The Cost Effectiveness of Long-Acting/Extended-Release Antipsychotics for the Treatment of Schizophrenia

Background

Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation.

Objective

The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint.

Methods

Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, ‘long-acting injection’, ‘economic evaluation’, ‘cost-effectiveness’ and ‘cost-utility’. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia.

Results

After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long-acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results.

Limitations

Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions.

Conclusions

Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.     

Cost-effectiveness analysis of switching antipsychotic medication to long-acting injectable risperidone in patients with schizophrenia

Background

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.

Objectives

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.

Methods

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 €, year 2005 values; hospital costs from source were in €, 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.

Results

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 (€405.80 vs €128.16) and 24 months (€407.33 vs €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 (€539.82 vs €982.13), without relapse (€519.67 vs €1242.03) and without hospitalization and without relapse (€597.22 vs €1059.39).

Conclusions

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.

     

Cost Effectiveness of Paliperidone Palmitate for the Treatment of Schizophrenia in Germany

Background

Treatment with antipsychotic medication is an important element of relapse prevention in the management of schizophrenia, and can reduce inpatient stays. Recently, the long-acting atypical antipsychotic paliperidone long-acting injectable (PLAI), a once-monthly LAI antipsychotic, was approved for treatment of schizophrenia in Germany.

Objective

To estimate, based on a previously published model, the cost effectiveness of PLAI compared with other common antipsychotic treatment strategies in patients diagnosed with schizophrenia in Germany.

Methods

A Markov decision analytic model was adapted to the German healthcare system. The model considers the cost effectiveness for PLAI as a maintenance treatment for patients with schizophrenia from the payer perspective. The patients transition between eight health states on a monthly basis over a 5-year time horizon. As therapeutic strategies, PLAI, quetiapine, risperidone long-acting injections (RLAI), oral olanzapine, oral risperidone, zuclopenthixol decanoate, olanzapine long-acting injections (OLAI), oral typical and oral atypical were compared. Probability of relapse, level of adherence, side effects and treatment discontinuation were derived from the Swedish original model. Input factors regarding resource use and costs were estimated and adjusted for the German healthcare system. A probabilistic sensitivity analyses (PSA) using cost-effectiveness scatter plots was performed to visualize the robustness of the results.

Results

In base-case scenario, PLAI is superior to RLAI in gained quality-adjusted life-years (QALYs) and avoided relapses. Relative to all other treatment strategies, PLAI is more effective with regard to gained QALYs and avoided relapses but results in higher treatment costs over a 5-year horizon in base-case scenario. The results were tested in PSA. If a cost-effectiveness threshold of €30,000 is assumed, for example, PLAI can be considered to be cost effective compared with RLAI in about 92.5 % of cases regarding gained QALYs, and in 78.6 % of cases regarding avoided relapse. Compared with OLAI, in about 94.4 % of cases regarding gained QALYs and in 99.9 % of cases regarding avoided relapse, cost effectiveness can be considered. Comparing PLAI and zuclopenthixol decanoate, cost effectiveness can be assumed in about 90.4 % of cases regarding gained QALYs, and in all cases regarding avoided relapse.

Conclusions

PLAI dominates RLAI and compared with the other treatment strategies PLAI has shown to be more effective but results in higher costs in base-case scenario.     

The impact on schizophrenia-related hospital utilization and costs of switching to long-acting risperidone injections in Sweden

Aim

To estimate changes in resource usage, hospitalization rates, and costs in actual practice in Sweden for schizophrenia patients after switching to long-acting injectable risperidone (Risperdal Consta).

Methods

A retrospective chart review within-subject mirror-image study using actual practice chart review data was used to compare annual hospital bed-days and annual hospital episodes for adults with schizophrenia or schizoaffective disorder before and after switching to Risperdal Consta in the period 1 January 2003 to 30 June 2005. Secondary endpoints included mean length of hospital stay per episode, the cost of hospitalization, and the cost of antipsychotic treatment. The base case analytical approach allocated all hospital episodes overlapping the switch date entirely to pre-switch treatment. In order to investigate the impact of inpatient care ongoing at the time of the switch, the change in bed-days per year was also estimated using an alternative analytical approach inspired by economic modelling.

Results

One-hundred sixty-four patients were enrolled at nine geographically diverse sites. The switch to Risperdal Consta was associated with a significant reduction in mean annual days in hospital from 39 to 21 days per year (45%), which was linked to a significant reduction in the number of hospitalizations from 0.86 to 0.63 per year (27%). The alternative “modelling-inspired” estimate of the reduction in mean annual days in hospital was also 27%.

Conclusion

A naturalistic mirror-image study found that switching to long-acting injectable risperidone led to sizeable reductions in inpatient resource use. These results coincide with the findings of other international studies.     

A mental health initiative to enhance schizophrenia treatment efficacy

Improving patient outcomes while containing costs can be a challenging goal to achieve. This article describes the initiatives undertaken by one mental health department to improve medication adherence among patients with schizophrenia by increasing psychoeducation, psychosocial services, and use of long-acting injectable antipsychotic agents. Achievement of this objective depended on a sustained departmental education program. The successful clinical outcome also significantly reduced the hospitalization and costs.     

Long-acting antipsychotics in the maintenance treatment of schizophrenia. Part II. Management of medications, integration of the multiprofessional team, and perspectives with the formulation of new a new generation of long-acting antipsychotics

Among various topics, this second part addresses indication and beginning of treatment, dose inter-individual variability and interval between injections, appointment frequency and special strategies during treatment relapse. Considering that poor adherence to antipsychotic treatment is a major factor in schizophrenic relapse, that the new generation of antipsychotic drugs, despite lower incidence of extrapyramidal side effects and better overall tolerability, did not change this condition in relation to conventional drugs and in view of the superiority of depot antipsychotics in comparison with conventional ones administered orally, the long-acting formulation of new generation antipsychotics can certainly improve the adherence and regularity of the medication regimen and decrease relapse rates in patients with schizophrenia. Furthermore, family participation in treatment is of great importance, as well as the attitude and integration of the medical team in realizing different tasks.     

Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States

Background

Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator), quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system.

Methods

A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained.

Results

The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544) followed by generic risperidone ($9,080). In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719). The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained.

Conclusion

The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and aripiprazole. Olanzapine may, therefore, be a cost-effective therapeutic option for patients with schizophrenia.     

Cost-Effectiveness of Long-Acting Risperidone Injection versus Alternative Atypical Antipsychotic Agents in Patients with Schizophrenia in China

Objectives:  To determine the most cost-effective strategy involving first-line treatment with long-acting risperidone, olanzapine, and quetiapine from the perspective of the Chinese health-care system.
Methods:  A decision analytical model was applied. The model used a time horizon of 2 years. The probabilities of treatment response of different agents and the relapse and hospitalization rates were estimated by a Delphi panel of 17 senior psychiatrists in China. The unit cost for each medical service was calculated from the price system database built by China National Development and Reform Commission and the medical resource utilization was estimated by the Delphi panel. The principal efficacy measure was the proportion of patients successfully treated. Various sensitivity analyses were carried out to test the robustness of the model.
Results:  The proportion of patients successfully treated over the 2-year period was 46.71% for long-acting risperidone, 39.93% for olanzapine, and 31.28% for quetiapine. The mean cost-effectiveness ratios were RMB189,427, RMB202,432, and RMB233,015 per successfully treated patient for long-acting risperidone, quetiapine and olanzapine, respectively. Results of the sensitivity analyses confirmed that the results were robust.
Conclusions:  The results showed that long-acting risperidone is more cost-effective than olanzapine and quetiapine for patients with schizophrenia in long-term maintenance treatment.     

Atypical Antipsychotics as First-Line Treatments for Schizophrenia

The poor efficacy and tolerability of conventional antipsychotic treatment in schizophrenia, together with discovery of the ‘atypical’ antipsychotic Clozapine, led to the development of several other atypical antipsychotic drugs. Those now available manifest clinically relevant differences in symptom efficacy and adverse effects, and most evidence supports their superior efficacy and tolerability compared with conventional treatment. Alongside these novel drugs have arrived concerns regarding new adverse effects, instead of the extrapyramidal phenomena which were one of the main drawbacks of conventional antipsychotics. These adverse effects comprise weight gain, diabetes mellitus and QTc interval prolongation. Overall, however, there is no evidence that atypical antipsychotics are more problematic than conventional antipsychotics, as there are marked differences between individual drugs in both classes. Current guidelines recommend the use of atypical antipsychotics as first-line treatments in a wide range of patients with schizophrenia, despite significant caveats regarding the quality of evidence to support use of these drugs in general. Advantages claimed over conventional antipsychotics are greater cost effectiveness, superior relapse prevention and possible benefits regarding quality of life and the natural course of schizophrenia. These advantages, if valid, will benefit stakeholders, whether they are consumers or providers of mental healthcare. However, major discrepancies remain between guidelines for first-line use and current practice. Poor take-up of atypical treatment and off-license use of both conventional and atypical drugs, particularly in primary care, are substantial problems that remain unaddressed. If guidance on first-line atypical therapy for schizophrenia is to be followed, processes such as audit must be applied widely to facilitate implementation of best-practice guidelines. Only then will the supposed benefits of first-line use be verified, or otherwise.     

A pharmacoeconomic evaluation of zuclopenthixol compared with haloperidol and risperidone in the treatment of schizophrenia

Zuclopenthixol and haloperidol are antipsychotic medications displaying different galenic forms, while risperidone is available on the market only in tablet form. The depot form presents advantages; the duration of action allows 3–4 weeks between administrations. A meta-analysis showed that zuclopenthixol patients had a higher response rate than haloperidol. A Markov model was developed to estimate the cost-effectiveness of the three antipsychotics in schizophrenia over a 5-year period. Model parameter estimates were based on a meta-analysis and literature. The viewpoint was that of the French National Health Insurance. When compared to haloperidol and risperidone, zuclopenthixol patients had additional 4 and 7 months without relapse correspondingly over a 5-year period. The estimated 5-year medical cost associated with zuclopenthixol was 800 and 1100 euros less than haloperidol and risperidone, respectively, per patient. Sensitivity analyses indicated that the results were robust to changes in key variables. The model indicates that the zuclopenthixol treatment strategy dominates haloperidol and risperidone.     

Outcomes and Costs of Risperidone versus Olanzapine in Patients with Chronic Schizophrenia or Schizoaffective Disorders: A Markov Model

OBJECTIVE: To compare expected outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders who are treated with risperidone versus olanzapine. METHODS: A Markov model was developed to examine outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders receiving risperidone or olanzapine. The time frame of interest was 1 year. The model focused particular attention on the likelihood of therapy switching and discontinuation as a result of treatment-emergent side effects, as the efficacy of these two agents is similar. Measures of interest included the incidence of relapse and selected side effects including extrapyramidal symptoms (EPS), prolactin-related disorders and diabetes, expected change in body weight, and the percentage of patients remaining on initial therapy at the end of 1 year. Costs of antipsychotic therapy and psychiatric and nonpsychiatric services also were examined. RESULTS: At 1 year, the rate of EPS was estimated to be slightly higher for risperidone, as was the incidence of symptomatic prolactin-related disorders. The expected incidence of diabetes mellitus, while low, was slightly higher for olanzapine. Approximately 25% and 4% of olanzapine and risperidone patients, respectively, were projected to experience an increase in body weight > or = 7%. The estimated percentage of patients remaining on initial therapy at the end of 1 year was higher for risperidone than olanzapine (76.9% vs. 45.6%, respectively). Expected mean total costs of care per month of therapy were $2163 for risperidone and $2316 for olanzapine. Results from sensitivity analyses suggest that the probability of therapy discontinuation following weight gain >5 kg would have to be lower than 0.1 for the number of patients remaining on therapy at the end of 1 year to be the same for risperidone and olanzapine. CONCLUSIONS: Compared with risperidone, treatment with olanzapine may result in greater increases in body weight, higher rates of therapy discontinuation, and higher costs of medical-care services.     

The Role of Peginterferon α-2a (40kD) Plus Ribavirin in the Management of Chronic Hepatitis C Mono-Infection

Although the incidence of new hepatitis C virus (HCV) infections may be declining, the prevalence of the diagnosed and treated chronic infection is set to increase over the next 2 decades because of the emergence of hepatic complications of the disease and the increased public awareness of hepatitis C and its transmission, which will prompt diagnosis and treatment of already infected individuals.Increased management costs and demands on support services are inevitable. As well as the costs of medical management of the disease and its complications, there are costs associated with the social, economic, and health-related quality-of-life (HR-QOL) issues for patients. Careful resource planning will be required, as the costs of not treating the disease are substantial.Patients with chronic hepatitis C experience a reduced HR-QOL, which is improved by the achievement of a sustained viral response (SVR; HCV RNA undetectable in serum) to treatment. Because adverse events associated with interferon-based regimens also impair the patient’s HR-QOL (during treatment), avoiding unnecessary or prolonged treatment is important. Identification of likely responders to treatment and treating patients for the minimum period of time with the best tolerated and most efficacious drugs could improve compliance and treatment outcomes and contribute to the effective use of available resources.A combination of subcutaneous peginterferon plus oral ribavirin has superseded unmodified interferon-α-based therapy for chronic hepatitis C, and is approved for the treatment of treatment-naive patients with chronic hepatitis C and compensated liver disease. Two peginterferons are available, peginterferon α-2a (40kD) [Pegasys®] and peginterferon α-2b (12kD) [PegIntron®], and both have shown significantly higher SVR rates than unmodified interferon-α when each was administered with ribavirin. There have been no head-to-head comparisons of these two agents in clinical trials.There are data from a study of peginterferon α-2a (40kD) plus ribavirin supporting the treatment of patients with chronic hepatitis C and persistently normal ALT activity. Achievement of an SVR with the peginterferon α-2a (40kD) combination was associated with an improvement in the HR-QOL of patients regardless of ALT activity.The efficacy and HR-QOL benefits of peginterferon α-2a (40kD) plus ribavirin for chronic hepatitis C may outweigh the increased acquisition costs of the drug, and this combination is estimated to be cost effective compared with unmodified interferon-based regimens (or no treatment in patients with chronic hepatitis C and persistently normal ALT activity).     

A 1-Year Cost-Effectiveness Model for the Treatment of Chronic Schizophrenia with Acute Exacerbations in Belgium

OBJECTIVE: A 1-year semi-Markov model was constructed to simulate the cost-effectiveness of atypical and typical antipsychotic treatments for schizophrenia. METHODS: The core model comprised nine 6-week cycles and includes events such as survival, response, adverse events, and compliance. The nature, duration, intensity, and timing of adverse events were incorporated. Compliance was modeled as a function of health state, time, and adverse events. Three first-line treatments were considered (risperidone, olanzapine, and haloperidol oral) and the transition probabilities of switching between five different therapies (haloperidol oral, haloperidol depot, risperidone, olanzapine and clozapine) were included. Effectiveness was modeled based on a modified method of TWiST (time without symptoms and toxicity). The direct costs of utilization of medical resources are taken into account, including five different patient care settings, consultations, neuroleptic medication, laboratory tests, and treatment of side-effects. RESULTS: This paper reports the methodology used to construct the model and the results obtained when it was applied to the treatment of patients with schizophrenia in the Belgian health care system. CONCLUSIONS: Over the study period, risperidone and olanzapine were more cost-effective than haloperidol and of the two major atypical drugs, risperidone was the more cost-effective.     

Cost-effectiveness of long-acting injectable risperidone versus flupentixol decanoate in the treatment of schizophrenia: a Markov model parameterized using administrative data

We use longitudinal patient-level data from a German sickness fund with 7.26 million insured in a Markov-simulation model to assess the cost-effectiveness of long-acting injectable risperidone (LAI-RIS) compared with long-acting injectable flupentixol (LAI-FLX) in the long-term management of schizophrenia. We simulate treatment costs from the payer’s perspective, hospitalization, the probability to be prescribed co-medication, and treatment discontinuation over a 2-year time horizon. Model inputs were derived from 935 patients hospitalized with schizophrenia between 2005 and 2008 who received either LAI-RIS or LAI-FLX for at least 1 month. After 2 years, 89.4 % (95.8 %) of patients who were initiated on LAI-RIS (LAI-FLX) discontinued the initial regimen. The number of days spent in hospital per month and patient was slightly lower with LAI-RIS (1.08 vs. 1.28 days, p < 0.001). The proportion of patients receiving side-effect co-medication was lower with LAI-RIS (8.3 vs. 15.0 % per month, p < 0.001). Mean total costs of treatment per patient and month were 1,015 € under LAI-RIS and 395 € under LAI-FLX, resulting in an ICER of 3,088 € (95 % CI [?913 €; 3,551 €]) for an avoided hospital day per patient and month in the base case scenario with a 15.1 % probability of LAI-FLX being the dominant treatment strategy. Cost differences were mainly attributable to the higher drug costs of LAI-RIS. The effectiveness of LAI-RIS in preventing hospital days appears to be similar to LAI-FLX, with a slight superiority in side-effect and switching rates. This comes at the cost of substantially higher treatment expenses. From a decision-maker’s point of view, the use of health insurance data as a source of input for decision models appears to be a reasonable alternative to models driven by clinical data only.     

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone,olanzapine, quetiapine,or haloperidol: the results of the EIRE study

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.     

A decision model to compare health care costs of olanzapine and risperidone treatment for schizophrenia in Germany

Second-generation atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride and ariprazole offer the potential to reduce the significant health care resource demands in the treatment of schizophrenia through improved levels of initial clinical response and reduced levels of long-term acute relapse. However, the optimal sequencing of these drugs remains unclear. To consider this issue from a health economic viewpoint a decision model approach was used comparing healthcare costs and clinical outcomes when treating patients with alternative sequences of atypical antipsychotic treatment. Treated patients were assumed to be in a current acute episode with at least a 10-year history of disease and to be naive to previous atypical treatments. Treatment strategies were based on either first-line olanzapine or risperidone with switching to the alternative drug as second-line treatment following an inadequate clinical response to first-line drug therapy. Clinical response data were derived from a pivotal published comparative study of both olanzapine and risperidone. Published data on the long-term use of antipsychotic drugs where used wherever possible to populate the model for relapse rates during the maintenance phase. Health care resource data were defined for Germany based on expert clinical opinion. A treatment strategy of first-line olanzapine was shown to be cost saving over a 1-year period, with additional clinical benefits in the form of avoided relapses. The model suggests that over the first year of treatment a strategy of first-line olanzapine is associated with lower risk of additional relapse (0.33 fewer acute relapses per 100 patients per year) and with cost savings (euro 35,306 per 100 patients per year). There is a need for longer term direct in-trial comparisons of atypical antipsychotics to confirm these indicative results.     

Aripiprazole Lauroxil Compared with Paliperidone Palmitate in Patients with Schizophrenia: An Indirect Treatment Comparison

Background

Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic recently approved for treatment of schizophrenia on the basis of a large-scale trial of two doses of AL versus placebo. There are no direct-comparison studies with paliperidone palmitate (PP; long-acting antipsychotic used most often in acute settings) for the acute psychotic episode.

Cost effectiveness of long-acting risperidone in Sweden

Background

In Sweden, risperidone long-acting injectable (RLAI) is generally used in a population of schizophrenia patients who are at a high risk of being non-compliant. However, RLAI might also be suitable for use in the general schizophrenia population.

Objectives

To analyse the clinical and economic effects of RLAI in the Swedish treatment practice using a discrete-event simulation (DES) model. Treatment outcomes and direct costs were analysed for both the high-risk non-compliant patient population and the general schizophrenia population.

Methods

An existing DES model was adapted to simulate the treatment of schizophrenia in Sweden. Model inputs were based on literature research and supplemented with expert opinion. In the high-risk non-compliant schizophrenia population, RLAI was compared with haloperidol LAI. The analysis was built upon differences in symptom reduction, time between relapses, compliance and adverse effect profile between the two drugs. Main outcomes were the predicted incremental (discounted) costs (€) and effects (QALYs). In the general schizophrenia population, RLAI was compared with oral olanzapine. This analysis was built upon differences in compliance and adverse effects between the drugs. Multivariate probabilistic sensitivity analyses (PSA) were carried out to assess the sensitivity of the results of the two analyses.

Results

In the high-risk non-compliant patient population, RLAI was predicted to generate 0.103 QALYs per patient over 3 years while realizing cost savings of €5013 (year 2007 values) compared with haloperidol LAI. The main driver of the cost effectiveness of RLAI was the difference in Positive and Negative Syndrome Scale (PANSS) reduction between the two drugs, followed by the difference in adverse effects. The PSA showed that, in this setting, RLAI had a probability of 100% of being cost effective at a willingness-to-pay (WTP) threshold of €43 300 per QALY gained, compared with haloperidol LAI. The probability that RLAI combines additional effectiveness with cost savings compared with haloperidol LAI was estimated at 94%. When analysing RLAI in the general schizophrenia population, it was predicted to generate 0.043 QALYs and save €239 per patient over 5 years compared with olanzapine. Compliance was the main driver of the cost effectiveness of RLAI in this scenario. In the PSA it was shown that RLAI had a probability of 78% of being cost effective at a WTP threshold of €43 300 per QALY gained, compared with olanzapine. The estimated probability that RLAI combines additional effectiveness with cost savings was 50% and the probability that RLAI is less effective and more costly than olanzapine was negligible (0.2%).

Conclusions

Treatment with RLAI is suggested to result in improved QALYs combined with cost savings compared with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia patient population. In the general schizophrenia population, RLAI also resulted in positive incremental QALYs and cost savings, when compared with olanzapine. However, the estimates used in the model for compliance and symptom reduction need further validation through naturalistic-based studies with reasonable follow-up to more definitely establish the real-life differences between RLAI and the comparators in the considered patient populations and to further reduce the uncertainty of these parameters.     

The long-acting depot antipsychotic drugs

The novel antipsychotics have reduced the use of depot medications, but the introduction of the atypical depot antipsychotic has rekindled an interest in the long-acting antipsychotic formulations. The use of atypical antipsychotics is recommended, except where patients are otherwise stable on classical antipsychotics without unwanted side effects.