Previous Antipsychotic Medication Research Articles

Unmet needs with antipsychotic treatment in schizophrenia and bipolar I disorder: patient perspectives from qualitative focus groups

BackgroundSchizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I.MethodsSix 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable.ResultsAmong participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem.ConclusionsPeople living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients’ experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles.

Hepatotoxicity of Clozapine : Case report and brief Review

IntroductionClozapine is an effective Atypical antipsychotic used in the treatment of resistant schizophrenia .However it can induce liver dysfunction from a simple transient asymptomatic cytolisis (30 to50 %) toa serious fulminant liver failure (0.001 %).ObjectivesTo show the heptotoxicity potential of Clozapine and adress the importance of monitoring the liver function tests in clozapine titration to prevent sever conditionsMethodsA case report of a fifty-year old Tunisian male patient diagnosed with resistant schizophrenia who developed a hepatototoxicity under a low dose of clozapine within five days of treatment .ResultsMr F is a 50 year old patient diagnosed with schizophrenia in 2018 . He had received various antypical and typical antipsychotic treatments including ( Haloperidol , Risperidone , Amisulpride , Olanzapine ) at effective doses and minimal periods of six weeks . He had no history of systemic diseases or substance use disorder . He smokes 10 cigarettes a day . He had a history of hepatotoxicity on olanzapine. These medications have failed to resolve the persecutory delusion and auditory hallucinations , and the trial of clozapine was institued . Baseline examination and laboratory tests were normal . The previous antipsychotic medication was not continued and a dose of 25 mg clozapine was administred . A marking drowsiness was present in the fisrt days , so we decided to keep the same dose . Five days later , he had high levels of Liver function test (LFT) : Elevated aspartate ( 5 times above normal) and alanine aminotransferase levels (4 times above normal ) , white blood cell count and bilirubine levels were normal . He had no fever or jaundice . The abdominal examination showed a mild sensiblity in the right upper quadrant . Clozapine was immediatly discontinuated . 24 hours later LFT continued to escalate to 5 times greater then normal . Then it decreased continueoslyConclusionsClozapine has a potential of hepatotoxicity even at lower dose . Screening liver function tests must be integrated in survey recommendations of clozapine treatment . Further researches must be conducted to understand the mechanism of this side effect in order to avoid sever conditions .Disclosure of InterestNone Declared

Risk factors and pattern of weight gain in youths using antipsychotic drugs

Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI) z score, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMI z score for a follow-up of < 15 weeks, 15–52 weeks or > 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMI z score points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMI z score increase per week β = 0.02, 95% CI 0.01–0.03, p = 0.002). A higher baseline BMI z score and the absence of stimulant use were associated with a higher BMI z score during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMI z score.

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication.

ObjectiveThe aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER) in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.MethodsIn this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d) based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ) score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S) and Personal and Social Performance (PSP) scores.ResultsMSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55]) to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set). The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001) improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20]) and PSP score (25.5 [15.0]). A total of 174 (10.28%) patients experienced adverse events (AEs). The most common (>10 patients) events were extrapyramidal disorder (n=84, 4.96%), poor quality sleep (n=18, 1.06%) and akathisia (n=13, 0.77%). The majority of AEs were mild to moderate in severity. No deaths occurred.ConclusionTreatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia.

A magnetic resonance imaging family study of cortical thickness in schizophrenia.

Schizophrenia is associated with abnormalities in cortical thickness, including both thicker and thinner cortices than controls. Although less reliably than in patients, non-psychotic relatives of schizophrenia patients have also demonstrated both thicker and thinner cortices than controls, suggesting an effect of familial or genetic liability. We investigated cortical thickness in 25 schizophrenia patients, 26 adult non-psychotic first-degree biological relatives, and 23 community controls using the automated program FreeSurfer. Contrary to hypotheses, we found relatives of schizophrenia patients had greater cortical thickness in all lobes compared to patients and controls; however, this finding was not as widespread when compared to controls. In contrast, schizophrenia patients only demonstrated a thinner right fusiform region than controls and relatives. Our finding of greater thickness in adult biological relatives could represent a maladaptive abnormality or alternatively, a compensatory mechanism. Previous literature suggests that the nature of abnormalities in relatives can vary by the age of relatives and change across the developmental period. Abnormalities in patients may depend on lifestyle factors and on current and previous anti-psychotic medication use. Our results speak to the need to study various populations of patients and relatives across the lifespan to better understand different developmental periods and the impact of environmental factors. © 2015 Wiley Periodicals, Inc.

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.

Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication

We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness.

THE IMPACT OF TREATMENT WITH RISPERIDONE LONG-ACTING INJECTION ON THE BELGIAN HEALTHCARE SYSTEM: RESULTS FROM A BUDGET IMPACT MODEL

Substantial evidence from randomised clinical trials has demonstrated that long-acting risperidone (RLAI) is efficacious and well tolerated in patients with schizophrenia. Recently, a long-term naturalistic study of treatment practices in Belgium, the electronic Schizophrenia Treatment Adherence Registry (e-STAR), reported that treatment with RLAI is associated with improvements in adherence and long-term outcomes. The present report describes the results of a budget impact model that analysed the Belgian e-STAR data, together with other available data, over a 3-year time horizon, in order to establish the potential impact of treatment with RLAI on total healthcare costs in Belgium. The model framework combined medical resource utilisation with costs of the population of interest in order to quantify the costs, and cost offsets, of RLAI treatment. For the purpose of this budget impact model, it was assumed that among patients who would discontinue their previous antipsychotic medication, 6.7% of patients would be switched to RLAI. The overall cost savings to the Belgian healthcare system were calculated to be € 2.3 million in Year 1, € 3.7 million in Year 2 and € 4.4 million in Year 3. The majority of these cost-savings resulted from the substantial reduction in hospitalisation costs associated with RLAI treatment. This report indicates that improvements in adherence and long-term outcomes previously demonstrated for RLAI treatment in Belgium may result in substantial cost benefits to the country’s healthcare system.

Insular volume abnormalities associated with different transition probabilities to psychosis

BackgroundAlthough individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM).MethodWe investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC.ResultsThe ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group.ConclusionsGMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities.

Prevalence of metabolic syndrome in patients with schizophrenia, and metabolic changes after 3 months of treatment with antipsychotics - results from a German observational study

BackgroundThis observational study explored the prevalence of metabolic syndrome (MetS) in adult in- and outpatients with untreated or treated schizophrenia at baseline, and month-3 after initiation or switch of antipsychotic treatment.MethodsMetS-prevalence (AHA/NHLB-definition) was assessed and Clopper-Pearson 95% confidence intervals (CIs) were calculated. Factors associated with MetS were explored through univariate and multivariate logistic regressions (both visits).ResultsMetS-prevalence was 44.3% (CI 39.8;48.9) at baseline and 49.6% (CI 45.0;54.2) at month-3. Previously unmedicated patients showed the lowest baseline MetS-prevalence (24.7%, CI 18.3;32.1). MetS-prevalence was not significantly different, regardless if patients previously received typical or atypical antipsychotics. Increased MetS-risk was associated with somatic comorbidity and non-smoking at both visits, and with non-psychiatric co-medication, male sex, and increased C-reactive protein at month-3.ConclusionsAt baseline, MetS was most prevalent in patients with previous antipsychotic medication. Limited metabolic changes were observed 3 months after switch/initiation of antipsychotic therapy.Trial Registration NumberClinicalTrials.gov Identifier: n.a.

A prospective, multicentre, open-label study to evaluate the effectiveness of aripiprazole in the treatment of a broad range of patients with schizophrenia

PurposeThe aim of this study is to evaluate the effectiveness of 12-week treatment with aripiprazole in a broad range of patients suffering from schizophrenia by using a variety of physicians, caregivers and patients scales. Subjects and methodsA total of 361 in- or outpatients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia received open-label aripiprazole (10–30mg per day) in this 12-week, prospective, multicentre, uncontrolled study. The primary endpoint was the Clinical Global Impression-Improvement (CGI-I) scale which measured effectiveness of study medication, including efficacy, safety and tolerability. A variety of physician-, patient- and caregiver-rated parameters were measured to gain a complete view of the effectiveness of aripiprazole. ResultsThe effectiveness of aripiprazole treatment was demonstrated in a broad range of schizophrenia patients (CGI-I score of 3.0; 95% confidence interval: 2.8, 3.2: last observation carried forward [LOCF]) as the upper bound of the 95% CI was less than 4 (score of “no change”). Both patient and caregiver PGI-I scores (LOCF: 95% CI: 2.79, 3.09 and, 95% CI: 2.74, 3.17, respectively) corroborate this finding. Aripiprazole had a positive effect on disease severity by study end, as assessed by an increase of the (physician-rated) CGI-S scores, with 57.3% of patients having improved disease, one-third maintaining their condition (30.8%) and 11.3% with worsening symptoms (LOCF). The Investigator Assessment Questionnaire (IAQ) showed a great improvement (>50% of patients). Patients reported significantly improved quality of life and overall, 71% of patients and 67% of caregivers preferred aripiprazole to their previous antipsychotic medication (LOCF; P<0.0001 over time). ConclusionAripiprazole was effective in a broad range of patients with schizophrenia.

P03-256 - Metabolic syndrome in schizophrenia patients observed in German clinical practice - how do untreated patients differ from patients with previous antipsychotic medication?

IntroductionFor antipsychotic therapy and for schizophrenia associations with increased prevalence of metabolic syndrome (MetS) have been reported. This post-hoc analysis of a German, prospective, observational study assessed MetS-prevalence at baseline and month-3 in adults with schizophrenia.MethodsPatients previously untreated (UT, N = 108; 60.2% females) or on different antipsychotic therapy (PT, N = 367; 47.7% females) were initiated or switched to new antipsychotic medication at baseline (choice unrestricted). Analyzed were patients with complete metabolic data (fasting blood samples, physical parameters, baseline/month-3) without medication change. Prevalence of MetS (AHA/NHLB-definition) and MetS-factors were determined; 95% confidence intervals (CI) were derived from exploratory ANCOVA analyses, adjusting for treatment group and sex.ResultsPT had significantly higher MetS prevalence at both visits than UT (baseline: 49.9% [CI 44.6;55.1] vs. 25.9% [18.0;35.3]; month-3: 54.5% [49.3;59.7] vs. 32.4% [23.7;42.1]); MetS prevalence increased by 4.6% in PT and 6.5% in UT. At baseline, UT had significantly better values than PT for triglycerides (p = 0.0048), HDL-cholesterol (p = 0.0044), blood pressure (SBP/ DBP; p = 0.0090/0.0067), fasting glucose (P = 0.0304), waist circumference (p=&lt; .0001). At month-3 differences were no longer significant, except for DBP (p = 0.0227). ANCOVA for both groups pooled revealed a significant effect on change from baseline for DBP (p = 0.0227), and a sex effect for fasting triglycerides (p = 0.0006) and HDL-cholesterol (p = 0.0015 in favor of women.ConclusionPhysical and metabolic parameters initially were better in UT, compared to PT. At month-3, UT and PT values had converged, indicating that antipsychotic treatment may be associated with increased metabolic burden in an at-risk population.

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.

Switching stable patients with schizophrenia from depot and oral antipsychotics to long‐acting injectable risperidone: efficacy, quality of life and functional outcome

This international, non-randomised study evaluated maintained efficacy and safety of Risperidone Long-Acting Injectable (RLAI) compared to previous medications. To investigate the possible effect of differences in national health care systems across Europe, the UK subset efficacy, health-related quality of life (HRQoL) and functioning data are reported here. Patients with schizophrenia or other psychotic disorders, symptomatically stable on antipsychotic medication, received intramuscular injections of RLAI 25 mg (to a maximum of 50 mg) every 2 weeks for 6 months. Of 182 UK patients recruited; 79% had schizophrenia (87% paranoid), 21% other psychotic disorders; 96% had been hospitalised at sometime. Improvement in mean Positive and Negative Syndrome Scale (PANSS) total score was significant at 1 month through to endpoint (p = 0.0001). There were significant improvements in PANSS subscales (p <or= 0.001), PANSS-Marder subscores (p <or= 0.0391), and in Clinical Global Impression-Severity (p = 0.0001) at endpoint. Patients reported improvements in: HRQoL (p < 0.05), Global Assessment of Functioning (p = 0.0001) and patient satisfaction (p = 0.0001) at endpoint. The proportion of patients rating RLAI treatment as 'very good' increased from 10% to 40%. 55% (22/40) of patients hospitalised at baseline were discharged by endpoint. Sustained, significant improvement in symptom control, HRQoL and functioning was seen in stable patients treated with RLAI over 6 months following a switch from previous antipsychotic medications.

A Randomized, Open-Label Comparison of 2 Switching Strategies to Aripiprazole Treatment in Patients With Schizophrenia

Although recent treatment guidelines for schizophrenia recommend that the prior antipsychotic agent should remain stable for at least 2 weeks when aripiprazole is introduced, there is no trial-based evidence to support this strategy. This study was designed to compare this strategy with another conventional one in patients with schizophrenia. We conducted a randomized, 14-week, open-label trial to compare the following 2 switching strategies: (1) add-on of aripiprazole on a current regimen, wait for 4 weeks, and the tapering of prior antipsychotics and (2) add-on of aripiprazole and the simultaneous tapering of prior antipsychotics in patients with schizophrenia. Aripiprazole was initiated at 12 mg/d and then titrated between 12 and 30 mg. The previous antipsychotic medication was reduced biweekly by 25%. Assessments included the Clinical Global Impression Scale Schizophrenia version, the Drug-Induced Extrapyramidal Symptoms Scale, and the Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition. Impressions toward their assigned strategy were also subjectively evaluated at baseline and end point. Fifty-three patients were enrolled, and 48 patients completed this trial. No significant differences were found in changes from the baseline in the total Clinical Global Impression Scale Schizophrenia version severity, Drug-Induced Extrapyramidal Symptoms Scale, and Subjective Well-being Under Neuroleptics, Short Version, Japanese Edition scores throughout the study period between the 2 strategies. Both strategies were judged by subjects to be tolerable and favorable without between-group differences. In conclusion, both strategies were found to be objectively safe and well tolerated. Taken together with similar results from subjective assessments, it would be reasonable to choose either of these 2 strategies in clinical practice based on a patients' preference.

Cost-Effectiveness Analysis of Switching Antipsychotic Medication to Long-Acting Injectable Risperidone in Patients with Schizophrenia

The availability of long-acting injectable risperidone may increase adherence to antipsychotic treatment and lead to improved clinical and economic outcomes for patients with schizophrenia. To investigate the cost effectiveness of treatment with long-acting injectable risperidone compared with previous antipsychotic regimens in patients with schizophrenia enrolled in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain. e-STAR is an international, long-term, ongoing, observational study of schizophrenia patients who, during their routine course of clinical practice, are started on a new antipsychotic treatment. In e-STAR, data are collected at baseline, retrospectively over a minimum period of 12 months and up to a maximum of 24 months, and prospectively at 3-month intervals for 24 months after the start of a new antipsychotic drug. For the purpose of this study, patients who started treatment with long-acting injectable risperidone during their routine clinical management and were enrolled in the e-STAR study in Spain were eligible. The effectiveness of long-acting injectable risperidone compared with previous antipsychotic treatment, defined as the absence of hospitalizations or relapses, was assessed at 12 and 24 months of treatment. Acquisition costs of antipsychotic drug therapy were based on the official registered price. Drug prices from source were in euro, year 2005 values; hospital costs from source were in euro, year 2001 values, and were inflated to reflect 2005 costs. Complete follow-up data were available for 788 patients at 12 months after starting long-acting injectable risperidone and for 757 patients at 24 months. In terms of effectiveness, at 12 months after switching to long-acting injectable risperidone, there was a higher percentage of patients who did not require hospitalization (89.1%), did not relapse (85.4%) or neither required hospitalization nor relapsed (82.4%) as compared retrospectively with the same period for the previous treatment (67%, 47.8% and 59.8%, respectively). The corresponding figures at 24 months also favoured treatment with long-acting injectable risperidone (85.2% vs 60%, 88.5% vs 47.4% and 77% vs 53.6%, respectively). Treatment with long-acting injectable risperidone was associated with higher medication costs per month compared with previous antipsychotic medication after 12 (euro 405.80 vs euro 128.16) and 24 months (euro 407.33 vs euro 142.77) of follow-up. Cost effectiveness per month per patient was lower for risperidone than previous antipsychotic medication in the three patient scenarios: without hospitalization (euro 539.82 vs euro 982.13), without relapse (euro 519.67 vs euro 1242.03) and without hospitalization and without relapse (euro 597.22 vs euro 1059.39). Treatment with long-acting injectable risperidone compared with previous antipsychotic medications resulted in a higher number of patients not requiring hospitalization, not relapsing, and not requiring hospitalization and not showing relapse, resulting in risperidone being more cost effective per month per patient.It is important to note that real-world variations in adherence would automatically be controlled from within a randomized control trial, and hence, any evaluation of variations in adherence inevitably requires a real-world focus. On the basis of these findings, which were obtained in real-world clinical practice, long-acting injectable risperidone is predicted to be the dominant strategy because it results in effective symptom control and direct medical cost savings. However, because of limitations in methodology, any conclusions should, at this stage, be treated as tentative, and confirmation in more detailed follow-up studies is required. Cost-effectiveness comparisons based on experimental evaluations of relapse minimization strategies are also required. In order to avoid estimation biases in the future, a prospectively designed study is needed.

Analisi costo-efficacia dello switch da un trattamento antipsicotico a risperidone iniettabile a rilascio prolungato in pazienti con schizofrenia

The aim of this economic evaluation was to investigate the cost effectiveness of treatment with long-acting injectable risperidone compared with previous antipsychotic regimens in patients with schizophrenia enrolled in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain. In e-STAR, data are collected at baseline, retrospectively over a minimum period of 12 months and up to a maximum of 24 months, and prospectively at 3-month intervals for 24 months after the start of a new antipsychotic drug. In terms of effectiveness, at 12 months after switching to long-acting injectable risperidone, there was a higher percentage of patients who did not require hospitalization (89.1%), did not relapse (85.4%) or neither required hospitalization nor relapsed (82.4%) as compared retrospectively with the same period for the previous treatment (67%, 47.8%, and 59.8%, respectively). Cost effectiveness per month per patient was lower for risperidone than previous antipsychotic medication in the three patient scenarios: without hospitalization (€ 539.82 vs € 982.13), without relapse (€ 519.67 vs € 1242.03) and without hospitalization and without relapse (€ 597.22 vs € 1059.39).

Clinical predictors of therapeutic response to clozapine in a sample of Turkish patients with treatment-resistant schizophrenia

Background Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. It would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS. Methods This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. Results Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks. Conclusion A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms.

High-Dose Olanzapine Orally Disintegrating Tablets for Treatment-Resistant Psychosis

Sir: Olanzapine is a thienobenzodiazepine antipsychotic that has a broad in vitro affinity for several receptors, including serotonergic, cholinergic, dopaminergic, and adrenergic receptors.1 Olanzapine is approved for treatment of psychoses at doses up to 20 mg/day.2 New research suggests benefits of higher doses of olanzapine.3 Anecdotal case reports highlight the benefits of olanzapine at 50 mg/day in patients with refractory schizoaffective disorders.4 In the United Kingdom, a trial of high-dose olanzapine (range, 20–60 mg/day) showed moderate to marked clinical improvement in patients with clozapine-resistant schizophrenia.5 Treatment-resistant psychosis is generally treated with clozapine, which requires frequent blood tests and is associated with several side effects, including weight gain, sedation, and agranulocytosis. Regular blood draws and the myriad of side effects often contribute to poor compliance with clozapine. However, when patients fail clozapine, few other options exist. We describe a patient who, after failing clozapine treatment, responded to the orally disintegrating formulation of high-dose olanzapine. Case report. Mr. A, a 44-year-old man, had a long history of schizoaffective disorder, bipolar type (DSM-IV criteria). Symptoms started at the age of 21 years and included auditory hallucinations, delusions of grandeur, and hyper-religiosity. He was hospitalized multiple times and, at the time of the presentation described here (1999), was being treated in an assertive community training (ACT) program. After several medication failures, including trials of risperidone, quetiapine, ziprasidone, and olanzapine, he started clozapine treatment. All previous antipsychotic medications were administered for an adequate duration at an adequate dose; the maximum dose of olanzapine prescribed in the past was 20 mg/day. He developed disabling fatigue soon after initiation of treatment with clozapine. He often missed his appointments because of his dislike of frequent blood tests; however, after staff members from ACT began working closely with Mr. A, his compliance improved, as demonstrated by therapeutic serum clozapine levels, but his psychosis continued. He subsequently stopped clozapine and had a relapse of symptoms, including an increase in hallucinations and delusions that required hospitalization. During hospitalization, Mr. A was administered the orally disintegrating formulation of olanzapine; this formulation improved his medication adherence, but his psychotic symptoms continued. After 2 weeks of treatment with olan-zapine, the dose was increased to 40 mg daily. He reported a decrease in auditory hallucinations and hyper-religiosity and continued to deny side effects. His family reported improvement in his social functioning and cognition. On the basis of his symptoms, olanzapine was titrated further to 60 mg daily. His condition improved, and he experienced no side effects. Over the next 3 months, his psychosis continued to decrease. His Brief Psychiatric Rating Scale6 score decreased from l4 (with clozapine) to 3 (with orally disintegrating olanzapine) on objective evaluation and from 6 to 2 on subjective evaluation. Disorganized thoughts and somatic preoccupations decreased significantly. His serum olanzapine level was 108.3 ng/mL (therapeutic range: 20–60 ng/mL). Mr. A had gained weight from 210 lb to 276 lb while taking a combination of valproic acid and clozapine prior to initiation of olanzapine. Weight gain and glucose dysregulation are known side effects associated with use of olanzapine.7–9 Several measures, including periodic monitoring of weight, diet management, and encouragement for regular exercise, were provided as part of the ACT program to counter the above-mentioned side effects. Mr. A was compliant with the recommendations and lost 10 lb over a period of 2 years. Periodic glucose monitoring showed no glucose dysregulation. Over the next year, he required no hospitalization, his level of independent functioning improved, and he resumed his education at a community college. The patient's improvement was probably multifactorial, but higher doses of olanzapine and the orally disintegrating formulation might have played a part. Use of olanzapine was not accompanied by the fatigue associated with clozapine and improved medication adherence. Prescribing guidelines for olanzapine suggest a maximum dose of 20 mg/day. Higher-dose olanzapine treatment has not been well researched, but in our patient, it was efficacious and produced fewer side effects than clozapine. Further, obviating the need for blood draws and use of orally disintegrating pills improved medication adherence and reduced the need for monitoring. Most importantly, the patient's symptoms improved without additional side effects. Since he had previously not responded to low-dose olanzapine, clinical improvement after starting higher doses of olanzapine suggests causality. Although more clinical trials are needed to establish the benefits of high-dose olanzapine treatment, it may be an option for patients with treatment-resistant psychosis. High-dose olanzapine in the orally disintegrating formulation offers several advantages, including ease of administration, limited need for blood draws, and potential for improved mood stabilization.

Symptom control, functioning and satisfaction among Swiss patients treated with risperidone long-acting injectable

Objective: To investigate antipsychotic efficacy and tolerability of risperidone long-acting injectable (RLAI) in Swiss patients with schizophrenia or other psychotic disorders, changed directly from their previous antipsychotic medication. Methods: Patients symptomatically stable for ≥1 month on their previous medication and considered to require a treatment change, received 25 mg RLAI (increased to 37.5 or 50 mg, if required) every 2 weeks for 6 months. Results: Of 60 patients enrolled (68.3% male, average age 40.4 years), most (81.7%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were with atypical antipsychotics (58.3% of patients), depot (38.3%) and conventional oral (13.3%) neuroleptics. Mean total PANSS scores were significantly reduced from baseline to treatment endpoint (76.1 vs. 64.4, P<0.001), as were all PANSS subscale and symptom factor scores. The CGI, GAF, and patient satisfaction with treatment were also significantly improved at endpoint (P<0.001). At endpoint, 37.0% of patients rated their satisfaction as “very good” compared with only 4.3% at baseline. Mean scores for total ESRS and Parkinsonism subscales were significantly reduced at endpoint (P<0.001). Conclusion: Treatment with RLAI significantly improved disease symptoms, functioning, patient satisfaction, and reduced movement disorders. It provides an important option for long-term treatment of patients with psychotic disorders.