Cost of the Illness of Treatment-Resistant Schizophrenia: A Mirror Image Study Comparing Clozapine With Other Antipsychotics.

PURPOSE/BACKGROUND: This study aimed to evaluate and compare the cost of illness in patients with treatment-resistant schizophrenia (TRS) during 3 months before starting clozapine and for the initial 3 months of treatment with clozapine. METHODS/PROCEDURES: Fifty-two patients with TRS were evaluated for the cost of illness (direct, indirect, and provider cost) by using a structured questionnaire for the period of 3 months before starting clozapine and then at the end of the 3 months of clozapine therapy. FINDINGS/RESULTS: Total treatment cost for the period of 3 months before starting clozapine was Indian rupees (INR) 40,372 (560.72 US dollars), and the total treatment cost for the first 3 months of clozapine therapy was INR 40,553 (563.23 US dollars). At both the assessments, indirect cost formed the main bulk of the total cost, with no significant difference in the indirect cost. The total direct treatment cost reduced from INR 13,931.6 (193.49 US dollars) to INR 8756 (121.61 US dollars), and the difference between the 2 assessments was statistically significant, with an advantage for clozapine. Overall, after starting clozapine, the total direct cost reduced from 34.5% to 21.6%, and the total indirect cost reduced from 54.3% to 40.2%. After starting clozapine, total provider cost increased from 11.2% to 38.2% of the totalcost. IMPLICATIONS/CONCLUSIONS: Treatment with clozapine is not associated with a significant increase in the overall treatment cost, in the short term. However, there is a significant reduction in direct treatment costs.

Costs in the Treatment of Schizophrenia in Adults Receiving Atypical Antipsychotics: An 11-Year Cohort in Brazil.

BACKGROUND: Schizophrenia is associated with significant economic burden. In Brazil, antipsychotic drugs and outpatient and hospital services are provided by the Brazilian National Health System (SUS) for patients with schizophrenia. However, few studies capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems. OBJECTIVE: Our objective was to use real-world data to describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010. METHODS: We integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. We assessed only direct medical costs and the study was conducted from a public-payer perspective. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables. RESULTS: We identified 174,310 patients with schizophrenia, with mean ± standard deviation (SD) annual costs of $US1811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of total costs, with a mean annual cost per patient of $US1578.74 ± 240.40. Mean annual costs per patient were $US2482.90 ± 302.92 for psychiatric hospitalization and $US862.96 ± 160.18 for outpatient psychiatric care. Olanzapine was used by 47.7% of patients and represented 62.8% of the total costs of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient for outpatient psychiatric care and psychiatric hospitalization. CONCLUSIONS: Atypical antipsychotics were responsible for the majority of the schizophrenia treatment costs, and psychiatric hospitalization costs were the highest mean annual cost per patient. Authorities should ensure efficient use of atypical antipsychotics and encourage outpatient psychiatric care over psychiatric hospitalization where possible.

The Business Case for Expanded Clozapine Utilization.

OBJECTIVE: In most settings, less than 25% of patients with treatment-resistant schizophrenia receive clozapine, the only medication proven effective for treatment-resistant schizophrenia. Therefore, a business case analysis was conducted to assess whether increasing clozapine utilization for treatment-resistant schizophrenia in a health care system would result in direct health care cost savings. METHODS: Veterans with treatment-resistant schizophrenia who were treated in the Veterans Health Administration (VHA) were studied. Treatment response, suicides, adverse drug reactions (and associated mortality), and effects on inpatient hospitalization related to clozapine were derived from a systematic review of published studies. A one-factor sensitivity analysis and a probabilistic sensitivity analysis (PSA) with Monte Carlo simulation were conducted to calculate the cost-benefits of increased clozapine utilization. RESULTS: Despite monitoring costs, in the base case analysis, the VHA would save $22,444 per veteran with treatment-resistant schizophrenia over the first year of clozapine therapy, primarily from 18.6 fewer inpatient days per patient. If current utilization was doubled, and 50% of those veterans continued clozapine treatment for one year, VHA would save an estimated $80 million. Cost savings were most sensitive to the proportion of treatment-resistant patients who received clozapine, decrease in inpatient days, cost of inpatient stays, clozapine response rate, and number of patients with treatment-resistant schizophrenia. In the PSA, initiation of clozapine for all VHA patients with treatment-resistant schizophrenia who were not currently treated with clozapine would save at least $290 million in 95% of simulations. CONCLUSIONS: Increased clozapine utilization would result in net cost savings for the VHA.

[Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia]. / Costo efectividad de los antipsicóticos en el tratamiento de mantenimiento de la esquizofrenia en Colombia.

OBJECTIVE: Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. METHODS: A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. RESULTS: The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. CONCLUSION: Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system.

Geographical disparities in prescription practices of lithium and clozapine: a community-based study.

OBJECTIVE: To explore the socioeconomic and health resource characteristics associated with geographical variations of lithium and clozapine dispensing rates in France. METHOD: The study was performed using reimbursement data from the French Insurance Healthcare system over the period 2006-2013 in a community-based sample of persons aged 16 years and over. An ecological design was used to assess whether lithium and clozapine prescribing rates were associated with socioeconomic and health resource characteristics of the zone of residence (n = 95 French administrative subdivisions). RESULTS: Large geographical disparities were observed in dispensing rates: lithium dispensing rates by zone of residence ranged from 0 to 6.6 per 1000 (mean 2.4 per 1000) and clozapine dispensing rates ranged from 0 to 4.9 per 1000 (mean 0.8 per 1000). Higher density of GPs and regular communication between mental health services and primary care were independently associated with higher rates of lithium and clozapine dispensing and with a higher proportion of lithium users among mood-stabilizer users. CONCLUSION: A sufficient density of GPs and an effective communication and collaboration between mental healthcare services and primary care seems to favor greater access to psychotropic drugs with demonstrated efficacy but often viewed as 'risky' to prescribe.

Clozapine revisited: Impact of clozapine vs olanzapine on health care use by schizophrenia patients on Medicaid.

BACKGROUND: Our purpose was to evaluate health care use and cost patterns for clozapine compared with olanzapine in the treatment of schizophrenia. METHODS: Health care outcomes were measured over a 1-year posttreatment period for episodes of antipsychotic therapy initiated between 1997 and 2002. Four episode categories were defined: restart after lapse in therapy, switch after break, switch without break, and augmentation. We estimated the impact of clozapine or olanzapine using mixed model regression for costs by type of service and days of uninterrupted drug therapy. Time to admission in an acute hospital, psychiatric hospital, or longterm care facility, and time to suicide attempt were compared using Cox proportional hazards models. RESULTS: Clozapine increased duration of therapy and decreased risk of psychiatric hospitalization or suicide attempts compared to olanzapine. However, increased drug costs and use of community mental health centers (CMHC) for complete blood count (CBC) monitoring overwhelmed any offsetting savings. CONCLUSIONS: Clozapine is more expensive than olanzapine over the first year of treatment, primarily due to frequent CMHC visits required for CBC monitoring. However, fewer psychiatric hospitalizations, reduced suicide attempts, and longer duration of treatment should generate more benefits over time, which could eventually outweigh clozapine's higher first-year costs.

Comparison of sole nurse and team-delivered community clozapine services for people with treatment-resistant schizophrenia.

AIM: To compare sole nurse and doctor-led multidisciplinary team delivery of community clozapine services for people with treatment-resistant schizophrenia. BACKGROUND: Around 20% of people with schizophrenia are treatment resistant and fail to respond to front line medications. Clozapine, a second-line treatment, has potentially serious side effects requiring regular monitoring. Different models of community clozapine services are emerging in the British National Health Service, but there is little evidence about which is best. DESIGN: Questionnaire survey of service users. METHODS: All patients on the lists of seven clozapine clinics (four sole nurse, three multidisciplinary team) in one trust were invited to participate, 2009-2010. Forward stepwise regression was used to investigate associations between patient well-being, functioning, self-efficacy and satisfaction, and clinic model attended, controlling for socio-demographic and health characteristics and processes of care. Use (and costs) of other health and social services accessed was compared between models. RESULTS: Sixty-six service users (35% participation rate) responded. Well-being and functioning were associated with patient characteristics and processes of care, not clinic model. Patients managed by sole nurses reported, over 3 months: more community psychiatric nurse visits and hospital psychiatrist appointments. Clinic list size affects costs per patient. CONCLUSIONS: Multidisciplinary team delivery may reduce use of other services. Although multidisciplinary team delivery is regarded as best practice, sole nurses can effectively provide clozapine services and may be warranted in areas of low population density.

Cost-effectiveness Analysis of Aripiprazole Once-Monthly for the Treatment of Schizophrenia in the UK.

BACKGROUND: Schizophrenia is a severe and debilitating psychiatric disorder. Pharmacological interventions aim to ameliorate symptoms and reduce the risk of relapse and costly hospitalisation. Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable (LAI) antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed and optimise long term patient outcomes. AIMS OF THE STUDY: To estimate the cost-effectiveness of aripiprazole once-monthly 400mg (AOM 400) vs. risperidone long acting injectable (RLAI), paliperidone long acting injectable (PLAI) and olanzapine long acting injectable (OLAI) in the maintenance treatment of chronic, stable schizophrenia patients in the United Kingdom. METHODS: A Markov model was developed to emulate the treatment pathway of a hypothetical cohort of patients initiating maintenance treatment with LAI antipsychotics. The economic analysis was conducted from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a 10 year time horizon. Efficacy and safety probabilities were derived from mixed treatment comparisons (MTCs) where possible. Analyses were conducted assuming pooled dosing from randomised clinical trials included in the MTCs. RESULTS: The model estimates that AOM 400 improves clinical outcomes by reducing relapses per patient comparative to other LAIs over the model time horizon (2.38, 2.53, 2.70, and 2.67 for AOM 400, RLAI, PLAI and OLAI respectively). In the deterministic analysis, AOM 400 dominated PLAI and OLAI; an incremental cost-effectiveness ratio (ICER) of GBP 3,686 per QALY gained was observed against RLAI. Results from the univariate sensitivity analyses highlighted the probability and cost of relapse as main drivers for cost-effectiveness. In the probabilistic sensitivity analysis, AOM 400 demonstrated a marginally higher probability of being cost-effective (51%) than RLAI, PLAI and OLAI (48%, 1% and 0%, respectively) at a willingness to pay threshold of GBP 20,000. DISCUSSION: The model was built to accommodate results of an adjusted MTC analysis. Furthermore the model effectively captures repercussions of deteriorating compliance to treatment by incorporating three levels of compliance with elevated risks of relapse for partial compliance and non-compliance. Limitations of the analysis include the limited number of studies incorporated in the MTC, the extrapolation of short term clinical data and the exclusion of the wider societal burden. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Comparative to other atypical antipsychotics, AOM 400 represents value for money in the maintenance treatment of chronic, stable schizophrenia; however, in light of the PSA findings and comparable cost-effectiveness (i.e. against RLAI), the product profile and wider benefits of the respective treatments must be taken into account when prescribing antipsychotics. IMPLICATIONS FOR FURTHER RESEARCH: Future research should assess the use of LAI antipsychotics earlier in the disease course of schizophrenia to see whether improved compliance and outcomes shortly following the onset of psychosis has the potential to alter the disease trajectory. Moreover it should be assessed whether changes in the disease trajectory can alleviate cost and resource pressures placed on national health services.

Cost-effectiveness of second-generation antipsychotics for the treatment of schizophrenia.

OBJECTIVE: To compare the cost-effectiveness of alternate treatment strategies using second-generation antipsychotics (SGAs) for patients with schizophrenia. METHODS: We developed a Markov model to estimate the costs and quality-adjusted life-years (QALYs) for different sequences of treatments for 40-year-old patients with schizophrenia. We considered first-line treatment with one of the four SGAs: olanzapine (OLZ), risperidone (RSP), quetiapine (QTP), and ziprasidone (ZSD). Patients could switch to another of these antipsychotics as second-line therapy, and only clozapine (CLZ) was allowed as third-line treatment. We derived parameter estimates from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study and published sources. RESULTS: The ZSD-QTP strategy (first-line treatment with ZSD, change to QTP if ZSD is discontinued, and switch to CLZ if QTP is discontinued) was most costly while yielding the greatest QALYs, with an incremental cost-effective ratio (ICER) of $542,500 per QALY gained compared with the ZSD-RSP strategy. However, the ZSD-RSP strategy had an ICER of $5,200/QALY gained versus the RSP-ZSD strategy and had the greatest probability of being cost-effective given a willingness-to-pay threshold between $50,000 and $100,000 per QALY. All other treatment strategies were more costly and less effective than another strategy or combination of other strategies. Results varied by different time horizons adopted. CONCLUSIONS: The ZSD-RSP strategy was most cost-effective at a willingness-to-pay threshold between $5,200 and $542,500 per QALY. Our results should be interpreted with caution because they are based largely on the CATIE trial with potentially limited generalizability to all patient populations and doses of SGAs used in practice.

Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden.

AIMS: To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden. METHODS: A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability. RESULTS: PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5-83.8%) were for institutional care; indirect costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations. CONCLUSION: PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

Cost-effectiveness of lurasidone vs aripiprazole among patients with schizophrenia who have previously failed on an atypical antipsychotic: an indirect comparison of outcomes from clinical trial data.

OBJECTIVE: Compare long-term costs and outcomes of lurasidone to aripiprazole among adults with schizophrenia in the US who previously failed ≥1 atypical antipsychotic (olanzapine, risperidone, quetiapine, or ziprasidone) based on an indirect comparison of outcomes data from clinical trials. METHODS: A 5-year Markov cohort model was developed to compare long-term effectiveness of lurasidone to aripiprazole, including total discontinuations, relapse rates, and hospitalization rates. Cost inputs included pharmacy, mental health, and medical costs associated with cardiometabolic risks (diabetes and cardiovascular [CV] events). Effectiveness inputs were derived from an indirect comparison of aripiprazole and lurasidone using common comparators from CATIE. Cardiometabolic risks were derived from claims data analysis for diabetes, weight change and CV events, and Framingham body mass index (BMI) risk equation. Cost inputs were derived from published sources and Red Book. Costs and outcomes were discounted at 3% and tested with sensitivity analyses. RESULTS: Over 5 years, total discounted costs for lurasidone and aripiprazole patients were $86,480 and $90,500, respectively. During this period, the number of relapses per patient, hospitalizations per patient, diabetes rates, and CV events per 1000 patients, respectively, were estimated to be lower for lurasidone (0.442, 0.245, 7.29%, and 37.3) than aripiprazole (0.478, 0.369, 7.36%, and 37.8). Results were sensitive to lurasidone and aripiprazole hospitalization rates. At a willingness-to-pay threshold of $50,000 per hospitalization avoided, lurasidone had a 100% probability of being more cost-effective than aripiprazole. LIMITATIONS: The model was based on results from various comparative clinical trials. Differences in patient population and study methods may change estimates from the model. The model does not account for patient heterogeneity. CONCLUSIONS: Based on this model, when switching from another atypical antipsychotic, lurasidone had fewer relapses and hospitalizations with a lower incidence of diabetes and CV events than aripiprazole. Additionally, lurasidone may be less costly than aripiprazole among adults with schizophrenia.

[Antipsychotic polypharmacy in high-utilising patients with schizophrenia]. / Antipsychotische Polypharmazie bei Patienten mit Schizophrenie und hoher Versorgungsinanspruchnahme.

OBJECTIVES: Although guidelines usually recommend monotherapy, in clinical practice, antipsychotic polypharmacy is common especially with chronically ill patients. We therefore assessed the current practice of antipsychotic polypharmacy in "high-utilising" patients with schizophrenia in Germany. METHODS: Antipsychotic medication was assessed using a representative sample of 638 patients with schizophrenia from two multi-centre studies. RESULTS: Antipsychotic combination treatment was administered to 43.9 % of the patients. Combination treatment not including clozapine was apparent in 36.2 %. CONCLUSIONS: Antipsychotic polypharmacy is prevalent in the treatment of patients with schizophrenia showing high service use also when excluding such combinations with clozapine. Differences between the study samples indicate possible influences linked with therapy resistance or treatment setting.

Underprescribing of clozapine and unexplained variation in use across hospitals and regions in the Canadian province of Québec.

BACKGROUND: Clozapine remains the antipsychotic of choice for people who, having met the criteria for a diagnosis of schizophrenia or a related psychotic disorder, do not respond adequately to other antipsychotic medications. Utilization rates appear highly variable across jurisdictions, with an overall tendency toward underuse. This paper describes patterns of clozapine use in the province of Québec, Canada. METHODS: Individuals with a diagnosis of schizophrenia were identified using linked government medical claims and hospitalization records for 2003 and 2004. Linked data on their filled prescriptions in 2004 were then used to determine clozapine-use rates at the level of the province, the region, and the hospital at which individuals received most of their services. Individual predictors of clozapine use were identified using logistic regression. RESULTS: Only 6.7% of the 29,155 individuals identified with schizophrenia received clozapine for six months or longer in 2004. Utilization rates ranged from 3.9 to 9.0% among regions with 1,000 or more people with schizophrenia. Over 8% of 61 hospitals did not prescribe clozapine at all. People with schizophrenia taking clozapine experienced 3.4 fewer days of hospitalization per year than those not taking clozapine-representing a cost offset of about $1,800 per year. Medication costs were higher, however, by about $3,000 per year. CONCLUSIONS: Given the increasingly clear benefits of clozapine for people who do not respond to other antipsychotics, measures to increase access to clozapine for people who can benefit from it are likely to be cost effective and are urgently needed.

Clozapine for the treatment of schizophrenia.

INTRODUCTION: Despite considerable progress in the pharmacological treatment of schizophrenia, about 30% of patients are minimally responsive to antipsychotics and there is still an excessively high rate of mortality in schizophrenia patients. Clozapine , a D(2)-5HT(2) antagonist, was the first antipsychotic to demonstrate efficacy in treatment-resistant patients, and to be associated with the lowest risk of death. AREAS COVERED: The pharmacodynamics, pharmacokinetics, clinical efficacy, safety and cost-effectiveness of clozapine are covered in this article, based on a literature review (PubMed) from 1975 to 2012. Pivotal, as well as supporting, randomized controlled trials are reviewed, along with observational and/or naturalistic safety studies. This review of clozapine will allow the reader to determine the place for clozapine in the schizophrenia treatment landscape. EXPERT OPINION: Studies conducted so far suggest that clozapine is the treatment of choice for schizophrenic patients who are refractory to treatment, display violent behaviors, or who are at high risk of suicide. However, it is also the antipsychotic with the worst side effect profile, the highest risk of complications, and the most difficult to prescribe. Experience with clozapine should therefore be included in the education of future physicians.

Where to position clozapine: re-examining the evidence.

OBJECTIVE: To review clozapine's position in treatment algorithms for schizophrenia. METHOD: Clozapine's status is reviewed in the context of its initial discovery and unique clinical and (or) pharmacological profile, withdrawal and link with hematologic concerns, reintroduction with monitoring guidelines, prototype for atypicality, positioning in treatment algorithms, and current evidence regarding efficacy, effectiveness, and side effects. RESULTS: The hematologic monitoring implemented with clozapine's reintroduction here in North America has proven successful in preventing clozapine-related deaths secondary to agranulocytosis. While its other side effects are not without concern, present evidence does not link clozapine to increased mortality rates; indeed, it appears better than other antipsychotics in this regard. Moreover, its clinical superiority compared with all other antipsychotics has been confirmed both in efficacy and in effectiveness trials. CONCLUSIONS: Schizophrenia continues to represent a treatment challenge, with many people demonstrating suboptimal response and poor functional outcome. Clozapine is routinely positioned as a third-line treatment in schizophrenia, but in light of existing evidence this warrants re-examination.

A translational research approach to poor treatment response in patients with schizophrenia: clozapine-antipsychotic polypharmacy.

Poor treatment response in patients with schizophrenia is an important clinical problem, and one possible strategy is concurrent treatment with more than one antipsychotic (polypharmacy). We analyzed the evidence base for this strategy using a translational research model focused on clozapine-antipsychotic polypharmacy (CAP). We considered 3 aspects of the existing knowledge base and translational research: the link between basic science and clinical studies of efficacy, the evidence for effectiveness in clinical research and the implications of research for the health care delivery system. Although a rationale for CAP can be developed from receptor pharmacology, there is little available preclinical research testing these concepts in animal models. Randomized clinical trials of CAP show minimal or no benefit for overall severity of symptoms. Most studies at the level of health services are limited to estimates of CAP prevalence and some suggestion of increased costs. Increasing use of antipsychotic polypharmacy in general may be a factor contributing to the under-utilization of clozapine and long delays in initiating clozapine monotherapy. Translational research models can be applied to clinical questions such as the value of CAP. Better linkage between the components of translational research may improve the appropriate use of medications such as clozapine in psychiatric practice.

Health-related quality of life (HRQL) and continuous antipsychotic treatment: 3-year results from the Schizophrenia Health Outcomes (SOHO) study.

OBJECTIVES: We investigated the association between continuous antipsychotic use and health-related quality of life (HRQL) 3-year change in the European Schizophrenia Outpatients Health Outcomes (EU-SOHO) study. METHODS: EU-SOHO is an observational study of outcomes associated with antipsychotic treatment for schizophrenia in an outpatient setting. HRQL was assessed at study entry and at 6, 12, 18, 24, 30, and 36 months using the EuroQol-5D (EQ-5D). UK population time trade-off (TTO) tariffs were applied to the self-rated EQ-5D health states to calculate HRQL ratings (0 = death, 1 = best). An epoch analysis approach was used as a conceptual framework to analyze the longitudinal data. Follow-up was divided into epochs or periods of continuous treatment. When a patient changed antipsychotic treatment, he or she was considered to have a new observation. Multilevel models were employed to evaluate the association of HRQL with medication and other clinical and sociodemographic variables for each epoch. A total of 9340 patients were analyzed (42.1% women; mean age 40 years). RESULTS: Mean EQ-5D scores increased over time; the largest improvement occurred in the first 6 months (mean increase of 0.19). Longer duration of illness and older age at first treatment were associated with worse baseline EQ-5D scores. Improvements in EQ-5D scores were greater for more socially active patients or those in paid employment. Few significant differences were found between antipsychotic medications. Olanzapine and clozapine were associated with higher HRQL increases. CONCLUSIONS: Continuous antipsychotic treatment is associated with important HRQL benefits at 3 years, most of which occurs during the first 6 months. Although some medications are associated with better HRQL outcomes, differences are small.