Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial

1. Journal Article Review
Dr V K Sahu
Molecular Psychiatry
Oct 2015
Optimal duration of risperidone or olanzapine
adjunctive therapy to mood stabilizer following
remission of a manic episode: A CANMAT
randomized double-blind trial

3. 3:1 ratio.
Sadock BJ,Sadock VA, Ruiz P, Course and Prognosis, Mood Disorder, Kaplana & Sadock’s synopsis of
Psychiatry, 11th edition, 370-372
Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA et al. The longterm natural history
of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002; 59: 530–537

9. Inclusion Criteria:

10. Inclusion criteria (Continued..)
(CGI-S)
or
(YMRS)

11. Exclusion criteria:

12. Trial design and interventions:
52

13. Trial design and interventions (Contd):
Three groups:
‘0-weeks’ group

14. Trial design and interventions (Contd):
24-weeks’ group:
‘52-weeks’ group:
Continued risperidone or olanzapine for 52
weeks. All patients continued the same mood
stabilizer

15. Trial design and interventions (Contd):
BZD
anti-parkinsonian medication

16. Trial design and interventions (Contd):
Patients were allowed to receive

17. Study Outcomes:
Clinical Global Impression-Improvement (CGI-I)
(last 2 were assessed 2 week onwards)

18. Study Outcomes (Continued):

19. Primary outcome measure:
15
15
3
3
Hospitalization mood symptoms

20. Secondary outcome measures :
Primary outcome events manic depressive

21. Sample size:
type I error rate
80% power

23. Patient Flow and Characteristics:

24. Patient Flow and Characteristics (Continued):
34 (21%) discontinued
Mean follow-up times 18, 25 and 24

25. Results

26. Results
Treatment Variables

27.  Primary outcomes:
 39 primary events
(depression = 25, mania
= 14) among 52 patients
in the 0-weeks group
 29 events (depression =
23, mania = 6) among 54
patients in the 24-weeks
group


28. Primary outcomes (Continued):
29
time to any mood episode longer both 52-weeks
24-weeks 0-weeks
similar 52-
weeks and 24-weeks groups.

29. Hazard ratio (HR
0.53
0.63
relative to
1.18

30. Secondary outcomes:
27 70
Time to a manic episode longer

31. Secondary outcomes (Continued):
Time to a manic episode shorter 52
not
Time to a depressive episode

32. Secondary outcomes (Continued):
The time to discontinuation -

33. Secondary outcomes (Continued):

35. Subgroup analysis:
Olanzapine subgroup
Time to any mood episode longer not

37. Subgroup analysis:
Risperidone subgroup
Time to any mood

38.  Patients in the 52-weeks group
gained significantly more weight
(also clinically significant weight gain
(⩾7% or more of baseline weight)
 Average change in glucose,
cholesterol or triglycerides levels
from baseline to last follow-up
were similar in all three groups
whether including all patients or in
either antipsychotic subgroup

39. Adverse events:

40. First study
maintenance
bipolar I after
Time to relapse of any mood episode was significantly
longer in the group that continued atypical antipsychotic
adjunctive therapy for 24 weeks compared with the group
that had their atypical antipsychotic discontinued at study
entry.

41. There was a trend for longer time to relapse of any mood
episode in the 52-weeks group compared with the 0-weeks
group.

44. First study
maintenance
bipolar I after

45. not

46. not

47. less recurrence
for 24

49. S.NO Criteria Yes (2) Partial
(1)
No (0) NA
1 Question/ objective sufficiently described?
√
2 Study design evident & appropriate?
√
3 Method of subjective/comparison group selection
or source of information/ input variable describe
and appropriate?
√
4 Subject ( and comparison group, if applicable)
characteristics sufficiently described? √

50. S No Criteria Yes (2) Partial (1) No (0) NA
5 If interventional and random allocation
was possible, was it described? √
6 If interventional and blinding of
investigators was possible, was it
reported?
√
7 If interventional and blinding of subjects
was possible, was it reported? √
8 Outcome and (if applicable) exposure
measures well-defined and robust to
measurement/misclassification bias?
Means of assessment reported
√

51. S No Criteria Yes (2) Partial (1) No (0) NA
9 Sample size appropriate?
√
10 Analytic methods described/justified and
appropriate? √
11 Controlled for confounding?
√
12 Results reported in sufficient detail?
√
13 Conclusions supported by the results?
√

53. Thank you