The role of asenapine in the treatment of manic or mixed states associated with bipolar I disorder

Figures & data

Table 1 Randomized controlled trials of asenapine versus olanzapine and placebo with outcomes analyzed by LOCF versus MMRM or OC methods: Least square mean changes in young mania rating scale scores (M ± SE)

Study	Asenapine dose	Olanzapine dose	Trial (weeks)	LOCF			MMRM
				Olanzapine (number of patients)	Asenapine (number of patients)	Placebo (number of patients)	Olanzapine (number of patients)	Asenapine (number of patients)	Placebo (number of patients)
McIntyre et al^Citation18 (Ares 7501005; clinical trial registry number: NCT00159796)	5–10 mg BID FLEX (Mean: 18.2 mg)	5–20 mg QD (Mean: 15.8 mg)	3	−12.6 ± 0.8 (188)	−10.8 ± 0.8 (189)	−5.5 ± 1.0 (103)	−13.9 ± 0.8 (188)	−13.1 ± 0.8 (189)	−7.4 ± 1.1 (103)
McIntyre et al^Citation20 (Ares 7501004; NCT00159744)	BID FLEX (Mean: 18.4 mg)	5–20 mg QD (Mean: 15.9 mg)	3	−14.6 ± 0.8 (203)	−11.5 ± 0.8 (183)	−7.8 ± 1.1 (94)	−16.1 ± 0.8 (203)	−14.2 ± 0.9 (183)	−10.8 ± 1.2 (94)
McIntyre et al^Citation21 (Ares 7501006; registry #NCT00143182)	5–10 mg BID FLEX	5–20 mg QD	9 (extension study)	−21.3 ± 9.6* (222)	−20.1 ± 10.7* (175)	–	−23.9 ± 7.9* (128)	−24.4 ± 8.7* (86)	–
McIntyre et al^Citation19 (A7501007, NCT00159783)	5–10 mg BID FLEX (Mean: 15.7 ± 4.1 mg placebo/asenapine group, 16.3 ± 3.7 mg asenapine group)	5–20 mg QD (Mean: 15.4 ± 4.0 mg)	40 (extension study)	−26.1 ± 8.4* (104)	−25.8 ± 10.3* (76)	–	−28.2 ± 6.8* (63)	−28.6 ± 8.1* (45)	–

Notes:

* M ± SD. Trial A7501007, NCT00159783 analyzed data by LOCF and OC methods.

Abbreviations: LOCF, last observation carried forward; MMRM, mixed model for repeated measures; YMRS, young mania rating scale; BID, twice daily; QD, once daily; FLEX, flexible.

Table 2 Randomized controlled trials of asenapine versus olanzapine and placebo with outcomes analyzed by LOCF versus MMRM or OC methods: Least square mean changes in secondary outcome measures (M ± SE)

Study	Outcome measure	Asenapine dose	Olanzapine dose	Trial (weeks)	LOCF			MMRM
					Olanzapine (number of patients)	Asenapine (number of patients)	Placebo (number of patients)	Olanzapine (number of patients)	Asenapine (number of patients)	Placebo (number of patients)
McIntyre et al^Citation18 (Ares 7501005; clinical trial registry number: NCT00159796)	CGI-BP	5–10 mg BID FLEX (Mean: 18.2 mg)	5–20 mg QD (Mean: 15.8 mg)	3	−1.4 ± 0.1 (188)	−1.2 ± 0.1 (189)	−0.7 ± 0.13 (103)	−1.6 ± 0.1 (188)	−1.5 ± 0.1 (189)	−1.0 ± 0.2 (103)
McIntyre et al^Citation18 (Ares 7501005; clinical trial registry number: NCT00159796)	MADRS	5–10 mg BID FLEX (Mean: 18.2 mg)	5–20 mg QD (Mean: 15.8 mg)	3	−4.2 ± 0.5 (183)	3.2 ± 0.5 (184)	−1.8 ± 0.7 (98)	–	–	–
McIntyre et al^Citation20 (Ares 7501004; NCT00159744)	CGI-BP	BID FLEX (Mean: 18.4 mg)	5–20 mg QD (Mean: 15.9 mg)	3	−1.5 ± 0.09 (203)	−1.2 ± 0.10 (183)	−0.8 ± 0.13 (94)	−1.7 ± 0.09 (203)	−1.6 ± 0.11 (183)	−1.1 ± 0.15 (94)
McIntyre et al^Citation20 (Ares 7501004; NCT00159744)	MADRS	BID FLEX (Mean: 18.4 mg)	5–20 mg QD (Mean: 15.9 mg)	3	−4.1 ± 0.4 (201)	−3.0 ± 0.4 (173)	−1.9 ± 0.6 (90)	–	–	–
McIntyre et al^Citation21 (Ares 7501006; registry #NCT00143182)	CGI-BP	5–10 mg BID FLEX	5–20 mg QD	9 (extension study)	–	–	–	−2.4 ± 0.1 (221)	−2.6 ± 0.1 (173)	–
McIntyre et al^Citation21 (Ares 7501006; registry #NCT00143182)	MADRS	5–10 mg BID FLEX	5–20 mg QD	9 (extension study)	–	–	–	2.4 ± 0.61 (222)	3.6 ± 0.69 (175)	–
McIntyre et al^Citation19 (A7501007, NCT00159783)	CGI-BP	5–10 mg BID FLEX (Mean: 15.7 ± 4.1 mg placebo/asenapine group, 16.3 ± 3.7 mg asenapine group)	5–20 mg QD (Mean: 15.4 ± 4.0 mg)	40 (extension study)	−3.2 ± 1.1 (104)	−3.2 ± 1.3 (76)	–	−3.5 ± 0.9 (63)	−3.6 ± 1.1 (45)	–
McIntyre et al^Citation19 (A7501007, NCT00159783)	MADRS	5–10 mg BID FLEX (Mean: 15.7 ± 4.1 mg placebo/asenapine group, 16.3 ± 3.7 mg asenapine group)	5–20 mg QD (Mean: 15.4 ± 4.0 mg)	40 (extension study)	−3.2 ± 8.6* (104)	−4.8 ± 6.5* (76)	–	−4.4 ± 5.4* (63)	−4.8 ± 5.8* (45)	–

Note:

* M ± SD.

Abbreviations: LOCF, last observation carried forward; MMRM, mixed model for repeated measures; OC, observed case; CGI-BP, Clinical Global Impression for Bipolar Disorder; MADRS, Montgomery–Åsberg Depression Rating Scale; BID, twice daily; QD, once daily; FLEX, flexible.

Table 3 Randomized controlled trials of asenapine versus olanzapine and placebo: adverse events

Study	Asenapine dose	Olanzapine dose	Trial (weeks)	Treatment-related adverse events			Discontinued			Discontinued because of adverse events			Discontinued because of lack of efficacy
				Olanzapine	Asenapine	Placebo	Olanzapine	Asenapine	Placebo	Olanzapine	Asenapine	Placebo	Olanzapine	Asenapine	Placebo
McIntyre et al^Citation18 (Ares 7501005; clinical trial registry number: NCT00159796)	5–10 mg BID FLEX (Mean: 18.2 mg)	5–20 mg QD (Mean: 15.8 mg)	3	52.9%	60.8%	36.2%	30.9%	37.1%	38.5%	4.2%	10.3%	6.7%	5.8%	8.2%	16.3%
McIntyre et al^Citation20 (Ares 7501004; NCT00159744)	BID FLEX (Mean: 18.4 mg)	5–20 mg QD (Mean: 15.9 mg)	3	46.8%	55.1%	27.6%	21.5%	33.0%	41.8%	3.4%	9.2%	4.1%	6.3%	7.6%	14.3%
McIntyre et al^Citation21 (Ares 7501006; registry #NCT00143182)	5–10 mg BID FLEX	5–20 mg QD	9 (extension study)	64% (53%)*	65%	–	36.2%	38.1% (46.8%)*	–	9.6%	13.3% (19.2%)*	–	3.9%	3.3% (5.3%)*	–
McIntyre et al^Citation19 (A7501007, NCT00159783)	5–10 mg BID FLEX (Mean: 15.7 ± 4.1 mg placebo/asenapine group, 16.3 ± 3.7 mg asenapine group)	5–20 mg QD (Mean: 15.4 ± 4.0 mg)	40 (extension study)	61.7% (53.1%)*	70.9%	–	36.4%	34.2% (59.4%)*	–	8.4%	8.9% (15.6%)*	–	2.8%	2.5% (3.1%)*	–

Note:

* Placebo/Asenapine group.

Abbreviations: LOCF, last observation carried forward; MMRM, mixed model for repeated measures; OC, observed case; CGI-BP, Clinical Global Impression for Bipolar Disorder; MADRS, Montgomery–Åsberg Depression Rating Scale; BID, twice daily; QD, once daily; FLEX, flexible.

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