and drug Baseline Changea Analyses
b
Mean SD Mean 95% CI Change from baseline Superiority over haloperidol
t (df=838) pc t (df=838) pc
Total
Clozapine 1.37 0.50 0.23 0.41 to 0.05 2.57 0.0105 2.01 0.0443
Olanzapine 1.00 0.49 0.22 0.37 to 0.06 2.73 0.0065 2.01 0.0443
Risperidone 1.19 0.51 0.10 0.27 to 0.06
Haloperidol 1.22 0.47 0.02 0.15 to 0.18

Social competence
Clozapine 1.06 0.76 0.24 0.45 to 0.03 2.28 0.0231
Olanzapine 0.70 0.67 0.27 0.45 to 0.08 2.77 0.0057
Risperidone 0.94 0.69 0.15 0.35 to 0.05
Haloperidol 0.86 0.59 0.07 0.27 to 0.13

Social interest
Clozapine 2.61 0.88 0.45 0.72 to 0.18 3.28 0.0011 1.76 0.0789
Olanzapine 2.17 0.82 0.43 0.70 to 0.16 3.08 0.0021
Risperidone 2.41 0.96 0.10 0.38 to 0.17
Haloperidol 2.48 0.76 0.11 0.38 to 0.15

Personal neatness
Clozapine 1.65 0.98 0.08 0.25 to 0.40
Olanzapine 0.99 0.83 0.19 0.49 to 0.12
Risperidone 1.47 1.12 0.04 0.35 to 0.28
Haloperidol 1.39 0.90 0.01 0.33 to 0.30

Irritability
Clozapine 1.08 1.12 0.45 0.77 to 0.13 2.78 0.0055
Olanzapine 0.74 0.83 0.12 0.38 to 0.15
Risperidone 0.94 0.91 0.12 0.42 to 0.17
Haloperidol 1.05 0.99 0.12 0.41 to 0.17

Manifest psychosis
Clozapine 1.29 1.00 0.52 0.82 to 0.21 3.33 0.0005 3.42 0.0007
Olanzapine 0.92 0.98 0.27 0.54 to 0.00 1.94 0.0527 2.39 0.0170
Risperidone 0.77 0.85 0.12 0.41 to 0.17
Haloperidol 0.97 0.81 0.22 0.07 to 0.51

Retardation
Clozapine 1.20 1.04 0.12 0.15 to 0.39
Olanzapine 0.90 0.69 0.02 0.28 to 0.25
Risperidone 1.22 0.94 0.18 0.45 to 0.10
Haloperidol 1.08 1.06 0.05 0.22 to 0.33
a
Change per one NOSIE item at study end point estimated on the basis of Hierarchical Linear Model (HLM) analysis. (For details on HLM,
see Volavka et al., 2002).
b
Confidence interval.
c
p values b 0.10 are listed.

endpoint were, respectively, 0.420 ( pb0.0001) and usually nurses who had minimal training in the
0.615 ( pb0.0001). administration of the scale, achieved very similar
Overall, the NOSIE results were remarkably results as the PANSS raters, usually scientists at a
consistent with the PANSS. The NOSIE raters, doctoral level, who had received rigorous training
 Letter to the Editors 129

reflected by a very high interrater reliability. The Volavka, J., Czobor, P., Sheitman, B., Lindenmayer, J.-P., Citrome,
results underscore the value of the information that L., McEvoy, J., Cooper, T.B., Chakos, M., Lieberman, J.A.,
2002. Clozapine, olanzapine, risperidone, and haloperidol in
can be obtained from ward personnel and research treatment-resistant patients with schizophrenia and schizoaffec-
nurses. The NOSIE can add a measure of functioning tive disorder. Am. J. Psychiatry 159, 255 – 262.
and validate outcomes assessed by the PANSS.
Jan Volavka*
Karen A. Nolan
Acknowledgements Linda Kline
Pal Czobor
NIMH grant (R10 MH53550) provided the Leslie Citrome
principal support for this project. Additional support Nathan Kline Institute, 140 Old Orangeburg Road,
was provided by the UNC-Mental Health and Orangeburg, NY 10962, United States
Neuroscience Clinical Research Center (MH E-mail address: volavka@nki.rfmh.org.
MH33127) and the Foundation of Hope, Raleigh *Corresponding author. Tel.: +845 398 6567;
North Carolina. We thank Janssen Pharmaceutica fax: 845 398 6566.
Research Foundation, Eli Lilly and Company,
Novartis Pharmaceuticals Corporation, and Merck Brian Sheitman
and Co. for their generous gifts of medications. Eli Dorothea Dix Hospital, 809 Ruggles Road, Raleigh,
Lilly and Company contributed supplemental fund- NC 27603, United States
ing that covered approximately 18% of the total
cost of the study. However, overall experimental Jean-Pierre Lindenmayer
design, data acquisition, statistical analyses, and Manhattan Psychiatric Center, Wards Island,
interpretation of the results were implemented NY 10035, United States
without any input from any of the pharmaceutical
companies. Joseph McEvoy
John Umstead Hospital, 1003 12th Street, Butner,
NC 27509, United States
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