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International Clinical Psychopharmacology:
doi: 10.1097/YIC.0000000000000030
Original Articles

A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea

Lee, Nam Younga,b; Kim, Se Hyunf; Cho, Seong Jinm; Chung, Young-Choc; Jung, In Kwai; Kim, Chang Yoonj; Kim, Duk Hon; Lee, Dong Geund; Lee, Yo Hano; Lim, Weon Jeongk; Na, Young Suke; Shin, Sang Eunq; Woo, Jong-Minl; Yoon, Jin Sangp; Yoon, Bo-Hyunr; Ahn, Yong Minf,g,h; Kim, Yong Sika,g

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Author Information

aDepartment of Neuropsychiatry, Dongguk University International Hospital

bDepartment of Neuropsychiatry, Dongguk University College of Medicine

cDepartment of Psychiatry, Inje University Ilsan Paik Hospital

dMaumpeunhan Psychiatry

ePuremind Psychiatry, Gyeonggi-do

fInstitute of Human Behavioral Medicine, Seoul National University Medical Research Center

gDepartment of Psychiatry and Behavioral Science, Seoul National University College of Medicine

hDepartment of Neuropsychiatry, Seoul National University Hospital

iDepartment of Neuropsychiatry, Korea University Guro Hospital

jDepartment of Neuropsychiatry, Asan Medical Center

kDepartment of Neuropsychiatry, Ewha Womans University Mokdong Hospital

lDepartment of Psychiatry, Inje University Seoul Paik Hospital, Seoul

mDepartment of Psychiatry, Gachon University Gil Hosptial, Incheon

nSanulrim Hospital, Gyeongbuk

oDepartment of Neuropsychiatry, St John of God Hospital

pDepartment of Psychiatry, Chonnam National University Hospital, Gwangju

qDepartment of Psychiatry, Seoul Metropolitan Eunpyeong Hospital, Eunpyeong-gu

rNaju National Hospital, Jeollanam-do, Korea

Clinical Trials Registration: Available at: http://clinicaltrials.gov/ct2/show/study/NCT00216528

Correspondence to Yong Sik Kim, MD, PhD, Department of Neuropsychiatry, Dongguk University International Hospital, 27 Dongguk-Ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, Korea Tel: +82 31 961 7235; fax: +82 31 961 9236; e-mail: kys@snu.ac.kr

Received June 15, 2013

Accepted January 14, 2014

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Abstract

This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression – Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression – Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1–3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1–3 on eight items of PANSS sustaining of at least 6 months’ duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study period, a total of 645 AEs were noted in 233 patients (49.3%) who were included in the ITT population. Sixty-nine serious AEs in 51 patients were reported, but all of them were not directly attributable to administration of RLAI. This prospective, open-label study showed improvements in symptom and AEs and a significant increase in BMI during 48 weeks of biweekly RLAI treatment. The rate of study completion was 39.0% and the remission rate among those who completed the study was 65.2%. None of the serious AEs were directly related to the administration of RLAI.
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Introduction

The main objectives of the antipsychotic treatment in patients with schizophrenia are to maintain symptom relief, reduce relapse rates, and improve functioning and quality of life (De la Gandara et al., 2009). Nonadherence to the medication, even for a brief period, could robustly contribute toward the psychotic exacerbation or relapse during the early course of schizophrenia (Subotnik et al., 2011). A long-acting injection (LAI) of antipsychotics was developed especially to promote compliance in patients with schizophrenia, and thereby to enhance relapse prevention (Lindquist et al., 2011). Several studies have shown the advantages of the depot preparations compared with oral antipsychotics in terms of the rate and the duration of rehospitalizations, and most guidelines recommend to consider LAI in patients who have previously showed treatment nonadherence or recurrent relapses related to nonadherence (Keith, 2009; Agid et al., 2010). Recently, new insight into LAI has been raised as a potential first step to treatment continuity and remission in the first episode of schizophrenia (Viala et al., 2012) and to community-based rehabilitation (Altamura et al., 2012).

The rates of LAI use in patients with schizophrenia are markedly different geographically, ranging from less than 20% to 20–40% of antipsychotic prescriptions (Agid et al., 2010). Even though first-generation antipsychotics such as haloperidol and fluphenazine were available as long-acting depot formulations in Korea until recently, only a few patients used LAI. The prescription rate of LAI in Korea is less than 1% of patients with schizophrenia (Kang et al., 2010), which suggests that LAIs are probably being underused for the maintenance treatment of schizophrenia despite the many reported advantages.

Risperidone long-acting injection (RLAI) is the first long-acting atypical antipsychotic agent and is reported to reduce risks of relapse and rehospitalization and to lead to better global outcomes (Simpson et al., 2006; Curtis et al., 2008; Rainer, 2008; Agid et al., 2010). In clinical trials, RLAI has been shown to be acceptable and well tolerated, along with a low discontinuation rate and indicated effectiveness of 8% in 12-week studies (Turner et al., 2004) and 35% in 12-month studies (Fleischhacker et al., 2003). Observations in clinical practices showed less favorable results than those of the above studies. The discontinuation rate was between 20.3% (Lasser et al., 2005b) and 67.6% (Young and Taylor, 2006) over 50–52 weeks and between 60.7 and 37.3% over 24 months (Taylor et al., 2004; Taylor et al., 2006; Moller, 2007; Curtis et al., 2008; Lambert et al., 2011). In a Korean 48-week study, the discontinuation rate was 37.5% (Lee et al., 2006). However, according to the 24-month study mentioned above, despite the considerable variability in the discontinuation rate, treatment with RLAI resulted in improved functioning and decreased psychiatric hospitalization rates in patients with schizophrenia from the USA, Spain, Australia, and Belgium, although healthcare delivery systems are different (Lambert et al., 2011).

The low prescription rate of RLAI in Korea seems to be complicated by various factors such as cultural background, attitude toward psychiatric illness, and medical delivery system, which contribute toward the low prescription rate in Korea (Roh and Kim, 2011). To enhance the prescription of RLAI in Korea, it should be elucidated whether or not (a) the use of RLAI might be associated with improvements in clinical and functional outcomes in Korean patients with schizophrenia and (b) Korean patients with RLAI show a low rate of side effects, such as extrapyramidal sign (EPS), and a low discontinuation rate, as reported in one study with a relatively small number of patients (Lee et al., 2006).

We investigated clinical outcomes, including remission and continuation rate, in Korean patients with schizophrenia treated with RLAI by carrying out this open-label multicenter naturalistic study.

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Methods

Study design

This open-label, 48-week, prospective study was carried out at 63 centers in South Korea from July 2005 to April 2007. The objective of this study was to investigate clinical outcomes in patients with schizophrenia or schizoaffective disorder treated with RLAI for 48 weeks. All patients or their legal representatives provided their written informed consent before enrollment in the study. The study was carried out in accordance with the guideline of the International Conference on Harmonization for Good Clinical Practice as stipulated in the Declaration of Helsinki and was approved by the Institutional Review Board of each center.

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Participants

Patients who ranged in age from 18 to 75 years and were diagnosed with schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorder, 4th ed. criteria were included. A history of relapse or hospitalization and necessity of long-term treatment with antipsychotics were assessed by the investigator according to the criteria of reoccurrence or worsening of schizophrenic symptoms on the basis of disease management of the psychiatric history. Participants were excluded for any of the following reasons: no history of treatment with antipsychotics; clozapine use within the preceding 3 months; recent or present serious medical diseases including abnormal laboratory findings; presence or history of tardive dyskinesia; history of neuroleptic malignancy syndrome; hypersensitivity or allergy to risperidone or nonresponse to risperidone; history or evidence of two-fold or more levels of normal range of aspartate aminotransferase or alanine aminotransferase; female pregnant or breast-feeding patients or those planning pregnancy during the trial; female patients of childbearing potential who did not use adequate contraception; a high risk of suicide or violent behavior; a history of RLAI treatment within the preceding 60 days.

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RLAI administration and concomitant therapy

Flexibility was allowed for the initial and maintenance dosage of RLAI according to the clinician’s judgment on an individual patient’s tolerability and/or efficacy. During the first 2–3 weeks after the initial injection, oral antipsychotics were allowed to the patients. There were no limitations of using concomitant medication, except antipsychotics.

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Outcomes

Clinical outcomes were divided into efficacy and safety categories. For efficacy, we investigated remission rate, continuation rate, and changes in clinical scales such as eight items of the Positive And Negative Symptom Scale (PANSS), the Clinical Global Impression – Severity (CGI-S), and the Schizophrenia Quality of Life Scale (SQLS). For safety, the Simpson-Angus rating Scale (SAS), adverse events (AEs), and BMI were investigated.

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The definition of remission

Remission was defined according to the criteria proposed by the Remission in Schizophrenia Working Group (Andreasen et al., 2005). This definition requires the simultaneous attainment of a score of 3 (mild), 2 (minimal), or 1 (absent) for at least 6 months in all of the following symptoms: delusion (P1), concept disorganization (P2), hallucinatory behavior (P3), unusual thought content (G9), mannerisms and posturing (G5), blunted affect (N1), passive/apathetic social withdrawal (N4), and lack of spontaneity and flow of conversation (N6). In this study, we explored the patients who obtained scores 1–3 in eight items of PANSS by the symptomatic criteria of the Schizophrenia Working Group in every scheduled visit (symptomatic remission not fulfilling the duration criteria) and identified those with symptomatic remission satisfying both the symptom severity and 6-month duration criteria in 24, 36, and 48 weeks (remission according to Andreasen’s criteria).

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Assessment

Symptom severity was assessed at baseline, 4, 12, 24, 36, and 48 weeks after baseline using eight items of PANSS and CGI-S. Quality of life was also assessed at baseline, 24, and 48 weeks after baseline using SQLS. To assess motor side effects induced by RLAI, the SAS was used at every scheduled visit. Height was estimated at baseline and weight was estimated at every scheduled visit.

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Statistical analysis

Patients who received RLAI at least once were included for assessment of the safety of the study drug, demographics, and characteristics of the baseline data. Patients who received RLAI at least once and had at least one efficacy data in the study period were included in the efficacy analysis. Patients who underwent assessments at baseline and at least once in the study period for eight items of PANSS were included in the intention-to-treat (ITT) population. Among the ITT population, patients who completed the study according to the study protocol were included in the per-protocol (PP) population. Endpoint was defined as the last scheduled visit. If the proportion of missing values in each scale (PANSS, CGI-S, and SQLS) was no more than 20%, the single imputation method using item-mean value was used. Statistical change in each scale over time was analyzed by one-way repeated-measures analysis of variance (ANOVA) in the last observation carried forward (LOCF) method. Efficacy measures such as eight items of PANSS, CGI-S, and SQLS were analyzed among the ITT and PP populations. The PANSS scores at each visit were analyzed (PP population) to determine whether patients fulfilled the remission criteria of Andreasen as well as symptomatic remission not fulfilling the duration criteria of Andreasen.

To determine predicting factors for remission, we considered some demographic and clinical characteristics as possible predictors as follows: age, sex, living with partner, unemployment, diagnosis, duration of illness, age at onset, hospitalization status at baseline, history of hospitalization, number of hospitalizations, initial dose of RLAI, and mean score of severity scales such as eight items of PANSS, CGI-S, and SQLS at baseline. The predicting factors for remission and completion were investigated by logistic regression analysis. All statistical analyses were carried out using SPSS 19.0 for windows (SPSS Inc., Chicago, Illinois, USA).

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Results

Demographic and clinical characteristics of participants

Among the 522 patients who were initially enrolled, 472 patients who underwent assessments for eight items of PANSS at baseline and at least once in the study period were included. The baseline demographic and clinical characteristics are shown in Table 1. The average age of the patients was 36.9±11.0 years in mean±SD and there were 229 (48.6%) male patients. A total of 442 (93.6%) patients had been diagnosed with schizophrenia. The average age at onset was 27.7±9.3 years in mean±SD and duration of illness was 9.1±7.0 years in mean±SD. Of the 472 patients, 46.5% were inpatients at baseline and the average number of hospitalizations in patients who had a history of hospitalization was 3.1±2.7 in mean±SD. Among the patients who had received antipsychotics before the study, 89.2% received only one antipsychotic drug and more than half of them received risperidone.

Table 1
Table 1
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Continuation and discontinuation rate of the study

Among the 472 patients included in the ITT analysis, 184 (39.0%) completed the study by finishing the 48-week follow-up (Fig. 1). The reasons for early discontinuation were follow-up loss (N=117), patient’s choice (N=64), lack of efficacy (N=35), AE (N=20), death (N=3), pregnancy (N=2), and others (N=50).

Fig. 1
Fig. 1
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Demographics were generally comparable between patients who completed the study and those who did not. Duration of illness, the mean haloperidol equivalent dose of previous antipsychotics, and the mean baseline SAS score were lower in patients who completed the study than in those who did not (P<0.01, P=0.04, and P=0.04, respectively). Also, among patients who completed the study there was a higher percentage of inpatients, higher number of patients living with a partner, and higher initial RLAI dosage (P<0.01, P=0.04, and P=0.04, respectively) than those who did not complete the study. However, age at onset, number of hospitalizations, baseline eight items of PANSS score and CGI-S score, and the average dose of RLAI did not differ between the two groups (Table 2).

Table 2
Table 2
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The mean follow-up duration among the 288 patients who discontinued prematurely was 3.6 months (SD 2.7). The number of patients who discontinued at each time point is presented in Fig. 2.

Fig. 2
Fig. 2
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Efficacy of RLAI
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Change in the total score of eight items in PANSS, CGI-S, and SQLS

Total scores of eight items of PANSS, CGI-S, and SQLS were reduced significantly from baseline to endpoint in both ITT and PP populations. The total scores in eight items of PANSS, CGI-S, and SQOL at each time point in the two groups are shown in Table 3.

Table 3
Table 3
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Remission rate

Among the PP population (N=184), 47 (25.5%) patients fulfilled symptomatic remission not fulfilling the duration criteria of Andreasen at baseline and 144 (78.3%) at 48 weeks. In total, 45 (24.5%) patients fulfilled the remission criteria of Andreasen at 24 weeks and 120 (65.2%) at 48 weeks (Fig. 2).

Patients who fulfilled the remission criteria of Andreasen at 48 weeks among the PP population had significantly lower baseline eight items of PANSS and CGI-S scores and lower average dose of RLAI compared with patients who did not. Demographic and other clinical characteristics (i.e. number of hospitalizations, age of onset, duration of illness) did not differ between the two groups (Table 4). Logistic regression showed that a lower baseline eight items of PANSS score led to a higher probability of remission.

Table 4
Table 4
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Safety of RLAI
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Adverse effect

Comedication: Four categories of medications were investigated: anticholinergics, β-blockers, benzodiazepines, and zolpidem. The number of patients with each medication during the study was 241, 108, 282, and 94, respectively. Among the 472 patients included in the analysis, 337 patients received at least one kind of medication mentioned above. The average number of comedications administered to 472 patients during the study was 1.5±1.2 in mean±SD. The number of patients who took one kind of medication above was 92, 130 for two, 87 for three, and 28 for four kinds of medications. The χ2-test showed a high dropout tendency in patients with a history of comedications such as anticholinergics, β-blockers, and benzodiazepines (all P<0.01). Only zolpidem did not affect completion status (P=0.75).

Simpson-Angus Rating Scale: The average score of the SAS at baseline of 472 patients was 1.6±3.5 in mean±SD and did not affect the final remission status in patients who did not fulfill the remission criteria at baseline (P=0.57; Table 4). One-way repeated-measures ANOVA showed a significant decrease in the mean score over time in LOCF (Greenhouse–Geisser correction: F=5.80, d.f.=2.48, P<0.01). This decreasing pattern was not affected by comedications of anticholinergics, β-blockers, benzodiazepines, and/or zolpidem, whereas the mean score of SAS tended to be high throughout the study in patients with a history of taking anticholinergics, β-blockers, and/or benzodiazepines, except zolpidem.

BMI: The mean BMI of 472 patients at baseline was 24.2±6.6. One-way repeated-measures ANOVA showed a significant increase in BMI over time in LOCF (Greenhouse–Geisser correction: F=20.7, d.f.=3.2, P<0.01). There were significant differences in increase in BMI between patients who fulfilled the remission criteria during the study and those who did not. Patients who fulfilled the remission criteria during the study tended to gain more weight than those who did not (one-way repeated-measures ANOVA with Greenhouse–Geisser correction: F=3.2, d.f.=3.2, P=0.02).

Adverse events: During the study period, a total of 645 AEs in 233 patients (49.3%) who were included in ITT analysis were noted. Among all the AEs, 164 were at least possibly related to RLAI [very likely N=31 (4.8%), probable N=46 (7.1%), and possible N=87 (13.5%)]. AE reported by over 10% of RLAI-treated patients in this trial was only insomnia (N=85, 17.9%). The next frequently observed AEs were anxiety (N=39, 8.2%), akathisia (N=30, 6.3), agitation (N=30, 6.3%), constipation (N=27, 5.7%), headache (N=25, 5.3%), increase in weight (N=23, 4.8%), and dizziness (N=19, 4.0%), in descending order. Pearson’s correlation between the occurrence of AEs and baseline symptom remission status, final remission status, and study completion did not show significant correlations: the P values were 0.445, 0.485, and 0.813, respectively.

Serious adverse events: Sixty-nine SAEs were reported in 51 patients: aggravation of schizophrenia and aggravation of psychotic symptoms were the most frequently reported SAEs, but all were not directly attributed to administration of RLAI. SAEs that were considered as related to RLAI were extrapyramidal disorder (probable) and akathisia (possible). Three deaths were reported, and all were suicides. They were not related to the study drug or the study procedure.

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Discussion

The main findings in this study were as follows: a 65.2% remission rate was found among the patients who completed the study and a 38.7% study completion rate was obtained after 48 weeks of RLAI treatment. This study also showed clinical improvements in various scales such as PANSS, CGI-S, and SQLS, an increase in the number of patients who achieved remission, and a reduction in scores on the EPS scale, with no SAEs directly attributed to biweekly RLAI treatment during 48 weeks.

In this study, the total scores of eight items of PANSS, CGI-S, SQLS, and SAS were reduced significantly from baseline to endpoint in both ITT and PP populations, suggesting the efficacy in psychopathology, quality of life, and reduction of EPS with RLAI treatment, in agreement with results reported by other researchers (Keith, 2009). Even though the overall efficacy, tolerability, and safety of RLAI appear to be high in this study, the interpretation of these results should be made with caution because of the limitations of an open-label, noncomparative approach itself and an unexpected policy change in the reimbursement system during the study period.

The discontinuation rate is often used as the outcome measure in clinical trials of antipsychotics (Rabinowitz et al., 2009). The discontinuation rate of 61.0% (288/472) in this study of a 48-week follow-up was quite high compared with other results in the range of 23–48% (Lasser et al., 2005b; Lee et al., 2006; Lindenmayer et al., 2007). The most frequent reasons for discontinuation were loss to follow-up, 40.6% (117/288), and patient’s choice, 22.2% (64/288), in this study. Rates of dropout because of insufficient response and AEs were 12.2% (35/288) and 6.9% (20/288), respectively, in this study, which appear to be relatively lower than 22.3 and 10.7%, respectively, reported in other studies (Lasser et al., 2005b). However, the rate of withdrawal from the study because of other reasons was up to 17.2% (50/288) in this study, which could be attributed to the sudden change in nationwide policy of the Health Insurance Review and Assessment Service. The sudden restriction in reimbursement for the RLAI treatment was enforced by the organization unexpectedly during the study period. Discontinuation rate because of AEs among patients who withdrew from the study was 6.9%, which was comparable with that reported in other long-term RLAI studies (Canas and Moller, 2010).

Interestingly enough, the preferences of LAI for the patients and caregivers were quite high compared with the very low use of LAI in Korea. In surveys for the preferences of LAI in Korea, 28–46.8% of patients or caregivers indicated a preference for the LAI antipsychotics (Kang et al., 2010; Lee et al., 2013). As for the huge difference between the low use and high preferences, there could be two major factors: the healthcare delivery system in Korea such as the high injection cost and the strict indications on the LAIs officially applied in the Health Insurance Review and Assessment Service. Another issue with respect to patients and physicians in the clinics could be the fear of injection itself, and concerns over long-term effects and AEs. However, caregivers whose patients were hospitalized more often and discontinued medications preferred LAI (Lee et al., 2013).

It has been reported that the rates of remission according to the Schizophrenia Working Group criteria by Andreasen may range between 22 and 55% in multiepisode samples of schizophrenia (Emsley et al., 2008). Of the PP population in this study, 47 (25.5%) patients fulfilled the symptomatic remission not fulfilling the duration criteria of Andreasen at baseline and 120 (65.2%) patients fulfilled the remission criteria of Andreasen at 48 weeks. Compared with the open-label, 50-week study in which 31.8% of patients achieved symptomatic remission not fulfilling the duration criteria of Andreasen at baseline and 41.2% fulfilled the remission criteria of Andreasen at the end point (Lasser et al., 2005b), this study showed a relatively high rate of patients who fulfilled the remission criteria of Andreasen. This study showed that RLAI treatment led to a continuous increase in the numbers of patients who achieved symptomatic remission not fulfilling the duration criteria during 48 weeks of the study period and also an increase in the numbers of patients who fulfilled the remission criteria of Andreasen 6 months after RLAI treatment. This means that maintaining reduced symptom severity with RLAI treatment could increase the likelihood of remission.

The previous LAI study reported that the severity of movement disorders measured by the Extrapyramidal Symptom Rating Scale was low and is comparable with placebo in all treatment groups throughout the study period (Lauriello et al., 2005). In a Korean 48-week open-label study (Lee et al., 2006), the severity of EPS measured by the Drug Induced ExtraPyramidal Symptoms Scale showed no significant difference. In this study, the severity of EPS, as measured using SAS, showed a significant decrease in the mean score over time, and was not affected by administration of comedications, anticholinergics, β-blockers, benzodiazepines, or zolpidem, whereas in patients with a history of taking anticholinergics, β-blockers, and benzodiazepines, except zolpidem, the mean score of SAS was high throughout the study. Overall, the result of this study showed that the long-term use of RLAI may reduce the incidence of EPS as indicated by the fact that patients switched to RLAI showed a low incidence of EPS and even improvement in EPS (Van Os et al., 2004; Lasser et al., 2005a; Moller, 2007; Keith, 2009).

In a prospective 3-year study of 211 consecutive patients treated with RLAI, patients who were younger, had longer duration of illness, were hospitalized at RLAI initiation, or had been administered 25 mg of RLAI every 2 weeks showed significant increases in risks of discontinuation of RLAI administration (Lambert et al., 2010). In this study, age and number of hospitalizations, initial RLAI dosage, and average administered dose of RLAI were not different between patients who discontinued and completed the study. Patients who completed the study were more likely to be living with a partner, had a longer duration of illness, and a higher mean haloperidol equivalent dose of previous antipsychotics. They also showed higher baseline SQLS, but no difference in the baseline score was found in eight items of PANSS and CGI-S. In this study, patients who achieved remission according to the criteria of Andreasen at the end point of 48 weeks showed lower baseline scores in eight items of PANSS and CGI-S, but no difference in the baseline SQLS score compared with those who did not achieve remission and did not fulfill the remission criteria. This finding suggests that better symptom severity at baseline might predict remission along with symptomatic remission (Lambert et al., 2010).

The interpretation of the results of this study is limited because of the open-label, noncomparative study design although this study was carried out as a multicenter study with a relatively large sample size. Also, there was an unexpected nationwide restriction in the reimbursement policy of RLAI treatment by the Health Insurance Review and Assessment Service, which is another limitation that makes generalization of the findings more difficult. Despite these limitations, this study showed considerable clinical improvements in psychopathology and AEs and also a significant increase in BMI during 48 weeks of biweekly RLAI treatment. Finally, the study completion rate was 39.0% and the remission rate among the patients who completed the study was 65.2%. There were no SAEs directly attributed to the use of RLAI.

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Acknowledgements

This study was carried out with the funding of Janssen Korea Co. Ltd.

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Conflicts of interest

Dr Y.S. Kim received grants, research support, and honoraria from AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, Organon, Otsuka, Sanofi–Aventis, and Servier. Dr Y.M. Ahn received research grants and served as a lecturer for AstraZeneca, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Otsuka, Pfizer, and Servier. Dr D.H. Kim, Dr C.Y. Kim, Dr Y.S. Na, Dr S.E. Shin, Dr J.M. Woo, Dr B.H. Yoon, Dr J.S. Yoon, Dr D.G. Lee, Dr Y.H. Lee, Dr W.J. Lim, Dr Y.C. Chung, Dr I.K. Jung, and Dr S.J. Cho received consultancy fee and grants from Janssen. Dr N.Y. Lee and Dr S.H. Kim have no conflicts of interest.

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Keywords:

remission rate; risperidone long-acting injectable; schizophrenia

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