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.

Acute inpatient treatment, hospitalization course and direct costs in bipolar patients with intellectual disability.

To explore the impacts of intellectual disability (ID) on psychotropic medication use, length of hospital stay (LOS) and direct hospitalization costs during inpatient treatment for acute bipolar episodes, all 17,899 index hospitalizations due to acute bipolar episodes between 1998 and 2007 in Taiwan were identified from a total population health insurance claims database, amongst which 544 subjects had a concomitant diagnosis of ID. Pattern of psychotropic medication use, LOS, discharge outcome and direct costs during hospitalization were compared between bipolar patients with ID and without ID and multivariate models controlling for major cost confounders were used to explore the impacts of ID on LOS, discharge outcome and inpatient costs. The results indicated that, compared to bipolar patients without ID, bipolar patients with ID were younger, had longer LOS and received significantly lower daily equivalent dosages of antipsychotics, mood stabilizers, lithium and benzodiazepines. Significantly more bipolar patients with ID could not be discharged successfully. The longer LOS possibly reflected slower clinical stabilization, conservative use of medications and difficulty in community placement. The lower average daily reimbursements indicated that treatment of bipolar patients with ID were under-funded, whereas the higher total direct costs resulting from prolonged LOS placed greater economic straint on healthcare system. The findings support that bipolar patients with ID are clinically unique but relatively under-supported during acute hospitalization. Modifying current pharmacological intervention, health care resources allocation and community supporting structure is paramount to reducing LOS and improving hospitalization outcome.

Cost effectiveness of adjunctive quetiapine fumarate extended-release tablets with mood stabilizers in the maintenance treatment of bipolar I disorder.

BACKGROUND: Bipolar I disorder (BPD I) is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. However, few studies have investigated the cost effectiveness of maintenance treatment options for BPD I. OBJECTIVE: To determine the cost effectiveness of maintenance treatment with quetiapine fumarate extended-release (XR) tablets in combination with mood stabilizers (lithium or divalproex) in comparison with the following treatments: placebo in combination with lithium or divalproex; no maintenance treatment; lithium monotherapy; lamotrigine monotherapy; olanzapine monotherapy; and aripiprazole monotherapy. METHODS: The analysis was conducted from the societal and payer perspectives in the US, using a Markov model. The model simulated a cohort of 1000 stabilized BPD I patients and estimated the quarterly risk in three health states: euthymia, mania and depression. Efficacy data were derived from two randomized, double-blind trials comparing quetiapine + lithium/divalproex with placebo + lithium/divalproex for up to 2 years, as well as other published literature. Resource data were extracted from published literature. Drug costs, hospitalizations and physician visits were among the direct costs. Indirect costs included absenteeism, and mortality rates included suicide. Benefits and costs were discounted at 3% and the price reference year was 2009. Endpoints included number of acute mood episodes, hospitalizations due to an acute mood event and costs per QALY. Probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty in the model inputs. RESULTS: Treatment with quetiapine XR + lithium/divalproex was associated with reductions in acute mania (46%), acute depression (41%) and related hospitalizations (44%) compared with placebo + lithium/divalproex, and similar reductions in events were observed relative to lithium monotherapy. In the base-case analysis from the payer perspective, the discounted incremental cost per QALY for quetiapine XR + lithium/divalproex compared with placebo + lithium/divalproex was $US22 959, and compared with lithium monotherapy was $US100 235, while all other comparators were dominated. PSA showed these results to be robust to select assumptions. CONCLUSIONS: Quetiapine XR + lithium/divalproex may be a cost-effective maintenance treatment option for patients with BPD I.

The new lithium clinic.

Until the early 1950s, no effective pharmacological treatment existed for bipolar affective disorder. By the early 1960s, specialty clinics were being set up to dispense lithium carbonate to bipolar patients. By the late 1980s, a new body of knowledge was influencing the perception of bipolar disorder and how the disease should be treated. The authors' lithium clinic from 1974 has grown and evolved from a lithium blood level monitoring model into a comprehensive care model with polypharmacy, psychoeducation, rehabilitation, cognitive therapy, social rhythm therapy, and employment counseling as well as a staff of 2 part-time psychiatrists and 1 clinical psychologist. This service delivery model may benefit both treatment and research in bipolar disorder. The evolution of psychopharmacological and psychosocial knowledge in treating bipolar illness has been integrated into our clinic. Case vignettes are presented to illustrate these points. The comparative cost of this model is discussed.

Cost-effectiveness of quetiapine with lithium or divalproex for maintenance treatment of bipolar I disorder.

BACKGROUND: Bipolar I disorder is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. Few studies have investigated the cost-effectiveness of maintenance treatment options. The objective of this analysis was to assess the cost-effectiveness of quetiapine (QTP) in combination with lithium (Li) or divalproex (DVP) compared with that of Li or DVP alone for maintenance treatment of bipolar disorder. METHODS: The cost-effectiveness of maintenance treatment with QTP in combination with Li or DVP was compared with placebo (PBO) in combination with Li or DVP from a US direct costs perspective using a Markov model. The model simulated a cohort of 1,000 stabilized patients with bipolar I disorder and estimated the quarterly risk in three health states: euthymia, mania, and depression. Efficacy data were derived from two randomized, double-blind, placebo-controlled trials comparing QTP + Li/DVP with PBO + Li/DVP for up to 2 years. Resource data were obtained from published literature. Direct costs included drug costs, hospitalizations, and physician visits. Outcomes and costs were discounted at 3% and the price reference year was 2007. Endpoints included the number of acute mood episodes, hospitalizations due to an acute mood event, and costs per quality-adjusted life-years. A probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty. RESULTS: In the base-case analysis, QTP + Li/DVP dominated PBO + Li/DVP. The PSA showed these results to be robust. In addition, treatment with QTP + Li/DVP was associated with reductions in acute manic episodes (46%), acute depressive episodes (41%), and related hospitalizations (44%) compared with PBO + Li/DVP. CONCLUSIONS: These analyses, based on two randomized clinical trials, suggest that QTP + Li/DVP is a cost-effective maintenance treatment option for patients with bipolar I disorder compared with Li or DVP alone.

The effect of adjunctive mood stabilizers on antipsychotic utilization pattern and health resource utilization for Medicaid enrollees with schizophrenia.

BACKGROUND: Prescribing adjunctive mood stabilizers to manage schizophrenia is prevalent, despite the lack of substantial evidence to support the long-term use of this treatment regimen. OBJECTIVE: The objective of this study was to assess the impact of using adjunctive mood stabilizers on antipsychotic utilization, total health expenditures, inpatient hospitalizations, long-term care stays, and emergency room (ER) visits for patients with schizophrenia. METHODS: Georgia Medicaid claims from 1999 through 2001 were analyzed to identify recipients diagnosed with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 295. XX). The treatment groups consisted of subjects who received combination therapy of mood stabilizers and antipsychotics (including both atypical and typical medications), while the comparison group consisted of subjects who were on antipsychotic medications without exposure to the mood stabilizers under investigation. Four treatment groups (valproate, lithium, carbamazepine, and combination mood stabilizer therapy) were formed based on the mood stabilizers patient received. Differences in annual health care use and expenditures were estimated between propensity score matched treatment and comparison groups controlling for comorbidity, prior utilization, demographic, and health provider specialty. RESULTS: During the 1-year observation period, subjects in treatment groups filled an average of 200-days supply of adjunctive mood stabilizers. These adjunctive mood stabilizer recipients had significantly longer antipsychotic treatment durations than the subjects who did not have exposure to mood stabilizers (valproate + antipsychotic vs. antipsychotic only, net difference: 56.47 days, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: 90.25 days, p < 0.0001; carbamazepine + antipsychotic vs. antipsychotic only, net difference: 41.27 days, p = 0.0439; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net difference: 83.14 days, p < 0.0001). The intensive pharmacotherapy associated with treatment groups resulted in $900-$1300 higher pharmacy costs than the comparison groups (valproate + antipsychotic vs. antipsychotic only, net difference: $1218.43, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: $985.79, p = 0.0015; carbamazepine + antipsychotic vs. antipsychotic only, net difference: $911.63, p = 0.0497; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net difference: $1281.91, p < 0.0047). However, there were no statistically significant differences for total health expenditures, hospitalizations, emergency room visits, and nursing home admissions between propensity-matched treatment and control groups. CONCLUSIONS: There were no differences in health care costs or utilization of ER, long-term care, and inpatient services between schizophrenia patients who did and did not receive adjunctive mood stabilizer; however, longer antipsychotic treatment durations were observed in patients receiving adjunctive mood stabilizers. Interpretation of these results is limited by the unknown selection bias between the treatment and the comparison groups and the relatively small number of patients in some treatment groups. The development of a better-controlled study to further evaluate this treatment regimen is warranted.

Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom.

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

The cost-effectiveness of lamotrigine in the maintenance treatment of adults with bipolar I disorder.

OBJECTIVE: To present an economic model and cost-effectiveness estimates for lamotrigine in maintenance treatment of bipolar I disorder (BD-I) using outcomes from the pivotal lamotrigine trials. The main comparator treatments in the pivotal trials were lithium and .no maintenance. (acute-only) treatment. A comparison with olanzapine was included as an indirect analysis following publication of data during the course of our research. METHODS: A Markov model was built around the 3 health states of euthymia, mania, and depression. The base-case model simulates a cohort of 1,000 patients with BD-I who have recently stabilized after resolution of a bipolar mania episode. The cohort was modeled for a period of 18 months. Resource-use estimates were derived from best available published data, treatment guidelines, a physician survey, and published unit cost data. Outputs were measured in terms of costs per acute mood episode avoided, costs per euthymic day gained, and costs per quality-adjusted life-years (QALYs). Direct health care payer costs are used in the analyses. RESULTS: The base-case model for patients with a recent manic episode indicated that lamotrigine is the most effective treatment for avoiding both acute depression episodes and all types of acute episodes (depression and mania). It is also the most effective treatment in terms of number of euthymic days achieved (309 days per patient per year). Olanzapine is most effective for avoiding acute mania episodes. Total direct costs of treatment are lowest for the lithium treatment arm (Dollars 8,710 per patient for the 18-month period). All maintenance therapies were cost effective compared with the no-maintenance (acute-only treatment) arm. In the base case, lamotrigine had incremental cost-effectiveness ratios of Dollars 30 per euthymic day and Dollars 2,400 per acute episode avoided compared with lithium. A QALY analysis indicated that lamotrigine is cost effective in patients with a recent manic episode at Dollars 26,000 per QALY. The base-case model indicated that lamotrigine dominates olanzapine, (that is, lamotrigine costs less and is more effective than olanzapine) in patients with a recent manic episode. In a sensitivity analysis using outcomes from the pivotal trial of recently depressed patients, lamotrigine, in comparison with lithium, was not shown to be as cost effective as in the recently manic patients, but it was still cost effective compared with no maintenance treatment. CONCLUSIONS: For a defined cohort of patients with BD-I, the pharmacoeconomic model indicated that prevention of mood episodes with lithium and lamotrigine is cost effective in patients with a recent manic, mixed, or hypomanic episode. The conclusions with respect to the indirect comparison with olanzapine should be validated if and when direct trial data become available. Cost-effectiveness of maintenance treatments for patients with BD-I (recently depressed as well as recently manic) are likely to improve in models with a broader costing perspective and that take a longer time frame. Further research into the outcome implications of health-related quality of life and other BD subgroups are recommended.