Patterns of relapse and associated cost burden in schizophrenia patients receiving atypical antipsychotics

Abstract

Objective:

To identify relapse in schizophrenia and the main cost drivers of relapse using a cost-based algorithm.

Methods:

Multi-state Medicaid data (1997–2010) were used to identify adults with schizophrenia receiving atypical antipsychotics (AP). The first schizophrenia diagnosis following AP initiation was defined as the index date. Relapse episodes were identified based on (1) weeks during the ≥2 years post-index associated with high cost increase from baseline (12 months before the index date) and (2) high absolute weekly cost. A compound score was then calculated based on these two metrics, where the 54% of patients associated with higher cost increase from baseline and higher absolute weekly cost were considered relapsers. Resource use and costs of relapsers during baseline and relapse episodes were compared using incidence rate ratios (IRRs) and bootstrap methods.

Results:

In total, 9793 relapsers were identified with a mean of nine relapse episodes per patient. Duration of relapse episodes decreased over time (mean [median]; first episode: 34 [4] weeks; remaining episodes: 8 [1] weeks). Compared with baseline, resource utilization during relapse episodes was significantly greater in pharmacy, outpatient, and institutional visits (hospitalizations, emergency department visits), with IRRs ranging from 1.9–2.4 (all p?<?0.0001). Correspondingly, relapse was associated with a mean (95% CI) incremental cost increase of $2459 ($2384–$2539) per week, with institutional visits representing 53% of the increase.

Limitations:

Relapsers and relapse episodes were identified using a cost-based algorithm, as opposed to a more clinical definition of relapse. In addition, their identification was based on the assumption from literature that ～54% of schizophrenia patients will experience at least one relapse episode over a 2-year period.

Conclusions:

Significant cost increases were observed with relapse in schizophrenia, driven mainly by institutional visits.     

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States

Abstract

Objective:

Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations.

Methods:

Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained.

Results:

Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations.

Limitations:

Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study.

Conclusions:

This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications.     

博思清与维思通治疗精神分裂症的药物经济学分析

目的比较博思清与维思通治疗精神分裂症的成本-效果。方法对50例住院精神分裂症患者应用博思清与维思通进行治疗,疗程6周。采用成本-效果分析法对两组进行分析。结果博思清与维思通治疗精神分裂症的有效率分别为96.0%和92.0%,两者疗效无显著性差异(P>0.05),成本分别为638.16元和647.8元。结论博思清治疗精神分裂症疗效与维思通相当,但起效更快,博思清(阿立哌唑)治疗精神分裂症较经济。     

东北干旱地区发展现代高水效农业的路径

东北地区在我国粮食生产和调配方面发挥着举足轻重的作用。国务院常务会议通过《吉林省增产百亿斤商品粮能力建设总体规划》,标志着东北地区成为保障国家粮食安全的重要增量因素。然而,东北地区水资源占有量又与其粮食主产区的地位和需要极不相称,以占全国9%的农业用水创造了全国16%的粮食产出。靠天吃饭、干旱缺水已成为东北农业生产的最大威胁。应当通过促进农艺抗旱节水措施的应用、加强农业用水服务管理的效率、不失时机地推进种植结构的调整等渠道,突破水资源瓶颈,发展现代高水效农业。     

Assessing the impact of nocturia on health-related quality-of-life and utility: results of an observational survey in adults

Background and aim: The impact of nocturia (getting up at night to void) on health-related quality-of-life (HRQoL) is often under-estimated. This study investigated the relative burden in terms of HRQoL and utilities of nocturia in a real-world setting.

Methods: Patient data were collected from two surveys: a nocturia-specific, cross-sectional survey of physicians and their patients (DSP), and a general UK population health survey (HSFE). Utilities (EQ-5D-5L), productivity (Work Productivity and Activity Index), and the impact of nocturia symptoms (Nocturia Impact Diary and Overactive Bladder Questionnaires) were assessed against the number of voids. A robust linear regression model with propensity score weights was used to control for confounding factors in estimating utilities.

Results: Physician-recorded data were available from 8,738 patients across the US, Germany, Spain, France, and the UK; of these, 5,335 (61%) included patient-reported outcomes. In total, 6,302 controls were drawn from the two surveys and compared to 1,104 nocturia patients. Deterioration of HRQoL was associated with increasing number of night-time voids (p?p?p?Limitations: The cause of nocturia is multifactorial and the mostly elderly patients may have several concomitant diseases. The authors tried to adjust for the most common ones, but there may be diseases or unknown relationships not included.

Conclusions: Nocturia negatively affected HRQoL and patient utility. A clear effect is seen already at two voids per night. Every effort should, therefore, be made to reduce nocturia below the bother threshold of two voids per night.     

Cost-effectiveness of asenapine in the treatment of schizophrenia in Canada

Objective:

Asenapine is the first tetracyclic antipsychotic approved in Canada for the treatment of schizophrenia (SCZ). Asenapine has shown a comparable efficacy profile to other atypical antipsychotics and it is associated with a favourable metabolic profile and less weight gain. This study aimed to assess the economic impact of asenapine compared to other atypical antipsychotics in the treatment of SCZ in Canada.

Methods:

A decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with other atypical antipsychotics. The decision tree takes into account the occurrence of extrapyramidal symptoms, the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases, and stroke. In the base-case analysis, asenapine was compared to olanzapine. Asenapine was also compared with other atypical antipsychotics commonly used in Canada in alternative scenarios. Analyses were conducted from both Canadian Ministry of Health (MoH) and societal perspectives over a 5-year time horizon.

Results:

In the treatment of SCZ, asenapine is a dominant strategy over olanzapine from both MoH and societal perspectives. Compared to quetiapine, asenapine is also a dominant strategy. Furthermore, asenapine has a favorable economic impact compared to ziprasidone and aripiprazole, as these antipsychotics are not cost-effective compared to asenapine from both MoH and societal perspectives.

Conclusion:

Despite the short time horizon, the lack of compliance data and the assumptions made, this economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine and to most of the atypical antipsychotics frequently used in Canada.     

Treatment discontinuation of long-acting injectables or oral atypical antipsychotics among Medicaid recipients with schizophrenia

Abstract

Aims: Among patients with schizophrenia, poor adherence and persistence with oral atypical antipsychotics (OAA) often results in relapse and hospitalization. Second-generation antipsychotic long-acting injectables (SGA LAI) have demonstrated higher adherence than first-generation antipsychotic LAI and OAA therapies. This study aimed to determine whether SGA LAIs are associated with better persistency compared to OAA among Medicaid recipients with schizophrenia.

Materials and methods: From the MarketScan Medicaid Database (January 1, 2010–June 30, 2016), patients aged ≥18?years with schizophrenia and ≥2 pharmacy claims more than 90?days apart for the same SGA LAI or OAA were selected. New users of the specific antipsychotic agent were classified, based on their index agent, as: OAA, paliperidone palmitate LAI (PPLAI), aripiprazole LAI (ALAI), and risperidone LAI (RLAI). Discontinuation during 1 year of follow-up was defined as a?≥?60-day gap in the index OAA or SGA LAI medication past the exhaustion of the previous claim’s supply. Inverse probability of treatment weights (IPTW) balanced the cohort characteristics, and weight outliers (<0.1 or >0.9) were excluded. IPTW-weighted Cox proportional hazards regression estimated hazard ratios for discontinuation.

Results: Cohorts included 7,029 OAA, 4,302 PPLAI, 586 ALAI, and 1,456 RLAI patients. Mean age was 38.0–41.0?years and 44.0–46.6% were female. Persistence was significantly longer in the SGA LAI cohorts than in the OAA cohort. Adjusted hazard ratios (95% confidence intervals) for discontinuation were 0.60 (0.56–0.64) for PPLAI, 0.69 (0.60–0.79) for ALAI, and 0.70 (0.64–0.77) for RLAI vs OAA.

Limitations: Results may not be generalizable to patients covered by commercial or Medicare insurance, and limitations inherent to any claims-based retrospective analysis apply.

Conclusions: SGA LAI may be a valuable option for treating schizophrenia given the improvement in persistence.     

Reduction in costs of inpatient stay associated with clozapine treatment: A retrospective study

Summary

Clozapine is an atypical antipsychotic drug used to treat the 10-25% of patients who suffer from schizophrenia who are treatment resistant or intolerant to standard antipsychotic drug treatment. A major issue associated with treatment is the high cost of the drug compared to standard antipsychotic drug treatment. Research carried out to date has suggested that despite the high cost of clozapine, it is overall a cost-effective treatment. This contention is based on the findings described elsewhere that clozapine treatment is associated with a dramatic decrease in psychiatric inpatient stay.

There are many ethical difficulties associated with a prospective double-blind controlled trial of clozapine treatment. We have therefore reported on a retrospective audit. A retrospective analysis was carried out by the examination of computerised patient records to determine if clozapine treatment had been associated with a reduction in psychiatric inpatient stay. Also examined was whether clozapine treatment had been associated with an overall shift from intensive therapeutic ward usage.

For example, patients are moved from intensive care and acute wards to wards with less intensive therapeutic input such as continuing care and rehabilitation wards. The inpatient stay details for 76 patients prescribed clozapine since early 1991 were examined before and after clozapine treatment commenced. The main problem with this retrospective analysis is that without any control group observed over the same time period, it is very difficult to assess how much of the decrease in bed usage is related to either the natural history of the disease and/or to changes in bed use over time associated with changes in mental health service provision and the development of community facilities.

Psychiatric inpatient stay decreased by a statistically non-significant average of 13.2 days (6%) in the first year of treatment (p=0.7692), a non-significant average of 34 days (15%) in the second year of treatment (p=0.0669), a significant average of 38.4 days (17%) in the third year of treatment (p=0.0007) and again by a significant average of 51.2 days (22%) in the fourth year of treatment (p=0.0011).

The average cost per inpatient bed-day for the main psychiatric hospital in the Health Board's area is £90.86 (based on 100% occupancy rate, 1994/95 prices). The reduction in bed days identified was equivalent to a saving of £1,200 per patient in the first year of treatment, £3,090 per patient in the second year, £3,490 per patient in the third year and £4,652 per patient in the fourth year. The average annual cost of clozapine per patient is approximately £2,500.

Clozapine treatment was also associated with a shift from intensive care and acute ward inpatient usage to continuing care and rehabilitative ward usage. In the year prior to clozapine treatment intensive care and acute ward stay accounted for 72.7% of total inpatient stay. In the first year of treatment this proportion decreased to 63.7%, in the second year to 39.5%, in the third year to 31.8% and in the fourth year to 24.6%. This represented potential savings of £500,000 per annum.

Overall, the data generated from this study indicated that clozapine treatment is associated with both a reduction in psychiatric bed usage and a shift to less therapeutically intensive care wards. However, the decrease identified is not as dramatic as the reduction quoted elsewhere in the literature. These findings provide useful costing information to support the view that clozapine is a cost-saving or cost-neutral treatment in terms of the provision of psychiatric services in the UK. However, the costs associated with the increased use of community services by the study group were not identified in this review. In order to establish whether or not clozapine is cost saving overall compared to standard antipsychotic treatment it would have been necessary to identify all costs, including the whole range of community costs, before and after treatment commenced.     

Cost-effectiveness of 3-month paliperidone treatment for chronic schizophrenia in Spain

Background: A 3-month long treatment of paliperidone palmitate (PP3M) has been introduced as an option for treating schizophrenia. Its cost-effectiveness in Spain has not been established.

Aims: To compare the costs and effects of PP3M compared with once-monthly paliperidone (PP1M) from the payer perspective in Spain.

Methods: This study used the recently published trial by Savitz et al. as a core model over 1 year. Additional data were derived from the literature. Costs in 2016 Euros were obtained from official lists and utilities from Osborne et al. The authors conducted both cost-utility and cost-effectiveness analyses. For the former, the incremental cost per quality-adjusted life-year (QALY) gained was calculated. For the latter, the outcomes were relapses and hospitalizations avoided. To assure the robustness of the analyses, a series of 1-way and probability sensitivity analyses were conducted.

Results: The expected cost was lower with PP3M (4,780€) compared with PP1M (5,244€). PP3M had the fewest relapses (0.080 vs 0.161), hospitalizations (0.034 v.s 0.065), and emergency room visits (0.045 v.s 0.096) and the most QALYs (0.677 v.s 0.625). In both cost-effectiveness and cost-utility analyses, PP3M dominated PP1M. Sensitivity analyses confirmed base case findings. For the primary analysis (cost-utility), PP3M dominated PP1M in 46.9% of 10,000 simulations and was cost-effective at a threshold of 30,000€/QALY gained.

Conclusions: PP3M dominated PP1M in all analyses and was, therefore, cost-effective for treating chronic relapsing schizophrenia in Spain. For patients who require long-acting therapy, PP3M appears to be a good alternative anti-psychotic treatment.     

Cost effectiveness of paliperidone palmitate versus oral antipsychotics in patients with schizophrenia and a history of criminal justice involvement

Abstract

Objective:

Conduct a cost effectiveness analysis for the Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) trial.     

Budget impact analysis of long acting injection for schizophrenia in Japan

Abstract

Aims: To estimate the budgetary impact of providing additional reimbursement for long acting injections for schizophrenia patients in psychiatric hospital settings in Japan to improve patient outcomes in schizophrenia.

Methods: Budget impact analysis of change in reimbursement policy using a prevalence-based model over a five-year time horizon. The results are reported as net change in expenditure and consequent cost/savings in Japanese yen at the time of analysis.

Results: The budget impact analysis shows that an increase in reimbursement for LAIs could lead to cumulative savings of an estimated 36.6 billion JPY over five years. These savings result from a decrease in hospitalization costs and an increased usage of LAI (assumed to be 10%). Based on the sensitivity analysis, the saving estimates are most sensitive to change in market share of generic and branded oral antipsychotics.

Limitations: Historical data were used to estimate the future costs of drug and hospitalization; however, it is not the best predictor of future, hence a source of potential bias. A good level of treatment adherence with oral antipsychotics was assumed, which is generally not the case; therefore, we might have overestimated the effectiveness of oral atypical antipsychotics. Additionally, the drug cost due to reimbursement might have also been overestimated because in clinical setting, the increase of LAI use may not have reached 10% of the market share. Lastly, patients’ behavior was derived from models, which may have loosely approximated the reality.

Conclusions: An additional reimbursement for the use of LAI in schizophrenia patients is likely to be cost neutral/cost saving and should be considered as a policy option to improve patient outcomes and budget sustainability.     

Cost-effectiveness of 3-month paliperidone therapy for chronic schizophrenia in the Netherlands

Background: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for 3 months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published.

Purpose: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands.

Methods: A previous 1-year decision tree was adapted, based on local inputs supplemented with data from published literature. The primary analysis used DRG costs in 2016 euros from the insurer perspective, as derived from official lists. A micro-costing analysis was also conducted. For the costing scenario, official list prices were used. Clinical outcomes included relapses (treated as outpatients, requiring hospitalization, total), and quality-adjusted life-years (QALYs). Rates and utility scores were derived from the literature. Economic outcomes were the incremental cost/QALY-gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and probability sensitivity analyses.

Results: The expected cost was lowest with PP3M (8,781€), followed by PP1M (10,325€), HAL-LAT (11,278€), RIS-LAT (11,307€), and oral-OLZ (13,556€). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39, 1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and 0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14, respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656, respectively). In both cost-effectiveness and cost-utility analyses, PP3M dominated all other drugs. Sensitivity analyses confirmed base case findings. In the costing analysis, total costs were, on average, 31.9% higher than DRGs.

Conclusions: PP3M dominated all commonly used drugs. It is cost-effective for treating chronic schizophrenia in the Netherlands. Results were robust over a wide range of sensitivity analyses. For patients requiring a depot medication, such as those with adherence problems, PP3M appears to be a good alternative anti-psychotic treatment.     

Hospitalisation rates in patients switched from oral anti-psychotics to aripiprazole once-monthly for the management of schizophrenia

Abstract

Objective:

To report the design and preliminary results of a mirror-image study comparing total psychiatric hospitalisation rates pre- and post-switch to aripiprazole once-monthly, an extended release injectable solution.

Methods:

A multi-center, open-label mirror-image study of patients (18–65 years) with schizophrenia to compare total psychiatric hospitalisation rates between retrospective treatment with oral standard-of-care (SOC) anti-psychotics and prospective treatment with aripiprazole once-monthly in a naturalistic community setting in North America. Total psychiatric hospitalisation rates were assessed between retrospective (Months ?4 to ?1) and prospective treatment periods (Months 4–6) for patients who completed ≥3 months aripiprazole once-monthly.

Results:

One hundred and eighty-three patients entered the prospective phase. After switching to aripiprazole once-monthly, total psychiatric hospitalisation rates for the 3-month prospective period were significantly lower (p?<?0.0001, Exact McNemar’s test) compared with the retrospective 3-month period when the same patients received SOC anti-psychotics (6.6% [n?=?8/121] vs 28.1% [n?=?34/121], respectively; rate ratio?=?0.24). Similarly, total psychiatric hospitalisation rates for all patients who entered the prospective treatment phase were significantly lower (p?<?0.0001, Exact McNemar’s test) for the prospective 6 months following switch to aripiprazole once-monthly, compared with the retrospective 6-month SOC period (14.2% [n?=?26/183] vs 41.5% [n?=?76/183], respectively; rate ratio?=?0.34). Common treatment-emergent adverse events (occurring in ≥5% of patients) were psychotic disorder (7.7%), akathisia (7.2%), and insomnia (7.2%). Discontinuation (all causes) during the prospective phase was 44.8% (n?=?82/183).

Limitations:

Mirror-image studies do not include a parallel active control; as each patient serves as their own control, it cannot be determined whether other treatments may have similar effects. Treatment and trial effects may be difficult to separate. Independent factors such as admission patterns, insurance coverage, availability of hospital beds, and community support may influence rates of hospitalisation.

Conclusions:

Switching to aripiprazole once-monthly substantially reduced total psychiatric hospitalisation rates compared with retrospective rates in the same patients taking oral SOC.     

Recovery outcomes of schizophrenia patients treated with paliperidone palmitate in a community setting: patient and provider perspectives on recovery

Objectives:

This study evaluated the effect of paliperidone palmitate long-acting injectable (LAI) antipsychotic on recovery-oriented mental health outcomes from the perspective of healthcare providers and patients during the treatment of patients with schizophrenia or schizoaffective disorders.

Methods:

Archival data for patients with a primary diagnosis of schizophrenia or schizoaffective disorder receiving ≥6 months of paliperidone palmitate LAI were retrieved from the electronic medical records system at the Mental Health Center of Denver. Mental health recovery was assessed from both a provider’s (Recovery Markers Inventory [RMI]) and patient’s (Consumer Recovery Measure [CRM]) perspective. A three-level hierarchical linear model (HLM) was utilized to determine changes in CRM and RMI scores by including independent variables in the models: intercept, months from treatment (slope), treatment time period (pretreatment and treatment), age, gender, primary diagnosis, substance abuse diagnosis, concurrent medications, and adherence to paliperidone palmitate LAI.

Results:

A total of 219 patients were identified and included in the study. Results of the final three-level HLMs indicated an overall increase in CRM scores (p?<?0.05), an overall increase (p?<?0.01), and an increased rate of change (p?<?0.05) in RMI scores during the paliperidone palmitate LAI treatment period vs the pre-treatment period.

Limitations:

This study contained a retrospective, non-comparative design, and did not adjust for multiplicity

Conclusions:

The current study demonstrates that changes in recovery-oriented mental health outcomes can be detected following the administration of a specific antipsychotic treatment in persons with schizophrenia or schizoaffective disorders. Furthermore, patients receiving paliperidone palmitate LAI can effectively improve recovery-oriented outcomes, thereby supporting the drug’s use as schizophrenia treatment from a recovery-oriented perspective.