Depot Haloperidol Research Articles

Antipsychotic Polypharmacy and Its Relation to Metabolic Syndrome in Patients With Schizophrenia: An Egyptian Study.

Few studies have examined the relationship between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. Some studies suggest that antipsychotic polypharmacy may be associated with greater metabolic risk, whereas other studies suggest that this is uncertain. To date, there have been no studies in Egypt or the Arab world that have investigated this relationship. We sought to compare subjects with schizophrenia receiving antipsychotic polypharmacy and monotherapy as regards metabolic outcomes and to investigate medication-related factors associated with metabolic syndrome. We recruited 118 subjects with schizophrenia and compared between those receiving antipsychotic polypharmacy (86 subjects) and monotherapy (32 subjects) as regards demographic, clinical, metabolic, and antipsychotic medication characteristics. We examined the effect of antipsychotic-related factors an outcome of metabolic syndrome. The prevalence of metabolic syndrome in our sample was 38.1%. Except for gender, there was no statistically significant difference as regards demographic and clinical characteristics, rates of metabolic syndrome, or for individual metabolic parameters. We found a statistically significant difference (P < 0.05) between the 2 groups as regards the number, dose, and duration of intake and for the number of subjects receiving typical antipsychotics (oral and depot) and a number of individual antipsychotic medications. Using logistic regression, receiving haloperidol depot was the only antipsychotic-related factor predictive for metabolic syndrome. The prevalence of metabolic syndrome does not differ in schizophrenia whether patients are receiving polypharmacy and monotherapy nor do they differ for individual metabolic parameters. Most antipsychotic-related characteristics did not predict for metabolic syndrome.

A Review of Clinical and Economic Evaluations Applied to Psychotropic Therapies Used in the Treatment of Schizophrenia in Argentina.

Schizophrenia is considered a serious mental disorder that affects over 21 million people worldwide, and is associated with disability that frequently affects the patient’s educational and working performance. In Argentina, two of the most widely used antipsychotics in the treatment of this disorder are haloperidol and risperidone. Both are provided free to patients without health coverage in public healthcare facilities. In this paper we seek to review the clinical and economic benefits of prescribing psychotropic therapies based on haloperidol (a first-generation antipsychotic that is part of the butyrophenone group of drugs) versus risperidone [an atypical or second-generation antipsychotic (neuroleptic) drug] in adult patients who have been diagnosed with schizophrenia. To achieve this objective, an exhaustive search of relevant articles published between 2006 and April 2017 was conducted. This literature search showed that intermittent treatment usually fails to prevent relapses due to irregular protection, therefore continuous treatment is more effective. Although the injectable formats of both drugs [haloperidol depot and long-acting injectable risperidone (LAIR)] have not proven to have significant differences with regard to clinical effectiveness vis-à-vis the tablet formats, they showed a lower cost-effectiveness ratio by reducing patients’ relapses. Moreover, LAIR exhibits superior cost effectiveness compared with haloperidol depot. Haloperidol is less expensive than risperidone but is less cost effective; in comparison with haloperidol, treatment with risperidone produces (1) an improvement in quality-adjusted life-years, and (2) a significant reduction in negative symptoms. In most cases, antipsychotic treatments are effective in controlling the positive and negative symptoms associated with schizophrenia, allowing patients to live in their communities without any impairments. However, it is extremely important to combine pharmacological treatment with other measures that constitute psychosocial therapy.

Case Report: Kikuchi disease and lupus erythematosus in a schizophrenic patient with extreme anorexia

Kikuchi-Fujimoto Disease (KFD) is a rare benign condition of necrotizing histiocytic lymphadenitis. The manifestations include localized lymphadenopathy, fever and weight loss. KFD has been described in association with systemic lupus erythematosus (SLE). This case describes a patient whose anorexia and deterioration were first interpreted as a manifestation of her schizophrenia. Diagnosis of a rare organic treatable disease resulted in improvement in her life threatening condition. A 36-year-old woman with schizophrenia treated with depot haloperidol experienced a general deterioration, extreme anorexia and fever up to 38°C for few months. On examination she was cachectic weighing 33kg and confined to bed. She had malar rash, cough, fever, and enlarged axillary lymph nodes. Primary laboratory tests revealed pancytopenia and LDH 1254U/L. For suspected atypical pneumonia, therapy with ceftriaxone and azithromycin was started with no improvement. Cotrimoxazole was initiated and appropriate tests ruled out PCP, TB and HIV. Her condition deteriorated further demonstrating neutropenia 600mm 3 , and coombs positive hemolytic anemia with hemoglobin 8g/L. Further lab tests revealed: positive ANA with titer of 1:60, elevated anti-smith, anti-RNP levels more than 200U. Anti-double stranded DNA was negative, C3: 62mg/dL, 24 hour protein urine collection showed 3.8g with no casts in urinary sediment. A total body CT scan revealed pleural effusion, enlarged axillary and mediastinal lymph nodes. A biopsy form a right axillary lymph node revealed histiocytic necrotizing lymphadenitis. The diagnosis of KFD associated with SLE was made based on a malar rash, pleural and pericardial effusion, nephrotic range proteinuria, positive ANA, Anti-Smith, Anti-RNP, pancytopenia and a positive coombs test. The pathology result was consistent with KFD. A follow up cardiac echocardiogram showed a new large pericardial effusion with right atrial compression and tachycardia. Parallel to high dose IV methylprednisolone treatment, a pericardiocentesis was performed and only 250ml were aspirated because of septations. A sternotomy with a pericardial window was performed. Following this procedure the patient's condition improved. Therapy with azathioprine 75mg/day and Prednisone 40mg/day was started. A second CT scan showed that the previously shown lymph nodes disappeared. Physiotherapy was started on admission and continued ongoing. Five months after admission the patient maintains a significant improvement in her daily function and activity. She gained 15kg. There was a decrease in her proteinuria and increase in the C3 level to 93 with a normal blood count. To conclude, we describe a case of KFD, a rare disease evolving in a SLE patient. Both diagnoses were made relatively late in the course of a chronic schizophrenic patient, leading to the appropriate therapy and saving her life.

A Review of Clinical and Economic Evaluations Applied to Psychotropic Therapies Used in the Treatment of Schizophrenia in Argentina

Introduction: Schyzophrenia is considered to be a serious mental disorder that affects over 21 million people all over the world, and is associated with disability that frequently affects the patient´s educational and working performance. In Argentina, two of the most widely used anti-psychotics in the treatment of this disorder are Haloperidol and Risperidone. Both of them are provided for free to patients without health coverage in the public health care facilities. Objective: In this paper we seek to evaluate the clinical and economic benefits of prescribing psychotropic therapies based on Haloperidol (a first-generation antipsychotic that is part of the group of the butyrophenone drugs) versus Risperidone (an atypical or second-generation antipsychotic-neuroleptic drug) on adult patients that have been diagnosed with schizophrenia. Methodology: An exhaustive survey of relevant articles published since 2006 up to the present day was carried out. Conclusions: Intermittent treatment usually fails to prevent relapses, due to irregular protection. That is why continuous treatment is more effective. Although the injectable formats of both drugs (Haloperidol DEPOT and long-term acting injectable Risperidone) have not proved to have significant differences regarding clinical effectiveness vis-a-vis the tablet formats, they show a higher cost-effectiveness ratio by reducing patients’ relapses. Moreover, long-term acting injectable Risperidone exhibits a higher ratio of clinical cost-benefits than Haloperidol DEPOT. Haloperidol is less expensive than Risperidone but shows a lower cost-effectiveness ratio; in comparison with Haloperidol, the treatment with Risperidone produces i) an improvement on the QALYs and iii) a significant reduction of the negative symptoms. Discussion: In most cases antipsychotic treatments are effective to control the positive and negative symptoms associated to schizophrenia, allowing patients to live in their communities without any impairments. However, it is extremely important to combine pharmacological treatment with other measures that constitute what is called psychosocial therapy.

Vitamin E and essential polyunsaturated fatty acids supplementation in schizophrenia patients treated with haloperidol

Objectives: Previously, oxidative damage has been associated with severity of clinical symptoms and supplementation with antioxidants and essential polyunsaturated fatty acids (EPUFAs) was proposed to have beneficial effects in schizophrenia. We evaluated the effects of supplementation with EPUFAs and vitamin E in patients treated with haloperidol depot injection.Design: This was a double-blind randomized placebo-controlled study with four arms (Placebo, vitamin E, EPUFAs, and vitamin E + EPUFAs). Biomarkers of oxidative stress, neurochemistry, psychopathology, and extrapyramidal symptoms were assessed at baseline and after 4 months.Results: In EPUFAs group of patients, reduced glutathione concentration was increased compared to placebo. Concentration of oxidized glutathione was decreased in patients receiving vitamin E. In addition, compared to placebo a non-significant trend of increased activity of catalase and superoxide dismutase was observed in all three treatment groups. Patients receiving vitamin E experienced less motor retardation. No difference in extrapyramidal symptoms was found.Discussion: Our study indicates that supplementation with vitamin E and EPUFAs may improve the antioxidative defense, especially glutathione system, while there is no major effect on symptoms severity. Supplemental treatment with EPUFAs and vitamin E in schizophrenia patients treated with haloperidol is potentially beneficial and a larger independent study appears warranted.

A neuroleptic malignant syndrome case with haloperidol depot

The development of depot antipsychotics are facilitated incompitable patient’s treatment process for in terms of chronic disease course. One of the disadvantages of depot antipsychotics, having various advantages and disadvantages, neuroleptic malignant syndrome (NMS) rate is higher than the oral form. NMS, rare but can be fatal, is an idiosyncratic reaction characterized by confusion, hyperthermia, autonomic dysfunction, muscle rigidity after use of neuroleptics. In this case, a schizophrenia patient used to haloperidol depot, named haldol decanoate in abroad used since1986 (Europe-US) but recently introduced in Turkey, with NMS was reported.

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.

Tardive Dyskinesia Induced by a Switch From Haloperidol Depot to Paliperidone Palmitate

Tardive Dyskinesia Induced by a Switch From Haloperidol Depot to Paliperidone Palmitate

1835 – Antipsychotics for schizophrenia: too little progress after 50 years?

Introduction ll antipsychotics act via dopaminergic receptor antagonism. This pharmacology is shared by all first (FGA) & second (SGA) generation antipsychotics. We reviewed the efficacy & safety of all antipsychotics in clinical use for BMJ Clinical Evidence (Barry et al 2012). Methods & questions Our paper summarises key results from this systematic review based on comprehensive literature search of the Medline, Embase, Cochrane Library, and other databases including safety information from the FDA and MHRA in UK. The main clinical questions of interest were: What is the efficacy of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? How effective are treatments for people with schizophrenia resistant to standard antipsychotic drugs? Results We found 51 systematic reviews, RCTs, or observational studies that met our inclusion/quality criteria and performed GRADE analysis to assess quality of evidence. Key results are presented for efficacy & safety for: amisulpiride, chlorpromazine, clozapine, depot haloperidol, haloperidol, olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine, aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol, zuclopenthixol, depot zuclopenthixol, and clozapine. Discussion The evidence for some ‘standard’ treatments is surprisingly weak. Up to 1/3 -1/2 of patients fail to respond to currently available antipsychotics, and all antipsychotics cause side effects in most people. This downbeat conclusion is not surprising, given clinical experience and the common mechanism of action of all antipsychotics. More efficacious antipsychotic medication will only be developed from understanding the biological pathogenesis of schizophrenia.Barry S, Gaughin T, and Hunter R. Schizophrenia. BMJ Clinical Evidence 13 July 2012. http://clinicalevidence.bmj.com/x/systematic-review/1007/overview.html .

Association of SOD2, GPX1, CAT, and TNF Genetic Polymorphisms with Oxidative Stress, Neurochemistry, Psychopathology, and Extrapyramidal Symptoms in Schizophrenia

There is a growing body of evidence confirming the involvement of oxidative stress and inflammation in pathogenesis of schizophrenia. Inter-individual variation in antioxidant capacity caused by different genetic profile could potentially influence patient's susceptibility to oxidative damage. In this study we evaluated the polymorphisms of manganese superoxide dismutase SOD2Val16Ala, glutathione peroxidase GPX1Pro200Leu, catalase CAT-262C>T and CATc.66+78C>T, and tumour necrosis factor-alpha TNF-308G>A by assessing their association with biomarkers of oxidative stress, neurochemistry, psychopathology of schizophrenia and extrapyramidal symptoms in Caucasian schizophrenia patients treated with haloperidol depot. TNF-308G>A was associated with the increased risk of parkinsonism. No major role of polymorphism of SOD2Val16Ala, CAT-262C>T nor GPX1Pro200Leu in psychopathology of schizophrenia or extrapyramidal symptoms was observed. SOD2Val16Ala polymorphism was associated with dopamine plasma concentration and blood concentration ratio between reduced and oxidised form of glutathione, while GPX1Pro200Leu was related with concentration of reduced glutathione. CATc.66+78C>T was associated with noradrenaline plasma concentration and PANSS negative score. PANSS positive and general scores, were associated with the increased risk of tardive dyskinesia. PANSS positive, negative, and general scores, and GAF score were all associated with the increased risk of akathisia.

Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis

Relapse prevention with antipsychotic drugs compared with placebo in patients with schizophrenia has not been sufficiently addressed by previous systematic reviews. We aimed to assess the association between such drugs and various outcomes in patients with schizophrenia to resolve controversial issues. We searched the Cochrane Schizophrenia Group's specialised register for reports published before Nov 11, 2008; and PubMed, Embase, and ClinicalTrials.gov for those before June 8, 2011. We also contacted pharmaceutical companies and searched the reference lists of included studies and previous reviews. Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible. Our primary outcome was relapse between 7 and 12 months. We also examined safety and various functional outcomes. We used the random effects model and verified results for the primary outcome with a fixed effects model. Heterogeneity was investigated with subgroup and meta-regression analyses. We identified 116 suitable reports from 65 trials, with data for 6493 patients. Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27%vs placebo 64%; risk ratio [RR] 0·40, 95% CI 0·33-0·49; number needed to treat to benefit [NNTB] 3, 95% CI 2-3). Fewer patients given antipsychotic drugs than placebo were readmitted (10%vs 26%; RR 0·38, 95% CI 0·27-0·55; NNTB 5, 4-9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference -0·62, 95% CI -1·15 to -0·09) and fewer aggressive acts (2%vs 12%; RR 0·27, 95% CI 0·15-0·52; NNTB 11, 6-100) with antipsychotic drugs than with placebo. Employment data were scarce and too few deaths were reported to allow significant differences to be identified. More patients given antipsychotic drugs than placebo gained weight (10%vs 6%; RR 2·07, 95% CI 2·31-3·25), had movement disorders (16%vs 9%; 1·55, 1·25-1·93), and experienced sedation (13%vs 9%; 1·50, 1·22-1·84). Substantial heterogeneity in size of effect was recorded. In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or second-generation drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0·31, 95% CI 0·21-0·41) more than did oral drugs (0·46, 0·37-0·57; p=0·03); depot haloperidol (RR 0·14, 95% CI 0·04-0·55) and fluphenazine (0·23, 0·14-0·39) had the greatest effects. The effects of antipsychotic drugs were greater in two unblinded trials (0·26, 0·17-0·39) than in most blinded studies (0·42, 0·35-0·51; p= 0·03). In a meta-regression, the difference between drug and placebo decreased with study length. Maintenance treatment with antipsychotic drugs benefits patients with schizophrenia. The advantages of these drugs must be weighed against their side-effects. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality of these drugs. German Ministry of Education and Research.

Long-Acting Injectable Antipsychotics for the Maintenance Treatment of Bipolar Disorder

Depot antipsychotics have been used as a strategy to reduce non-adherence to medications in schizophrenia and bipolar disorder (BD). This article reviews the literature on the efficacy and safety of first- and second-generation depot antipsychotics (FGDA and SGDA, respectively) for the maintenance treatment of BD. Although FGDA have been studied in BD, they have not been approved for use in this disease. Among the SGDA, only depot risperidone has been studied and approved for the maintenance treatment of BD. We found eight studies on FGDA (three on flupenthixol, two on depot haloperidol, one on fluphenazine and flupenthixol, two on a mix of diverse antipsychotics) and ten studies on SGDA (all on depot risperidone). Differences in efficacy and safety were found between the two classes of depot antipsychotics. Although FGDA may be effective in reducing manic relapses, they possibly increase the risk of worsening depression. Depot risperidone is effective as a maintenance treatment in BD with effect noted predominantly for preventing mania. However, no worsening in depression was observed. Depot risperidone also is better tolerated than FGDA, mainly in relation to extrapyramidal symptoms. Studies with the new depot antipsychotics, olanzapine pamoate and paliperidone palmitate, are needed in BD patients. Further, there is currently little information on the metabolic changes (apart from bodyweight gain) that may occur with the use of depot risperidone in patients with bipolar disorder, and this issue needs further investigation.

The threshold rate of oral atypical anti-psychotic adherence at which paliperidone palmitate is cost saving

Objective:To identify, estimate, and compare ‘real world’ costs and outcomes associated with paliperidone palmitate compared with branded oral atypical anti-psychotics, and to estimate the threshold rate of oral atypical adherence at which paliperidone palmitate is cost saving.Methods:Decision analytic modeling techniques developed by Glazer and Ereshefsky have previously been used to estimate the cost-effectiveness of depot haloperidol, LAI risperidone, and, more recently, LAI olanzapine. This study used those same techniques, along with updated comparative published clinical data, to evaluate paliperidone palmitate. Adherence rates were based on strict Medication Event Monitoring System (MEMS) criteria. The evaluation was conducted from the perspective of US healthcare payers.Results:Paliperidone palmitate patients had fewer mean annual days of relapse (8.7 days; 6.0 requiring hospitalization, 2.7 not requiring hospitalization vs 17.8 days; 12.4 requiring hospitalization, 5.4 not requiring hospitalization), and lower annual total cost ($20,995) compared to oral atypicals (mean $22,481). Because paliperidone palmitate was both more effective and less costly, it is considered economically dominant. Paliperidone palmitate saved costs when the rate of adherence of oral atypical anti-psychotics was below 44.9% using strict MEMS criteria. Sensitivity analyses showed results were robust to changes in parameter values. For patients receiving 156 mg paliperidone palmitate, the annual incremental cost was $1216 per patient (ICER = $191 per day of relapse averted). Inclusion of generic risperidone (market share 18.6%) also resulted in net incremental cost for paliperidone palmitate ($120; ICER = $13). Limitations of this evaluation include use of simplifying assumptions, data from multiple sources, and generalizability of results.Conclusions:Although uptake of LAIs in the US has not been as rapid as elsewhere, many thought leaders emphasize their importance in optimizing outcomes in patients with adherence problems. The findings of this analysis support the cost-effectiveness of paliperidone palmitate in these patients.

Quality of life of schizophrenic patients treated with haloperidol depot and injection preparation of long-lasting risperidone

In the last decades psychiatric patients' quality of life attracts great attention of researchers. Improving the quality of life of schizophrenic patients is increasingly becoming an imperative in pharmacological therapy. Analysis of certain aspects of quality of life in patients with schizophrenia treated with depot formulations of a typical antipsychotic (haloperidol) and injection preparation of a long-acting atypical antipsychotic (risperidone). Research was conducted as a cross-sectional study that included 60 patients of both genders. Examinees diagnosed with schizophrenia (ICD-10, F20.0-F20.9) were divided into two groups: the group of patients that received haloperidol depot (n = 30) and the group of patients that received injection preparation of long-acting risperidone (n = 30). In order to assess the quality of life, social functioning scale (SFS), satisfaction with life scale (SWLS), and short version of World Health Organization quality of life scale (WHO-QoL-Brief) were applied. Results showed statistically significant differences when it comes to social activity and satisfaction with life in favour of patients treated with injection preparation of long-acting risperidone. Examinees from this group were much more satisfied with themselves, their health and sleep compared to those on haloperidol depot. There was no statistically significant difference found on the quality of life scale. Applying the scales for the assessment of the quality of life of schizophrenic patients in terms of psychosocial functioning, statistically significant difference between groups was found. Results showed higher scores in the group of patients treated with injection preparation of long-acting risperidone concerning social activities and life satisfaction.

Resolution of Tardive Dyskinesia After Addition of Aripiprazole to Haloperidol Depot

Resolution of Tardive Dyskinesia After Addition of Aripiprazole to Haloperidol Depot

Depot Haloperidol Treatment in Outpatients With Schizophrenia on Monotherapy: Impact of CYP2D6 Polymorphism on Pharmacokinetics and Treatment Outcome

Haloperidol and several other antipsychotic drugs are at least partially metabolized by the polymorphic cytochrome P450 2D6 (CYP2D6). The interindividual variation in metabolic capacity of CYP2D6 might be of importance when dosing. In this study, 26 outpatients with schizophrenia and depot haloperidol as monotherapy were genotyped. The authors found 1 patient with no functional alleles, 8 with one functional allele, 16 with two functional alleles, and 1 with three functional alleles. The daily dose of haloperidol ranged from 0.45 to 14.29 mg. Steady state plasma concentrations were measured at peak (range, 1.6-67 nmol/L) and at trough (range, 1.0-49 nmol/L). The Positive and Negative Syndrome scale for Schizophrenia and the Extrapyramidal Symptom Rating Scale were used to evaluate the clinical effect. The authors found a clear correlation between haloperidol plasma concentration and number of active CYP2D6 alleles. No correlation was found between plasma concentration of haloperidol or number of CYP2D6 alleles and treatment outcome or side effects. A model to predict plasma concentration from dose and number of active CYP2D6 alleles was formed from the obtained data by means of multiple linear regression.

Antipsychotiques atypiques et dysfonction sexuelle : à propos de cinq cas associés à la rispéridone

Antipsychotiques atypiques et dysfonction sexuelle : à propos de cinq cas associés à la rispéridone

Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany

Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and for patients at high risk of being non-compliant. The long-acting risperidone strategy was calculated to avoid 0.23 and 0.33 relapses per patient, decrease the cumulative symptom score by 25 and 33 points, and decrease the costs by 2017 Euro and 6096 Euro per patient (1608 Euro and 5422 Euro discounted), compared with the haloperidol depot and olanzapine strategies, respectively, over a 5-year period (year of costing 2004). Among high-risk non-compliant patients, long-acting risperidone was estimated to avoid 0.23 and 0.47 relapses and save 4822 Euro and 10,646 Euro per patient (4107 Euro and 9490 Euro discounted), compared with the haloperidol depot and olanzapine strategies, respectively. Sensitivity analyses showed that the results were robust and mainly sensitive to changes in the reported relative effectiveness of atypical and conventional formulations for preventing symptom recurrence, and in the relative compliance with oral and long-acting formulations. In this model, long-acting risperidone is a dominant strategy compared with a haloperidol depot or oral atypical antipsychotic agent, being both more effective and less costly over a 5-year period. Results for long-acting risperidone are even more favourable among patients at high risk of being noncompliant or with more severe disease.

Modelling the impact of compliance on the costs and effects of long-acting risperidone in Canada

Schizophrenia is a chronic, relapsing disease that requires more healthcare resources to manage than any other single psychiatric illness. The main cost of treatment is hospitalization as a result of the exacerbation of symptoms often caused by poor compliance. Although the costs of hospitalization and relapse have been well documented, the differential effects of various medications on healthcare expenditure are still being determined. The aim of the present study was to estimate the cost effectiveness of long-acting risperidone in the treatment of high-risk, non-compliant patients with schizophrenia over a 5-year period in Canada. A discrete event model was developed comparing three scenarios, each with a different starting treatment: haloperidol depot, long-acting risperidone or oral risperidone. Second and third-line treatment options were olanzapine and clozapine, respectively, for all three scenarios. On the basis of 3000 simulated patient characteristics, the model generated individual patient histories. Outcomes included the number and duration of psychotic episodes, the cumulative Positive and Negative Syndrome Scale (PANSS) score and direct medical costs. The time horizon of the model was 5 years and a 5% discount rate was used for costs and effects. The perspective of the model was that of the Canadian healthcare system. After 5 years, treatment with long-acting risperidone saved Canada dollars 6908 and Canada dollars 13,130 (discounted) and avoided 0.28 and 0.54 relapses per patient, compared with haloperidol depot and oral risperidone, respectively. In this model, initiating treatment of high-risk, non-compliant patients with schizophrenia with long-acting risperidone was the dominant strategy. With long-acting risperidone, direct costs were lower and clinical effectiveness was greater, compared with haloperidol depot or oral risperidone, during years 4 and 5.

Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA

The availability of long-acting risperidone injection may increase adherence and lead to improved clinical and economic outcomes for individuals with schizophrenia. The objective of this study was to assess the cost effectiveness of long-acting risperidone, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot in patients with schizophrenia over 1 year from a healthcare system perspective. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were utilized to populate a decision analytical model comparing the seven treatment alternatives. The model captured rates of patient compliance, the rates, frequency and duration of relapse, incidence of adverse events, and healthcare resource utilization and associated costs. Primary outcomes were expressed in terms of percentage of patients relapsing per year, number of relapse days per year (number and duration of relapses per patient per year), and total direct 2003 medical cost per patient per year. On the basis of model projections, the proportions of patients experiencing a relapse requiring hospitalization in 1 year were 66% for haloperidol depot, 41% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 26% for long-acting risperidone, whereas the proportions of patients with an exacerbation not requiring hospitalization were 60% for haloperidol depot, 37% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 24% for long-acting risperidone. The mean number of days of relapse requiring hospitalization per patient per year were 28 for haloperidol depot, 18 for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 11 for long-acting risperidone, whereas the mean number of days of exacerbation not requiring hospitalization were eight for haloperidol depot, five for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and three for long-acting risperidone. This would translate into direct medical cost savings with long-acting risperidone compared with oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot of US dollars 161, 1425, 508, 259, 1068, and 8224, respectively. These findings were supported by sensitivity analyses. The utilization of long-acting risperidone is predicted to result in better clinical outcomes and lower total healthcare costs than its comparators, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot. Long-acting risperidone may therefore be a cost saving therapeutic option for patients with schizophrenia.