Spotlight on long-acting risperidone in schizophrenia

Long-acting risperidone (Risperdal Consta?) is a novel, intramuscular formulation of the atypical antipsychotic risperidone, which has shown efficacy in the treatment of patients with schizophrenia. Long-acting risperidone is pharmacokinetically equivalent to and causes less plasma drug concentration fluctuation than the oral formulation. This novel formulation is an aqueous suspension of microspheres comprising risperidone and a biodegradable copolymer. Significant release of risperidone from the microspheres begins 3 weeks after the first injection; thus, administration of another antipsychotic is necessary during this period only. Steady-state plasma concentrations are reached after the fourth injection. Elimination is complete 7–8 weeks after the last injection. Long-acting risperidone 25 or 50mg every 2 weeks demonstrated significantly greater antipsychotic efficacy than placebo and equivalent efficacy to oral risperidone 2–6 mg/day in two randomized, double-blind, double-dummy, 12-week trials of patients with schizophrenia. Additionally, in one of these trials, improvements in health-related quality of life (HRQOL) were superior with long-acting risperidone than placebo. Compared with baseline, improvements in the symptoms of schizophrenia in stable patients were significant with long-acting risperidone 25 or 50mg (12-month trial) and 25, 37.5 or 50mg (12-week trial) every 2 weeks, in two noncomparative, multicenter trials. Patient satisfaction with their medication and patient HRQOL mental health scores improved significantly in the 12-month trial. Long-acting risperidone is generally well tolerated, with a low incidence of injection site pain and an otherwise similar profile of adverse effects to the oral formulation. The overall incidence of extrapyramidal disorders in clinical trials was low (≤10%) with similar, yet minimal, changes in extrapyramidal symptom severity between patients treated with long-acting risperidone, oral risperidone or placebo. Tardive dyskinesia was reported in the 12-month trial, in 0.7% of patients. Conclusion: Long-acting risperidone is effective and generally well tolerated in patients with schizophrenia, including those patients with stable symptoms. Long-acting risperidone is the first atypical antipsychotic vailable in a formulation which offers a sustained, steady release of drug and is thus an attractive, new option in the treatment of patients with schizophrenia.     

Long-acting risperidone injection.

PURPOSE: The pharmacology, pharmaceutics, clinical efficacy, adverse effects, cost, and dosage and administration of long-acting risperidone injection are reviewed. SUMMARY: Risperidone is the first atypical antipsychotic available in a long-acting injectable formulation. After a single injection, significant plasma levels of the drug are achieved at week 3 and sustained through week 6, subsiding by weeks 7-8. Steady state is achieved after four injections. Peak levels are less than those seen with comparable doses of oral risperidone. A 12-week double-blind placebo-controlled study and a one-year open-label study demonstrated the efficacy, safety, and tolerability of long-acting risperidone injection in patients with schizophrenia and schizoaffective disorder. Those who were considered stable on their previous medication showed continued clinical improvement and an increase in health-related quality of life during a year of treatment with long-acting risperidone injection. In the 12-week study, risperidone was well tolerated, with adverse-effect rates similar to those seen with placebo. Weight gain with long-acting risperidone injection is similar to that found with oral treatment. Extrapyramidal symptom ratings have shown improvement from baseline following administration of this agent. Individuals with schizophrenia who previously received oral risperidone therapy have shown a reduction in prolactin levels after a switch to the long-acting formulation. CONCLUSION: With its unique tolerability and efficacy, long-acting risperidone injection has the potential to extend the benefits of assured medication delivery and improved long-term outcomes to more patients with schizophrenia.     

Long-acting injectable risperidone for the treatment of schizophrenia: clinical perspectives

Schizophrenia remains a severe disorder that is associated with a poor outcome in a large subgroup of patients. Major efforts should be made to improve treatment for all patients who have this debilitating disease. Second-generation antipsychotics were a major step forward in this respect; however, important unmet needs remain, such as a better solution for frequent noncompliance problems. Depot formulations are known to have advantages in this respect. However, for a long time, only depot formulations of conventional antipsychotics were available, with their high risk of extrapyramidal adverse effects. Therefore, there has been only very restricted use of depot antipsychotics, which mainly focused on patients with chronic disease who were difficult to treat and had a high risk of noncompliance. The situation may change with the advent of a depot formulation of an atypical antipsychotic. The first depot formulation of an atypical antipsychotic to be introduced to the market is long-acting injectable risperidone. On the basis of the pharmacokinetic properties of the depot formulation, a 2-week interval between administrations is recommended. The antipsychotic efficacy of long-acting risperidone was demonstrated in two 12-week, double-blind, randomised, phase III studies, one versus placebo and the other versus oral risperidone. These two studies, together with one open-label, long-term study over 12 months, belong to the core group of trials that were relevant for the licensing of long-acting risperidone. A relapse-prevention, control group study comparing the long-acting formulation versus oral risperidone was not performed because of the known principal methodological problems of such a comparison. Instead, as much clinical data as possible was collected from observational studies that investigated questions relevant for clinical practice, such as efficacy, safety and tolerability in different subgroups, and transition from pre-treatment with different kinds of antipsychotics to long-acting risperidone. On the basis of these data, it can be stated that the efficacy of the long-term formulation of risperidone is proven, and that the safety and tolerability are more or less comparable to those of oral risperidone. The local tolerability at the injection site is good. Because it is well known that noncompliance is a frequent feature of the treatment of schizophrenia, and considering the advantages of atypical antipsychotics, consideration of whether long-acting atypical antipsychotics should have a broader indication than is the case with the depot formulations of the classical antipsychotics is warranted.     

Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics

Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.     

Evaluation of amphetamine-induced hyperlocomotion and catalepsy following long-acting risperidone administration in rats

It has been proposed that long-acting risperidone could provide a constant antipsychotic efficacy associated with a reduced liability to induce extra-pyramidal symptoms. To ascertain this hypothesis, antagonism of amphetamine-induced hyperlocomotion and catalepsy were analyzed in rats for a period of 1–6 weeks following long-acting risperidone (20–60 mg/kg) injection. Long-acting risperidone reduced amphetamine-induced hyperlocomotion after 2–5 weeks from drug injection, without producing significant extra-pyramidal symptoms. Following the administration of long-acting risperidone a constant ability to antagonize amphetamine-induced hyperlocomotion was observed during the day, but not when the antipsychotic was chronically administered using a short-acting formulation. The pre-clinical results confirmed that long-acting risperidone may represent an advance in antipsychotic therapy.     

Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia

Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each long-acting injectable antipsychotic drug.     

Clinical experience and management considerations with long-acting risperidone

BACKGROUND: Risperidone is the first atypical anti-psychotic available in a long-acting injectable formulation. OBJECTIVE: To provide an overview of the initial clinical experience gained with long-acting risperidone during clinical trials and in general treatment, including specific case studies, as well as providing practical advice on how to initiate treatment with this new drug. METHODS: Studies published between January 2002 and June 2005 that evaluated the pharmacokinetics, efficacy and safety of long-acting risperidone for the treatment of schizophrenia were reviewed, as identified from literature searches using Medline and EMBASE. Although not peer-reviewed, abstracts and posters on long-acting risperidone presented at key psychiatry and schizophrenia congresses during this period were also reviewed where available in the public domain. RESULTS: Clinical studies have consistently demonstrated that long-acting risperidone, available in dosage strengths of 25, 37.5 or 50 mg, given once every 2 weeks, is both effective and well tolerated in patients with schizophrenia. Furthermore, significant and sustained clinical improvement has been reported in patients switched to long-acting risperidone from other oral and long-acting antipsychotic agents. Several patients groups, including the young, the elderly and patients with schizoaffective disorder, have also been shown to derive significant benefit from long-acting risperidone. CONCLUSION: A wide variety of patient groups may benefit from treatment with long-acting risperidone, including patients with suboptimal efficacy, particularly as a result of partial compliance, patients experiencing side-effects with another antipsychotic agent or those with a first episode of schizophrenia. Furthermore, long-acting risperidone, with its assured medication delivery, should improve patient compliance and assist patients in achieving remission, an important step towards functional recovery.     

Clinical experience with the long-acting injectable formulation of the atypical antipsychotic,risperidone

BACKGROUND: To detail specific effects of long-acting risperidone on individuals with schizophrenia and their way of life in a series of four cases. METHOD: Four patients with schizophrenia were selected from four different psychiatric centres. Patients were established on an oral dose of risperidone (1-4 mg/day) for 2 weeks. Based on their oral dose, they then received intramuscular injections of 25 mg or 50 mg of long-acting risperidone every 2 weeks, which could be adjusted according to clinical response. Assessments of efficacy (Positive And Negative Syndrome Scale, Clinical Global Impression-Severity) and safety (Extrapyramidal Symptom Rating Scale) were made at intervals throughout a 1-year period. RESULTS: Patients demonstrated a variety of reasons for receiving a long-acting injectable antipsychotic drug, including insufficient control of symptoms, adverse events and convenience. After 1 year of treatment with long-acting risperidone, all patients showed improvements in their symptoms of schizophrenia over their original stable condition, and benefited from a considerable reduction or total disappearance of pre-existing extrapyramidal symptoms. Patients were more socially interactive, with no signs of sedation, fatigue, confusion, depression or anxiety, and none were considered to have relapsed or to require hospitalisation. Three of the four patients were considered to have had no signs of illness after 1 year, one of whom had returned to college and another to work. They demonstrate that patients can be switched from oral and depot medications without problems. There was little pain or discomfort and no inflammatory response experienced at the injection site. CONCLUSION: The cases demonstrate the suitability of long-acting risperidone in patients benefiting from long-term treatment and suggest its potential in all patients who are at risk of relapse.     

Long-acting risperidone compared with oral olanzapine and haloperidol depot in schizophrenia: a Belgian cost-effectiveness analysis

Patients with schizophrenia suffer numerous relapses and rehospitalizations that are associated with high direct and indirect medical expense. Suboptimal therapeutic efficacy and, in particular, problems with compliance are major factors leading to relapse. Atypical antipsychotic agents offer improved efficacy and a lower rate of extrapyramidal adverse effects compared with conventional antipsychotic drugs. Long-acting intramuscular risperidone combines these benefits with improvements in compliance associated with depot injections. To assist decision making regarding the place of long-acting risperidone in therapy, a cost-effectiveness analysis of strategies involving first-line treatment with long-acting risperidone, oral olanzapine or depot haloperidol was performed from the perspective of the Belgian healthcare system. A decision tree model was created to compare the cost effectiveness of three first-line treatment strategies in a sample of young schizophrenic patients who had been treated for 1 year and whose disease had not been diagnosed for longer than 5 years. The model used a time horizon of 2 years, with health state transition probabilities, resource use and cost estimates derived from clinical trials, expert opinion and published prices. The four health states in the model were derived from an analysis of the literature. The principal efficacy measure was the proportion of patients successfully treated, defined as those who responded to initial treatment and who had none to two episodes of clinical deterioration without needing a change of treatment over the 2-year period. Comprehensive sensitivity analysis was carried out to test the robustness of the model. A greater proportion of patients were successfully treated with long-acting risperidone (82.7%) for 2 years, compared with those treated with olanzapine (74.8%) or haloperidol (57.3%). Total mean costs per patient over 2 years were 16,406 Euro with long-acting risperidone, 17,074 Euro with olanzapine and 21,779 Euro with haloperidol (year of costing 2003). The mean cost-effectiveness ratios were 19,839 Euro, 22,826 Euro and 38,008 Euro per successfully treated patient for long-acting risperidone, olanzapine and haloperidol, respectively. Results of the sensitivity analysis confirmed that the results were robust to a wide variation of different input variables (effectiveness, dosing distribution, patient status according to healthcare system). Long-acting risperidone was the dominant strategy, being both more effective and less costly than either oral olanzapine or depot haloperidol. Long-acting risperidone appears to represent a favourable first-line strategy for patients with schizophrenia requiring long-term maintenance treatment.     

Extended-release intramuscular paliperidone palmitate: a review of its use in the treatment of schizophrenia

Extended-release intramuscular paliperidone palmitate (Xeplion?; Invega? Sustenna?) [henceforth referred to as intramuscular paliperidone palmitate] is a long-acting injectable (LAI) formulation of the well established atypical antipsychotic agent paliperidone (9-hydroxyrisperidone), which is the major active metabolite of risperidone. This article reviews, from an EU perspective, the therapeutic efficacy and tolerability of intramuscular paliperidone palmitate in the treatment of adults with schizophrenia, and the pharmacology of paliperidone that is relevant to the intramuscular formulation. Intramuscular paliperidone palmitate 25-150 mg equivalents (mg eq.) effectively reduced symptoms of schizophrenia in most short-term (9-13 weeks) placebo-controlled trials, as demonstrated by improvements in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint that were significantly greater in intramuscular paliperidone palmitate than placebo recipients. The onset of clinical response was 8 days in patients who received the recommended initial 150 mg eq. dose of intramuscular paliperidone palmitate into the deltoid muscle on day 1. In a longer-term (24-week maintenance phase and variable length double-blind phase) placebo-controlled trial, intramuscular paliperidone palmitate was associated with a significantly longer time to relapse than placebo in patients with schizophrenia at a preplanned interim analysis conducted after 68 relapse events. Because of these favourable results, the study was terminated early. In two 13-week trials, one of which was conducted in Chinese patients, intramuscular paliperidone palmitate administered using the recommended initiation dosage regimen was noninferior to LAI-risperidone in patients with schizophrenia in terms of the between-group treatment difference (intramuscular paliperidone palmitate vs LAI-risperidone) for the mean change from baseline to endpoint in PANSS total score. The tolerability of intramuscular paliperidone palmitate was generally acceptable in clinical trials of schizophrenia. No new safety concerns were revealed compared with oral paliperidone, except for injection site-related reactions. In conclusion, intramuscular paliperidone palmitate is a useful option for the treatment of patients with schizophrenia.     

Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia

Introduction: Patient non-adherence increases the risk for relapse and the long-term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D₂ partial agonist available in a long-acting formulation for the treatment of schizophrenia.

Areas covered: This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 – 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double-blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (≥5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation.

Expert opinion: AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia.     

Long-acting injectable antipsychotics in the elderly: guidelines for effective use

The elderly are at increased risk for psychosis because of age-related deterioration of cortical areas and neurochemical changes, comorbid physical illnesses, social isolation, sensory deficits and polypharmacy. The prevalence of psychiatric and neuropsychiatric disorders requiring treatment with an antipsychotic agent is expected to increase dramatically among people aged >64 years. Antipsychotic agents are effective in the treatment of schizophrenia, schizoaffective disorder, behavioural symptoms in patients with dementia, and mood disorders with psychosis. However, failure to adhere to a prescribed medication regimen by patients with psychosis is one of the most frustrating problems faced by mental healthcare providers, because of the high risk of relapse associated with partial compliance. For patients with psychosis who will not or cannot take oral medications on a regular daily basis or have other characteristics, such as memory, vision or auditory impairment, which contribute to partial compliance, long-acting injectable antipsychotic medication offers a solution.Older patients are especially at risk of adverse effects associated with traditional antipsychotic agents, such as motor effects, postural hypotension, excessive sedation, and anticholinergic effects because of age-related pharmacokinetic and pharmacodynamic factors, coexisting medical illnesses and concomitant medications. Therefore, drug dosage recommendations in the elderly are much more conservative than in younger patients. The appropriate starting dose of an antipsychotic in older individuals is 25% of the usual adult dose; total daily maintenance doses ranges from 25-50% of the adult dose.There are few studies regarding the use of depot antipsychotics in elderly patients. Studies that are available indicate that traditional antipsychotic agents given as depot injections are associated with positive outcomes in the elderly. Because the risks for extrapyramidal symptoms and tardive dyskinesia are reduced dramatically with atypical antipsychotics compared with traditional agents, the development of long-acting atypical antipsychotic formulations has been pursued. Of the atypical antipsychotics, risperidone is the first agent to be approved in a long-acting injectable formulation. Unpublished clinical data have revealed that patients treated with long-acting injectable risperidone (25mg, 50mg or 75mg) are more likely to show significant clinical improvement than placebo. In addition, hospitalisation rates decreased continuously and significantly during 1 year of treatment for patients who received long-acting injectable risperidone.Long-acting injectable antipsychotic medication should be considered for older patients for whom long-term treatment is indicated. The choice of which drug to use should be based on patients' history of response and personal preference, clinician's previous experience and pharmacokinetic properties.     

Second-generation long-acting injectable antipsychotic agents: an overview

For over 40 years, antipsychotic drugs have been used as long-term maintenance treatment to control symptoms and reduce relapse rates in patients with schizophrenia. 'First-generation' oral agents such as haloperidol and chlorpromazine are associated with high levels of unwanted neurological effects and poor rates of patient adherence.1,2 Long-acting ('depot') injections of antipsychotics were developed to try to improve adherence. 'Second-generation' antipsychotic agents (also known as atypical antipsychotics) were introduced into clinical practice over 16 years ago. Although these agents have a lower propensity to cause extrapyramidal side effects, they are associated with a range of other unwanted effects (e.g. weight gain and its sequelae).1,3,4 Initially, second-generation agents were only available as orally administered medicines. Three long-acting injectable formulations of second-generation antipsychotics are now available in the UK: θolanzapine embonate injection (ZypAdhera), θpaliperidone injection (Xeplion) and θrisperidone injection (Risperdal Consta). In this article we review the evidence for these agents and discuss the practical implications of their use.     

Long-term safety and tolerability of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder.

Subjects were patients with schizophrenia or schizoaffective disorder enrolled in extension studies (Study A and Study B) after participating in 12-week studies of long-acting injectable risperidone [Kane, J.M., Eerdekens, M., Lindenmayer, J.-P., Keith, S.J., Lesem, M., Karcher, K., 2003. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am. J. Psychiatry 160, 1125-1132; Lindenmayer, J.-P., Eerdekens, L., Berry, S., Eerdekens, M., 2004. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J. Clin. Psychiatry 65, 1084-1089]. Twelve months of treatment were completed by 55% of Study A patients and 52% of Study B patients. The median modal dose of long-acting injectable risperidone was 50 mg/14 days in both studies. Most frequent adverse events were psychosis, headache, insomnia, agitation, and rhinitis. EPS-related adverse events were reported in 33% of patients in Study A and 22% in Study B. Patients with Clinical Global Impressions ratings of "not ill" and "mild" increased from 14% at baseline to 54% at endpoint in Study A and from 42% to 65% in Study B. It is concluded that treatment with long-acting injectable risperidone for 1 year or longer appeared to be safe and well tolerated in patients with schizophrenia or schizoaffective disorder.     

Healthcare resource utilization during 1-year treatment with long-acting, injectable risperidone

BACKGROUND: Schizophrenia is associated with disproportionately high costs, mainly due to hospitalization rates. This study assessed healthcare resource use in patients with schizophrenia and schizoaffective disorder during treatment with long-acting risperidone. METHODS: Patients (n = 397 [inpatients, 24%; outpatients, 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 resource 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 (outpatients, 4.9 days; inpatients, 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 resource 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.     

第一个长效非典型抗精神病药:注射用利培酮微球

注射用利培酮微球是第 1个长效非典型抗精神病药 ,兼有口服非典型抗精神病药和长效抗精神病药的优点。其血浆药物水平稳定 ,疗效明显优于安慰剂 ,与利培酮片剂相当 ,但更利于长期维持治疗。该药的耐受性好 ,适应证广 ,适用人群大于长效传统抗精神病药。推荐起始剂量为 2 5mg ,肌内注射 ,每 2周 1次 ,前 3wk合并口服制剂     

Pharmacokinetic profile and clinical efficacy of long-acting risperidone: potential benefits of combining an atypical antipsychotic and a new delivery system

Continuous long-term antipsychotic therapy is required for patients with schizophrenia to optimise treatment benefits. The use of long-acting antipsychotic preparations can help to ensure compliance with therapy and has been shown to improve efficacy in relapse prevention when compared with oral agents. How- ever, the use of long-acting agents has been limited, since this approach to patient care has only been available with conventional drugs. The atypical antipsychotic agents have provided a new option for the treatment of schizophrenia. However, entwined with health system limitations, partial or non-compliance remains a problem with oral atypical antipsychotic agents. Combining the attributes of the atypical antipsychotic class with the pharmacokinetic profile and compliance advantages of a long-acting formulation could potentially be an important advance in the management of patients requiring continuous anti- psychotic therapy. This review considers the available clinical data supporting possible advantages for the only long-acting atypical agent currently available, long-acting risperidone, as a microsphere formulation. The drug-delivery technology employed provides a sustained therapeutic plasma level, with administration once every 2 weeks, and this is translated into improved symptom control and improved quality of life, even in patients already deemed clinically stable on an oral agent or on a conventional depot antipsychotic.     

Olanzapine pamoate for the treatment of schizophrenia

Introduction: Nonadherence is still a major problem in the long-term treatment of schizophrenia. Long-acting injectable or depot atypical antipsychotics are associated with better maintenance. Olanzapine pamoate, available since 2010, is the second depot atypical antipsychotic. Areas covered: This review covers data on the efficacy and tolerability/safety of olanzapine pamoate, the long-acting formulation of the atypical antipsychotic olanzapine. Administered as a pamoate salt, it has an elimination half-life of 30 days, allowing a 2- or 4-week injection interval. Antipsychotic efficacy was documented in an 8-week trial in 404 acutely ill schizophrenia patients with maintenance therapy in a 24-week trial in 1065 chronic patients. The side-effect profile is comparable to that of oral olanzapine. The most relevant adverse event is the post-injection delirium/sedation syndrome, occurring at a rate of 0.07% of injections or 1.4% of patients. It requires administration by qualified personnel in settings where a post-injection observation period for 3 h by medical personnel is available. Expert opinion: Olanzapine pamoate is an efficacious formulation, particularly for patients with a history of good response to oral olanzapine and doubtful adherence. Psychiatrists should reconsider their negative attitudes toward long-acting or depot antipsychotics and should offer this administration to the majority of patients, not only to a negatively selected population.     

Minimal injection site pain and high patient satisfaction during treatment with long-acting risperidone

Long-acting injectable antipsychotic formulations of conventional antipsychotics were developed to address the problem of partial adherence among patients with schizophrenia. Injection site pain, other skin reactions and patient satisfaction with treatment were assessed in two large, multicentre studies of long-acting injectable risperidone (Risperdal CONSTA, Janssen Pharmaceutica Products, Titusville, New Jersey, USA), the first available long-acting atypical antipsychotic agent. Patients rated injection site pain using a 100-mm Visual Analogue Scale (VAS), and investigators rated injection site pain, redness, swelling and induration. Patient satisfaction with treatment was assessed with the Drug Attitude Inventory (DAI). VAS pain ratings were low at all visits across all doses in both studies, and decreased from first to final injection. In the 12-week, double-blind study, mean +/- SD VAS scores at the first and final injections were 15.6 +/- 20.7 and 12.5 +/- 18.3 for placebo-treated patients, and 11.8 +/- 14.4 (first) and 10.0 +/- 12.4 (final) for 25 mg; 16.3+/-21.9 (first) and 13.6 +/- 21.7 (final) for 50 mg; and 16.0 +/- 17.9 (first) and 9.6 +/- 16.0 (final, P<0.01) for 75 mg of long-acting risperidone. Mean VAS scores in the 50-week, open-label study at the first and final injection were: 17.9 +/- 22.2 (first) and 9.5 +/- 16.7 (final, P<0.0001) for 25 mg; 18.1 +/- 19.7 (first) and 10.4 +/- 14.8 (final, P<0.0001) for 50 mg; and 18.5 +/- 21.6 (first) and 13.6 +/- 19.9 (final, P = 0.0001) for 75 mg of long-acting risperidone. Overall, there was no or minimal injection site pain and skin reactions were rare. Mean DAI ratings were available for the 50-week study and indicated high patient satisfaction throughout the trial (baseline = 7.30; endpoint = 7.70; P<0.0001 versus baseline). These findings may positively affect patient and clinician attitudes towards long-term therapy with long-acting injectable risperidone.