Effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine for agitation associated with schizophrenia

Figures & data

Figure 1 Study design.

Notes: Gray-colored table cells refer to the original study period. Not Gray (clear) table cells refer to the extension study period. “Others” includes four consecutive days of administration of RAIM and several time points of administration of RAIM not on consecutive days.
Abbreviation: RAIM, rapid-acting intramuscular olanzapine.

Table 1 Baseline patient characteristics and concomitant drug therapies

Characteristics	n (%)	Mean±SD
N	522
Age (years)		45.9±15.2
<65	446 (85.4)
≥65 to <75	58 (11.1)
≥75	18 (3.4)
Gender
Male	248 (47.5)
Female	274 (52.5)
Duration of disease (years)	371	16.6±13.3
History of diabetes in a family member
Absent	381 (73.0)
Present	5 (1.0)
Unknown	136 (26.1)
Inpatient/outpatient status at the start of treatment
Inpatient	448 (85.8)
Outpatient	74 (14.2)
Medical history	40 (7.7)
Complications	136 (26.1)
Diabetes-related complicationsa	16 (3.1)
Concomitant drug therapyb	332 (63.6)
Psychotropic drugc	323 (61.9)
Antipsychotic	202 (38.7)
Mood-stabilizing drug	67 (12.8)
Benzodiazepine	203 (38.9)
Anticholinergic drug	66 (12.6)
Antidepressants	14 (2.7)
Others (psychotropic drug)	50 (9.6)
Other concomitant drug therapy	97 (18.6)

Notes:

a Diabetes-related disease complications included high HbA1c and high blood glucose, but patients were not diagnosed as diabetes.

b Concomitant drug therapy was defined as medication (other than rapid-acting intramuscular olanzapine and oral olanzapine) that was administered during the observational period and a day before the observational period.

c Same patients select multiple psychotropic drugs.

Abbreviations: N, total number of patients; n, number of patients.

Table 2 Oral olanzapine dose after administration of 10 mg on the last day of rapid-acting intramuscular olanzapine

The last day of rapid-acting intramuscular olanzapine during the original study period		Oral olanzapine dose at the next day of rapid-acting intramuscular olanzapine final administration during the original study period
Daily dosage of rapid-acting intramuscular olanzapine (mg)	Oral olanzapine daily dose (mg)	0 mg	2.5 mg	5 mg	7.5 mg	10 mg	12 mg	15 mg	20 mg	25 mg	30 mg	Total
10	0	17	3	6	3	85	0	4	37	1	1	157
	2.5	0	3	0	0	0	0	0	0	0	0	3
	5	0	0	33	0	1	0	1	1	0	0	36
	7.5	0	0	0	2	0	0	0	0	0	0	2
	10	2	0	0	0	147	0	2	8	0	0	159
	12	0	0	0	0	0	1	0	0	0	0	1
	15	0	0	0	0	1	0	13	0	0	0	14
	20	0	0	0	0	1	0	0	101	0	0	102
	30	0	0	0	0	0	0	0	0	0	1	1
	Total	19	6	39	5	235	1	20	147	1	2	475

Figure 2 PANSS-EC score.

Note: PANSS-EC score points estimates and CI at each time point of the observation period for all patients during the use of RAIM.
Abbreviations: d, days; h, hours; LOCF, last observation carried forward; n, number of patients; PANSS-EC, Positive and Negative Syndrome Scale-Excited Component; PO, Per Os (by mouth, orally); RAIM, rapid-acting intramuscular olanzapine.

Table 3 TEAEs and adverse drug reactions based on the dose pattern of olanzapine

Dose pattern of olanzapine use	Days for onset of TEAEs	TEAEs	Potentially related to oral olanzapine
RO-O-O-O-O-O-O	3	Constipation	Yes
RO-O-O-O-O-O-O	2	Abnormal blood glucose	No
RO-O-O-O-O-O-O	6	Constipation	Yes
RO-O-O-O-O-O-O	2	Akathisia	Yes
RO-O-O-O-O-O-O	3	Dyslalia	Yes
	3	Tremor	Yes
	3	Constipation	Yes
RO-O-O-O-O-O-O	1	Dyslalia	No
RO-O-O-O-O-O-O	2	Abnormal hepatic function	Yes
RO-O-O-O-O-O-O	2	Abnormal hepatic function	Yes
	2	Renal impairment	Yes
RO-O-O-O-O-O-O	2	Dyslalia	Yes
RO-O-O-O-O-O	6	Somnolence	Yes
RO-O-O-O-O	5	Blood creatine phosphokinase increased	Yes
RO-O-O-O	4	Neuroleptic malignant syndrome	Yes
RO-O-O	3	Somnolence	Yes
RO-RO-O-O-O	2	Urinary incontinence	No
	3	Epistaxis	No
	5	Hemorrhage subcutaneous	No
	5	Lip hemorrhage	No
	5	Dysphagia	Yes
	6	Eye contusion	No
	6	Ocular hyperemia	No
	6	Sudden cardiac death	Yes
	6	Rhinorrhea	Yes
	6	Salivary hypersecretion	Yes
RO-O-RO-O-O-O-O	1	Somnolence	No
R-O-O-O-O-O-O	2	Abnormal hepatic function	Yes
R-O-O-O-O-O-O	1	Dehydration	No
R-O-O-O-O	2	Akathisia	Yes
	2	Dyslalia	Yes
R-R-R-O-O-O-O	1	Somnolence	No
R-RO-RO-O-O-O-O	3	Blood creatine phosphokinase increased	No

Note: RO indicates dose pattern of olanzapine use.

Abbreviations: O, oral; R, rapid-acting intramuscular olanzapine administration; TEAEs, treatment-emergent adverse events.

Table S1 Oral olanzapine dose after administration of 5 and 20 mg on the last day of rapid-acting intramuscular olanzapine

The last day of rapid-acting intramuscular olanzapine during the original study period		Oral olanzapine dose at the next day of rapid-acting intramuscular olanzapine final administration during the original study period
Daily dosage of rapid-acting intramuscular olanzapine (mg)	Oral olanzapine daily dose (mg)	0 mg	2.5 mg	5 mg	7.5 mg	10 mg	12 mg	15 mg	20 mg	25 mg	30 mg	Total
5	0	2	1	4	0	2	0	0	2	0	0	11
	2.5	0	0	0	0	0	0	0	0	0	0	0
	5	0	0	6	0	0	0	0	0	0	0	6
	7.5	0	0	0	0	0	0	0	0	0	0	0
	10	0	0	0	0	5	0	0	0	0	0	5
	12	0	0	0	0	0	0	0	0	0	0	0
	15	0	0	0	0	0	0	1	0	0	0	1
	20	0	0	0	0	0	0	0	1	0	0	1
	30	0	0	0	0	0	0	0	0	0	0	0
20	0	5	0	1	0	1	0	0	4	0	0	11
	2.5	0	0	0	0	0	0	0	0	0	0	0
	5	0	0	0	0	0	0	0	0	0	0	0
	7.5	0	0	0	0	0	0	0	0	0	0	0
	10	0	0	0	0	1	0	0	0	0	0	1
	12	0	0	0	0	0	0	0	0	0	0	0
	15	0	0	0	0	0	0	0	0	0	0	0
	20	0	0	0	0	0	0	0	10	0	0	10
	30	0	0	0	0	0	0	0	0	0	1	1
	Total	7	1	11	0	9	0	1	17	0	1	47