Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Chinese subpopulation analysis of a double-blind, randomized, placebo-controlled study

Figures & data

Figure 1 Patient disposition.

Note: ^aIncludes one patient randomized to the olanzapine group who was excluded from the safety population but later determined to have received treatment.

Table 1 Baseline demographics and illness characteristics of Chinese study participants with bipolar depression treated with olanzapine or placebo

Characteristic	Placebo (n=70)	Olanzapine (n=140)	Total (n=210)
Female, n (%)	37 (52.9)	77 (55.0)	114 (54.3)
Age, years, mean ± SD	32.0±11.5	33.3±10.6	32.9±10.9
Age at onset of bipolar disorder, years, mean ± SD	25.6±10.3	26.6±9.7	26.3±9.9
Weight, kg, mean ± SD	64.4±12.5	62.6±11.3	63.2±11.7
Number of previous episodes, mean ± SD
Manic	2.41±2.00	2.28±2.19	2.32±2.12
Depressive	2.40±2.20	2.69±2.18	2.60±2.18
Mixed	0.17±0.68	0.09±0.49	0.11±0.56
Illness severity scores, mean ± SD
MADRS total	29.19±5.29	29.55±4.97	29.43±5.07
YMRS total	1.49±1.67	1.61±1.36	1.57±1.47
HAMD-17 total	22.10±3.25	22.24±2.99	22.19±3.07
CGI-BP
Mania	1.01±0.12	1.01±0.08	1.01±0.10
Depression	4.74±0.72	4.74±0.64	4.74±0.67
Bipolar	4.73±0.74	4.71±0.64	4.72±0.67

Abbreviations: CGI-BP, Clinical Global Impressions-Bipolar Version; HAMD-17, Hamilton Depression Rating Scale-17; MADRS, Montgomery-Åsberg Depression Rating Scale; SD, standard deviation; YMRS, Young Mania Rating Scale.

Figure 2 Visit-wise change from baseline in LS mean MADRS total score ±95% CI for entire Chinese subpopulation.

Notes: ● = olanzapine, □ = placebo.
Abbreviations: CI, confidence interval; LS, least-squares; MADRS, Montgomery-Åsberg Depression Rating Scale.

Table 2 Baseline to endpoint least-squares mean changes in CGI-BP, HAMD-17, and YMRS

Efficacy measure	Placebo (n=70)	Olanzapine (n=140)	P-value
	LS mean ± SE	LS mean ± SE
CGI-BP mania	0.12±0.05	0.04±0.03	0.152
CGI-BP depression	−1.32±0.16	−1.44±0.11	0.523
CGI-BP bipolar	−1.23±0.15	−1.41±0.11	0.320
HAMD-17 total	−9.73±0.88	−11.50±0.63	0.102
YMRS total	0.45±0.41	−0.66±0.29	0.029

Abbreviations: CGI-BP, Clinical Global Impressions-Bipolar Version; HAMD-17, Hamilton Depression Rating Scale-17; LS, least-squares; SE, standard error; YMRS, Young Mania Rating Scale.

Table 3 Response, symptomatic remission, and recovery rates

Depression measure	Placebo (n=70)	Olanzapine (n=140)	P-value
	n (%)	n (%)
Response (≥50% reduction in MADRS)	30 (42.9)	73 (52.1)	0.24
Symptomatic remission
MADRS ≤12	30 (42.9)	70 (50.0)	0.38
MADRS ≤7	14 (20.0)	31 (22.1)	0.86
MADRS ≤5	13 (18.6)	16 (11.4)	0.20
Recovery (MADRS total score ≤12 for ≥4 weeks)	6 (8.6)	14 (10.0)	0.81

Abbreviation: MADRS, Montgomery-Åsberg Depression Rating Scale.

Figure 3 Visit-wise change of MADRS total score from baseline (LOCF) for individual subjects with emergence of mania in placebo and olanzapine group.

Notes: Dashed lines show the mean change for the overall population. Open symbols represent Chinese subjects; filled symbols represent US subjects.
Abbreviations: LS, least-squares; MADRS, Montgomery-Åsberg Depression Rating Scale; LOCF, last-observation-carried-forward.

Table 4 Treatment difference between olanzapine and placebo groups in least-squares mean change in MADRS total score (95% confidence interval) using the MADRS score of the visit before mania emergence and excluding patients with emergence of mania

Exclusion condition	Overall population	Chinese subpopulation
	LS mean (95% CI)	LS mean (95% CI)
Not considering mania episode	−2.15 (−3.93, −0.36)	−1.05 (−3.75, 1.65)
Using MADRS score of the visit before mania emergence	−2.45 (−4.23, −0.68)	−1.74 (−4.42, 0.93)
Excluding patients with emergence of mania	−2.46 (−4.26, −0.66)	−1.76 (−4.48, 0.95)

Abbreviations: CI, confidence interval; LS, least-squares; MADRS, Montgomery-Åsberg Depression Rating Scale.

Table 5 Common TEAEs occurring in ≥2% of patients with any treatment

Preferred term	Placebo (n=70)	Olanzapine (n=139)	P-value
	n (%)	n (%)
Patients with ≥1 TEAE	27 (38.6)	62 (44.6)	0.460
Hypersomnia	2 (2.9)	12 (8.6)	0.148
Weight increase	2 (2.9)	9 (6.5)	0.342
Abnormal hepatic function	1 (1.4)	7 (5.0)	0.273
Constipation	0 (0.0)	6 (4.3)	0.182
Dizziness	2 (2.9)	6 (4.3)	0.721
Dry mouth	1 (1.4)	5 (3.6)	0.666
Increased appetite	1 (1.4)	5 (3.6)	0.666
Somnolence	3 (4.3)	5 (3.6)	1.000
ALT increase	0 (0.0)	4 (2.9)	0.303
Asthenia	1 (1.4)	3 (2.2)	1.000
Nasopharyngitis	0 (0.0)	3 (2.2)	0.552
Palpitations	0 (0.0)	3 (2.2)	0.552
Hypersalivation	1 (1.4)	3 (2.2)	1.000
Tremor	1 (1.4)	3 (2.2)	1.000
Bipolar I disorder	3 (4.3)	1 (0.7)	0.110
URTI	4 (5.7)	1 (0.7)	0.044
Decreased appetite	2 (2.9)	0 (0.0)	0.111

Abbreviations: TEAEs, treatment-emergent adverse events; URTI, upper respiratory tract infection; ALT, alanine aminotransferase.

Table 6 Mean change from baseline to endpoint values in laboratory analytes (except glucose and lipid panel)

Laboratory analyte	Mean ± SD change from baseline		P-value*
	Placebo (n=52–65)	Olanzapine (n=119–129)
ALB, g/L	0.48±3.10	−0.66±3.08	0.023
ALT, IU/L	1.52±17.95	9.88±27.06	0.007
AST, IU/L	2.22±12.76	4.74±14.34	0.028
Basophils, ×10^9/L	0.01±0.02	−0.00±0.03	0.010
Creatinine, µmol/L	−0.63±6.02	−2.93±6.76	0.015
GGT, IU/L	0.95±7.16	6.02±15.84	<0.001
Hematocrit, proportion	0.01±0.03	−0.00±0.03	0.044
Hemoglobin, mmol/L	0.14±0.40	−0.01±0.53	0.048
Hemoglobin A1c, %	−0.03±0.31	0.04±0.26	0.035
Lymphocytes, atypical, ×10^9/L	0.00±0.02	−0.00±0.00	0.049
Potassium, mmol/L	−0.12±0.36	−0.00±0.36	0.013
Prolactin, µg/L	−0.57±28.60	15.23±28.89	<0.001
UA-specific gravity	0.00±0.01	−0.00±0.01	0.038
Uric acid, µmol/L	−7.28±49.67	20.03±55.31	<0.001

Note:

* Wilcoxon’s rank-sum test.

Abbreviations: SD, standard deviation; UA, urinalysis; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase.