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 Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia. 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. Oral versus Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia and Special Populations at Risk for Treatment Nonadherence: A Systematic Review Risperidone Long-Acting Injectable Monotherapy in the Maintenance Treatment of Bipolar I Disorder Long-acting injectable vs oral risperidone for schizophrenia and co-occurring alcohol use disorder: a randomized trial. Switching Patients with Stable Schizophrenia or Schizoaffective Disorder from Olanzapine to Risperidone Long-Acting Injectable Long-acting injectable risperidone v. olanzapine tablets for schizophrenia or schizoaffective disorder. Randomised, controlled, open-label study. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. Psychotic spectrum disorders and alcohol abuse: a review of pharmacotherapeutic strategies and a report on the effectiveness of naltrexone and disulfiram. Functional recovery results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE). Long-term remission in schizophrenia and schizoaffective disorder: results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE) Efficacy and safety of long-acting risperidone in elderly patients with schizophrenia and schizoaffective disorder. Healthcare resource usage of schizophrenia patients initiating long-acting injectable antipsychotics vs oral Relapse Prevention in Schizophrenia and Schizoaffective Disorder with Risperidone Long-Acting Injectable vs Quetiapine: Results of a Long-Term, Open-Label, Randomized Clinical Trial Lack of impact of race on the efficacy and safety of long-acting risperidone versus placebo in patients with schizophrenia or schizoaffective disorder An 8-week, double-blind, randomized, placebo-controlled study of olanzapine long-acting injection in acutely ill patients with schizophrenia. A comparative study of paliperidone palmitate and risperidone long-acting injectable therapy in schizophrenia Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder Healthcare resource utilization during 1-year treatment with long-acting, injectable risperidone. Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory Rapid Tranquilization of Severely Agitated Patients With Schizophrenia Spectrum Disorders: A Naturalistic, Rater-Blinded, Randomized, Controlled Study With Oral Haloperidol, Risperidone, and Olanzapine
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 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 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 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 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 OBJECTIVE Alcohol use disorders worsen the course of schizophrenia . Although the atypical antipsychotic clozapine appears to decrease alcohol use in schizophrenia , risperidone does not . We have proposed that risperidone 's relatively potent dopamine D2 receptor blockade may partly underlie its lack of effect on alcohol use . Since long-acting injectable ( LAI ) risperidone both results in lower average steady-state plasma concentrations than oral risperidone ( with lower D2 receptor occupancy ) and encourages adherence , it may be more likely to decrease heavy alcohol use ( days per week of drinking 5 or more drinks per day ) than oral risperidone . METHOD Ninety-five patients with DSM-IV-TR diagnoses of schizophrenia and alcohol use disorder were r and omized to 6 months of oral or LAI risperidone between 2005 and 2008 . Explanatory ( efficacy ) analyses were carried out to evaluate the potential benefits of LAI under suitably controlled conditions ( in contrast to real-world setting s ) , with intent-to-treat analyses being secondary . RESULTS Explanatory analyses showed that heavy drinking in the oral group worsened over time ( P = .024 ) and that there was a statistical trend toward significance in the difference between the changes in heavy drinking days in the oral and LAI groups ( P = .054 ) . Furthermore , the 2 groups differed in the mean number of drinking days per week ( P = .035 ) . The intent-to-treat analyses showed no difference in heavy drinking but did show a difference in average drinking days per week similar to that obtained from the explanatory analyses ( P = .018 ) . Neither explanatory nor intent-to-treat analyses showed any between-group differences in alcohol use as measured by intensity or the Alcohol Use Scale . The plasma concentrations of the active metabolite 9-hydroxyrisperidone were significantly lower in patients taking LAI ( P < .05 ) , despite their significantly ( overall ) better treatment adherence ( P < .005 ) . CONCLUSION For the population considered here , schizophrenia patients with alcohol use disorder appear to continue drinking some alcohol while taking either form of risperidone . Nonetheless , our data suggest that injectable risperidone may be a better choice than the oral form for these dual diagnosis patients . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00130923 Abstract Background : Patients with schizophrenia or related disorders often switch antipsychotic therapy , most commonly due to lack of efficacy and side effects . The differences in anticipated efficacy and tolerability among atypical antipsychotics may drive switching behaviours . Switching to long-acting antipsychotics may improve adherence . Improving adherence is essential as relatively short medication gaps significantly increase the risk of schizophrenia hospitalizations . Long-term treatment with risperidone long-acting injectable ( RLAI ) , the first available long-acting atypical antipsychotic , versus oral atypical antipsychotics showed better adherence with RLAI .  Stable patients with schizophrenia or related disorders treated with a stable dose of antipsychotic showed improved efficacy when switched to flexible doses of RLAI . The most common reason for patients to switch from olanzapine to another antipsychotic is excessive weight gain . Metabolic dysfunction also occurs more commonly with olanzapine than with risperidone . Patients switching from olanzapine to risperidone experienced significant decreases in body weight , body mass index and triglyceride levels , whereas patients switching from risperidone to olanzapine experienced significant increases in body weight and triglyceride levels . The efficacy , tolerability and safety of RLAI in non-acute patients with schizophrenia or schizoaffective disorder previously treated with oral olanzapine  needs to be explored . Objective : The objective of this study was to evaluate the efficacy , tolerability and safety of switching from oral olanzapine to RLAI . Methods : This was a six-month , prospect i ve , multicentre , non-r and omized , single-arm , open-label trial . The trial evaluated non-acute adult patients with psychotic disorders treated with a stable olanzapine dose who required a treatment change . Three weeks after RLAI initiation , olanzapine was tapered off over 1 week or 3 weeks . Efficacy and safety measures included the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression-Severity ( CGI-S ) , Global Assessment of Functioning ( GAF ) and treatment-emergent adverse events ( TEAEs ) . Results : Among 96 patients analysed , significant endpoint efficacy changes versus baseline were observed for PANSS , CGI-S and GAF ( all p < 0.0001 ) . PANSS total score improvement was ≥20 % for 65.6 % of patients and ≥50 % for 31.3 % . TEAEs were similar in the 1- and 3-week taper groups ( 40.0 % and 46.5 % , respectively ) . TEAEs were generally mild ( 34.5 % ) or moderate ( 49.0 % ) in intensity . Conclusion : Switching non-acute patients with schizophrenia or schizoaffective disorder requiring a treatment change from a stable dose of oral olanzapine to RLAI improved psychiatric symptom control , functioning and patient treatment satisfaction . RLAI was generally well tolerated 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 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 . ) The rate of substance-use disorders in patients with mental illnesses within the psychotic spectrum , such as schizophrenia , schizoaffective disorder , and bipolar disorder , is higher than the rate observed in the general population and is associated with significant morbidity and mortality . Although there are currently 3 medications approved by the Food and Drug Administration for the treatment of alcohol dependence , no medications have been approved for the specific treatment of dually diagnosed patients . A small but growing body of literature supports the use of 2 of these medications , disulfiram and naltrexone , in dually diagnosed individuals . This article outlines a review of the literature about the use of disulfiram and naltrexone for alcoholism and in patients with comorbid mental illness . In addition , results are presented of a 12-week r and omized clinical trial of disulfiram and naltrexone alone and in combination for individuals with Axis I disorders and alcohol dependence who were also receiving intensive psychosocial treatment . Individuals with a psychotic spectrum disorder , including schizophrenia , schizoaffective disorder , and bipolar disorder , had worse alcohol outcomes than those without a psychotic spectrum disorder . Individuals with a psychotic spectrum disorder had better alcohol-use outcomes on an active medication compared with placebo , but there was no clear advantage of disulfiram or naltrexone or of the combination .  Retention rates and medication compliance in the study were high and exceeded 80 % . Pharmacotherapeutic strategies should take into account the advantages and disadvantages of each medication . Future directions of pharmacotherapeutic options are also discussed OBJECTIVE ConstaTRE is an open-label , r and omised , controlled , relapse prevention trial in patients with stable schizophrenia or schizoaffective disorder switched to risperidone long-acting injectable ( RLAI ) or oral quetiapine , and was design ed to test the hypothesis that injectable antipsychotic treatment with risperidone would be more effective than oral therapy with quetiapine . Here we report the functional recovery results from the ConstaTRE trial . METHODS Clinical ly stable adults previously treated with oral risperidone , olanzapine , or oral first-generation antipsychotics were r and omised to RLAI or quetiapine for 24 months . Functional recovery was assessed using the Social and Occupational Functioning Assessment Scale ( SOFAS ) and two quality -of-life ( QoL ) measures [ Medical Outcomes Survey Short Form-12 ( SF-12 ) and Schizophrenia Quality -of-Life Scale Revision 4 ( SQLS-R4 ) ] . RESULTS A total of 666 patients were r and omised and treated with RLAI ( n = 329 ) or quetiapine ( n = 337 ) . Relapse occurred in 16.5 % RLAI and 31.3 % quetiapine patients . Significant improvements in SOFAS , SF-12 , and SQLS-R4 scores were observed from baseline to month 24 with both RLAI and quetiapine . At months 6 , and 12 , and endpoint , improvement in SOFAS score was significantly greater for RLAI than quetiapine ( p < 0.05 ) . CONCLUSIONS Among patients with stable schizophrenia or schizoaffective disorder , the likelihood of functional recovery appears to be higher in those switching to RLAI than to quetiapine , although improvements in functional status and QoL were observed with both treatments Objective : The objective of this study was to report the long-term remission results from the ConstaTRE relapse prevention trial , in which clinical ly stable adults with schizophrenia or schizoaffective disorder treated with oral risperidone , olanzapine , or oral conventional antipsychotics  were r and omized to risperidone long-acting injectable ( RLAI ) or oral quetiapine , dosed according to package-insert recommendations . Methods : In the ConstaTRE trial , efficacy and tolerability were recorded for up to 24 months . This post hoc analysis presents remission data , defined , according to the Schizophrenia Working Group criteria , as achieving and maintaining eight core symptoms of schizophrenia that are mild or less over 6 months . Additional secondary outcome measures are also presented . Results : A total of 710 patients were r and omized to RLAI ( n = 355 ) or quetiapine ( n = 355 ) . Mean mode ± st and ard deviation ( SD ) drug doses were RLAI 33 ± 10 mg every 2 weeks and quetiapine 413 ± 159 mg daily . Full remission was achieved by 51.1 % of patients with RLAI and 39.3 % with quetiapine ( p = 0.003 ) . Mean ± SD of full remission duration s were not significantly different with RLAI ( 540 ± 181 days ) and quetiapine ( 508 ± 188 days ) . Overall tolerability was similar between treatment groups . Conclusions : Among stable patients with schizophrenia or schizoaffective disorder  , remission was more likely after switching to RLAI than quetiapine BACKGROUND Elderly patients are often an underserved population in terms of optimizing treatment outcomes . Long-acting risperidone , the first long-acting injectable atypical antipsychotic , can improve outcomes through continuous medication delivery . OBJECTIVE To assess the efficacy and safety of long-acting injectable risperidone in elderly patients with psychotic disorders . METHODS This is a sub analysis of 57 patients aged > or = 65 years enrolled in an open-label study of long-acting risperidone that included 725 symptomatically stable patients with schizophrenia or schizoaffective disorder . Patients were assigned to receive 25 , 50 , or 75 mg of long-acting risperidone every 2 weeks for up to 50 weeks . RESULTS Fifty-seven elderly patients ( mean + /- SE age , 70.9 + /- 0.7 years ) were enrolled . Mean Positive and Negative Syndrome Scale ( PANSS ) total scores improved significantly throughout the study and at endpoint ( p < 0.001 ) . The PANSS factor scores ( positive symptoms , negative symptoms , disorganized thoughts , uncontrolled hostility/excitement , and anxiety/depression ) also significantly improved ( p < 0.01 ) . Clinical improvement ( > or = 20 % reduction in PANSS total scores ) was achieved by 49 % of these stable patients , and 55 % improved on the Clinical Global Impressions scale . Severity of movement disorders ( Extrapyramidal Symptom Rating Scale scores ) was reduced significantly . Adverse events reported in > 10 % of patients were insomnia ( 14 % ) , constipation ( 12 % ) , and bronchitis ( 12 % ) . CONCLUSIONS Long-acting risperidone was associated with significant symptom improvements in stable elderly patients with schizophrenia or schizoaffective disorder . Treatment was well tolerated 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 Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse . An open-label , r and omized , active-controlled , 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone , olanzapine , or conventional neuroleptics to risperidone long-acting injectable ( RLAI ) or oral quetiapine .  Primary effectiveness evaluation was time-to-relapse . Safety evaluations included adverse events ( AEs ) reported for the duration of the study , Extrapyramidal Symptom Rating Scale ( ESRS ) , clinical laboratory tests , and vital signs . A total of 666 patients ( n=329 RLAI , n=337 quetiapine )  were evaluable for effectiveness measures . Baseline demographics were similar between treatment groups . Kaplan – Meier estimate of time-to-relapse was significantly longer with RLAI ( p<0.0001 ) . Relapse occurred in 16.5 % of patients with RLAI and 31.3 % with quetiapine . RLAI and quetiapine were both safe and well tolerated . Weight gain affected 7 % of patients with RLAI and 6 % with quetiapine , with mean end point increases of 1.25±6.61 and 0±6.55 kg , respectively . There were no significant between-group differences in weight gain . ESRS total scores decreased similarly after r and omization to either RLAI or quetiapine . Extrapyramidal AEs occurred in 10 % of patients with RLAI and 6 % with quetiapine . Treatment-emergent potentially prolactin-related AEs were reported in 15 ( 5 % ) patients with RLAI and 5 ( 2 % ) patients with quetiapine ; hyperprolactinemia was reported in 43 ( 13.1 % ) patients with RLAI and 5 ( 1.5 % ) patients with quetiapine . Somnolence occurred in 2 % of patients with RLAI and 11 % with quetiapine . To our knowledge , this is the first report of a r and omized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy . Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients r and omized to RLAI compared with those r and omized to oral quetiapine . Both antipsychotics were generally well tolerated This analysis aim ed to assess the relationship between race and clinical response to long-acting , injectable risperidone treatment in patients with schizophrenia or schizoaffective disorder . In a 12-week , r and omized , double-blind study , patients with schizophrenia or schizoaffective disorder received placebo or long-acting risperidone ( 25 , 50 or 75 mg every 2 weeks ) . Data were stratified by race as identified by demographic information : Caucasian , African-American or Other .  Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale ( PANSS ) ; movement disorders by the Extrapyramidal Symptom Rating Scale ( ESRS ) ; adverse events ( AEs ) were reported spontaneously . Data were available for 439 patients : 193 Caucasian ( 44 % ) , 174 ( 40 % ) African-American and 72 ( 16 % ) Other patients . Baseline characteristics were similar between racial groups , as were study completion rates ( overall : 30 % placebo ; 48 % long-acting risperidone ) . There was a significant effect of treatment ( P<0.001 ) , but not of race , on improvement in PANSS total scores from baseline to endpoint . ESRS scores were low throughout the study , and no significant impact of race was observed . Overall rates of AEs were similar among the racial groups . Race did not appear to impact the efficacy and tolerability of long-acting risperidone OBJECTIVE To examine the efficacy and tolerability of a new injectable formulation of olanzapine , olanzapine long-acting injection ( LAI ) , relative to placebo for treatment of acutely ill patients with schizophrenia . METHOD Patients with DSM-IV or DSM-IV-TR schizophrenia in this 8-week , double-blind study were r and omly assigned to receive 210 mg/2 weeks , 300 mg/2 weeks , or 405 mg/4 weeks of olanzapine LAI or placebo/2 weeks . No oral antipsychotic supplementation was permitted . The primary efficacy measure was mean baseline-to-end point change in Positive and Negative Syndrome Scale ( PANSS ) total score . The study was conducted from June 2004 to April 2005 . RESULTS Mean baseline-to-end point decreases in PANSS total scores were significantly greater for all olanzapine LAI regimens relative to placebo ( all p values < .001 ) . The 300 mg/2 weeks and 405 mg/4 weeks olanzapine LAI groups separated from placebo on the PANSS total at 3 days after starting treatment , and all olanzapine LAI groups separated from placebo by 7 days . Rates of clinical improvement ( end point Clinical Global Impressions-Improvement scale score < or= 3 ) were significantly higher for all olanzapine LAI groups relative to placebo ( p < .001 ) . Incidences of sedation and increased appetite were significantly higher for 300 mg/2 weeks olanzapine LAI relative to placebo ( p < .05 ) . Mean weight gain ( 3.2 - 4.8 vs. 0.3 kg , p < .001 ) and incidence of weight gain > or= 7 % of baseline ( 23.6 - 35.4 % vs. 12.4 % , p < or= .046 ) were significantly greater for olanzapine LAI relative to placebo . Significant differences between all olanzapine LAI groups and placebo were observed regarding mean baseline-to-end point changes in fasting total cholesterol ( 5.5 - 10.4 vs. -7.0 mg/dL ; p < or= .015 ) and between the 210 mg/2 weeks and 405 mg/4 weeks groups ( 26.3 - 30.3 vs. -9.4 mg/dL ; p < or= .016 ) , but not the 300 mg/2 weeks group ( 17.6 mg/dL ; p = .055 ) , and placebo for fasting triglycerides . CONCLUSIONS In this 8-week study , olanzapine LAI administered at 2- or 4-week injection intervals was significantly more efficacious than placebo for the treatment of acutely ill patients with schizophrenia despite no use of supplemental oral antipsychotics . Consistent with changes previously observed with oral olanzapine , clinical ly significant weight gain and changes in some lipid parameters were observed in patients treated with olanzapine LAI This open-label , rater-blinded , parallel-group study was design ed to evaluate noninferiority of paliperidone palmitate ( PP ) , a once-monthly injectable atypical antipsychotic , to once-biweekly risperidone long-acting injectable ( RIS-LAI ) in adult Chinese patients with acute schizophrenia . Eligible Chinese adults ( N=452 ) with schizophrenia were r and omized ( 1:1 ) to either PP  ( N=229 ; deltoid injections on day 1 [ 150 mg eq. ] and day 8 [ 100 mg eq. ] ; then once-monthly deltoid or gluteal injections , flexibly dosed [ 50 , 100 , or 150 mg eq. ] ) , or RIS-LAI ( N=223 ; once-biweekly gluteal injections , flexibly dosed [ 25 , 37.5 or 50 mg ] ) .  RIS-LAI-treated  patients received oral risperidone supplementation ( 1 - 6 mg/day ) at initiation and with RIS-LAI dose increases . Mean ( SD ) Positive and Negative Syndrome Scale ( PANSS ) total score at baseline was 83.2 ( 12.44 ) . Mean ( SD ) change from baseline to endpoint in PANSS total scores ( primary efficacy measure ) was : -23.6 ( 16.28 ) for PP group and -26.9 ( 15.43 ) for RIS-LAI group . PP was noninferior to RIS-LAI ( least squares mean difference [ 95 % CI ] : -2.3 [ -5.20 ; 0.63 ] ; predetermined non-inferiority margin : -5.5 ) . Mean ( SD ) change from baseline to endpoint in Clinical Global Impression-Severity scale score was : -1.5 ( 1.24 ; PP group ) , -1.7 ( 1.16 ; RIS-LAI group ) and in Personal and Social Performance Scale scores was : 16.8 ( 14.76 ; PP group ) , 18.6 ( 13.92 ; RIS-LAI group ) . The incidence of treatment-emergent adverse events ( TEAEs ) was similar between the two groups ( 73 % [ PP ] ; 75 % [ RIS-LAI ] ) . The most common TEAEs were akathisia , tremor , and insomnia . The study demonstrated the noninferiority of PP ( 50 - 150 mg eq. , flexibly dosed , without oral paliperidone supplementation ) to risperidone-LAI ( 25 - 50 mg , flexibly dosed , with oral risperidone supplementation ) for the treatment of acute schizophrenia in adult Chinese patients . PP injections were generally tolerable , and no new safety signals were detected in this population Rationale Due to the episodic and chronic nature of bipolar disorder ( BD ) , maintenance therapy represents a critical part of treatment ; however , there is a paucity of studies comparing effectiveness of available long-term treatments . Objective The aim of this study is to determine and compare the efficacy of pharmacological treatments for maintenance treatment of BD by means of the number needed to treat ( NNT ) . Methods The efficacy of drugs used for maintenance treatment of BD , as emerging from the results of r and omized controlled trials , was assessed using the size effect measure of NNT . PubMed search es were conducted on English- language articles published until May 2010 using the search terms “ bipolar disorder , ” “ mania , ” “ mixed episode , ” or “ bipolar depression , ” cross-referenced with trial characteristic search phrases and generic names of medications . The search was supplemented by manually review ing reference lists from identified publications . Results In 15 studies , aripiprazole , olanzapine , quetiapine , risperidone long-acting injection , lithium , lamotrigine , and divalproex proved effectiveness in terms of NNTs ( ≥10 % advantage over placebo ) for prevention of relapse into any mood episode . Quetiapine , lithium , risperidone long-acting injection , aripiprazole , and olanzapine are effective in manic recurrence prevention .  Lamotrigine , quetiapine , and lithium present significant NNTs for prevention of depressive relapses . Conclusions All of the pharmacological agents assessed were effective in the prevention of any kind of mood episode ; however , different efficacy profiles were found for prevention of manic and /or depressive relapses . The comparison of NNT values of the available agents may represent a useful tool in clinical setting s , in order to facilitate implementation of long-term pharmacological interventions in patients with BD BACKGROUND Schizophrenia is associated with disproportionately high costs , mainly due to hospitalization rates . This study assessed healthcare re source use in patients with schizophrenia and schizoaffective disorder during treatment with long-acting risperidone .  METHODS Patients ( n = 397 [ in patients , 24 % ; out patients , 76 % ] ) receiving stable doses of an antipsychotic for > or=4 weeks were eligible to enter this 1-year , open-label study . Following a 2-week run-in period ( oral risperidone 1 - 6 mg/day ) , patients received intramuscular long-acting risperidone ( 25 or 50 mg modal dose ) every 2 weeks . Healthcare re source use in the previous 12 weeks was assessed at baseline and 12-weekly intervals . RESULTS Patients needing hospitalization decreased significantly and continuously from 38 % during the 12 weeks before study entry to 12 % during the last 12 weeks . Mean hospitalization length during the study was 30.5 days ( out patients , 4.9 days ; in patients , 110 days ) . This included 28 patients ( 7 % ) who remained in hospital throughout the study . During treatment , 71 % of those hospitalized at baseline were discharged . Partial hospitalization decreased significantly from 7 % of patients during the 12 weeks before treatment to 3 % during the last 12 weeks . Outpatient consultations also decreased significantly from 70 % of patients to 30 % in the first 12 weeks of treatment and remained stable thereafter . Only 9 % of patients required an emergency room visit ; mostly for non-psychiatric conditions . CONCLUSION Healthcare re source use is significantly reduced in patients with stable schizophrenia or schizoaffective disorder receiving long-acting  risperidone . It is highly likely that these reductions will decrease healthcare costs in patients receiving long-acting risperidone CONTEXT Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia ( SZ ) have a dysregulated trajectory of frontal lobe myelination . Prior MRI studies suggested that early in treatment of SZ , antipsychotic medications initially increase frontal lobe white matter ( WM ) volume , which subsequently declines prematurely in chronic stages of the disease . Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence , it may be modifiable by long acting injection ( LAI ) formulations . OBJECTIVES Examine the impact of antipsychotic formulation on the myelination trajectory during a r and omized six-month trial of LAI risperidone ( RLAI ) versus oral risperidone ( RisO ) in first-episode SZ subjects . DESIGN Two groups of SZ subjects ( RLAI , N=11 ; and RisO , N=13 ) that were matched in pre-r and omization oral medication exposure and 14 healthy controls ( HCs ) were prospect ively examined . Frontal lobe WM volume was estimated using inversion recovery ( IR ) MRI images . A brief neuropsychological battery that focused on reaction times was performed at the end of the study . MAIN OUTCOME MEASURE WM volume change scores . RESULTS WM volume remained stable in the RLAI and decreased significantly in the RisO groups result ing in a significant differential treatment effect , while the HC had a WM change intermediate and not significantly different from the two SZ groups . WM increase was associated with faster reaction times in tests involving frontal lobe function . CONCLUSIONS The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance . Better adherence provided by LAI may underlie the modified trajectory of myelin development . In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions Introduction Agitation is a major problem in acute schizophrenia . Only a few studies have tested antipsychotic agents in severely agitated patients , mainly because of legal issues . Furthermore , most studies were limited to the first 24 hours . We aim ed to investigate the efficacy of oral haloperidol , risperidone , and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospect i ve , r and omized , rater-blinded , controlled design within a naturalistic treatment regimen . Methods In total , 43 severely agitated patients at acute care psychiatric units were enrolled . Participants were r and omly assigned to receive either daily haloperidol 15 mg , olanzapine 20 mg , or risperidone 2 to 6 mg over 5 days . Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable . A mixed-model analysis was applied . Results All drugs were effective for rapid tranquilization within 2 hours . Over 5 days , the course differed between agents ( P < 0.001 ) , but none was superior . Dropouts occurred only in the risperidone and olanzapine groups . Men responded better to treatment than did women during the initial 2 hours ( P = 0.046 ) as well as over the 5-day course ( P < 0.001 ) . No difference between drug groups was observed regarding diazepam or biperiden use . Conclusions Oral haloperidol , risperidone , and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders . Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study
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 ) .