Oral versus Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia and Special Populations at Risk for Treatment Nonadherence: A Systematic Review Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study. Maintenance treatment with long-acting injectable risperidone in first-episode schizophrenia: a randomized effectiveness study. Working alliance and its relationship to outcomes in a randomized controlled trial (RCT) of antipsychotic medication Long-acting risperidone and oral antipsychotics in unstable schizophrenia. Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral A long-term prospective study on the outcome of bipolar patients treated with long-acting injectable risperidone Efficacy and safety of direct transition to risperidone long-acting injectable in patients treated with various antipsychotic therapies Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. Financial incentives to improve adherence to antipsychotic maintenance medication in non-adherent patients: a cluster randomised controlled trial. Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI) versus paliperidone LAI in comorbid psychosis and substance use disorder: impact on clinical status, substance craving, and quality of life Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia Long-acting injectable risperidone v. olanzapine tablets for schizophrenia or schizoaffective disorder. Randomised, controlled, open-label study. Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Cost-effectiveness analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia Risperidone Long-Acting Injectable Monotherapy in the Maintenance Treatment of Bipolar I Disorder
Long-acting injectable antipsychotics ( LAIs ) should offer better efficacy and tolerability , compared to oral antipsychotics due to improved adherence and more stable pharmacokinetics . However , data on LAIs has been mixed , with some studies finding that they are more effective and tolerable than oral antipsychotics , and others finding the contrary . One possibility for the disparate results may be that some studies administered different antipsychotics in the oral and injectable form . The present systematic review examined the efficacy and tolerability of LAIs versus their oral equivalents in r and omized and naturalistic studies . In addition , it examined the impact of LAIs  on special population s such as patients with first-episode psychosis , substance use disorders , and a history of violence or on involuntary outpatient commitment . R and omized studies suggest that not all LAIs are the same ; for example , long-acting risperidone may be associated with equal or less side effects than oral risperidone , whereas fluphenazine decanoate and enanthate may be associated with equal or more side effects than oral fluphenazine . They also suggest that LAIs reduce risk of relapse versus oral antipsychotics in schizophrenia out patients when combined with quality psychosocial interventions . For their part , naturalistic studies point to a larger magnitude of benefit for LAIs , relative to their oral equivalents particularly among first-episode patients Until relatively recently , long-acting injectable ( LAI ) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics ( SGA ) increased . Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice , this is not seen in recent r and omized clinical trials . PROACTIVE ( Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy ) relapse prevention study incorporated efficacy and effectiveness features . At 8 US academic centers , 305 patients with schizophrenia or schizoaffective disorder were r and omly assigned to LAI risperidone ( LAI-R ) or physician 's choice oral SGAs . Patients were evaluated during the 30-month study by masked , central ized assessors using 2-way video , and monitored biweekly by on-site clinicians and assessors who knew treatment assignment . Relapse was evaluated by a masked Relapse Monitoring Board . Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant . Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group . In contrast , the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores . There were no other between-group differences in symptoms or functional improvement . Despite the advantage for psychotic symptoms , LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization . Biweekly monitoring , not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm , may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials BACKGROUND Because long-acting injectable ( LAI ) antipsychotics are largely reserved for persistently ill patients , little is known about the use of LAIs early in the course of illness for first-episode out patients . METHOD A prospect i ve , open-label , r and omized controlled trial was conducted in which out patients with first-episode DSM-IV schizophreniform disorder , schizophrenia , or schizoaffective disorder were enrolled from December 2004 to March 2007 . Participants were r and omly assigned at a 2:1 ratio to a recommendation of changing to LAI risperidone microspheres ( RLAI ) ( n = 26 ) or continuing oral antipsychotic treatment ( n = 11 ) for up to 104 weeks . Primary outcomes were time until initial nonadherence ( medication gap of ≥ 14 days ) and medication attitudes as assessed with the Rating of Medication Influences scale . Patients r and omly assigned to an RLAI recommendation could decline the recommendation , so analysis defined treatment groups by intent-to-treat and as-actually-treated . RESULTS Eighty-one percent of patients ( 30/37 ) stopped medication within 104 weeks . There was a trend toward an initial adherence benefit favoring RLAI acceptors at 12 weeks ( P = .058 ) , but no significant difference between RLAI and oral antipsychotic treatment in time to initial nonadherence during the overall study ( P = .188 ) . Medication attitudes did not differ between groups . CONCLUSIONS Acceptance of RLAI was associated with an initial adherence benefit that was not sustained over time . Early introduction of LAI therapy did not adversely affect adherence attitudes . The small size of the study and low power limit interpretation , but the few patients who remained adherent into a second year were all receiving RLAI . Nonadherence was almost universal in our first-episode cohort , but nonadherence was more easily detected among first-episode patients treated with LAI therapy than it was with oral antipsychotics . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00220714 Background Long acting injections ( LAI ) have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications . Method R and omized controlled trial with ( 50 ) participants with a diagnosis of schizophrenia r and omized to risperidone LAI or oral atypical antipsychotic medication .  The main outcome was the Working Alliance Inventory ( WAI ) with background variables ( symptoms , side effect , social functioning , quality of life ) measured before r and omization and at two years . Results At follow-up ( 14 risperidone LAI and 16 oral medication ) analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change . Sensitivity analyses showed ( i ) a significant detrimental effect of LAI on WAI and ( ii ) the pattern of results was not affected by change in symptoms over the study . Conclusion This is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment BACKGROUND Long-acting injectable risperidone , a second-generation antipsychotic agent , may improve adherence to treatment and outcomes in schizophrenia , but it has not been tested in a long-term r and omized trial involving patients with unstable disease . METHODS We r and omly assigned patients in the Veterans Affairs ( VA ) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of long-acting injectable risperidone every two weeks or to a psychiatrist 's choice of an oral antipsychotic . All patients were followed for up to 2 years . The primary end point was hospitalization in a VA or non-VA psychiatric hospital . Symptoms , quality of life , and functioning were assessed in blinded videoconference interviews . RESULTS Of 369 participants , 40 % were hospitalized at r and omization , 55 % were hospitalized within the previous 2 years , and 5 % were at risk for hospitalization . The rate of hospitalization after r and omization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics ( 39 % after 10.8 months vs. 45 % after 11.3 months ; hazard ratio , 0.87 ; 95 % confidence interval , 0.63 to 1.20 ) . Psychiatric symptoms , quality of life , scores on the Personal and Social Performance scale of global functioning , and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments . Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms . CONCLUSIONS Long-acting injectable risperidone was not superior to a psychiatrist 's choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization , and it was associated with more local injection-site and extrapyramidal adverse effects . ( Supported by the VA Cooperative Studies Program and Ortho-McNeil Janssen Scientific Affairs ; Clinical Trials.gov number , NCT00132314 . ) Abstract Objective : To compare hospitalizations and incidence of relapses among patients with schizophrenia initiating long-acting injectable ( LAI ) antipsychotics vs oral antipsychotics .  Methods : Patients with schizophrenia initiating LAI antipsychotics or oral antipsychotics ( index events ) were identified from large data bases ( MarketScan ; Truven Health Analytics , CA ) , containing commercial and Medicare healthcare cl aims and their pre-index ( 12-month baseline period ) and post-index ( 12-month follow-up period ) hospitalizations and relapse rates were compared . Descriptive and bivariate statistics were utilized to compare demographics , clinical characteristics , and hospital re source usage among cohorts . Multivariate analysis was used to evaluate the impact of initiating LAI vs oral antipsychotics on differences in the number of hospitalizations and length of stay ( LOS ) between follow-up and baseline periods . Results : Commercially insured patients initiating LAI antipsychotics ( n = 394 ) had significant reductions in inpatient healthcare usage after initiating antipsychotic therapy : mean number ( ±st and ard deviation ) of all cause hospitalizations ( 1.60 ± 1.66 vs 0.70 ± 1.20 , p < 0.001 ) , LOS ( 16.9 ± 20.7 vs 6.6 ± 14.4 days , p < 0.001 ) , schizophrenia-related hospitalizations ( 1.03 ± 1.26 vs 0.43 ± 0.86 , p < 0.001 ) , associated LOS ( 12.3 ± 17.7 vs 4.8 ± 12.8 days , p < 0.001 ) . Patients initiating LAI vs oral antipsychotics ( n = 2610 ) had significantly greater reductions during the follow-up period vs baseline period in the mean number of all cause hospitalizations ( −0.90 ± 1.77 vs 0.02 ± 1.49 , p < 0.001 ) , LOS ( −10.3 ± 23.2 vs 0.7 ± 16.7 days , p < 0.001 ) , schizophrenia-related hospitalizations ( −0.60 ± 1.37 vs 0.05 ± 0.99 , p < 0.001 ) and associated LOS ( −7.5 ± 20.7 vs 0.6 ± 12.5 days , p < 0.001 ) . These results were further supported by multivariate analyses in which patient characteristics were taken into consideration . Limitations : This study attempted to minimize the impact of differences in patient characteristics by having patients serve as their own controls in the before vs after comparison followed by multivariate regressions , however one still may not be able to account for all confounders in this non-r and omized study population . Conclusion : Patients with schizophrenia who initiated  LAI vs oral antipsychotics experienced reductions in hospitalizations and schizophrenia relapses after drug initiation , which may be indicative of improved disease management Background : Risperidone is the first atypical antipsychotic to become available in a long-acting , injectable formulation . This is the first prospect i ve study to assess the effectiveness of long-acting risperidone in a cohort of bipolar patients . Methods : Twenty-nine DSM-IV acutely manic bipolar in patients with a history of poor or partial adherence to medication entered the mirror- design observational study . They received naturalistic treatment for a manic episode plus long-acting , injectable risperidone for a mean period of 2 years . The following measures were used to assess the effectiveness of risperidone  : the number of hospitalizations , the number of manic , mixed , and depressive episodes leading to hospitalization , the mean duration of hospitalizations , time to relapse , treatment adherence , aggression and suicide attempts . The Clinical Global Impressions ( CGI ) was used for clinical relevance as well . Results : During the follow-up , there was a significant decrease in the number of hospitalizations per patient ( Z−2.72 P<0.006 ) , in the number of manic or mixed episodes leading to hospitalization ( Z−2.68 P<0.007 ) but not in the hospitalizations due to depressive episodes , a decrease in the average length of hospitalization per patient ( Z−3.27 P<0.001 ) , a significant increase in the time to any new episode ( first relapse ) ( Z−3.28 , P<0.001 ) , and significant improvements in treatment adherence ( P<0.0001 ) and hetero-aggressive episodes ( P<0.0001 ) , but not suicide attempts ( P = NS ) . At study endpoint 14 patients ( 48 % ) were very much improved according to the CGI . Discussion : This observational long-term study provides support to long-acting injectable risperidone being effective for the maintenance treatment of mania and improving treatment adherence , reducing relapses and re-hospitalization rates The maintained antipsychotic efficacy of risperidone long-acting injectable ( RLAI ) was investigated in patients with schizophrenia or other psychoses who were transitioned directly from their previous antipsychotic medication . Patients symptomatically stable , but considered to require a treatment change , received 25 mg of RLAI ( increased to 37.5 or 50 mg , if necessary ) every 2 weeks for 6 months . Assessment s included Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression – Severity ( CGI-S ) , Global Assessment of Functioning ( GAF ) , SF-36 Health-Related Quality of Life Question naire and Extrapyramidal Symptoms Rating Scale ( ESRS ) .  Of 1876 patients enrolled , 74 % completed the 6-month study . The most frequent reasons for treatment change were non-compliance ( 38 % ) , insufficient efficacy ( 33 % ) and side-effects ( 26 % ) . There was a significant reduction from baseline to endpoint in mean total PANSS score and in the scores on all PANSS subscales and symptom factors ( P<0.001 ) . CGI-S improved significantly , as did mean GAF score , all factors on the SF-36 and patient satisfaction with treatment . Scores on ESRS showed significant , sustained improvements throughout the study period . Direct initiation of RLAI was effective and well tolerated . RLAI provides an advancement in the treatment options available for a wide range of patients requiring long-term antipsychotic therapy OBJECTIVE Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication 's efficacy . Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics . This post-hoc analysis assessed supplementation of olanzapine long-acting injection ( olanzapine-LAI ) with oral olanzapine . SUBJECTS AND METHODS We used 12 months of data from an open-label , single-arm extension study of patients with schizophrenia or schizoaffective disorder ( N=931 ) treated with olanzapine-LAI .  The prevalence , duration , time to first supplementation , and best predictors of oral supplementation were assessed . RESULTS Oral supplementation occurred in 21 % of patients for a median of 31 days with mean modal dose of 10.8 mg/day . Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients ( 47 vs. 97 days , p<0.001 ) . Best predictors of oral supplementation included a more severe illness profile at baseline , lower olanzapine-LAI dose prior to oral supplementation , supervised living arrangements , and being African-American . CONCLUSION Supplementation of olanzapine-LAI appears to be infrequent , of relatively short duration , and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse BACKGROUND The long-term safety and efficacy of long-acting injectable risperidone , the first long-acting second-generation antipsychotic , were evaluated in stable patients with schizophrenia . METHOD After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone , patients received injections of 25 mg , 50 mg , or 75 mg of long-acting risperidone every 2 weeks for 12 months . Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale ( ESRS ) , and efficacy was assessed with the Positive and Negative Syndrome Scale ( PANSS ) . This study was conducted from March 29 , 1999 to July 19 , 2000 . RESULTS The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone .  The 12-month trial was completed by 65 % of patients . Treatment was discontinued because of adverse events in 5 % of patients . Extrapyramidal symptoms as adverse events were reported by 25 % of the patients . Severity of extrapyramidal symptoms ( according to ESRS scores ) was low at baseline and decreased in each of the groups during the 12 months . The other most common adverse events were anxiety in 24 % , insomnia in 21 % , psychosis in 17 % , and depression in 14 % of the patients . Little pain was associated with the injections . Severity of symptoms of schizophrenia was improved in each group , with significant reductions in PANSS total scores ( p < .01 ) and positive ( p < .01 ) and negative ( p < .001 ) factor scores . CONCLUSION In terms of both safety and efficacy , symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone BACKGROUND Poor adherence to long-term antipsychotic injectable ( LAI ) medication in patients with psychotic disorders is associated with a range of negative outcomes . No psychosocial intervention has been found to be consistently effective in improving adherence . OBJECTIVES To test whether or not offering financial incentives is effective and cost-effective in improving adherence and to explore patient and clinician experiences with such incentives . DESIGN A cluster r and omised controlled trial with economic and nested qualitative evaluation . The intervention period lasted for 12 months with 24 months ' follow-up . The unit of r and omisation was mental health teams in the community . SETTING Community teams in secondary mental health care . PARTICIPANTS Patients with a diagnosis of schizophrenia , schizoaffective psychosis or bipolar illness , receiving ≤ 75 % of their prescribed LAI medication . In total , 73 teams with 141 patients ( intervention n = 78 and control n = 63 ) were included . INTERVENTIONS Participants in the intervention group received £ 15 for each LAI medication . Patients in the control group  received treatment as usual . MAIN OUTCOME MEASURES PRIMARY OUTCOME adherence to LAI medication  ( the percentage of received out of those prescribed ) . SECONDARY OUTCOMES percentage of patients with at least 95 % adherence ; clinical global improvement ; subjective quality of life ; satisfaction with medication ; hospitalisation ; adverse events ; and costs . Qualitative evaluation : semistructured interviews with patients in the intervention group and their clinicians . RESULTS PRIMARY OUTCOME outcome data were available for 131 patients .  Baseline adherence was 69 % in the intervention group and 67 % in the control group . During the intervention period , adherence was significantly higher in the intervention group than in the control group ( 85 % vs. 71 % ) [ adjusted mean difference 11.5 % , 95 % confidence interval ( CI ) 3.9 % to 19.0 % ; p = 0.003 ] . Secondary outcome : patients in the intervention group showed statistically significant improvement in adherence of at least 95 % ( adjusted odds ratio 8.21 , 95 % CI 2.00 to 33.67 ; p = 0.003 ) and subjective quality of life ( difference in means 0.71 , 95 % CI 0.26 to 1.15 ; p = 0.002 ) . Follow-ups : after incentives stopped , adherence did not differ significantly between groups , neither during the first 6 months ( adjusted difference in means -7.4 % , 95 % CI -17.0 % to 2.1 % ; p = 0.175 ) nor during the period from month 7 to month 24 ( difference in means -5.7 % , 95 % CI -13.1 % to 1.7 % ; p = 0.130 ) . Cost-effectiveness : the average costs of the financial incentives was £ 303 . Overall costs per patient were somewhat higher in the intervention group , but the difference was not significant . Semistructured interviews : the majority of patients and clinicians reported positive experiences with the incentives beyond their monetary value . These included improvement in the therapeutic relationship . The majority of both patients and clinicians perceived no negative impact after the intervention was stopped after 1 year . CONCLUSIONS Financial incentives are effective in improving adherence to LAI medication . Health-care costs ( including costs of the financial incentive ) are unlikely to be increased substantially by this intervention . Once the incentives stop , the advantage is not maintained . The experiences of both patients and clinicians are largely , but not exclusively , positive . Whether or not financial incentives are effective for patients with more favourable background , those on oral mediation or for shorter or longer time periods remains unknown . TRIAL REGISTRATION Current Controlled Trials IS RCT N77769281 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 70 . See the NIHR Journals Library website for further project information Background To overcome nonadherence in patients with psychosis switch to long-acting injectable ( LAI ) antipsychotic formulations is adopted . Most oral versus LAI comparisons showed similar antipsychotic responses . Psychoses often overlap with substance use disorder ( SUD ) . Head-to-head LAI comparisons have hitherto focused only on non-comorbid population s. Objective The objective of this study was to compare two LAIs , administered for 12 months , in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life ( QoL ) outcomes . Patients and methods In patients were recruited during 2016 and switched r and omly to 400 mg intramuscular aripiprazole monohydrate ( AM ) ( N=50 ) or to 100 mg intramuscular paliperidone palmitate ( PP ) once-monthly ( N=51 ) ; patients were discharged and followed up for 12 months . Patients were rated at baseline and after 1 year through the Clinical Global Impression scale – severity ( CGIs ) , substance craving intensity was rated through a visual analog scale for substance craving , and QoL through the World Health Organization ( WHOQOL-BREF ) scale . We addressed confounders with backward stepwise logistic regression and three-way analysis of variance . Results PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM , but AM had a stronger craving for substances at baseline . Both LAIs were associated with significant improvements in all outcomes , with AM displaying stronger effect sizes than PP . The two groups did not differ on baseline WHOQOL-BREF scores in any domain , but at the 1-year follow-up , AM fared better on all domains . The two groups did not differ in final severity , but PP scored higher than AM in craving at the 1-year endpoint . Limitation : The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias . Conclusion 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity . AM , compared to PP , improved craving and QoL at the 1-year follow-up CONTEXT Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia ( SZ ) . Prior MRI studies suggested that early in the treatment of SZ , antipsychotic medications initially increase frontal lobe intracortical myelin ( ICM ) volume , which subsequently declines prematurely in chronic stages of the disease . Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics , it may be modifiable by long acting injection ( LAI ) formulations . OBJECTIVES Assess the effect of risperidone formulation on the ICM trajectory during a six-month r and omized trial of LAI ( RLAI ) versus oral ( RisO ) in first-episode SZ subjects . DESIGN Two groups of SZ subjects ( RLAI , N=9 ; and RisO , N=13 ) matched on pre-r and omization oral medication exposure were prospect ively examined at baseline and 6 months later , along with 12 healthy controls ( HCs ) . Frontal lobe ICM volume was assessed using inversion recovery ( IR ) and proton density ( PD ) MRI images . Medication adherence was tracked . MAIN OUTCOME MEASURE ICM volume change scores were adjusted for the change in the HCs . RESULTS ICM volume increased significantly ( p=.005 ) in RLAI and non-significantly ( p=.39 ) in the RisO groups compared with that of the healthy controls . A differential between-group treatment effect was at a trend level ( p=.093 ) . SZ subjects receiving RLAI had better medication adherence and more ICM increases ( chi-square p<.05 ) . CONCLUSIONS The results suggest that RLAI may promote ICM development in first-episode SZ patients . Better adherence and /or pharmacokinetics provided by LAI may modify the ICM trajectory . In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action BACKGROUND The efficacy and safety of long-acting injectable risperidone have not been compared with those of an oral atypical antipsychotic . AIMS To compare long-acting risperidone and oral olanzapine in 377 patients with DSM-IV schizophrenia or schizoaffective disorder . METHOD Patients were r and omised to receive long-acting risperidone ( 25 mg or 50 mg every 14 days ) or olanzapine ( 5 - 20 mg/day ) . RESULTS In the 13-week phase , long-acting risperidone was at least as effective as ( not inferior to ) oral olanzapine . In the 12-month phase , significant improvements in the Positive and Negative Syndrome Scale ( PANSS ) total and factor scores from baseline to month 12 and end-point were seen in both groups of patients . Few patients discontinued treatment because of an adverse event . CONCLUSIONS Both treatments were efficacious and well tolerated BACKGROUND Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics . Long-acting injectable antipsychotics-developed specifically to address the problem of adherence-might have an important role to play in treating early psychosis . OBJECTIVE The effects of oral antipsychotics versus risperidone long-acting injection ( RLAI ) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa . METHODS Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a r and omized controlled trial of flexible doses of oral risperidone or haloperidol .  Inclusion criteria for both studies were age 16 to 45 years ; confirmed diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder ; < or=2 hospitalizations for psychosis ; and lifetime exposure to < or=12 weeks of antipsychotic medication . The dose of RLAI was 25 mg every 2 weeks , which could be increased to 50 mg . Doses of oral risperidone or haloperidol began at 1 mg/d and were increased if necessary up to a maximum dose of 4 mg/d ( 8 mg/d in exceptional cases ) . Study assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Extrapyramidal Symptom Rating Scale ( ESRS ) , and body mass index ( BMI ) . RESULTS The RLAI group included 50 patients ( 32 men and 18 women ; mean [ SD ] age , 25.4 [ 7.4 ] years ; BMI , 20.6 [ 4.6 ] kg/m(2 ) ) . The oral risperidone or haloperidol group included 47 patients ( 27 men and 20 women ; mean [ SD ] age , 25.9 [ 5.8 ] years ; BMI , 20.1 [ 3.4 ] kg/m(2 ) ) . Compared with patients treated with oral risperidone or haloperidol , RLAI-treated patients had significantly fewer all-cause discontinuations ( 26.0 % [ 13/50 ] vs 70.2 % [ 33/47 ] at 24 months ; P < 0.005 ) , greater reduction on the PANSS total score ( -39.7 vs -25.7 ; P = 0.009 ) , higher remission rate ( 64.0 % [ 32/50 ] vs 40.4 % [ 19/47 ] ; P = 0.028 ) , and lower relapse rate ( 9.3 % [ 4/43 ] vs 42.1 % [ 16/38 ] ; P = 0.001 ) among the responders . Extrapyramidal symptoms were significantly lower in the RLAI group than in patients treated with oral risperidone or haloperidol , as measured by the maximum change in the mean [ SD ] ESRS total score ( 1.40 [ 2.60 ] vs 5.61 [ 5.21 ] vs 9.04 [ 6.21 ] , respectively ; P < or= 0.001 ) . The increase in BMI after 6 months was significantly greater in the RLAI group than in oral haloperidol-treated patients ( mean [ SD ] , 3.9 [ 1.9 ] vs 2.2 [ 1.3 ] kg/m(2 ) ; P = 0.001 ) but not significantly different from oral risperidone ( 3.4 [ 2.0 ] kg/m(2 ) ; P = NS ) . Four patients in the RLAI group had adverse events that were possibly related to prolactin , compared with 1 each in the oral risperidone and haloperidol groups . CONCLUSIONS The findings of this post hoc analysis suggest that there were advantages in terms of efficacy , fewer extrapyramidal symptoms , and more weight gain with long-acting injectable second-generation antipsychotics as compared with oral antipsychotic treatment in early-episode psychosis Background The availability of long-acting injectable risperidone may increase adherence to antipsychotic treatment and lead to improved clinical and economic outcomes for patients with schizophrenia . Objectives To investigate the cost effectiveness of treatment with long-acting injectable risperidone compared with previous antipsychotic regimens in patients with schizophrenia enrolled in the electronic Schizophrenia Treatment Adherence Registry ( e-STAR ) in Spain . Methods e-STAR is an international , long-term , ongoing , observational study of schizophrenia patients who , during their routine course of clinical practice , are started on a new antipsychotic treatment . In e-STAR , data are collected at baseline , retrospectively over a minimum period of 12 months and up to a maximum of 24 months , and prospect ively at 3-month intervals for 24 months after the start of a new antipsychotic drug . For the purpose of this study , patients who started treatment with long-acting injectable risperidone during their routine clinical management and were enrolled in the e-STAR study in Spain were eligible . The effectiveness of long-acting injectable risperidone compared with previous antipsychotic treatment , defined as the absence of hospitalizations or relapses , was assessed at 12 and 24 months of treatment . Acquisition costs of antipsychotic drug therapy were based on the official registered price . Drug prices from source were in € , year 2005 values ; hospital costs from source were in € , year 2001 values , and were inflated to reflect 2005 costs . Complete follow-up data were available for 788 patients at 12 months after starting long-acting injectable risperidone and for 757 patients at 24 months . Results In terms of effectiveness , at 12 months after switching to long-acting injectable risperidone , there was a higher percentage of patients who did not require hospitalization ( 89.1 % ) , did not relapse ( 85.4 % ) or neither required hospitalization nor relapsed ( 82.4 % ) as compared retrospectively with the same period for the previous treatment ( 67 % , 47.8 % and 59.8 % , respectively ) . The corresponding figures at 24 months also favoured treatment with long-acting injectable risperidone ( 85.2 % vs 60 % , 88.5 % vs 47.4 % and 77 % vs 53.6 % , respectively ) . Treatment with long-acting injectable risperidone was associated with higher medication costs per month compared with previous antipsychotic medication after 12 ( € 405.80 vs € 128.16 ) and 24 months ( € 407.33 vs € 142.77 ) of follow-up . Cost effectiveness per month per patient was lower for risperidone than previous antipsychotic medication in the three patient scenarios : without hospitalization ( € 539.82 vs € 982.13 ) , without relapse ( € 519.67 vs € 1242.03 ) and without hospitalization and without relapse ( € 597.22 vs € 1059.39 ) . Conclusions Treatment with long-acting injectable risperidone compared with previous antipsychotic medications result ed in a higher number of patients not requiring hospitalization , not relapsing , and not requiring hospitalization and not showing relapse , result ing in risperidone being more cost effective per month per patient . It is important to note that real-world variations in adherence would automatically be controlled from within a r and omized control trial , and hence , any evaluation of variations in adherence inevitably requires a real-world focus . On the basis of these findings , which were obtained in real-world clinical practice , long-acting injectable risperidone is predicted to be the dominant strategy because it results in effective symptom control and direct medical cost savings . However , because of limitations in methodology , any conclusions should , at this stage , be treated as tentative , and confirmation in more detailed follow-up studies is required . Cost-effectiveness comparisons based on experimental evaluations of relapse minimization strategies are also required . In order to avoid estimation biases in the future , a prospect ively design ed study is needed BACKGROUND Treatment adherence is a significant problem in patients with bipolar disorder . This study was design ed to determine the efficacy of risperidone long-acting injectable ( LAI ) in the maintenance treatment of bipolar I disorder . METHODS Eligible patients with current or recent manic or mixed episodes ( n = 559 , aged 18 - 65 years ) were treated with open-label oral risperidone for 3 weeks ( period II ) and open-label risperidone LAI for 26 weeks ( n = 501 ; period III ) . Patients who maintained response ( n = 303 ) were r and omly allocated 1:1 to placebo injections ( n = 149 ) or to continue risperidone LAI ( n = 154 ) for up to 24 months ( period IV ) . RESULTS Most ( 77 % ) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV . Time to recurrence for any mood episode ( primary outcome variable ) was significantly longer in the risperidone LAI group versus placebo ( p < .001 ) ; the difference was significant for time to recurrence of elevated-mood episode ( p < .001 ) but not time to recurrence of depressive episode ( p = .805 ) . Weight gains > or = 7 % ( compared with the period 's baseline ) occurred in 15 % of patients in period III ; in 12 % of patients on risperidone LAI and 3 % of patients on placebo in period IV . CONCLUSIONS Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes , versus placebo , in this controlled , r and omized study in patients with bipolar I disorder . Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI
Risperidone long-acting injectable was found to be effective in protecting from any mood/manic symptom compared to placebo , but not from depressive recurrences .
Add-on or monotherapy paliperidone palmitate in SAD patients  protected from psychotic , depressive , and manic symptoms .
In patients with BD-I with a manic episode at study enrolment , aripiprazole monohydrate significantly delayed time to recurrence of manic episodes without inducing depressive episodes .
LAIs  are effective and well-tolerated maintenance treatments for BD and SAD .
They showed better efficacy in preventing mania than depression .
LAIs may be first-line for BD-I and SAD patients with a manic predominant polarity and with non-adherence problems
Long-Acting Injectable Antipsychotics ( LAIs ) are used to overcome non-compliance in psychoses , mainly schizophrenia spectrum disorders .
We aim ed to summarize available evidence of studies comparing the efficacy of LAIs to placebo or oral medications for Bipolar Disorder ( BD ) and /or Schizoaffective Disorder ( SAD ) .