Effects of asenapine on agitation and hostility in adults with acute manic or mixed episodes associated with bipolar I disorder

Figures & data

Table 1 Baseline scores on efficacy scales and items related to hostility and agitation

Efficacy scale	Placebo patients (n)	Placebo, mean (SD)	Asenapine patients (n)	Asenapine, mean (SD)
YMRS hostility subgroupa
YMRS total score	260	30.2 (5.94)	481	30.3 (5.97)
YMRS disruptive–aggressive behavior item score	260	3.3 (1.31)	481	3.3 (1.22)
YMRS irritability item score	260	4.1 (1.14)	481	4.1 (1.20)
PANSS total score	259	64.5 (17.37)	476	62.8 (15.41)
PANSS positive subscale score	259	18.2 (5.74)	476	17.8 (5.24)
PANSS hostility item (P7) score	259	2.7 (1.19)	476	2.7 (1.18)
PANSS-EC score	259	13.6 (3.72)	476	13.6 (3.75)
PANSS hostility subgroupb
YMRS total score	236	29.8 (6.02)	452	29.9 (6.08)
YMRS disruptive–aggressive behavior item score	236	3.1 (1.51)	452	3.1 (1.45)
YMRS irritability item score	236	4.0 (1.30)	452	4.0 (1.29)
PANSS total score	238	66.5 (17.04)	455	64.7 (15.12)
PANSS positive subscale score	238	18.9 (5.54)	455	18.5 (4.96)
PANSS hostility item (P7) score	238	3.1 (0.93)	455	3.0 (0.94)
PANSS-EC score	238	14.2 (3.31)	455	14.1 (3.43)
PANSS-EC agitation subgroupc
YMRS total score	115	31.9 (6.36)	232	32.4 (6.21)
YMRS disruptive–aggressive behavior item score	115	3.6 (1.48)	232	3.5 (1.43)
YMRS irritability item score	115	4.5 (1.29)	232	4.4 (1.36)
PANSS total score	116	75.0 (17.04)	233	71.2 (14.84)
PANSS positive subscale score	116	21.8 (5.77)	233	20.8 (5.19)
PANSS hostility item (P7) score	116	3.4 (1.14)	233	3.4 (1.15)
PANSS-EC score	116	16.8 (2.67)	233	16.7 (2.60)

Notes:

a YMRS hostility subgroup comprised patients with baseline YMRS hostility-related item scores ≥2.

b PANSS hostility subgroup comprised patients with baseline PANSS hostility item scores ≥2.

c PANSS-EC agitation subgroup comprised patients with PANSS-EC score ≥14, and one or more individual PANSS-EC item scores ≥4 at baseline.

Abbreviations: PANSS, Positive and Negative Syndrome Scale; PANSS-EC, PANSS-excited component; SD, standard deviation; YMRS, Young Mania Rating Scale.

Figure 1 Changes from baseline to day 21 in YMRS hostility-related items in the YMRS hostility subgroup.

Notes: Patients in this subgroup had baseline YMRS hostility-related item scores ≥2. *P<0.05; **P<0.01, ***P<0.001. Error bars indicate the standard error of the mean.
Abbreviations: LS, least squares; YMRS, Young Mania Rating Scale.

Table 2 Change from baseline to day 21 in YMRS total score and individual items in the YMRS hostility subgroupa (MMRM)

	Placebo (n=260)		Asenapine (n=481)		Asenapine vs placebo
	Baseline mean (SD)	LS mean change (SE)	Baseline mean (SD)	LS mean change (SE)	LSMD (95% CI)	ES	P-value
YMRS total score	30.2 (5.94)	−9.7 (0.76)	30.3 (5.97)	−14.0 (0.55)	−4.3 (−6.16, −2.54)	0.45	<0.0001
YMRS items
Disruptive–aggressive behavior	3.3 (1.31)	−0.9 (0.13)	3.3 (1.22)	−1.5 (0.09)	−0.7 (−0.99, −0.37)	0.45	<0.0001
Irritability	4.1 (1.14)	−1.3 (0.14)	4.1 (1.20)	−1.9 (0.10)	−0.5 (−0.87, −0.22)	0.32	0.0010
Appearance	1.2 (0.84)	−0.4 (0.06)	1.2 (0.90)	−0.6 (0.04)	−0.2 (−0.30, −0.01)	0.21	0.0329
Insight	1.0 (1.29)	−0.2 (0.06)	1.0 (1.31)	−0.3 (0.04)	−0.2 (−0.30, −0.02)	0.22	0.0286
Language–thought disorder	2.3 (0.62)	−0.8 (0.07)	2.2 (0.66)	−1.0 (0.05)	−0.2 (−0.35, −0.00)	0.19	0.0475
Increased motor activity–energy	2.9 (0.71)	−1.1 (0.09)	2.9 (0.64)	−1.4 (0.07)	−0.3 (−0.52, −0.09)	0.24	0.0052
Elevated mood	2.6 (0.95)	−0.9 (0.08)	2.8 (0.88)	−1.3 (0.06)	−0.4 (−0.65, −0.24)	0.39	<0.0001
Sleep	2.4 (0.90)	−0.8 (0.09)	2.4 (0.89)	−1.2 (0.06)	−0.4 (−0.64, −0.23)	0.32	<0.0001
Sexual interest	1.6 (1.18)	−0.6 (0.08)	1.6 (1.16)	−0.8 (0.06)	−0.3 (−0.44, −0.07)	0.24	0.0076
Content	4.4 (2.24)	−1.5 (0.16)	4.3 (2.11)	−2.2 (0.11)	−0.6 (−1.01, −0.27)	0.26	0.0008
Speech	4.4 (1.55)	−1.8 (0.15)	4.4 (1.57)	−2.3 (0.11)	−0.5 (−0.82, −0.11)	0.28	0.0101

Note:

a Patients with baseline YMRS hostility-related item scores ≥2.

Abbreviations: CI, confidence interval; ES, effect size; LS, least squares; LSMD, LS mean difference; MMRM, mixed-effects model for repeated measures; SD, standard deviation; SE, standard error of the mean; YMRS, Young Mania Rating Scale.

Figure 2 Changes from baseline to day 21 in PANSS-derived scores (MMRM).

Notes: (A) PANSS hostility item (P7) score changes in the PANSS hostility subgroup (patients with baseline hostility item scores ≥2). (B) PANSS-EC total score changes in the PANSS-EC agitation subgroup (patients with PANSS-EC total score ≥14 and score ≥4 on ≥1 individual item at baseline). Error bars indicate the standard error of the mean. *P<0.05; **P<0.01.
Abbreviations: LS, least squares; MMRM, mixed-effects model for repeated measures; PANSS, Positive and Negative Syndrome Scale; PANSS-EC, PANSS-excited component.

Table S1 Change from baseline to day 21 in YMRS total score and individual items in the PANSS hostility subgroupa (MMRM)

	Placebo (n=236)		Asenapine (n=452)		Asenapine vs placebo
	Baseline mean (SD)	LS mean change (SE)	Baseline mean (SD)	LS mean change (SE)	LSMD (95% CI)	ES	P-value
YMRS total score	29.8 (6.02)	−10.5 (0.79)	29.9 (6.08)	−14.6 (0.58)	−4.1 (−5.97, −2.25)	0.49	<0.0001
YMRS items
Disruptive–aggressive behavior	3.1 (1.51)	−0.7 (0.14)	3.1 (1.45)	−1.4 (0.10)	−0.7 (−0.97, −0.34)	0.38	<0.0001
Irritability	4.0 (1.30)	−1.3 (0.14)	4.0 (1.29)	−1.8 (0.10)	−0.5 (−0.84, −0.17)	0.32	0.0033
Appearance	1.2 (0.86)	−0.4 (0.06)	1.2 (0.91)	−0.6 (0.05)	−0.1 (−0.27, 0.02)	0.11	0.0852
Insight	0.9 (1.29)	−0.2 (0.06)	1.0 (1.30)	−0.4 (0.04)	−0.1 (−0.26, 0.01)	0.21	0.0669
Language–thought disorder	2.3 (0.61)	−0.8 (0.08)	2.2 (0.66)	−1.1 (0.06)	−0.2 (−0.41, −0.05)	0.29	0.0109
Increased motor activity – energy	2.9 (0.68)	−1.1 (0.10)	2.9 (0.65)	−1.4 (0.07)	−0.3 (−0.55, −0.11)	0.32	0.0039
Elevated mood	2.6 (0.96)	−0.9 (0.09)	2.8 (0.88)	−1.4 (0.06)	−0.5 (−0.68, −0.28)	0.47	<0.0001
Sleep	2.3 (0.91)	−0.9 (0.09)	2.4 (0.92)	−1.3 (0.07)	−0.4 (−0.66, −0.23)	0.47	<0.0001
Sexual interest	1.6 (1.20)	−0.6 (0.08)	1.6 (1.17)	−0.9 (0.06)	−0.3 (−0.52, −0.13)	0.31	0.0013
Content	4.4 (2.27)	−1.7 (0.17)	4.4 (2.12)	−2.3 (0.12)	−0.5 (−0.89, −0.12)	0.21	0.0103
Speech	4.5 (1.51)	−1.9 (0.16)	4.4 (1.56)	−2.5 (0.11)	−0.6 (−0.94, −0.21)	0.28	0.0020

Note:

a Patients with baseline PANSS hostility item scores ≥2.

Abbreviations: CI, confidence interval; ES, effect size; LS, least squares; LSMD, LS mean difference; MMRM, mixed-effects model for repeated measures; PANSS, Positive and Negative Syndrome Scale; SD, standard deviation; SE, standard error of the mean; YMRS, Young Mania Rating Scale.