Review Article

Oral versus Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia and Special Populations at Risk for Treatment Nonadherence: A Systematic Review

Table 2

Randomized and naturalistic studies comparing LAIs with their oral equivalents.

StudyNDurationIn/out, patientDesignAntipsychotic doseDropouts Relapse Dropouts Side effects Comments

Zuardi et al. [47]2216 weeksInRDM
DB
HAL DEC
20 mg IM/4 w : 1 mg/d
PO*
NDNDLAI = marginally better efficacy and more EPS
Kinross-Wright and Charalampous [48]406 weeksInRDM
DB
FLZ ETH#
25 mg IM/2 w versus 2.5–7.5 mg
PO
NDND
Ravaris et al. [49]3924 weeksInRDM
DB
FLZ ETH
12–25 mg IM/2 w versus 2.5–10 mg
PO
5% (LAI) 0% (PO)5% (LAI) 6% (PO)
Haider [50]436 weeksInRDM
DB
FLZ ETH
25 mg IM/2-3 w versus 2.5–10 mg/d
PO
NDNDLAI = more EPS
van Praag et al. [51]504 weeksInRDM
DB
FLZ ETH#
25 mg IM/3 w versus 7 mg/d
PO
NDNDLAI = more EPS
Del Giudice et al. [52]8815 monthsOutRDM
SBP
FLZ ETH#
25 mg IM/2 w versus 22 mg/d
PO
NDNDLAI = longer time to relapse and more EPS
Rifkin et al. [53]7312 monthsOutRDM
DB
FLZ DEC
12.5 mg IM/2 w: 5 mg/d
PO+
4% (LAI) 7% (PO)22% (LAI) 4% (PO)LAI = more EPS
Hogarty et al. [54]10524 monthsOutRDM DBFLZ DEC
34–43 mg IM/2 w versus 10–12 mg/d
PO
23% (LAI+ST) 50% (LAI) 55% (PO) 66% (PO+ST)9% (LAI) 0% (PO)LAI = more anxiety/depression, but less positive symptoms
Schooler et al. [55]21412 monthsOutRDM DBFLZ DEC#
34 mg IM/3 w versus 25 mg/d
PO
24% (LAI) 33% (PO)5% (LAI) 4% (PO)
Arango et al. [56]4612 monthsOutRDM OLZUC DEC#
233 mg IM/2 w versus 35 mg/d
PO
4% (LAI) 5% (PO)NDLAI = less violence
Chue et al. [26]5413 monthsBothRDM DBRIS MIC
25–75 mg IM/2 w versus 2–6 mg/d
PO
4% (LAI) 3% (PO)6% (LAI) 5% (PO)LAI = less prolactin elevation
Bai et al. [57]5012 monthsInRDM SBIRIS MIC
25–50 mg IM/2 w versus 4–6 mg/d
PO
8% (LAI) 0% (PO)4% (LAI) 0% (PO)LAI = lower UKU score, lower EPS and prolactin levels
Eli Lily [58]52424 monthsOutRDM OLOLZ PAM
150–405 mg IM/4 w versus 5–20 mg/d
PO
16% (LAI) 10% (PO)10% (LAI) 10% (PO)LAI = less rehospitalisations
Kane et al. [25]10656 monthsOutRDM DBOLZ PAM
45 mg IM/4 w versus 150 mg IM/2 w versus 405 mg IM/4 w versus 300 mg IM/2 w versus 10, 15, 20 mg/d
PO
6% (LAIHI) 13% (LAIMD) 19% (LAILO) 8% (PO)3% (LAIHI) 3% (LAIMD) 5% (LAILO) 3% (PO)
Kim et al. [60]5024 monthsOutNAT (FEP)RIS MIC#
29 mg/2 w versus 3 mg/d
PO
23% (LAI) 75% (PO)NDLAI = lower relapse rate
Zhu et al. [59]29912 monthsOutNATHAL DEC#
100 mg/4 w versus 11 mg/d
PO FLZ DEC#
25 mg/2 w versus 12 mg/d PO
NDNDLAI = longer time to discontinuation
Tiihonen et al. [61]22303.6 years#OutNAT (FEP)PER DEC versus oral equivalentNDNDLAI = lower risk of rehospitalization
Tiihonen et al. [9]258824 monthsOutNAT (FEP)RIS MIC, HAL DEC, PER DEC, ZUC DEC versus oral equivalentNDNDLAI = lower risk of rehospitalization

In = inpatients; Out = outpatients; # = mean; * = ratio; +ST = fluphenazine decanoate + social therapy;  : = ratio; FEP = first-episode psychosis; UKU = Udvalg for Kliniske Undersøgelser Side Effect Rating Scale; LAI = long-acting injectable antipsychotic; PO = oral equivalent; NAT = naturalistic design; RDM = randomized; DB = double blind; SBI = investigator blind; SBP= patient blind; OL = open label; ND = no usable data; FLZ DEC = fluphenazine decanoate; FLZ ETH = fluphenazine enanthate; ZUC DEC = zuclopenthixol decanoate; HAL DEC = haloperidol decanoate; PER DEC = perphenazine decanoate; RIS MIC = risperidone microspheres; OLZ PAM = olanzapine pamoate; HI = high dose; MD = medium dose; LO = low dose; + = the typical patient was treated with 10–20 mg oral fluphenazine.