Risperidone Long-acting Injection Research Articles

P03-61 - Antipsychotic injectable treatment in patients with involuntary ambulatory treatment

IntroductionInvoluntary Ambulatory Treatment (IAT) is a judicial measure existing in Spain. Its aim is to ensure the adherence to treatment of seriously ill patients, with poor insight and repeated hospitalization. This is done by means of the regular and involuntary administration of antipsychotic intramuscular medication.ObjectivesTo assess the treatment used in patients undergoing IAT in a local clinic, to assess the type of medicaments and their dosage and to verify adherence to treatment and evolution.Material and methodA revision was made of the clinical backgrounds of all the patients of a psychiatric outpatient clinic who have been submitted to IAT (n = 37). A note was made of socio-demographic variables as well as psychiatric diagnoses according to DSM-IV-TR criteria and the number of hospitalizations and treatments used.ResultsAll but one patient had been hospitalized and average of 3.53 times before IAT. Since undergoing IAT only 6 patients have been admitted (16%). Four of them relapsed having abandoned treatment.In seven cases (19%) the patients gained insight and the antipsychotic treatment was changed from injectable to oral treatment at the patients’ request. In these cases IAT was ceased.The antipsychotic prescribed in 59% of the cases was Long-Acting Injectable Risperidone. This percentage was higher in non- schizophrenic patients (84%).ConclusionsIn our environment IAT could be an effective tool for severe patients with nil insight, since it can bring about an improvement in treatment adherence and evolution, as well as insight.

P03-52 - Antipsychotic and anticholinergic drug prescribing pattern in psychiatry:Implications for evidence - based practice

ObjectivesTo determine the antipsychotic prescribing pattern and the prevalence of concurrent anticholinergic prescribing for patients with psychotic disorders.MethodsA retrospective audit of prescriptions issued for outpatients at the Psychiatric Hospital in Bahrain.ResultsAntipsychotic monotherapy was prescribed for 89.2% patients, whereas polytherapy with two- and three- drugs in 10.4 and 0.4%, respectively. Atypical antipsychotics were prescribed more often (67.7%) than typical antipsychotics. Risperidone and haloperidol were the most frequently prescribed antipsychotics. Majority of the study population (93.2%) were prescribed an oral antipsychotic, whereas 3.1% each were on depot preparation or on depot plus an oral antipsychotic. Long-acting risperidone injection was the only depot preparation prescribed. The mean antipsychotic dose expressed as chlorpromazine equivalents (CPZeq; mg/day) was 242 (220 for monotherapy and 414 for polytherapy). The prevalence of high dose antipsychotic (mean CPZeq>1000 mg/day) was 1.8%, prescribed at a mean CPZeq dose of 1531 (1925 for monotherapy and 1137 for polytherapy) mainly attributed to haloperidol. Anticholinergics were co-prescribed for almost two third of patients receiving antipsychotics, particularly for those on polytherapy (monotherapy 57.3%; polytherapy 87.5%). Antipsychotic polytherapy, high dose of antipsychotics and co-prescription of an oral with a depot antipsychotic preparation were strongly associated with concurrent prescription of anticholinergics. Procyclidine and orphenadrine were the most often prescribed anticholinergics.ConclusionAntipsychotic monotherapy is the common practice for outpatients with psychotic disorders. Some of the antipsychotic polytherapies, dosage strategies, and high prevalence of anticholinergic use are therapeutic issues that need to be addressed to foster evidence-based prescribing practice.

A comparative study of paliperidone palmitate and risperidone long-acting injectable therapy in schizophrenia

This open-label, rater-blinded, parallel-group study was designed 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 randomized (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.

Are the Long-Acting Intramuscular Formulations of Risperidone or Paliperidone Palmitate Associated with Post-Injection Delirium/Sedation Syndrome? An Assessment of Safety Databases

Long-acting injectable (LAI) formulations of antipsychotics are valuable treatment alternatives for patients with psychotic disorders, and understanding their safe use is critical. Post-injection delirium/sedation syndrome (PDSS) has been reported following treatment with one atypical antipsychotic LAI. Clinical databases of risperidone LAI and paliperidone palmitate were explored to identify if cases of PDSS had been observed.No cases of PDSS were identified in 15 completed trials of 3,164 subjects (approximately 115,000 injections) or the postmarketing safety database of risperidone LAI. Only one case of PDSS was identified among 10 completed trials (3,817 subjects, 33,906 injections) of paliperidone palmitate—that case having been reported in a patient randomized to treatment with placebo. Examination of these prospective databases finds no evidence that risperidone LAI and paliperidone palmitate are associated with PDSS and suggest that findings seen with another antipsychotic LAI are not generalizable.

A Case of Relapsing Priapism Associated With Long-Acting Injectable Risperidone

To the Editor: Priapism is a well-documented side effect of antipsychotic medications, including the atypical antipsychotic risperidone.1 Wang et al2 report a case involving a patient taking the long-acting injectable form of risperidone (Risperdal Consta, Janssen Pharmaceutica). In that case, the patient developed a series of prolonged, self-resolving erections of less than 5 hours' duration following the first injection. This was followed by 2 episodes of frank priapism requiring emergency treatment. The authors did not emphasize the challenges of treating relapsing priapism that resolves only after the drug has been cleared from the system. We present a second report of relapsing priapism following administration of long-acting injectable risperidone and draw special attention to the difficulties of recurrent treatment. Case report. Mr A, a 49-year-old man, presented in March 2006 to our emergency department with priapism that had persisted for the previous 16 hours. His history was significant for paranoid schizophrenia, which had initially been treated with fluphenazine 37.5 mg/d orally. Because of lack of compliance, he was switched to long-acting injectable risperidone every 2 weeks. He had a remote history of alcohol, cocaine, and marijuana abuse but denied ingestion of any illicit drugs or alcohol concurrent with the use of antipsychotic medications. A toxicology screen was negative. Mr A developed priapism 1 week after his third injection of risperidone. The patient was on no medications other than risperidone at the time he developed priapism. Blood aspirated from the corpora cavernosa of the erect penis was dark and thus consistent with ischemic priapism. The patient was treated with aspiration of blood from the corpora cavernosa followed by irrigation with dilute phenylephrine solution with resultant complete detumescence. The patient returned to the emergency department an additional 3 times with relapsing priapism over the next 7 days. Each episode of priapism rapidly and completely responded to phenylephrine injections of the corpora. Mr A was switched back to oral fluphenazine and experienced no further episodes of priapism over the subsequent 18 months. He was subsequently lost to follow-up. Although numerous cases of risperidone-related priapism have been reported,2 little attention has been drawn to relapsing priapism caused by the long-acting injectable form. Clinicians and patients should be aware that such priapism may return even after repeated pharmacologic treatments because of the drug's sustained release, and appropriate plans should be made for follow-up. Presumably, the risk of relapse decreases over a several-week period of time as the risperidone is excreted from the body. This case also illustrates the broader point that long-acting antipsychotics can have a variety of long-lasting adverse effects, including more persistent forms of neuroleptic malignant syndrome and acute dystonic reactions.3 These risks, however, must be weighed against the added convenience that long-acting injectable antipsychotics may offer patients.4

Hospital Resource Use by Patients with Schizophrenia: Reduction after Conversion from Oral Treatment to Risperidone Long-Acting Injection

The chronic relapsing nature of schizophrenia is associated with significant resource use. The William Osler Health System, Brampton Civic Hospital site, in Brampton, Ontario, provides comprehensive in-patient and outpatient mental health services to the community it serves, including patients with schizophrenia. The clinical benefits observed in patients with schizophrenia treated through the injection clinic led the hospital to evaluate the costs, resource use and potential savings associated with injectable compared with oral therapy. The substantial savings accruing to the hospital and the healthcare system provide a strong economic rationale for injectable therapy as an alternative level of care for patients with schizophrenia.

Comparisons of methamphetamine psychotic and schizophrenic symptoms: A differential item functioning analysis

The concept of negative symptoms in methamphetamine (MA) psychosis (e.g., poverty of speech, flatten affect, and loss of drive) is still uncertain. This study aimed to use differential item functioning (DIF) statistical techniques to differentiate the severity of psychotic symptoms between MA psychotic and schizophrenic patients. Data of MA psychotic and schizophrenic patients were those of the participants in the WHO Multi-Site Project on Methamphetamine-Induced Psychosis (or WHO-MAIP study) and the Risperidone Long-Acting Injection in Thai Schizophrenic Patients (or RLAI-Thai study), respectively. To confirm the unidimensionality of psychotic syndromes, we applied the exploratory and confirmatory factor analyses (EFA and CFA) on the eight items of Manchester scale. We conducted the DIF analysis of psychotic symptoms observed in both groups by using nonparametric kernel-smoothing techniques of item response theory. A DIF composite index of 0.30 or greater indicated the difference of symptom severity. The analyses included the data of 168 MA psychotic participants and the baseline data of 169 schizophrenic patients. For both data sets, the EFA and CFA suggested a three-factor model of the psychotic symptoms, including negative syndrome (poverty of speech, psychomotor retardation and flatten/incongruous affect), positive syndrome (delusions, hallucinations and incoherent speech) and anxiety/depression syndrome (anxiety and depression). The DIF composite indexes comparing the severity differences of all eight psychotic symptoms were lower than 0.3. The results suggest that, at the same level of syndrome severity (i.e., negative, positive, and anxiety/depression syndromes), the severity of psychotic symptoms, including the negative ones, observed in MA psychotic and schizophrenic patients are almost the same.

Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia

The introduction of antipsychotic medication has been a major advance in the treatment of schizophrenia and allows millions of people to live outside of institutions. It is generally believed that long-acting intramuscular antipsychotic medication is the most effective approach to increasing medication adherence and thereby reduce relapse in high-risk patients with schizophrenia, but the data are scant. To report the design of a study to assess the effect of long-acting injectable risperidone in unstable patients and under more realistic conditions than previously studied and to evaluate the effect of this medication on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs. The trial was an open randomized clinical comparative effectiveness trial in patients with schizophrenia or schizo-affective disorders in which parenteral risperidone was compared to an oral antipsychotic regimen selected by each control patient's psychiatrist. Participants had unstable psychiatric disease defined by recent hospitalization or exhibition of unusual need for psychiatric services. The primary endpoint was hospitalization for psychiatric indications; the secondary endpoint was psychiatric symptoms. Overall, 382 patients were randomized. Determination of a persons' competency to understand the elements of informed consent was addressed. The use of a closed-circuit TV interview for psychosocial measures provided an economical, high quality, reliable means of collecting data. A unique method for insuring that usual care was optimal was incorporated in the follow-up of all subjects. Patients with schizophrenia or schizo-affective disorders and with the common co-morbid illnesses seen in the VA are a challenging group of subjects to study in long-term trials. Some techniques unique in the VA and found useful may not be generalizable or applicable in other research or treatment settings. The trial tested a new antipsychotic medication early in its adoption in the Veterans Health Administration. The VA has a unique electronic medical record and database which can be used to identify the endpoint, that is, first hospitalization due to a psychiatric problem, with complete ascertainment. Several methodologic solutions addressed competency to understand elements of consent, the costs and reliability of collecting interview data gathering, and insuring usual care.

Table of Contents

AbstractDHA Supplements During Pregnancy for Postpartum Depression Not EffectiveDextromethorphan Plus Quinidine to Be Approved for Pseudobulbar AffectEffects of Duloxetine on Antipsychotic Drug ConcentrationsDHA Supplementation Fails to Slow DementiaFDA Proposes Plan to Reduce Opioid AbuseRisperidone LAI for Schizophrenia Relapse PreventionAntidepressant Efficacy for MDD and Comorbid Axis III DisordersResidual Effects of Zolpidem on Next‐Day DrivingRisperidone Long‐Acting Injection in Huntington's DiseaseNovember 2010 Safety Labeling ChangesNew Approvals

Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia

Background:Long-acting injectable antipsychotics may improve medication adherence, thereby improving overall treatment effectiveness. This study aimed to evaluate the effectiveness, safety, and tolerability of risperidone long-acting injection in schizophrenic patients switched from oral antipsychotic medication.Methods:In a 12-month, multicenter, open-label, noncomparative study, symptomatically stable patients on oral antipsychotic medication with poor treatment adherence during the previous 12 months received intramuscular injections of risperidone long-acting injection (25 mg starting dose) every 2 weeks. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score.Results:Of the 60 patients who were screened, 53 received at least one injection (safety population), and 51 provided at least one postbaseline assessment. Mean PANSS total scores improved significantly throughout the study and at endpoint. Significant improvements were also observed in Clinical Global Impression of Severity, Personal and Social Performance, and Drug Attitude Inventory scales. Risperidone long-acting injection was safe and well-tolerated. Severity of movement disorders on the Extrapyramidal Symptom Rating Scale was reduced significantly. The most frequently reported adverse events were insomnia (22.6%), increased prolactin (17.0%), and weight gain (13.2%).Conclusion:Risperidone long-acting injection was associated with significant symptomatic improvements in stable patients with schizophrenia following a switch from previous antipsychotic medications.

Risperidone long-acting injection: safety and efficacy in elderly patients with schizophrenia.

Antipsychotic medication is considered the cornerstone of the treatment in elderly patients with schizophrenia. Long acting risperidone injection was the first antipsychotic available for use in this group of patients. Current scientific literature revealed that long-acting risperidone is effective in treating the positive and negative symptoms of schizophrenia and some improvements in cognition and functioning have also been found. In terms of efficacy, there is a paucity of randomized trials but the studies suggest that long-acting risperidone is efficient in the long-term management of schizophrenia, with a safety profile similar to that of oral risperidone. It seems that patient acceptance of treatment is greater when patients are switched from a traditional oral medication to depot risperidone and some improvements in cognition and functioning might be related. Further long-term comparisons with other oral and long-acting antipsychotic medications are needed. These studies should include cost-effectiveness data. Research into metabolic side effects is also needed.

Six Months Course of Risperidone Long-acting Injection in the Academic Medical Center: A clinical investigation of 57 cases of chronic schizophrenia and schizoaffective disorder outpatients

Six Months Course of Risperidone Long-acting Injection in the Academic Medical Center: A clinical investigation of 57 cases of chronic schizophrenia and schizoaffective disorder outpatients

Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America

BackgroundRisperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America.MethodsData were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered.ResultsPatients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores.ConclusionsRLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.

A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia

This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or 100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25mg), days 36, 50 (25 or 37.5mg) and days 64, 78 (25, 37.5 or 50mg). RIS-LAI-treated patients received oral supplementation with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n=1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (-18.6 [15.45]) and RIS-LAI (-17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [-1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings.

Explicit review of risperidone long-acting injection prescribing practice

Long-acting injectable (LAI) antipsychotics are recommended for those people with a preference for this form of treatment and those who experience negative outcomes due to non-adherence with oral medication. LAI antipsychotics have been associated with improved outcomes and lower treatment discontinuation rates when compared with oral formulations. Risperidone long-acting injection (RLAI) treatment is effective and well-tolerated in clinical trials. The aim of this study was to review RLAI prescribing practice and compare prescribing to best practice recommendations (including indication, initiation, dose and co-prescribing) for adults receiving care from five clinical practice settings of New Zealand. Patients starting publicly funded RLAI between 1 October 2005 and 31 October 2006 in five mental health services were included in the study. Data were retrospectively collected for 443 patients 1 year pre- and post-RLAI initiation at seven cross-sectional time-points (12, 6 and 3 months before; initiation; and 3, 6 and 12 months after). Patient characteristics (gender, age, ethnicity), DSM-IV-TR diagnosis, duration of mental illness, mental health act utilization, treatment setting and antipsychotic treatment (reasons for starting RLAI) were obtained from patient records. The patients were mostly male (64,3%), of European background (42.9%) with a medium age of 34. In line with treatment recommendations, most had a diagnosis of schizophrenia or related psychoses, a history of medication adherence problems and previously been prescribed oral risperidone (72%). Treatment initiation also reflected recommended guidance; most were started on 25 mg/2 weeks (81.9%) and had treatment crossover (93.3%) until RLAI stabilized. For 58.3% of the group who continued for ≥ 12 months, mean fortnightly doses increased from 36.2 mg (3 months) to 41.3 mg (12 months); within the licensed range of 25-50 mg/2 weeks. Areas differing from recommended practice included high rates of antipsychotic co-prescribing at three cross-sectional time-points and ongoing at 12 months (12.3%). Patients prescribed higher RLAI starting doses were more likely to be prescribed higher doses 12 months later. To our knowledge this is the largest multi-site explicit review of RLAI use in real world clinical practice. The review found that clinicians were using RLAI in clinical practice predominantly in accordance with best practice recommendations. However, high rates of antipsychotic co-prescribing with RLAI were identified which differ from practice reported in other small reviews of RLAI use and local studies of antipsychotic prescribing. We have demonstrated that clinical audit of practice is a powerful tool to identify areas of potentially poor practice, such as ongoing high rates of antipsychotic co-prescription cross-sectionally and 12 months after RLAI initiation and that this is an area of practice requiring further evaluation. Feedback to clinicians and stakeholders followed by re-audit of practice is needed in order to complete the audit cycle.

Comparative Effectiveness of Long-Acting Risperidone in New Zealand

Schizophrenia affects approximately 1% of the population and is associated with a considerable economic burden to society. The healthcare costs of the disorder are high and are compounded by substantial productivity losses. Failure to adhere to medication regimens, with subsequent relapse and hospitalization, is a key driver of these costs. A long-acting injectable formulation of the second generation antipsychotic risperidone (risperidone long-acting injection [risperidone LAI]) was licensed in New Zealand and received full government funding in October 2005. Second generation antipsychotics may have some efficacy advantages, be associated with fewer adverse effects and could improve adherence. However, the acquisition cost of risperidone LAI is higher than that of first generation antipsychotics and healthcare decision makers need information that allows them to determine whether risperidone LAI represents a cost-effective investment in terms of improved outcomes. To explore real-world outcomes and costs of patients treated with risperidone LAI within New Zealand. A mirror-image retrospective study was conducted comparing outcomes and costs 12 months post- versus 12 months pre-initiation of risperidone LAI in all adults receiving approval for risperidone LAI between 1 October 2005 and 31 October 2006 in five health services. Continuation rates, compulsory treatment status, psychiatric hospitalization (admission number, bed-stay and cost) and treatment data were collected from clinical files and patient information systems for the 12 months on either side of the first risperidone LAI prescription. Hospitalization costs were valued using estimates for cost per admission and cost per hospital day ($NZ, year 2009 values). 58.3% of patients remained on risperidone LAI 12 months after initiation. Compared with the pre-risperidone LAI treatment period the mean number of admissions for the total study population was significantly lower in the post-risperidone LAI treatment period (1.38 vs 0.61, p<0.001) but the mean length of bed-stay increased (37.2 vs 53.3 days, p<0.001), as did compulsory treatment use. Overall hospital bed-nights (hospitalization days) increased by 6877 in the post-index period, driven mostly by those who discontinued treatment. Patients who continued risperidone LAI had fewer admissions and days in hospital post-risperidone LAI than patients who discontinued risperidone LAI use in the first year. The reduction in total hospital admission rates between the two treatment periods was significantly greater in the continuation group and mean difference in bed-days between the two treatment periods was significantly less for continuers (5.4 vs 31.1 days, p<0.001). Applying a cost per admission, hospitalization costs reduced by approximately $NZ1.7 million in the post risperidone LAI-period. Applying a daily hospitalization cost resulted in an increase of approximately $NZ3.5 million in the post-risperidone LAI period. This study suggests that patients have reduced hospital admissions but longer bed-stay after starting risperidone LAI. Longer admissions were driven by those that discontinued treatment and continuation was associated with improved resource and cost outcomes compared with those who discontinued. These findings have potential implications for payers, providers and patients that require further investigation over a longer time frame.

Risperidone long-acting injectable (Risperdal Consta®) for maintenance treatment in patients with bipolar disorder

Poor adherence to pharmacotherapy during maintenance-phase treatment of bipolar disorder is a common occurrence, exposing patients to a high risk of illness relapses, rehospitalization and other negative outcomes. In view of this, there has been a reawakening of interest in the potential of long-acting injectable antipsychotic medications to improve treatment outcome during bipolar maintenance therapy. Indeed, long-acting injectable medications have practical advantages of assuring delivery of medication at a prescribed dose, and perhaps also making it easier to monitor adherence, at least to the long-acting drug. However, there are important limitations to the long-term use of depot typical neuroleptics in patients with bipolar disorder, including risk of extrapyramidal side effects and tardive dyskinesia, which may exceed that of patients with schizophrenia, and the potential for treatment-emergent exacerbation of depressive symptoms. Long-acting injectable risperidone (RLAI) has recently been approved for maintenance treatment in patients with bipolar I disorder. Evidence supporting the use of RLAI for this indication consists of several nonrandomized, open-label studies; one randomized, open-label trial; and two adequately powered randomized, double-blind trials. In general, these studies have shown RLAI to be effective for the prevention of relapse or hospitalization during bipolar maintenance treatment. In the double-blind studies, RLAI was associated with reduced relapse rates, increased time to relapse and greater control of clinical symptoms during maintenance treatment following initial stabilization, compared with oral medication treatment or placebo injection. RLAI appeared to be more effective for preventing manic/mixed episodes than depressive episodes. RLAI showed good tolerability across studies; however, dose-related extrapyramidal effects, sedation, weight gain and prolactin elevation may occur during long-term treatment. Responder-enriched designs and exclusion of important clinical subgroups in the double-blind trials may limit translation of these results to routine care settings.

Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder

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. 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). The efficacy of drugs used for maintenance treatment of BD, as emerging from the results of randomized controlled trials, was assessed using the size effect measure of NNT. PubMed searches 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 reviewing reference lists from identified publications. 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. 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 settings, in order to facilitate implementation of long-term pharmacological interventions in patients with BD.

Galantamine augmentation of long-acting injectable risperidone for cognitive impairments in chronic schizophrenia

Background Galantamine, a reversible cholinesterase inhibitor with effects on nicotinic receptors, has shown mixed effects on cognitive impairments in patients with schizophrenia. Given these mixed results we examined whether galantamine compared to adjunctive placebo may improve cognitive functions in patients treated concomitantly with a long acting atypical antipsychotic. Method The parent study was a 52-week double-blind, randomized study of treatment with long-acting injectable risperidone 25 mg or 50 mg every two weeks. Adjunctive galantamine or placebo treatment was administered from Month 6 to 12. Outcome measures were neurocognitive, psychopathology, social and quality of life functions. Patients were randomized to blinded galantamine up to 24 mg/day or matching placebo tablets. All patients were maintained on their randomized long-acting injectable risperidone regimen for the duration of the trial. Results 32 patients were included in the intent-to-treat analysis. No statistically significant differences were found for Attention Vigilance, Declarative Memory, Processing Speed, Reasoning/Problem Solving, Working Memory domains and the Neurocognitive Composite Score. Group specific analysis showed a statistically significant group interaction ( p = 0.043) with the Social Cognition domain showing in the galantamine group significantly lower scores at endpoint than placebo patients. The PANSS general psychopathology subscale showed significantly higher scores in the galantamine group at endpoint ( p = 0.05). ANCOVA model for within treatment group comparisons showed a significant increase of 7.3 points for the total PANSS score for the galantamine group. Conclusion Galantamine showed no ameliorative effects on cognitive measures in this 6 month, double-blind study of patients with schizophrenia treated with an assured and stable antipsychotic medication delivery system. Galantamine may not be an appropriate augmentation agent for cognitive impairments in patients with schizophrenia at the dose used.

Cost Effectiveness of Long-Acting Risperidone in Sweden

In Sweden, risperidone long-acting injectable (RLAI) is generally used in a population of schizophrenia patients who are at a high risk of being non-compliant. However, RLAI might also be suitable for use in the general schizophrenia population. To analyse the clinical and economic effects of RLAI in the Swedish treatment practice using a discrete-event simulation (DES) model. Treatment outcomes and direct costs were analysed for both the high-risk non-compliant patient population and the general schizophrenia population. An existing DES model was adapted to simulate the treatment of schizophrenia in Sweden. Model inputs were based on literature research and supplemented with expert opinion. In the high-risk non-compliant schizophrenia population, RLAI was compared with haloperidol LAI. The analysis was built upon differences in symptom reduction, time between relapses, compliance and adverse effect profile between the two drugs. Main outcomes were the predicted incremental (discounted) costs (€) and effects (QALYs). In the general schizophrenia population, RLAI was compared with oral olanzapine. This analysis was built upon differences in compliance and adverse effects between the drugs. Multivariate probabilistic sensitivity analyses (PSA) were carried out to assess the sensitivity of the results of the two analyses. In the high-risk non-compliant patient population, RLAI was predicted to generate 0.103 QALYs per patient over 3 years while realizing cost savings of €5013 (year 2007 values) compared with haloperidol LAI. The main driver of the cost effectiveness of RLAI was the difference in Positive and Negative Syndrome Scale (PANSS) reduction between the two drugs, followed by the difference in adverse effects. The PSA showed that, in this setting, RLAI had a probability of 100% of being cost effective at a willingness-to-pay (WTP) threshold of €43,300 per QALY gained, compared with haloperidol LAI. The probability that RLAI combines additional effectiveness with cost savings compared with haloperidol LAI was estimated at 94%. When analysing RLAI in the general schizophrenia population, it was predicted to generate 0.043 QALYs and save €239 per patient over 5 years compared with olanzapine. Compliance was the main driver of the cost effectiveness of RLAI in this scenario. In the PSA it was shown that RLAI had a probability of 78% of being cost effective at a WTP threshold of €43,300 per QALY gained, compared with olanzapine. The estimated probability that RLAI combines additional effectiveness with cost savings was 50% and the probability that RLAI is less effective and more costly than olanzapine was negligible (0.2%). Treatment with RLAI is suggested to result in improved QALYs combined with cost savings compared with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia patient population. In the general schizophrenia population, RLAI also resulted in positive incremental QALYs and cost savings, when compared with olanzapine. However, the estimates used in the model for compliance and symptom reduction need further validation through naturalistic-based studies with reasonable follow-up to more definitely establish the real-life differences between RLAI and the comparators in the considered patient populations and to further reduce the uncertainty of these parameters.