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.     

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 antipsychotic drugs

In recent years several new antipsychotics have come to market in the Netherlands (i.e. risperidone, olanzapine and quetiapine). These compounds are called atypical for their lack of the extrapyramidal side effects typical of older antipsychotics. Clozapine, which was developed earlier, is also an atypical antipsychotic drug. The new antipsychotics have proven to be more effective than the old ones in reducing the negative symptoms and in improving the cognitive deficits of schizophrenia. Moreover, they indeed induce less extrapyramidal side effects than the older antipsychotics. Head-to-head comparisons of the atypical antipsychotics are sparse. Studies comparing low-dose regimens of the typical antipsychotics with the atypical drugs as well as relapse prevention studies are needed before it can be decided whether the atypical drugs can replace the older compounds.     

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.     

Drug-induced akathisia

Akathisia (restlessness and characteristic movements of the legs) is one of the most disagreeable extrapyramidal side effects and often causes non-compliance. Dopamine blocking agents such as antipsychotics and antiemetics, may induce akathisia. Particular care must be taken to distinguish akathisia from psychotic agitation and restless legs. The prevalence of akathisia in patients using classical antipsychotics is 20-30% and for users of clozapine, olanzapine and quetiapine (atypical antipsychotics) it is lower. Risk factors are a high dosage of antipsychotics, akathisia in a previous treatment, and diabetes mellitus. The treatment of akathisia starts, if possible, with the antipsychotic being withdrawn or the dose administered being lowered. Another treatment possibility is switching to clozapine, olanzapine or quetiapine, or adding a beta-blocking agent, an anticholinergic or mianserin.     

Diabetes mellitus associated with atypical antipsychotic medications: new case report and review of the literature.

BACKGROUND: Since the introduction of atypical antipsychotic medications, beginning with clozapine in 1990, several case reports in the psychiatric literature have suggested that they might be associated with new onset of diabetes mellitus as well as with diabetic ketoacidosis. METHODS: We report the case of a 38-year-old patient with schizophrenia who suddenly developed diabetes mellitus and ketoacidosis 12 months after starting olanzapine. Similar cases in the literature were found through a MEDLINE-assisted search using the key words "schizophrenia," "diabetes mellitus," "ketoacidosis," and "adverse drug reaction." RESULTS: Including this case, 30 patients have been reported in the literature to have developed diabetes or have lost diabetic control after starting clozapine, olanzapine, or quetiapine. Twelve of these 30 developed diabetic ketoacidosis. Two limited quantitative studies have added evidence toward this association. CONCLUSION: Although a causal relation has not been definitively proved, the number of cases reported in the literature suggests there might be an association between atypical antipsychotic medications and diabetes mellitus. Primary care physicians who care for patients with schizophrenia should be aware of this possible association.     

Cost-Effectiveness of Olanzapine as First-Line Treatment for Schizophrenia: Results from a Randomized, Open-Label, 1-Year Trial

OBJECTIVES: This randomized, open-label trial was designed to help inform antipsychotic treatment policies. It compared the 1-year cost-effectiveness of initial treatment with olanzapine (OLZ) (n = 229) versus a "fail-first" algorithm on conventional antipsychotics (then olanzapine if indicated) (CON) (n = 214); and versus initial treatment with risperidone (RIS) (n = 221). METHODS: Individuals with schizophrenia or schizoaffective disorder were recruited from May 1998 to September 2001. Clinical, functioning, and resource utilization data were collected at baseline and five postbaseline visits. Brief Psychiatric Rating Scale scores defined "clinical effectiveness;" Lehman Quality of Life Scale social relations scores defined "social effectiveness." RESULTS: Requiring failure on less expensive antipsychotics before use of olanzapine did not result in total cost savings, despite significantly higher antipsychotic costs with OLZ. Total 1-year mean costs were 21,283 dollars for CON; 20,891 dollars for OLZ; and 21,347 dollars for RIS (pair-wise comparisons nonsignificant). Intent-to-treat effectiveness comparisons (nonsignificant) were augmented by analyses that adjusted for duration on initial antipsychotic treatment, and by comparisons of patients remaining on initial antipsychotic treatment versus those who required switching. When accounting for differential switching rates (OLZ 0.14 vs. CON 0.53, P < 0.0001; vs. RIS 0.31, P < 0.0001), OLZ was significantly more effective than CON on clinical (P = 0.025) and social (P = 0.043) measures, and significantly more effective than RIS on the social (P = 0.002) measure. Further, patients initiated on an antipsychotic from which they needed to switch required additional resources for hospitalization (P = 0.036) and crisis services (P = 0.029). CONCLUSIONS: Approaches that integrate costs, effectiveness, and treatment patterns are important for providing optimal information regarding the value of first-line antipsychotic options for schizophrenia.     

The Use of Conventional Antipsychotic Medications for Patients with Schizophrenia in a Medicaid Population: Therapeutic and Cost Outcomes over 2 Years

Objective: To evaluate the association between drug therapy patterns achieved with conventional antipsychotics and direct healthcare costs over 2 years.
Methods: Paid claims data from the California Medicaid (Medi-Cal) program were used to identify 2476 patients with schizophrenia for whom 2 years of data were available. Ordinary least squares (OLS) regression models were used to estimate the association between lack of antipsychotic drug therapy, delayed therapy, changes in medications, and continuous therapy on healthcare costs over a 2-year period.
Results: Nearly 99% of Medi-Cal patients with schizophrenia were treated with conventional antipsychotics. Patients with schizophrenia consumed nearly $48,000 in direct costs over 2 years. Over 16% of patients did not use any antipsychotic medication for 2 years. Untreated patients used more healthcare resources than treated patients did ($10,833, P = .0422), especially psychiatric hospital care ($8,027, P = .0004). However, treated patients frequently experienced suboptimal drug use patterns. Nearly 33% of treated patients delayed antipsychotic therapy for up to 2 years. Delayed therapy was associated with increased costs of $12,285 ( P = .070). Over 56% of patients experienced changes in therapy that were associated with higher total direct costs ($17,644, P < .0001). Finally, only 3.2% of treated patients used an antipsychotic medication consistently for 2 years. However, continuous drug therapy was not associated with lower costs.
Conclusion: Suboptimal drug use patterns are common and costly in Medi-Cal patients with schizophrenia who initiated therapy with conventional antipsychotics.     

Current pharmacotherapy of schizophrenia

Second generation antipsychotics have become the standard of modern pharmacotherapy of schizophrenia. Amisulprid, clozapine, olanzapine, quetiapine, risperidone, sertindol, ziprasidone are the second generation antipsychotics registered in Hungary. They are more efficacious and their side effects are less stigmatizing than those of the first generation of antipsychotic drugs. Their use is limited by the availability of different formulations, by the lack of experience of some physicians, however the main limitation is the economic barrier.     

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.     

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.     

5种非典型抗精神病药临床应用药物经济学分析

目的:评价常用非典型抗精神病药物治疗精神分裂症的经济学效果。方法:250例接受单一抗精神病药物治疗的患者入组;试验时间为1年;以阳性与阴性症状量表评分减少量评价疗效,并进行最小成本分析。结果:241例患者完成研究,5组药物疗效相近,不良反应发生率氯氮平最高,齐拉西酮最低,齐拉西酮组泌乳素水平低于其他4组;治疗总成本由低到高依次为:氯氮平、利培酮(维思通)、齐拉西酮(卓乐定)、喹硫平(思瑞康)、奥氮平(再普乐)。结论:在治疗精神分裂症方面,氯氮平最具经济性,利培酮适合中国国情。     

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.     

Quetiapine: a well-tolerated and effective atypical antipsychotic

Quetiapine is an atypical antipsychotic, licensed in the UK for the treatment of schizophrenia. This review of published literature identifies the evidence that quetiapine is both effective and well-tolerated and highlights the particular indications in which quetiapine will be of most value to clinicians and patients.     

Efficacy and adverse reactions of antipsychotics for neuropsychiatric symptoms in dementia: a systematic review

OBJECTIVE: To assess the efficacy and adverse reactions of typical and atypical antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to examine the evidence for the cerebrovascular events warning for atypical antipsychotics. DESIGN: Systematic review. METHOD: Using Medline, Cinahl, PsyclNFO, Embase and the Cochrane central register of controlled trials (1980-2005), double-blind randomized controlled trials with intention-to-treat analysis were selected, which evaluated efficacy and adverse reactions of antipsychotics in the treatment of neuropsychiatric symptoms in dementia. The studies underwent a standardised validity assessment. RESULTS: After screening 950 studies, 14 studies on the effect of haloperidol, risperidone, olanzapine, quetiapine, tiapride, loxapine and perphenazine were selected. In 7 out of 10 studies, haloperidol, risperidone and olanzapine appeared to be more effective than placebo in the treatment of aggression and psychosis. Direct comparison between typical and atypical antipsychotics revealed no statistically significant difference. The most common adverse reactions were extrapyramidal symptoms and somnolence. These adverse reactions were less frequent with low-dose risperidone than with haloperidol or olanzapine, but risperidone and olanzapine were found to be associated with a higher risk of cerebrovascular events in two studies. CONCLUSION: The efficacy of typical and atypical antipsychotics is comparable, but only low-dose risperidone seems to be associated with fewer (extrapyramidal) side effects. The adverse reactions are inadequately described in the published data and consequently the warning of an increased risk of mortality could not be confirmed.     

The Impact of Open Access to Atypical Antipsychotics on Treatment Costs for Medi-Cal Patients with Bipolar Disorder

Background

The California Medicaid Program (Medi-Cal) provided open access to atypical antipsychotics in October 1997. This study investigated the impact of open access to atypical antipsychotics on the costs and duration of therapy for patients with bipolar disorders.

Methods

Paid claims data from Medi-Cal were used to identify episodes of treatment using antipsychotics, antidepressants, mood stabilizers, or selected anticonvulsants initiated by patients with bipolar disorders. Episodes of treatment were assigned to one of three time periods based on the start date: closed access (July 1994 to September 1997); a transition period (October 1997 to March 1998); and open access (April 1998 to August 1999). Ordinary least squares models for the cost and duration of drug therapy were estimated for episodes of treatment started after a break in all bipolar-related drug therapy (restarts) and switching/augmentation episodes.

Results

123 796 restart and 206 157 switching/augmentation episodes were identified. Patients with bipolar disorders cost between $US8000 and $US9000 annually (year of values 1998). Open access increased total costs by $US165–203 per year for restart episodes and $US75–125 per year for switching/augmentation episodes, primarily due to increased drug costs of $US101–103 for restart episodes (p < 0.001) and $US124 for switching/augmentation episodes (p < 0.001). Days of therapy decreased by 3.67 days for restart episodes (p < 0.001) and increased by 2.59–2.62 days for switching/augmentation episodes (p < 0.001) from the closed access period to the open access period.

Conclusions

Conventional antipsychotic medications are not used for long-term drug therapy for bipolar disorders, and the long-term effectiveness of atypical antipsychotics was not well established in October 1997. It is not surprising that open access to atypical antipsychotics had only limited effects on the costs and duration of therapy for these patients.

     

Relationship between Initial Quetiapine Dose and Effectiveness as Reflected in Subsequent Mental Health Service Use among Patients with Schizophrenia or Bipolar Disorder

OBJECTIVE: To investigate the association between initial quetiapine dose and effectiveness as gauged by subsequent use of mental health services. METHODS: Using a health plan database, we identified patients with bipolar disorder or schizophrenia treated with quetiapine monotherapy for at least four consecutive months. The stability of each patient before and after quetiapine treatment was measured by use of mental health services other than antipsychotic drug, measured primarily by charges reported on claims. Regression models controlling for patient differences measured associations between initial quetiapine dose and subsequent mental health service use. RESULTS: Commercially insured patients with schizophrenia (n = 581) or bipolar disorder (n = 2421) received quetiapine monotherapy at mean (SD) initial daily doses of 237 (198) mg and 147 (171) mg, respectively. Both groups showed negative associations between initial daily dose and subsequent mental health charges. Among patients with schizophrenia, mental health charges decreased by US 1.28 dollars for each additional milligram of quetiapine (P = 0.1097). Among patients with bipolar disorder, there was a significant decrease of US 1.31 dollars per additional milligram of quetiapine (P = 0.0484). For schizophrenia, hospitalizations were reduced by 0.4% for each additional milligram of quetiapine (P = 0.0189). For bipolar disorder, the association between quetiapine dose and outpatient charges was negative and trended toward significance (P = 0.074), showing a US 0.54 dollars reduction in these charges for each additional milligram of quetiapine; the association with hospitalization was not significant. CONCLUSIONS: In patients with schizophrenia or bipolar disorder, higher initial doses of quetiapine may be more effective in stabilizing patients as reflected in lower subsequent mental health service use.     

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.