Efficacy and Safety of Long Acting Injectable Atypical Antipsychotics - A Review

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Current Clinical Pharmacology, 2013, 8, 000-000 1

1574-8847/13 $58.00+.00 2013 Bentham Science Publishers

Efficacy and Safety of Long Acting Injectable Atypical Antipsychotics: A

Review

Domenico De Berardis1,2,*, Stefano Marini

1,2, Alessandro Carano

2,3, Antonella Padovan Lang

5,

Marilde Cavuto4, Monica Piersanti

6, Michele Fornaro

7, Giampaolo Perna

8, Alessandro Valchera

9,

Monica Mazza10

, Felice Iasevoli11

, Giovanni Martinotti2 and Massimo Di Giannantonio

2

1NHS, 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;

7Department 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; 10

Department of Health Science, University of L'Aquila; L'Aquila, Italy; 11

Laboratory 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 long-

acting 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 second-generation antipsychotics long-acting injections (SGAs-LAIs) 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: [email protected]

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)

2 Current Clinical Pharmacology, 2013, Vol. 8, No. 3 De Berardis et al.

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

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 second-generation 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 Current Clinical Pharmacology, 2013, Vol. 8, No. 3 3

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

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 micro- crystalline 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 5-HT6 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


Table 1. 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-to-

treat 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,

parallel-

group

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 CGI-

S 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 dose-

related 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 1-

year 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.


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

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 post-injection 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].

Table 2. 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.


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].

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.

CONCLUSIONS

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 long-acting injection in use.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

ACKNOWLEDGEMENTS

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

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

PP = Paliperidone palmitate

PSP = Personal and Social Performance Scale

QTc = Corrected QT interval

RCT = Randomized controlled trial

RLAI = Risperidone long acting injection

SGAs-LAIs = Second-generation antipsychotics long-acting injections

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Received: October 09, 2012 Revised: October 10, 2012 Accepted: December 14, 2012

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Efficacy and Safety of Long Acting Injectable Atypical Antipsychotics - A Review