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Current Clinical Pharmacology, 2013, 8, 000-000

Efficacy and Safety of Long Acting Injectable Atypical Antipsychotics: A

Review
Domenico De Berardis1,2,*, Stefano Marini1,2, Alessandro Carano2,3, Antonella Padovan Lang5,
Marilde Cavuto4, Monica Piersanti6, Michele Fornaro7, Giampaolo Perna8, Alessandro Valchera9,
Monica Mazza10, Felice Iasevoli11, Giovanni Martinotti2 and Massimo Di Giannantonio2
1

NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital G. Mazzini, Asl 4,
Teramo, Italy; 2Department of Neurosciences and Imaging, Chair of Psychiatry, University G. dAnnunzio of Chieti,
Italy; 3NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital C. G. Mazzoni
Ascoli Piceno, Italy; 4IASM, LAquila, Italy; 5NHS Health Trust n.10 Veneto Orientale, Department of Mental Health,
Unit of Psychiatry, Portogruaro, Italy; 6Pharmaceutical Service, Hospital G. Mazzini, Asl 4, Teramo, Italy;
7
Department of Formative Sciences, University of Catania; 8Department of Clinical Neurosciences, Villa San Benedetto
Hospital, Hermanas Hospitalarias, Albese con Cassano, Italy; 9Villa S. Giuseppe Hospital, Hermanas Hospitalarias,
Ascoli Piceno, Italy; 10Department of Health Science, University of L'Aquila; L'Aquila, Italy; 11Laboratory of Molecular
Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of
Medicine "Federico II", Naples, Italy
Abstract: Schizophrenia is a chronic, severe and recurrent brain disorder that requires continuous, long-term treatment
with antipsychotic medication to minimize relapse and provide clinical benefit to patients. For patients with
schizophrenia, non-adherence to medication is a major risk factor for relapse and re-hospitalization. Long-acting
injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the
potential for improved adherence. Currently, three drugs are available for the treatment of schizophrenia, risperidone longacting injectable, olanzapine pamoate and paliperidone palmitate. Several studies have also demonstrated efficacy and
safety of such drugs in patients with acute schizophrenia. In the present paper the literature on LAI atypical antipsychotics
will be reviewed and practical advice will be given concerning the use of these drugs in the clinical practice.

Keywords: Long-acting, second-generation antipsychotics, risperidone long-acting, olanzapine pamoate, paliperidone

palmitate, schizophrenia, adherence, efficacy, tolerability.
INTRODUCTION
Schizophrenia is characterized by positive, negative,
cognitive, and affective symptoms [1-3]. It is complicated by
the potential occurrence of suicide, violent behavior,
substance abuse, and medical comorbidity that can emerge
over an illness course that entails exacerbations and
remissions and, in several cases, sustained morbidity and
disability [4-7]. Long-acting injections (LAIs) may be
considered as an adherence intervention for patients who are
non-compliant with the oral medication they have been
prescribed [8]. However, the availability of the secondgeneration antipsychotics long-acting injections (SGAsLAIs) represent an advance in the long-term management of
schizophrenia, particularly regarding subjective tolerability
[9]. In fact, SGAs-LAIs have been shown to have superior
efficacy and to be associated with less propensity to induce
movement disorders compared with conventional anti

*Address correspondence to this author at the National Health Service,

Department of Mental Health, Psychiatric Service of Diagnosis and
Treatment, G. Mazzini Hospital, p.zza Italia 1, 64100 Teramo, Italy;
Tel: +39 0861429708; Fax: +39 0861429706; E-mail: dodebera@aliceposta.it
1574-8847/13 $58.00+.00

psychotic agents, although some second generation agents

may be associated with an increased incidence of metabolic
side effects [10].
Currently, three are thre available: risperidone,
paliperidone palmitate and olanzapine pamoate with other
depot medications in development. In the present review the
literature on SGAs-LAIs will be reviewed and practical
advice will be given concerning the use of this drug in the
clinical practice.
METHODS
A literature search was performed from January 1966
through May 2012 with the help of a professional librarian
(MC). PubMed, Embase, Psychinfo and Scopus databases
were used to find studies for inclusion in the present review.
Keywords used for the search were: long acting atypical
antipsychotics, risperidone injection, olanzapine pamoate,
paliperidone
palmitate,
psychosis,
schizophrenia,
schizophrenia patients and schizophrenic patients. In each
search, keywords were used together with logical operators:
and, in. Each study was required to meet all of the
following criteria in order to be included in the review: a)
2013 Bentham Science Publishers

2 Current Clinical Pharmacology, 2013, Vol. 8, No. 3

diagnosis of schizophrenia in accordance to the criteria of the

Diagnostic and Statistical Manual of Mental Disorders
(DSM) [11] or International Classification of Diseases
(ICD); b) SGAs-LAIs administration; c) a minimum of one
month of therapy. Preferences for inclusion in the present
review was given to randomized controlled trials (RCT), but
also other papers of potential interest were evaluated and,
eventually, included. DDB, SM, AC, AV screened each
abstract and copies of any potentially relevant article were
obtained. Other authors independently reviewed the articles
and any disagreements in selecting the studies were resolved
by discussion. The search retrieved 120 citations, 60 of
which met the study inclusion criteria or were considered
relevant to the topic and included in the review.
THE PROBLEM OF MEDICATION NON-ADHERENCE
IN SCHIZOPHRENIA
It is widely recognized that medication non-adherence is
a striking problem in the treatment of schizophrenia with
reported discontinuation rates greater than 50% in several
studies [12-14]. It has been demonstrated that adherence
with both old and new antipsychotics is poor in both short
and long term and is associated with relapse, but it is unclear
whether medication non-adherence precedes the relapse or is
a consequence of it [15-17]. In the 18-month Clinical
Antipsychotic Trials for Intervention Effectiveness (CATIE)
study [18] a noteworthy 74% of patients discontinued the
treatment prematurely. In such study, the patient choice, the
lack of effect or intolerability of side-effects were the most
common reasons for discontinuation. Moreover, the
European First Episode Schizophrenia Trial (EUFEST)
reported that up to 42% of patients discontinued their
treatment within one year after the disease onset [19].
There are some factors that may play a role in causing
nonadherence such as lack of insight, subjective discomfort
as a result of side effects, fear of potential side effects, poor
medication efficacy with symptoms persistence and the
uncorrect belief that treatment is no longer needed [20-22].
Moreover, the comorbidity with substance abuse problems,
the presence of cognitive deficits, the relative lack of social
and familiar support, homelessness as well as failure of
therapeutic alliance, the complexity of treatment regimen
and, last but not least, the stigma associated with psychiatric
disorders and antipsychotics usage, may further contribute to
cause non-adherence [23-25]. Recently, it has been
suggested that schizophrenia patients with no adherence
performed better on tests of executive functioning, verbal
learning and memory and had higher intelligence quotient
(IQ) than patients with better adherence [26].
The effects of medication non-adherence may include not
only the disorder relapse, but also the increased mortality
[27]. In fact, it has been clearly demonstrated that
nonadherence may be associated with increased suicide rates
and death for consequences of medical ilnessess such as
diabetes, cardiovascular disorders, cancer and stroke [28-30].
Concerning current guidelines on LAIs use in
schizophrenia treatment, the American Psychiatric Association
[31] recommends LAIs for patients with recurrent relapses
related to partial or full nonadherence. Moreover, also the
Canadian clinical practice [32] recommends LAIs to lower

De Berardis et al.

nonadherence in patients with recurrent and multiple

episodes and/or with persistent positive symptoms. The
International Psychopharmacology Algorithm Projects
(IPAPs) schizophrenia algorithm (http://www.ipap.org/schiz/)
proposes the utilization of LAIs in patients with partial or
complete noncompliance. The National Institute for Health
and Clinical Excellence (NICE) guidelines [33] recommend
that long-acting antipsychotics may be given after an acute
episode of schizophrenia if the patient prefers, and to avoid
covert non-adherence to oral medication.
In general, the current guidelines on schizophrenia
treatment consider depot or long-acting injectable
antipsychotics as drugs of choice for long-term therapy in
patients who are nonadherent with antipsychotic medication
and the use of such medications, especially SGAs-LAIs, may
represent a promising strategy that should be employed in
such patients to achieve symptom remission, prevent relapse
and reduce all-causes mortality [34]. In addition, there are
growing evidences that point out a favourable outcome when
SGAs-LAIs (especially risperidone long-acting injection,
RLAI) are prescribed in patients with first-episode
schizophrenia [35].
RISPERIDONE LONG-ACTING INJECTION (RLAI)
RLAI represents the first long acting form of secondgeneration antipsychotic drugs, launched in North America
in 2004, available for the treatment of schizophrenia and
closely related psychiatric conditions [36].
RLAI is composed by biodegradable microspheres
loaded with risperidone and suspended in sterile saline [37].
It is available in dosage of 25, 37,5 and 50 mg [36]. Many
studies has been conducted from past up to date. RLAI
pharmacological profile is now well known [38-43].
Risperidone has high affinity for dopaminergic D2 receptors.
It is widely (90%) bound in plasma to albumin and alpha-1
acid glycoprotein. Risperidone is principally metabolized by
cytochrome P (CYP) 450 2D6, and in a lesser extent by CYP
3A4 enzyme to the active metabolite 9-OH-risperidone
(paliperidone). Steady-state levels are usually reached by 6-8
weeks from the begining of the therapy.
Several studies demostrated that RLAI administered once
every 2 weeks, has notably efficacy and well tolerated
in both schizophrenia and schizoaffective disorder patients
[44-49]. Due to its tolerability, RLAI is an important
antipsychotic treamtment available for use in vulnerable
groups of patients, as elderly patients with psychosis [50].
Retention and discontinuation rates of RLAI administration
are discordant, and some authors reported that long acting
injections are stigmizing and just accetable for patients
[18,51,52]. Some authors reported improvements in quality
of life, social integration and quality of relationships due to
efficacy and tolerability of RLAI that might help patients
achieve and maintain remission. Infact, no significant
differences were observed between RLAI 25 mg treatment
patients group and US control individuals aged 35-44 years
[53-56].
Compared to oral atypical and conventional long-acting
agents, RLAI reduced the numbers of relapses in
schizophrenia patients [57-60]. In addiction, concomitant

Efficacy and Safety of Long Acting Injectable Atypical Antipsychotics

medications as anticholinergics, anxiolytics, hypnotics,

sedatives, antipsychotics used in combination, antidepressants
and mood stabilizers were reported to be reduced in use
[44,61].
RLAI has been successfully employed also in the
treatment of first-episode schizophrenia, reducing risk for
relapse and leading to significant improvements in clinical
and functional outcomes in such patients [62-67]. Overall,
RLAI tolerability in first-episode schizophrenia was
comparable to that reported in other studies [62-64,66,67].
RLAI demonstrated efficacy in the treatment for bipolar
disorder [68-73], particuarly for manic, but not for
depressive episodes, both as monotherapy and as an
adjunctive maintenance treatment [74,75].
Side effects are reported to be similar to those of oral
risperidone and are mainly represented by extrapyramidal
symptoms (EPS), metabolic side effects, anxiety, insomnia,
depression, headache, elevation in prolactine levels and
injection site pain. Cases of increase in the corrected QT
(QTc) interval prolungations are reported among patients
taking all three doses of RLAI [74,75].
Several studies have reported substantial cost benefits to
the country's healthcare system due to minor hospitalization
supported by improvements in adherence and long term
outcomes with RLAI treatment, compared to oral
antipsychotics administrations therapies [76-79], but
reported also an increase of outpatients services [80] and a
longer bed-stay after RLAI discontinuation [81].
PALIPERIDONE PALMITATE (PLAI)
The paliperidone long-acting injection (PLAI) is the
palmitate salt ester of paliperidone (9-OH-risperidone), wich
uses a nanocrystal technology formulation with low water
solubility [82]. Paliperidone is the major active metabolite of
risperidone. Pharmacodynamic and pharmacokinetic
properties has been elucidated by many studies. Paliperidone
is a dopamine-D2 and serotonin-2A (5-HT2A) receptors
antagonist. It has an important action on alpha 1, alpha 2
adrenergic and histaminergic H1 receptors, and little affinity
for cholinergic muscarinic and beta1 and beta2 adrenergic
receptors. Because of similar binding properties between
paliperidone and risperidone, the reason to choose one or
another treatment is represented by the interval of the dose
administration or financial considerations. In vivo,
paliperidone is metabolized by dealkylation, hydroxylstion,
dehydrogenation and benzisoxazole scission. A deltoid
administration is recommended for the first two injection to
facilitate a rapid time to steady-state plasma concentrations
[83-88].
The efficacy and safety of PLAI has been assessed in
acute treatment and in long-term maintenance treatment of
schizophrenia. Four acute treatment studies enrolled patients
with schizophrenia with a baseline Positive And Negative
Syndrome Scale (PANSS) total score between 70-120 (one
study 60-120), and a body mass index (BMI) range different
for each study. In acute treatment studies PLAI showed
significantly improvements in PANSS, Personal and Social
Performance Scale (PSP) and Clinical Global Impression
Severity of Illness Scale (CGI-S) scores compared to

Current Clinical Pharmacology, 2013, Vol. 8, No. 3

placebo. Particularly, major doses (100 mg and 150 mg eq)

showed greater responses [89-92]. Post-hoc analysis of
Pandina et al. [92] study, confirmed that acute treatment
with monthly doses of 100 and 150 mg eq significantly
improved clinical symptoms, global illness ratings, and
functioning compared with placebo [93]. It has also been
pointed out that hospitalizations significantly decreased for
patients with schizophrenia treated with paliperidone
palmitate [94]. In addition, researchers found a trend towards
differential treatment effect by BMI baseline categories
(minor baseline BMI correlated with major improvements)
[95]. Two long term maintenance studies investigated
relapse prevention in schizophrenia [96,97]. Discontinuation
rate was 6% due to lack of efficacy; 6% of patients reported
worsening of schizophrenia symptoms. The most frequently
PLAI dose used was 100 mg. The results demonstrated the
good tolerabilty and the well acceptance by patients for a
once-monthly gluteal injection (Table 1).
Comparative efficacy and tolerability trials were studied
between PLAI and RLAI. The efficacy and the incidence of
adverse events was similar in both treatment groups.
Particularly, two authors reported a similar PLAI efficacy
when compared to RLAI. One study did not demostrate
comparable efficacy between PLAI and RLAI [98-100].
The most common adverse events associated to PLAI
were prolactin plasma levels elevation, extrapyramidal
symptoms, injection site-reaction, dizziness, somnolence/
sedation, weight gain, headache, nasopharyngitis, modest
QTc prolungation and warsening of schizophrenia [97,101].
No published data exist for PLAI use in renal and severe
hepatic impairment. No dose adjustment is required in
patients with mild or moderate hepatic impairment [102].
Interestingly, important cost-effectiveness has been reported
[103].
To date, there are no studies on PLAI in patient with first
episode schizophrenia.
Potential advantages for PLAI are represented by: a) no
oral antipsychotic supplementation; b) possibily of flexible
doses; c) once-monthly administration; d) deltoid or gluteal
injection; e) possibility to use in acute treatment; f) good
tolerability [104,105].
OLANZAPINE PAMOATE (OLAI)
Olanzapine long-acting injection (OLAI) is a microcrystalline salt composed of olanzapine and pamoic acid
suspended in an acqueous solution, which permits a slowly
dissociation into separate components, called depot
intramuscular formulation. Mechanism of action and
metabolism of OLAI are similar to those of the corrispective
atypical antipsychotic oral olanzapine [106-114].
Olanzapine is an atypical antipsychotic (dibenzothiazepine
structurally similar to clozapine), that shares higher affinity
to 5-HT2A receptors than D2 receptors (high 5-HT2A/ D2
ratio). Olanzapine binding properties are represented by high
affinity for serotoninergic 5-HT2A, 5-HT2C, 5-HT3, and 5HT6 receptors and for histamine H1 receptors (the higest
affinity between antypsychotics), medium affinity for
dopaminergic D1-D5, and muscarinic M1-M5 receptors, low
affinity for adrenergic 1 and 2 receptors, a very low affinity

4 Current Clinical Pharmacology, 2013, Vol. 8, No. 3

Table 1.

De Berardis et al.

RCT, DB, PC Paliperidone Palmitate Clinical Trials in Patients with Schizophrenia

Authors

Year

Reference
nr.

Study
Design

Duration

Number of
Patients

Treatments

Main Findings

Gopal
et al. 2010

2010

89

RCT, DB,
PC

13 weeks

388 acutely
symptomatic
patients with
schizophrenia

Placebo
PLAI 50 mg eq
PLAI 100 mg eq
PLAI 150 mg eq

The change from baseline in

PANSS total score at endpoint
was significant only in the
100mg eq group
The paliperidone palmitate
50 and 100mg eq groups showed
significant improvement in the
Personal and Social Performance
score from baseline to endpoint
versus placebo
CGI-S scale improvements were
significant only in the paliperidone
palmitate 100 mg eq group

Kramer
et al.

2010

90

RCT, DB,
PC

9 weeks

197, intent-totreat analysis set

Placebo
PLAI 50 mg eq
PLAI 100 mg eq

PANSS total scores showed

significant improvement at
endpoint for both the 50 and 100
mg eq groups
CGI-S scores improved at endpoint.
PLAI well tolerated in both groups.

Nasrallah
et al.

2010

91

RCT, DB,
parallelgroup

13 weeks

518

Placebo
PLAI 25 mg eq
PLAI 50 mg eq
PLAI 100 mg eq

All PLAI dose groups showed

significant improvement vs placebo
in the PANSS total score and CGIS score at endpoint
All doses PLAI were well tolerated,
both locally and systemically

Pandina
et al.

2010

92

RCT, DB,
PC

13 weeks

652,
schizophrenia
diagnosis
documented
as present for at
least 1 year
before study
screening

Placebo
PLAI 25 mg eq
PLAI 100 mg eq
PLAI 150 mg eq

The mean change in PANSS total

score from baseline to endpoint
improved significantly in all the
PLAI dose groups versus placebo
Mean PSP scores showed a doserelated improvement in the PLAI
treatment groups, which was
significant for the 100 and 150 mg
eq groups
CGI-S scores decreased
significantly only in the PLAI 100
and 150 mg eq groups

Sliwa
et al.

2011

93

Post hoc
analysis of
Pandina
et al. trial,
RCT, DB,
PC

13 weeks

216

Placebo
PLAI 25 mg eq
PLAI 100 mg eq
PLAI 150 mg eq

Acute treatment with monthly doses

of 100 and 150 mg eq significantly
improved clinical symptoms, global
illness ratings, and functioning
compared with placebo.
PLAI well tolerated in all groups.

Kozma
et al.

2011

94

Health
resource
utilization
data, RCT,
DB, PC

variable-duration
followed by a 1year open-label
extension

323 symptomatic
and stable
patients with
schizophrenia

Placebo
PLAI 50 mg eq
PLAI 100 mg eq
PLAI 150 mg eq

Hospitalizations significantly
decreased for patients with
schizophrenia treated with PLAI

Abbreviations: CGI-S, Clinical Global Impression-Severity; DB, double-blind; PANSS, Positive And Negative Syndrome Scale; PC, placebo-controlled; PLAI, paliperidone
palmitate; PSP, Personal and Social Performance Scale; RCT, randomized controlled trial.

Efficacy and Safety of Long Acting Injectable Atypical Antipsychotics

for 5-HT1A, 1B, 1D and histamine H2, H3 receptors and no

appreciable affinity for beta-adrenergic, glutamate, opiate,
GABA and benzodiazepine receptors.
OLAI demonstrated efficacy both in acutely ill and
stabilized patients affected by schizophrenia (or schizoaffective
disorder for the maintenance treatment) with flexibile doses
from 2 to 4 weeks [115]. The use and the efficacy of OLAI
have been evaluated in the short-term treatment of patients
with schizophrenia (in acutely and in stable patients switched
to OLAI) and in the maintenance treatment of patients with
schizophrenia or schizoaffective disorder. In short-term
treatment (8 weeks) of schizophrenic patients, olanzapine
pamoate (210 mg/2 wk, 300 mg/2 wk and 405 mg/4 wk)
were found to be statistically significant superior to placebo
in improving PANSS total scores (-26.32, -22.57, and 22.49, respectively changes from baseline, compared with 8.51 for placebo) and in CGI-I scale scores. It was found that
300 mg/2 wk and 405 mg/4 wk doses induced a more rapid
improvement compared to 210 mg/2 wk (3 days versus 7
days for PANSS) [116]. OLAI showed to be effective in
maintenance treatment of adult patients with schizophrenia
or schizoaffective disorder [117]. No psychotic exacerbation
occurred during the 24 weeks of the treatment with all three
doses (improvement in CGI-S scores). In addition, it was
demonstrated the equivalent efficacy against psychotic
symptoms and in quality of life between depot doses and oral
olanzapine [113]. During a 4 years investigation study,
schizophrenia and schizoaffective disorder patients were
reported to reduce psychotic symptoms, supported by a
significant decrease in PANSS and CGI-S scores. These
improvements remained stable during all the period of the
study, demostrating a long term efficacy of OLAI treatment
[118] (Table 2). Moreover, it has been demonstrated that
Table 2.

Current Clinical Pharmacology, 2013, Vol. 8, No. 3

OLAI treatment improved functioning within 8 weeks of

initiating treatment [119].
Safety data about the use of OLAI in schizophrenia and
schizoaffective disorder patients were reported by some
studies and were collected in to a unique database [120]. No
significant differences in adverse events between oral
olanzapine and the depot formulation were reported, even if
higer injection dose showed greater efficacy, but also caused
more frequently adverse events compared to lower dose
[121]. Two patients experienced a new potential safety risk
characterized by sedation and delirium consistent with
inadvertent intravascular injection event, called postinjection delirium sedation syndrome (PDSS), that can occur
from 20 minutes to 3 hours postinjection [122]. This event
consists of sedation (ranged from drowsiness to deep coma),
confusion, dizziness, altered speech/dysarthria, and somnolence.
These symptoms are consistent with those reported during
oral olanzapine overdose. The first symptoms reported are
feeling of weakness, dizziness, irritability, or general
malaise, and then symptoms worsen with delirium, heavy
sedation and coma. For these reasons, a carefull observation
of the patients, specially during the first injection, is required.
Weight gain, sedation/somnolence, increased hepatic enzymes
and inefficient control of psychotic symptoms were the major
causes of discontinuation. Three deaths, apparently not
related to the drug, occurred [120].
Data on OLAI injection in deltoid muscle are not yet
available. Limited data are avaible about switching to OLAI
from either oral or other LAI antipsychotics, but some
findings suggested that directly swithcing from oral to OLAI
did not increase the risk of relapse when initiated on an
appropriate OLAI dose [123].

RCT, DB, PC Olanzapine Pamoate Clinical Trials in Patients with Schizophrenia

Authors

Year

Reference nr.

Study Design

Duration

Number of Patients

Treatments

Main Findings

Lauriello et
al.

2008

116

RCT, DB, PC

8 weeks

404 acutely ill patients

with schizophrenia

placebo
OLAI 210 mg
OLAI 300 mg
OLAI 405 mg

All doses showed

improvements in PANSS
and CGI-S scores. No
statistical differences
between groups.

Kane et al.

2010

113

RCT, DB, PC

24 weeks

1065 stable patients

with schizophrenia

placebo
OLAI 210 mg
OLAI 300 mg
OLAI 405 mg

Time to relapse shorter

for low dose group.
Increase in health-related
quality of life.

McDonnell
et al.

2011

117

RCT, DB, PC,

interim analysis of
a flexible doses
extension study

190 weeks

909 patients with

schizophrenia and 22
with schizoaffective
disorder

placebo
OLAI 210 mg
OLAI 300 mg
OLAI 405 mg

Mean CGI-S scores

remained stable
throughout the period of
the study.

Witte et al.

2012

119

RCT, DB, PC

8 weeks

404 stable patients with

schizophrenia

placebo
OLAI 210 mg
OLAI 300 mg
OLAI 405 mg

OLAI improved
functioning within 8
weeks of initiating
treatment.

Abbreviations: CGI-S, Clinical Global Impression-Severity; DB, double-blind; OLAI, Olanzapine Long-Acting Injection; PANSS, Positive And Negative Syndrome Scale; PC,
placebo-controlled; RCT, randomized controlled trial.

6 Current Clinical Pharmacology, 2013, Vol. 8, No. 3

Because of the efficacy of olanzapine in the treatment of

bipolar mania, and, in combination with fluoxetine, for the
treatment of bipolar depression, OLAI might represent in
future an important therapeutic option for low compliance
bipolar disease patients [114]. No studies have been yet
performed in bipolar disorder patients [124].

De Berardis et al.

EPS

Extrapyramidal symptoms

ICD

International Classification of Diseases

IPAPs

International
Psychopharmacology
Algorithm Projects

IQ

Intelligence quotient

LAIs

Long-acting injections

NICE

National Institute for Health and Clinical

Excellence

OLAI

Olanzapine long acting injection

PANSS

Positive And Negative Syndrome Scale

PC

Placebo-controlled

PDSS

Postinjection delirium sedation syndrome

PLAI

Paliperidone long acting injection

CONCLUSIONS

PP

Paliperidone palmitate

All atypical antipsychotics long-acting injection have

been approved for long-term treatment of patients with
schizophrenia or schizoaffective disorders. Studies have
reported that PLAI and OLAI were as effective as RLAI.
One author reported non comparable efficacy between PLAI
and RLAI. RLAI demostrated efficay both as monotherapy
and as an adjunctive maintenance treatment for mania in
bipolar disorder. No studies have been yet performed about
efficacy of OLAI and PLAI in the long-term treatment of
bipolar disorder. Due to its tolerability, RLAI is an important
antipsychotic treamtment available for use in at-risk group of
patients, such as elderly patients with psychosis. Some
authors reported improvements in quality of life and in social
integration due to efficacy and tolerbility of long-acting
injection treatments, that might help patients achieve
and maintain remission and reduce relapses. Unlike RLAI,
PLAI and OLAI do not need an oral antipsychotic
supplementation. Long-acting injection treatments have been
reported to reduce healthcare costs. Compared to RLAI and
PLAI, OLAI is the cheapest atypical antipsychotic longacting injection in use.

PSP

Personal and Social Performance Scale

QTc

Corrected QT interval

RCT

Randomized controlled trial

RLAI

Risperidone long acting injection

SGAs-LAIs

Second-generation antipsychotics longacting injections

An open label study reported OLAI did not differ

significantly from risperidone long-acting injection in
medication effectiveness [125]. Data reported by this study
must be taken with caution due to selection bias and other
confounding variables, including countries where the study
was conducted.
Finally, compared to RLAI and PLAI, OLAI was the
cheapest atypical antipsychotic long-acting injection in use
[126].
To date, there are no studies on OLAI in patient with first
episode schizophrenia.

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[1]
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[4]
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[6]

CONFLICT OF INTEREST
The authors confirm that this article content has no
conflict of interest.
ACKNOWLEDGEMENTS

[7]

[8]

Declared none.
ABBREVATIONS
5-HT

Serotonin

BMI

Body mass index

CGI-S

Clinical Global Impression Severity of

Illness Scale

CYP

cytochrome P

DB

Double-blind

DSM-IV-TR

Diagnostic and Statistical Manual of

Mental Disorders. 4th ed. Text Revision

[9]
[10]
[11]

[12]
[13]

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Revised: October 10, 2012

Accepted: December 14, 2012