Review of the safety, efficacy, and side effect profile of asenapine in the treatment of bipolar 1 disorder

Figures & data

Table 2 Summary of efficacy and discontinuation data for asenapine using last observation carried forward analyses

	3-week trial (n = 185) 7501004	3-week trial (n = 194) 7501005	9 weeks^c (n = 275)	40 weeks^c (n = 112)
Efficacy	Mean change from baseline ± standard deviation
YMRS	−11.5 ± 0.8^Table Footnotea,Table Footnoteb	−10.8 + 0.8^a	−24.4 ± 8.7	−25.8 ± 10.3
Clinical global impression for bipolar disorder	−1.2 ± 0.10^Table Footnotea,Table Footnoteb	−1.2 + 0.1^a	−2.8 ± 0.09	−3.2 ± 1.3
Montgomery–Asberg depression rating scale	−3.0 ± 0.4	−3.2 +0.5	−3.6 ± 0.69	−4.8 ± 6.5
Response (≥50% improvement on YMRS)	78 (43%)	81 (42%)^a	212 (77%)	110 (98%)^d
Remission (≤12 YMRS)	67 (36%)	78 (40%)^a	206 (75%)	110 (98%)^d
Dropout rates	61 (33%)	72 (37%)	113 (41%)	46 (41%)

Notes:

a Differs from placebo;

b differs from olanzapine favoring olanzapine;

c no placebo group;

d response and remission rates were reported as one percentage.

Abbreviation: YMRS, Young mania rating scale.

Table 1 Side effect profiles across four clinical trials of asenapine

Side effects	3 weeks^b (n = 379) (%)	4–12 weeks^c (n = 181) (%)	13–52 weeks^c (n = 79) (%)	Olanzapine 13–52 weeks (n = 107) (%)
Sedation	14	14	17	16
Somnolence	14	12	14	16
Insomnia	–	13	20	12
Headache	–	21	14	14
Dizziness	11	24	13	6
Nausea	–	8	13	13
Constipation	–	10	6	6
Dry mouth	4	7	–	–
Vomiting	5	–	–	–
Appetite increase	4	–	–	–
Depression	–	–	15	8
Metabolic^a
Weight gain	7	19	31	55
Blood glucose levels (elevated or decreased levels)	12	12	18	22
Triglycerides	0	–	–	–
Weight loss	2	7	–	–
Prolactin	0	3	3	3
EPS
Tremor	–	–	8	5
Akathisia	4	–	11	10
Parkinsonism	2	–	8	4
Dystonia	4	–	4	1
Bradykinesia	2	–	4	2
Dyskenisia	1	–	1	0
Gait disturbance	0	–	3	0
Masked facies	–	–	1	0
Tardive dyskinesia	–	–	3	0

Notes:

a Percentages denote clinically significant changes;

b average of 3-week trial data;

c percentages do not include the placebo/asenapine group that started asenapine after a 3-week delay.

Abbreviation: EPS, extrapyramidal symptoms.

Table 3 Side effect profiles of antipsychotics in adults with bipolar disorder

	FDA indication	Sedation	Weight gain	Diabetes	EPS	Prolactin elevation	QTc prolongation
Aripiprazole	Manic/mixed episodes and maintenance	−	+/−	−	+	−	−
Asenapine	Manic/mixed episodes	++	++	++	+	+/−	+
Chlorpromazine	Mania	+++	++	++	++	++	++
Haloperidol	Psychosis	+	+	+	+++	+++	+
Olanzapine	Manic/mixed episode and maintenance	++	+++	+++	+/−	+	+
Quetiapine	Manic episodes and depressive episodes and maintenance	++	++	++	−	−	++
Risperidone	Manic/mixed episodes	+	+	++	++/+	+++	+
Ziprasidone	Manic/mixed episodes	+	+/−	−	+/−	+/−	++

Notes:

+++, very common side effect;

++, common side effect;

+, less common side effect;

−, uncommon side effect.

Abbreviations: EPS, extrapyramidal symptoms; FDA, US Food and Drug Administration.