Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection

Figures & data

Figure 1 Flow chart for study selection.

Table 1 General information on aripiprazole long-acting injection

Pharmacokinetics
Tmax (days)	5–7
t½ (days)	29.9–46.5
Time to steady state concentration	After dose 4
Major metabolism	Hepatic (CYP2D6 and CYP3A4)
Needle gauge	21
Approved injection site	Gluteal muscle
Dosing and administration
Injection interval	4 weeks
Recommended initial and monthly dose	400 mg
Dosage adjustments related to CYP metabolism
CYP2D6 poor metabolizers	300 mg
CYP2D6 poor metabolizers + concomitant CYP3A4 inhibitors	200 mg
Patient initially tolerant to ALAI 400 mg taking concomitant
Strong CYP2D6 or CYP3A4 inhibitors	300 mg
CYP2D6 and CYP3A4 inhibitors	200 mg
CYP3A4 inducers	Avoid use
Patient initially tolerant to ALAI 300 mg taking concomitant
Strong CYP2D6 or CYP3A4 inhibitors	200 mg
CYP2D6 and CYP3A4 inhibitors	160 mg
CYP3A4 inducers	Avoid use
Dosage adjustments for missed doses
Missed second or third doses
4–5 weeks since last injection	Administer as soon as possible
>5 weeks since last injection	Restart concomitant oral ARP for 14 days with the next injection
Missed fourth or subsequent doses
4–6 weeks since last injection	Administer as soon as possible
>6 weeks since last injection	Restart concomitant oral ARP for 14 days with the next injection
Pregnancy category	C
Pediatric use (<18 years)	Not established
Geriatric use (>60 years)	Not established

Note: Data used to compile this table are from.^16,17

Abbreviations: ARP, aripiprazole; CYP, cytochrome P450; t_½, terminal elimination half-life; T_max, time to maximum plasma concentration of aripiprazole long-acting injection.

Table 2 Summary of clinical trials of investigating efficacy of aripiprazole once monthly in patients with schizophrenia

Study	Duration	Design	Daily dose (mg/4 weeks)	na	Primary outcome	Results
Kane et al^Citation21	52 weeks	RCT	ALAI (300–400)	269	Time to exacerbation of psychotic symptoms/impending relapse	ALAI > placebo IM*** for time to impending relapse
			Placebo IM	134
Kane et al^Citation23	49 weeksb	Open-label, mirror image	Oral antipsychoticsc	183	Hospitalization rates	Hospitalization rate ALAI < oral antipsychotics***
			ALAI (300–400)	183
Fleischhacker et al^Citation24	52 weeks	RCT	ALAI (300–400)	265	Rate of exacerbation of psychotic symptoms/impending relapse	ALAI (300–400) = oral ARP ALAI (300–400) and oral ARP > ALAI (25–50)** in relapse rate
			Oral ARP (10–30 mg/day)	266
			ALAI (25–50)	131

Notes:

a Total number of intent-to-treat patients

b 24 weeks of treatment with oral antipsychotics, one week of stabilization, and 24 weeks of ALAI

c standard of care

** P<0.01

*** P<0.001.

Abbreviations: ALAI, aripiprazole long-acting injection; ARP, aripiprazole; RCT, randomized controlled trial; IM, intramuscular route.

Table 3 Safety and tolerability of aripiprazole once-monthly in patients with schizophrenia

Fleischhacker et al^Citation26			Mallikaarjun et al^Citation16
Adverse event	Group		Adverse event	Group
	ALAI 400 (%) (n=269)	Placebo (%) (n=134)		ALAI 200 (%) (n=10)	ALAI 300 (%) (n=15)	ALAI 400 (%) (n=14)
Insomnia	27 (10.0)	12 (9.0)	Injection site pain	0 (0.0)	0 (0.0)	4 (28.6)
Weight gain	26 (9.7)	13 (9.7)	Tremor	0 (0.0)	1 (6.7)	3 (21.4)
Anxiety	16 (5.9)	10 (7.5)	URTI	1 (10.0)	2 (13.3)	4 (28.6)
Headache	16 (5.9)	7 (5.2)	Vomiting	0 (0.0)	2 (13.3)	2 (14.3)
Tremor	16 (5.9)	2 (1.5)	Muscular symptoms	0 (0.0)	0 (0.0)	4 (28.6)
Akathisia	15 (5.9)	8 (6.0)	Sedation	0 (0.0)	0 (0.0)	2 (14.3)
Nasopharyngitis	10 (3.7)	7 (5.2)	Rash	0 (0.0)	0 (0.0)	2 (14.3)
Worsening psychosis	8 (3.0)	9 (6.7)	Headache	2 (20.0)	0 (0.0)	2 (14.3)
Injection site pain	8 (3.0)	5 (3.7)	Weight gain	1 (10.0)	2 (13.3)	3 (21.4)

Abbreviations: ALAI, aripiprazole long-acting injection; URTI, upper respiratory tract infection including nasopharyngitis.

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