Risperidone Long-acting Injection Research Articles

A Non-Interventional Naturalistic Study of the Prescription Patterns of Antipsychotics in Patients with Schizophrenia from the Spanish Province of Tarragona.

BackgroundThe analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes.ObjectiveTo determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain).MethodsA naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013.ResultsThe most used antipsychotic was risperidone, identified in 463 (26.3%) patients, followed by olanzapine in 249 (14.1%), paliperidone in 225 (12.7%), zuclopenthixol in 201 (11.4%), quetiapine in 141 (8%), aripiprazole in 100 (5.7%), and clozapine in 100 (5.7%). Almost 8 out of 10 patients (79.3%) were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI) formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6%) were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94–40.97), LAI (OR 9.99, 95% CI 6.45–15.45), psychiatric co-medications (OR 4.25, 95% CI 2.72–6.64), and paliperidone (OR 3.13, 95% CI 1.23–7.92) were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35–0.83) and older age (OR 0.98, 95% CI 0.97–0.99) were related to a low polypharmacy probability.ConclusionsPolypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy is associated with the use of quetiapine or paliperidone, use of a LAI, younger age, and psychiatric co-medication.

Medication adherence in patients with psychotic disorders: an observational survey involving patients before they switch to long-acting injectable risperidone.

BackgroundMaintaining antipsychotic therapy in psychosis is important in preventing relapse. Long-acting depot preparations can prevent covert non-adherence and thus potentially contribute to better patient outcomes. In this observational survey the main objective is to evaluate medication adherence and its determinants for oral treatment in a large sample of patients with psychosis.MethodsIn this cross-sectional survey medication adherence for oral treatment was assessed by patients using the patient-rated Medication Adherence Questionnaire (MAQ). Data were collected by physicians on patients with a recent acute psychotic episode before switching to long-acting injectable risperidone. Other evaluations included disease severity (Clinical Global Impression – Severity), patients’ insight (Positive and Negative Syndrome Scale item G12), treatment acceptance (clinician-rated Compliance Rating Scale), and therapeutic alliance (patient-rated 4-Point ordinal Alliance Scale).ResultsA total of 399 psychiatrists enrolled 1,887 patients (mean age 36.8±11.9 years; 61.6% had schizophrenia). Adherence to oral medication was “low” in 53.2% of patients, “medium” in 29.5%, and “high” in 17.3%. Of patients with psychiatrist-rated active acceptance of treatment, 70% had “medium” or “high” MAQ scores (P<0.0001). Medication adherence was significantly associated with therapeutic alliance (4-Point ordinal Alliance Scale score; P<0.0001). Patient age was significantly associated with adherence: mean age increased with greater adherence (35.6, 36.7, and 38.6 years for patients with “low”, “medium”, and “high” levels of adherence, respectively; P=0.0007), while age <40 years was associated with “low” MAQ classification (P=0.0003). Poor adherence was also associated with a diagnosis of schizophrenia (P=0.0083), more severe disease (Clinical Global Impression – Severity ≥4; P<0.0001), and lower insight (Positive and Negative Syndrome Scale-G12 ≥4; P<0.0001).ConclusionSelf-reported adherence was low in most patients, with a strong positive association between self-reported adherence and psychiatrists’ assessment of treatment acceptance. Understanding factors associated with poor medication adherence may help physicians to better manage their patients, thereby improving outcomes.

Enhancing adherence, subjective well-being and quality of life in patients with schizophrenia: which role for long-acting risperidone?

This study evaluated adherence to treatment, quality of life and subjective well-being in patients with psychosis treated with long-acting injectable risperidone. Subjects enrolled were part of a larger study where patients were observed in an adherence to treatment program of the University of Rome Tor Vergata. A total of 27 nonadherent patients (21 men, six women; mean age: 36.1 years; range: 23-63 years) were enrolled. Maximum observational period was 30 months. A total of 12 patients were under treatment for 30 months (44.44%) but only nine had a valid 30-month follow up, while the remaining three patients initially treated at our unit continued long-acting risperidone at their local centre. Reductions of monthly mean values of Scale for the Assessment of Positive Symptoms (SAPS) [repeated measures analysis of variance (rm-ANOVA): p < 0.0001] and Scale for Assessment of Negative Symptoms (SANS) (p < 0.0001), increase of monthly mean values of Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) (p < 0.0001) and Schizophrenia Quality of Life Scale (S-QoL) (p < 0.01) were observed. Significant differences with respect to SAPS baseline values from the sixth month, SANS baseline values from the seventh month, SWN baseline values from the eighth month, S-QoL baseline values from the eighteenth month were shown in post hoc tests. Reduction of SAPS mean values was associated with increase of SWN (p < 0.0001) and S-QoL (p < 0.0001) mean values as demonstrated by correlation analysis. The same inverse correlation was found between reduction of SANS mean values and increases of SWN (p < 0.0001) and S-QoL (p = 0.0001) mean values. Long-term treatment with long-acting risperidone may be associated with improvement to adherence to therapy and quality of life. Patients may show improvement in psychopathological symptoms, subjective well-being and quality of life.

Expanding Therapy With Long-Acting Antipsychotic Medication in Patients With Schizophrenia.

Long-acting injectable (LAI) antipsychotic medications are significantly underused. In light of their documented efficacy for treatment of psychotic symptoms and robust effect on relapse prevention, their relative lack of use is unfortunate. There are several reasons for this therapeutic neglect, including clinical settings where injections are not part of the usual routine; a belief that LAI medications are reserved for acute intervention or for aggressive or nonadherent patients; and the perception of stigmatization associated with their use. Moreover, randomized clinical trials (RCTs) comparing oral antipsychotic medications with LAI medications have often failed to document the expected advantage of assuring adherence with LAI medications because study participant selection often excludes those who are unable to adhere to the study protocol. Finally, physicians routinely overestimate patients’ adherence to oral medication regimens. In this context, 2 articles 1,2 in JAMA Psychiatry regarding the use of LAI medications may stimulate reconceptualization of this aspect of pharmacotherapy for treating schizophrenia. Subotnik and colleagues 1 describe a 12-month RCT that compared oral risperidone with LAI risperidone in patients with recent-onset schizophrenia. The study was conducted in a clinic with intensive clinical care. Outcomes with LAI risperidone were superior on measures of relapse and symptom control, and the between-group difference was partially, but importantly, related to adherence. The conduct of the study in people who are in the early course of their illness and have not established a pattern of medication adherence helps control for the selection bias observed with multiepisode schizophrenia and may account, in part, for the observed robust difference in efficacy between LAI and oral risperidone. Berwaerts and colleagues 2 used a multiple-stage design in

Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial.

Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. Psychotic relapse and control of breakthrough psychotic symptoms. Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ21 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ21 =11.1; P = .003) and control of breakthrough psychotic symptoms (β = 0.2; t79 = 2.1; P = .04). The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness. clinicaltrials.gov Identifier: NCT00333177.

Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge.

Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice.

Korean Medication Algorithm for Bipolar Disorder 2014: comparisons with other treatment guidelines.

Our goal was to compare the recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2014 (KMAP-BP 2014) with other recently published guidelines for the treatment of bipolar disorder. We reviewed a total of four recently published global treatment guidelines and compared each treatment recommendation of the KMAP-BP 2014 with those in other guidelines. For the initial treatment of mania, there were no significant differences across treatment guidelines. All recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or the combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2014 did not prefer monotherapy with MS or AAP for dysphoric/psychotic mania. Aripiprazole, olanzapine, quetiapine, and risperidone were the first-line AAPs in nearly all of the phases of bipolar disorder across the guidelines. Most guidelines advocated newer AAPs as first-line treatment options in all phases, and lamotrigine in depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs – such as asenapine, paliperidone, lurasidone, and long-acting injectable risperidone – became prominent. This comparison identifies that the treatment recommendations of the KMAP-BP 2014 are similar to those of other treatment guidelines and reflect current changes in prescription patterns for bipolar disorder based on accumulated research data. Further studies are needed to address several issues identified in our review.

Five-year patient outcomes with risperidone long-acting injection or oral aripiprazole.

This study examined 5-year outcomes of patients prescribed risperidone long-acting injection (RLAI) or aripiprazole in a clinical setting, using treatment discontinuation as a measure of effectiveness. Patients who received RLAI or aripiprazole in the 18 months following their respective UK launches were included. Two-year outcome data were previously reported for these cohorts; this study reported an additional 3 years of follow up for each group. Data were collected from pharmacy records and by retrospective case note review. Patients were classified as continuers or discontinuers at 5 years and reasons for treatment discontinuation noted. The number of patients remaining on treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI and aripiprazole respectively. Two patients treated with RLAI and three treated with aripiprazole were lost to follow up. Therefore, 5-year outcome data were available for 50 patients. Fifteen patients from each group were continuers at 5 years. Of these, four receiving RLAI and three receiving aripiprazole were coprescribed other antipsychotics at study endpoint. Reasons for discontinuation of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and patient death (n = 2; n = 0). There was no significant difference between the proportions of patients continuing RLAI or aripiprazole for 5 years. Continuation rates were relatively low (18% and 16% of the original RLAI and aripiprazole cohorts respectively), whilst coprescription of other antipsychotics at endpoint was relatively common. Lack of effectiveness was the most common reason for discontinuation of both compounds. These findings suggested that clinical effectiveness was somewhat disappointing, although the long period of follow up and number of patients previously treated with clozapine in the original cohorts were confounding factors.

Risperidone long-acting injection and 1-year rehospitalization rate of schizophrenia patients: A retrospective cohort study.

We wanted to present a picture of patients with schizophrenia receiving risperidone long-acting injection (RLAI) treatment in a real-world setting. This was a retrospective cohort study; 379 patients with schizophrenia were enrolled and treated with different kinds of antipsychotic agents at E-Da Hospital, and received a 12-month follow up. The patients were distributed into three groups: the all-oral antipsychotic, oral risperidone and RLAI groups. The antipsychotic agents and dosages they used were recorded. The rate of rehospitalization, length of hospital stay, emergency room visits and medical expenditures were assessed. The RLAI group had a significantly higher rate of hospitalization before enrolment (the all-oral antipsychotic group was 32.1%, the oral risperidone group, 35.9%, and the RLAI group, 88.4%, P < 0.0001). After a 1-year follow up, all three groups were similar in rehospitalization rates (the all-oral antipsychotic group was 28.9%, the oral risperidone group, 30.1%, and the RLAI group, 30.2%, P > 0.999), length of hospital stay and number of emergency room visits during follow up. The most commonly used oral antipsychotics were risperidone (0.5-7 mg/day), quetiapine (65-1200 mg/day), and olanzapine (2-25 mg/day). Using RLAI reduces the severity of disease in more difficult patients.

Switching from risperidone long-acting injectable to paliperidone long-acting injectable or oral antipsychotics: analysis of a Medicaid claims database.

This report examines relapse risk following a switch from risperidone long-acting injectable (RLAI) to another long-acting injectable antipsychotic [paliperidone palmitate (PP)] versus a switch to oral antipsychotics (APs). Truven Health’s MarketScan Multistate Medicaid Database compared relapses following switches from RLAI. New user cohorts for these two groups were created on the basis of first incidence of exposure to the ‘switched to’ drug. Groups were balanced using 1:1 propensity score matching. Time-to-event analysis assessed schizophrenia-related hospital/emergency department visits. A total of 188 patients switched from RLAI to PP, and 131 patients switched from RLAI to oral AP. Propensity score-matched cohort included 109 patients who switched to PP and 109 patients who switched to an oral AP. Patients who switched from RLAI to PP had fewer events (26 vs. 32), longer time to an event (mean 70 vs. 47 days), and lower risk of relapse (hazard ratio, 0.54; 95% confidence interval, 0.32–0.92; P=0.024) compared with those who switched from RLAI to oral AP. Switching from RLAI to PP may be associated with a lower risk for relapse and longer duration of therapy compared with switching to oral AP. Given the limitations of observational studies, these results should be confirmed by other prospective evaluations.

Co-morbid Psychiatric Symptoms Influencing the Metabolic Syndrome in Patients Treated with Long Acting Injectable Antipsychotics

Introduction In patients receiving long acting injectable (LAI) antipsychotics, the risk of medication side effects needs serious attention. Objectives The study objective is to determine in which measure co-morbid psychiatric symptoms influence the presence of the metabolic syndrome (MS). Aims Patients receiving LAI antipsychotics have a history of medication non-adherence, with recurrences and partial remissions. The aim of the study is to assess the contribution of residual psychiatric symptoms in the development of the MS in these patients. Methods The study includes two samples of psychotic remitted subjects, one including patients on olanzapine LAI and the other one patients receiving risperidone LAI for at least six months. The presence of co-morbid symptoms was assessed with BPRS. The International Federation of Diabetes diagnostic criteria for the MS were used. The following information was analyzed: medication, gender, fasting glycemia, lipid profile, waist circumference, blood pressure, and psychiatric symptoms. Results The study included 28 patients, 15 (53.6%) on olanzapine LAI, and 13 (46.4%) on risperidone LAI. 15 patients were women and 13 men. 11 (39.2%) patients were diagnosed with MS. The whole sample presented higher scores at the following BPRS items: anxiety, somatic concern, and motor retardation. Conclusions Symptoms such as anxiety, somatic concern, and motor retardation may contribute to the development of the MS. 39% of the subjects presented the criteria of the MS.

Long-Term Clinical Outcome of Patients Using Risperidone Long-Acting Injectable: The Romanian e-STAR Database

The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients; prospectively to assess the reasons of treatment initiation, medication usage patterns; to document (long-term) clinical efficacy; and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies; however, the incidence of extrapyramidal signs and weight gain was lower than expected.

A Post-Authorisation Safety Survey Evaluating Risperidone Long-Acting Injectable in Romania

Background: The main treatment objectives for schizophrenia, a chronic disease, include clinical response and symptom resolution, relapse prevention, and recovery. Objectives: The primary aim of this prospective survey is to confirm the safety of Risperidone Long-Acting Injectable (RLAI) under marketed conditions. Secondary objectives are to investigate the reasons for the initiation of treatment, effectiveness, and quality of life of patients on RLAI, alongside with compliance, clinical outcome and patients’ and clinicians’ satisfaction with treatment. Methods: In total, 1354 subjects were recruited by 253 investigational sites in Romania. All patients treated with RLAI, as decided after agreement between the physician and the patient, were eligible for inclusion in this survey. Subjects were either patients requiring a switch from previous antipsychotic medication, or patients at onset of schizophrenia. Data was collected at baseline and at one or more data collection moments. The analysis focussed on the 6 and 12 month timepoints. Results: After intake of RLAI, one third of the patients experienced a treatment-emergent AE. The most common reported AEs were psychiatric disorders related to the underlying disease (insomnia, anxiety, depression and psychotic disorder). Other reported AEs included extrapyramidal symptoms, weight gain, and endocrine disorders (amenorrhea, galactorrhea). The frequencies of these AEs were overall in agreement with those described in the current Summary of Product Characteristics. All parameters assessing drug efficacy showed a statistical significant improvement except for the number and the duration of hospitalizations which increased compared to the 6 months pre-study period. Conclusion: Treatment-emergent AEs observed during this study were consistent with the established safety profile of RLAI. In addition, treatment with RLAI resulted in the expected, statistically relevant improvement of psychiatric status in subjects eligible for such treatment, in most cases subjects diagnosed with schizophrenia and schizoaffective disorders.

The Effect of a Psycho-Educational Program on Psychiatric Symptoms, Drug Attitude and Treatment Satisfaction of Patients with Schizophrenia

The purpose of this study was to determine the effect of a Comprehensive Psycho-Educational Approach and Scheme Set (COMPASS) for patients with schizophrenia who were treated with risperidone long-acting injectable (RLAI), on their psychiatric symptoms, drug attitudes, and treatment satisfaction levels. Participants were sixty-five patients at thirteen hospitals in Japan who met ICD-10 F2 criteria for schizophrenia or schizo-affective disorder and were treated with RLAI. A correlational study design was used to measure the effect of the COMPASS on the psychiatric symptoms, drug attitudes, and treatment satisfaction levels of patients treated with RLAI. Using the following evaluation indicators: The Subjective Satisfaction to Treatment Scale (SSTS), Brief Psychiatric Rating Scale (BPRS), Global Assessment of Functioning (GAF), Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), and Drug Attitude Inventory-10 (DAI-10), measurements were taken at the beginning of the program (baseline), at the end of the program, and six months after (endpoint). Data analysis included descriptive statistics, Mann-Whitney U test or Wilcoxon signed-rank test, and Spearman’s rank correlation coefficient. Significant differences were observed in BPRS total (p < 0.001), sub-scales of BPRS positive (p < 0.001), BPRS negative (p < 0.01), BPRS affective (p < 0.01), and GAF (p < 0.001). However, there was no significant change in subscale of BPRS manic, DAI-10, DIEPSS, or SSTS but significant positive correlations were found between SSTS and DAI-10 and GAF at baseline; a negative correlation was found between SSTS and BPRS. The findings of the study suggested the benefit of using the COMPASS in conjunction with RLAI to decrease patients’ psychiatric symptomatology and improve treatment satisfaction. In addition, patient satisfaction was found to be an important factor to be considered by the psychiatrist.

Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials

BackgroundTreatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia.ObjectiveThis study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety.Data sourcesA systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013.Study selectionStudies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo.Data extractionData extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms.Data synthesisData were analyzed by applying a mixed treatment comparison competing risks model (efficacy) and using binary models (safety). There was no statistically significant difference between any study outcome, including the risk of relapse, the risk of discontinuations, and safety outcomes.ConclusionsAripiprazole once-monthly is similarly efficacious to other LAIs with relatively low rates of discontinuation due to AEs and due to reasons other than AEs than other LAIs.

Improved Treatment Acceptance and Adherence Following the Diagnosis of Multiple Malformations of Cortical Development in a Patient with Psychosis

The increased use of neuroimaging has revealed a variety of malformations of cortical development (MCDs) presenting with a range of neuropsychiatric disorders, including psychotic illnesses. Non-adherence with antipsychotic medication is a common barrier to the effective treatment for psychosis. This case illustrates improved treatment acceptance and adherence following the diagnosis of two separate MCDs (bilateral periventricular heterotopia and focal cortical dysplasia) in a 48-year-old Caucasian male with psychosis. By incorporating the neuroimaging findings into a cognitive behavioral therapy approach, the patient was more amenable to accepting psychotropic medications including long-acting risperidone injection. This in turn led to an improvement in his overall functioning. Furthermore, this case adds to the literature by describing the first instance of psychotic symptoms occurring in the setting of both bilateral periventricular heterotopia and focal cortical dysplasia.

Cost-effectiveness analysis of paliperidone palmitate versus long-acting risperidone as maintenance treatment in schizophrenia patients in Italy

Objective To evaluate the cost-effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PP) compared with long-acting injectable risperidone (RRP) in multi-episode patients (two or more relapses) with schizophrenia in Italy. Methods A pre-existing Markov model was utilized to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 12 or 24 month horizon from the perspective of the Italian National Health Service. Therapeutic strategies consisted of treatment with long-acting injectable risperidone (mean dose 37.5 mg every 2 weeks) or paliperidone palmitate (mean dose 75 mg equivalent [eq.] every month). Probability of relapse, level of adherence, side effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. The cost-effectiveness analysis considered quality adjusted life-years (QALYs) and direct medical costs. QALYs and costs (expressed in 2014 euro) were discounted at 3% annually. A one-way sensitivity analysis and a probabilistic sensitivity analysis were conducted. Results Paliperidone palmitate is the dominant long-acting injectable therapeutic option: a more effective (additional QALYs, less relapses) and less costly treatment option compared with long-acting injectable risperidone over a 12 or 24 month horizon. Results were robust when tested in sensitivity and probabilistic analyses. Conclusions Paliperidone palmitate was cost-saving from the Italian National Health Service perspective compared with long-acting injectable risperidone in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.

Cost-effectiveness analysis of paliperidone palmitate versus long-acting risperidone as maintenance treatment in schizophrenia patients in Italy

Objective To evaluate the cost-effectiveness of paliperidone palmitate (paliperidone long-acting injectable; PP) compared with long-acting injectable risperidone (RRP) in multi-episode patients (two or more relapses) with schizophrenia in Italy. Methods A pre-existing Markov model was utilized to simulate the history of a cohort of multi-episode patients transitioning through different health states on a monthly basis over a 12 or 24 month horizon from the perspective of the Italian National Health Service. Therapeutic strategies consisted of treatment with long-acting injectable risperidone (mean dose 37.5 mg every 2 weeks) or paliperidone palmitate (mean dose 75 mg equivalent [eq.] every month). Probability of relapse, level of adherence, side effects (extrapyramidal symptoms, tardive dyskinesia, weight gain and diabetes) and treatment discontinuation (switch) were derived from long-term observational data when feasible. The cost-effectiveness analysis considered quality adjusted life-years (QALYs) and direct medical costs. QALYs and costs (expressed in 2014 euro) were discounted at 3% annually. A one-way sensitivity analysis and a probabilistic sensitivity analysis were conducted. Results Paliperidone palmitate is the dominant long-acting injectable therapeutic option: a more effective (additional QALYs, less relapses) and less costly treatment option compared with long-acting injectable risperidone over a 12 or 24 month horizon. Results were robust when tested in sensitivity and probabilistic analyses. Conclusions Paliperidone palmitate was cost-saving from the Italian National Health Service perspective compared with long-acting injectable risperidone in the long-term treatment of multi-episode (two or more relapses) schizophrenia patients.

Dose and dosing frequency of long-acting injectable antipsychotics: a systematic review of PET and SPECT data and clinical implications.

Brain imaging data of antipsychotics have mainly been derived from oral antipsychotic drugs, which hampers our understanding of the requirement of dose/dosing frequency of long-acting injectable (LAI) antipsychotics for the maintenance treatment of schizophrenia. A systematic literature search was performed to identify positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies that assessed dopamine D2 receptor occupancy levels with LAI antipsychotic drugs in humans, using PubMed, EMBASE, and PsycINFO (last search, February 2013). Twenty studies (15 PET and 5 SPECT studies) were identified. The most investigated drug in these PET and SPECT studies was haloperidol decanoate (44 subjects; 11 studies), followed by risperidone LAI (24 subjects; 3 studies), olanzapine pamoate (14 subject; 1 study), and fluphenazine decanoate (12 subjects; 3 studies). The data have demonstrated high and continuous D2 receptor blockade with LAIs; the effects of LAI first-generation antipsychotics on the central nervous system may persist for several months. The prospective and cross-sectional studies showed that continuous dopamine D2 receptor blockade above 65% (ie, the lower end of the established therapeutic window for the acute phase treatment) was not always necessary for maintenance treatment for at least some of the patients. In conclusion, because of the limited brain imaging data on LAI antipsychotics, we still do not know the best way to dose them. Still, the currently available brain imaging data raises a possibility that the dosing interval of LAI antipsychotics may be extended beyond the currently indicated range in some patients.

The impact of missing data on the results of a schizophrenia study.

Missing data pose a serious challenge to the integrity of randomized clinical trials, especially of treatments for prolonged illnesses such as schizophrenia, in which long-term impact assessment is of great importance, but the follow-up rates are often no more than 50%. Sensitivity analysis using Bayesian modeling for missing data offers a systematic approach to assessing the sensitivity of the inferences made on the basis of observed data. This paper uses data from an 18-month study of veterans with schizophrenia to demonstrate this approach. Data were obtained from a randomized clinical trial involving 369 patients diagnosed with schizophrenia that compared long-acting injectable risperidone with a psychiatrist's choice of oral treatment. Bayesian analysis utilizing a pattern-mixture modeling approach was used to validate the reported results by detecting bias due to non-random patterns of missing data. The analysis was applied to several outcomes including standard measures of schizophrenia symptoms, quality of life, alcohol use, and global mental status. The original study results for several measures were confirmed against a wide range of patterns of non-random missingness. Robustness of the conclusions was assessed using sensitivity parameters. The missing data in the trial did not likely threaten the validity of previously reported results.