journal club: A Randomized Double-Blind Study of Risperidone and Olanzapine in the Treatment of Schizophrenia or Schizoaffective Disorder(Am J Psychiatry 2001; 158:765–774)

2.  A Randomized Double-Blind Study of
Risperidone and Olanzapine in the Treatment
of Schizophrenia or Schizoaffective Disorder.
(American Journal of Psychiatry
2001; 158:765–774)

3.  Robert R. Conley, M.D
comparing the clinical effects of newer
antipsychotics in people with schizophrenia
 Ramy Mahmoud, M.D., M.P.H.
 Centre:USA

4.  As risperidone and olanzapine are most
commonly used drugs in our set up, so,
which one to choose in day to day practice.
 Knowledge of comparative efficacy, eps, ade
of these 2 drugs help us to decide.

5.  well tolerated and efficacious.
 half of all new prescriptions
 Large separate trials>Both superior to
haloperidol in amelioration of negative
symptoms and that risperidone is superior in
amelioration of the positive symptoms of
schizophrenia.

6.  Advantages in alleviating refractory symptoms,
negative symptoms, depression, and suicidal
behavior have been reported.
 Second-generation drugs do provide clear
advantages in terms of fewer adverse effects,
particularly drug-induced parkinsonism,
akathisia,and tardive dyskinesia.
 Not much done methodologically in establishing
the relative merits of specific drugs in these
multiple domains of interest (6).
 Establishing relative efficacy and safety

7.  Both reduced positive and negative
symptoms, with no significant between-
group differences except on one of multiple
measures of negative symptoms, where
olanzapine was superior to risperidone.
 More olanzapine than risperidone
participants were rated as treatment
responders (defined as >40% reduction in
scores on the Positive and Negative Syndrome
Scale), and fewer reported adverse events.

8.  Equally effective as acute treatments.
 Risperidone was more effective for treatment
of psychotic symptoms at 6 months, but
otherwise the 2 medications were equally
effective in the routine clinical care of
patients with schizophrenia.
 If low (<6 mg/day) doses of risperidone are
used, the 2 medications have comparable
rates of parkinsonian side effects.

9.  The safety and efficacy of risperidone and
olanzapine were compared in a double-blind
trial that used doses widely accepted in
clinical practice.

10.  A multicenter, randomized, double-blind,
parallel-group study in 41 sites in the united
states.
 2 excluded.
 Auditing of all 377 participant files.
 Informed consent.
 Oral antipsychotics were discontinued 1wk
before and depot 1 cycle ago.
 Risperidone (2–6 mg/day) or olanzapine(5–20
mg/day) for 8 weeks.

11.  Inclusion criteria
◦ DSM-IV diagnosis of schizophrenia or schizoaffective disorder.
◦ baseline Positive and Negative Syndrome Scale (12) score of 60 to
120 (calculated by using 1–7 scoring).
◦ 18–64 years.
◦ Outpatients or inpatients hospitalized ≤4 weeks.
◦ Informed consent.
 Exclusion criteria
 DSM-IV axis I diagnosis other than schizophrenia or
schizoaffective disorder.
 DSM-IV diagnosis of substance abuse in the 3 months before
selection.
 CNS disease
 mood stabilizers or antidepressants,
 Clozapine for 4 wks
 Sensitive or resistant to RSPD/OLNZ

12. DAYS RISPERIDONE(mg/day) OLANZAPINE(mg/day)
1-2 2 10
3-7 2-4 5-10
8-14 2-6 5-15
15-56 2-6 5-20

13.  once a week visit
 EPS(Extrapyramidal Symptom Rating Scale)
 Psychopathology(Positive and Negative
Syndrome Scale, total scores and scores on
five Positive and Negative Syndrome Scale
factors)
 Baseline and at weeks 2, 4, 6, and 8 (or
withdrawal).
 Overall by CGI/ severity by CGI change scale.
 Clinical improvement=PANSS≥20% reduction

14.  Adverse events (weekly)
 Vital signs and Standard lab tests
(randomization and weeks at 2, 4, 6, and 8
or withdrawal).
 ECG (screening and at week 8 or
withdrawal)
 self-assessment questionnaires(baseline
and week 8 or withdrawal)
 symptoms potentially related to prolactin in
three areas (menstrual changes, breast or
chest symptoms, and male sexual function).

15.  The 5%, two-tailed significance level.
 Between-group comparisons(investigator,
baseline values, PANSS Scale and EPS Scale)
and age> single multivariate F test
 Within-group differences> paired t tests.
 Results at week 8 (observed-case analysis)
and endpoint (missing data estimated by
carrying the last observation forward).
 Overall differences in categoric measures>
chi-square test.

16.  Ratio of beneficial to adverse changes>
Dividing the reduction from an above-normal
score at baseline to a normal score by the
increase from a normal score at baseline to
an above normal score.
 Between-treatment risk ratios> the previous
ratio for the risperidone group divided by the
value for the olanzapine group.

17.  Most participants were men (72.7%, N=274).
 Mean age of the group was 40.0 years
(SD=10.8), 86.2% (N=325)
 65.5% of those had the paranoid type,
N=213), and 79.0% (N=298) were
outpatients.
 Baseline PANSS score of the group was 80.9
(SD=13.0).

19.  No significant differences in background
characteristics between the two treatment
groups, except that the participants who
received olanzapine were slightly younger
than those who received risperidone.

20.  Similar proportions of the participants in the
two treatment groups completed the study.
 Mean duration of treatment was 45.8 days
(SD=18.8) in the risperidone group and 48.9
days (SD=16.5) in the olanzapine group.

21.  Trial >4.8 mg/day (SD=1.2) of risperidone and 12.4
mg/day (SD=4.6) of olanzapine.
 Endpoint mean doses were 4.7 mg/day (SD=1.4) of
risperidone and 13.1 mg/day (SD=5.1) of olanzapine;
endpoint median doses were 4 mg/day and 10
mg/day, respectively.
 Distribution of the modal daily doses was as follows:
2 mg of risperidone was received by 6.9% of the
risperidone participants(N=13), 4 mg by 47.3%
(N=89), and 6 mg by 45.7% (N=86);5 mg of
olanzapine was received by 10.1% of the olanzapine
participants (N=19), 10 mg by 51.3% (N=97), 15 mg
by 18.5% (N=35), and 20 mg by 20.1% (N=38).

23.  Severity of extra pyramidal symptoms (Extra
pyramidal Symptom Rating Scale total scores)
was significantly reduced from baseline to week8
and endpoint in both treatment groups, with no
significant between-group differences.
 Anti parkinsonian medications were received by
32.4% of the risperidone participants (N=61) and
28.0% of the olanzapine participants (N=53)
during the trial (Cochran-Mantel- Haenszel
χ2=1.30, df=1, p=0.26).

25.  On all PANSS measures, score reductions from baseline
were significant at treatment week 2 and throughout
the study (p<0.01)
 Significantly greater improvement on two Positive and
Negative Syndrome Scale factors (positive symptoms
and anxiety/depression) was seen in participants
receiving risperidone than in those receiving olanzapine
(p<0.05)
 Clinical improvement, 50.7% of the risperidone group
(N=69) and 47.6% of the olanzapine group (N=68) at
week 8 and in 45.4% and 44.5%, respectively, at
endpoint (N=79 for the risperidone group; N=81 for the
olanzapine group).

29.  Risperidone than of olanzapine 20%–40%
reductions in the PANSS scores at both week 8
and endpoint, and these between group
differences were significant at the 40% reduction
level at week 8 (25.4% [N=34] for the risperidone
participants versus 16.0% [N=23] for the
olanzapine participants ;and at endpoint (24.0%
[N=42] for the risperidone participants versus
15.5% [N=28] for the olanzapine participants;
χ2=4.79, df=1, p<0.03). Few patients achieved
50% symptom reduction.

30.  No significant between group differences. At
week 8, 45.1% of the risperidone group
(N=60) and 40.0% of the olanzapine group
(N=58) were rated as much or very much
improved. At endpoint, 40.1% (N=71) and
35.9% (N=65), respectively, were so rated.

32.  Serious adverse events were experienced by
8.0% of the risperidone participants (N=15)
and 11.6% of the olanzapine participants
(N=22)
 Dry mouth (11.2% of the risperidone
participants [N=21] and 22.2% of the
olanzapine participants [N=42]).

33.  At endpoint, the mean weight gain was 7.2 lb
(SD=11.2) in the olanzapine group versus 3.4 lb
(SD=7.8) in the risperidone group (F=14.26, df=1,
282, p<0.001)
 The mean body mass index increase was 1.1 kg/m2
(SD=1.7) in the olanzapine group versus 0.5 kg/m2
(SD=1.2) in the risperidone group (F=15.72, df=1,
282, p<0.001).
 Increase in body weight of ≥7% was seen in 27.3% of
the olanzapine participants (N=44 of 161) and 11.6%
of the risperidone participants (N=18 of 155)

37.  Risk ratios for change were worse for
olanzapine in relation to liver transaminases
and lipid profiles and worse for risperidone in
relation to prolactin.
 ECG> Between-group difference was not
significant (F=2.09, df=1, 287, p=0.15).

38.  Both treatments were well tolerated and
efficacious. The frequency and severity of
extrapyramidal symptoms were similar in the
two treatment groups. Greater reductions in
severity of positive and affective symptoms
were seen with risperidone than with
olanzapine treatment among study
completers. There was no measure on which
olanzapine was superior. Greater weight gain
was associated with olanzapine than with
risperidone treatment.

40.  Title reflects what the study has examined.
 This study improves previous findings.
 Original, bigger than other, helps to remove pitfalls of previous
studies, relevant.
 As therapy related>>RCT
 A multicenter,randomized, double-blind, parallel-group,so Systemic
bias minimized.
 Adequate sample size> 41 sites in the united states
 Tools are valid(DSM4,PANSS,EPS scale and SEVERITY score, CGI and
severity)
 Assessment blind, outcomes meaningfully measured.
 Relevant data presented.
 Compared with already present datas, difference is present and
significant.
 Valid conclusions and Its relevant in our setting.

41.  Title is not appropriate, as a good title should not
contain description of study design.
 Objective of study should also contain dose range of
drug also, not merely clinically effective dose.
 Review of literature about comparison of 2 drugs is very
less, also all from same region.
 Why PANSS 60 to 120,not explained.
 Oral antipsychotics stopped only 1wk before, depot I
cycle before which may be in blood during study.
 Drug dosing regime is not clear, as weekly range may
lead to difference drug dose in different population.
 Few table contents are not discussed anywhere in
between study.

42. Thank you