The real world cost and health resource utilization associated to manic episodes: The MANACOR study.

INTRODUCTION: Bipolar disorder is a relapsing-remitting condition affecting approximately 1-2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. METHODS: Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. RESULTS: One hundred sixty-nine patients patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4,771. The 77% (€3,651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score>41 significantly predicted a higher direct cost. CONCLUSIONS: Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder.

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.

Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin litigation.

BACKGROUND: Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain. METHODS: We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court's findings).We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom. RESULTS: We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship. CONCLUSIONS: Taken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis's publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers.

Which psychosocial interventions in bipolar depression?

This review of psychosocial interventions in bipolar disorders demonstrates that some therapies, when combined with medication, are more efficacious at preventing or delaying depressive relapse, and can be more effective than medication alone in reducing time to recovery from an acute bipolar depressive episode. However, apparent benefits diminish over time, suggesting that maintenance or « booster ¼ therapy sessions may be needed. Given the scarcity of trained therapists, further studies are needed to determine which bipolar depressed patients should be targeted and to establish more clearly the potential cost and benefits of such interventions.

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.

Healthcare costs of atypical antipsychotic use for patients with bipolar disorder in a Medicaid programme.

BACKGROUND: A large body of clinical studies have demonstrated the efficacy of atypical antipsychotic use in the treatment of bipolar disorder. Facing increasing budget pressure, third-party payers, such as state Medicaid programmes in the US, are demanding better understanding of the medical costs beyond atypical antipsychotic drug costs alone in treating bipolar disorder. OBJECTIVE: To examine healthcare costs associated with the atypical antipsychotic treatments for bipolar disorder from a US third-party payer perspective. METHODS: This was a retrospective cohort study using an intent-to-treat approach. Using the North Carolina Medicaid claims database (August 2000 to January 2005), 3328 patients with bipolar disorder were identified who were continuously eligible for 3 months pre-initiation and 12 months post-initiation of treatment with an atypical antipsychotic (AP2) or mood stabilizer (MS). Patients were classified into three groups based on the treatment types during the first 30 days after treatment initiation: AP2 monotherapy, AP2 + MS combination therapy, and MS monotherapy. Bipolar-related and total health-related costs were examined for the 12-month period. Propensity score matching was employed to balance baseline characteristics among the three comparison groups. Generalized linear models were further employed to estimate the average treatment effect on the cost outcomes. RESULTS: Compared with MS monotherapy, AP2 monotherapy and AP2 + MS combination therapy incurred higher medication costs during the 12-month treatment period. Patients receiving AP2 monotherapy had significantly lower bipolar-related medical costs (-$US698; p = 0.002) [year 2004 values] than patients receiving MS monotherapy. However, the inclusion of the medication cost produced no statistically significant difference in bipolar-related total cost (p = 0.14). Similar results were observed for all health-related costs. Patients receiving AP2 + MS therapy incurred significantly higher bipolar-related total costs (+$US1659; p < 0.0001) and all health-related total costs (+$US2115; p < 0.0001) than patients receiving MS monotherapy, which was attributable largely to the higher medication cost. CONCLUSIONS: From a third-party payer perspective, atypical antipsychotic monotherapy generated higher drug costs but lower medical care costs, resulting in equivalent total healthcare costs over a 1-year period.

Pattern of healthcare resource utilization and direct costs associated with manic episodes in Spain.

BACKGROUND: Although some studies indicate that bipolar disorder causes high health care resources consumption, no study is available addressing a cost estimation of bipolar disorder in Spain. The aim of this observational study was to evaluate healthcare resource utilization and the associated direct cost in patients with manic episodes in the Spanish setting. METHODS: Retrospective descriptive study was carried out in a consecutive sample of patients with a DSM-IV diagnosis of bipolar type I disorder with or without psychotic symptoms, aged 18 years or older, and who were having an active manic episode at the time of inclusion. Information regarding the current manic episode was collected retrospectively from the medical record and patient interview. RESULTS: Seven hundred and eighty-four evaluable patients, recruited by 182 psychiatrists, were included in the study. The direct cost associated with healthcare resource utilization during the manic episode was high, with a mean cost of nearly 4,500 euros per patient, of which approximately 55% corresponded to the cost of hospitalization, 30% to the cost of psychopharmacological treatment and 10% to the cost of specialized care. CONCLUSIONS: Our results show the high cost of management of the patient with a manic episode, which is mainly due to hospitalizations. In this regard, any intervention on the management of the manic patient that could reduce the need for hospitalization would have a significant impact on the costs of the disease.

The management of individuals with bipolar disorder: a review of the evidence and its integration into clinical practice.

Bipolar disorder is a common, debilitating, chronic illness that emerges early in life and has serious consequences such as long-term unemployment and suicide. It confers considerable functional disability to the individual, their family and society as a whole and yet it is often undetected, misdiagnosed and treated poorly. In the past decade, many new treatment strategies have been trialled in the management of bipolar disorder with variable success. The emerging evidence, for pharmacological agents in particular, is promising but when considered alone does not directly translate to real-world clinical populations of bipolar disorder. Data from drug trials are largely based on findings that identify differences between groups determined in a time-limited manner, whereas clinical management concerns the treatment of individuals over the life-long course of the illness. Considering the findings in the context of the individual and their particular needs perhaps best bridges the gap between the evidence from research studies and their application in clinical practice. Specifically, only lithium and valproate have moderate or strong evidence for use across all three phases of bipolar disorder. Anticonvulsants, such as lamotrigine, have strong evidence in maintenance; whereas antipsychotics largely have strong evidence in acute mania, with the exception of quetiapine, which has strong evidence in bipolar depression. Maintenance data for antipsychotics is emerging but at present remains weak. Combinations have strong evidence in acute phases of illness but maintenance data is urgently needed. Conventional antidepressants only have weak evidence in bipolar depression and do not have a role in maintenance therapy. Therefore, this paper summarizes the efficacy data for treating bipolar disorder and also applies clinical considerations to these data when formulating recommendations for the management of bipolar disorder.

Medicating mood with maintenance in mind: bipolar depression pharmacotherapy.

OBJECTIVES: Bipolar depression is a core feature of bipolar disorder, a phase in which many patients spend the majority of time and one that confers a significant degree of burden and risk. The purpose of this paper is to briefly review the evidence base for the pharmacotherapy of bipolar depression and to discuss the recommendations for its optimal management. METHODS: A detailed literature review was undertaken with a particular emphasis on pharmacological treatment strategies for bipolar depression across the acute and maintenance phases of the illness. Electronic library and Web-based searches were performed using recognised tools (MEDLINE, PubMED, EMBASE and PsychINFO) to identify the pertinent literature. A summary of the evidence base is outlined and then distilled into broad clinical recommendations to guide the pharmacological management of bipolar depression. RESULTS: Partitioning treatment into acute and maintenance therapy is difficult based on the paucity of current evidence. The evidence from treatment trials favours the use of lithium and lamotrigine as first-line treatment in preference to valproate, and indicates that, for acute episodes, quetiapine and olanzapine have perhaps achieved equivalence at least in terms of efficacy. However, the effectiveness of the atypical antipsychotics in maintenance therapy is constrained by the potential for significant side effects of individual agents and the lack of both long-term research data and clinical experience in treating bipolar disorder as compared to other agents. Conversely, lithium and the anticonvulsants are generally slower to effect symptomatic change, and this limits their usefulness. CONCLUSIONS: There has been a tendency for research trials of bipolar depression to differentiate the illness cross-sectionally into the acute and maintenance phases of bipolar depression; however, in clinical terms, bipolar depression invariably follows a longitudinal course in which the phases of illness are inextricably linked, and useful acute treatments are typically continued in maintenance. Therefore, when medicating mood in acute bipolar depression it is imperative to keep maintenance in mind as it is this aspect of treatment that determines long-term success.

Long-term mental health resource utilization and cost of care following group psychoeducation or unstructured group support for bipolar disorders: a cost-benefit analysis.

OBJECTIVE: To explore the short- and long-term mental health resource utilization and cost of care in a sample of 120 individuals with bipolar disorders who participated in a randomized controlled efficacy trial of group psychoeducation versus unstructured group support. METHOD: Prospective, independent monitoring of DSM-IV bipolar disorder type I or II patients aged 18 to 65 years was conducted during the intervention phase (6 months) and follow-up phase (5-year postintervention) of a randomized controlled trial reporting clinical outcomes and inpatient and outpatient mental health service utilization, with estimation of cost of treatment per patient. The study was conducted from October 1997 through October 2006. RESULTS: Compared with individuals with bipolar disorder receiving the control intervention, psychoeducated patients had twice as many planned outpatient appointments, but the estimated mean cost of emergency consultation utilization was significantly less. There were trends for psychoeducated patients to opt for self-funded psychotherapy after completing group psychoeducation and to utilize more medications. However, inpatient care accounted for 40% estimated total cost in the control group but only about 15% in the psychoeducation group. CONCLUSIONS: This study demonstrates the importance of taking a long-term overview of the cost versus benefits of adjunctive psychological therapy in bipolar disorders. If viewed only in the short-term, the psychoeducation group used more mental health care resources without clear additional health gain. However, extended follow-up demonstrated a long-term advantage for psychoeducated individuals, such that, compared to an unstructured support group intervention, group psychoeducation is less costly and more effective.

Treatment costs and health care utilization for patients with bipolar disorder in a large managed care population.

OBJECTIVES: This study measured the treatment cost of bipolar disorder (BPD), decomposed the cost into that portion which was directly BPD-related and that attributable to comorbidities, and compared health-care utilization and costs across groups of patients with different drug regimens. METHODS: Using a multistate managed-care-organization claims database, a cohort of 67,862 BPD patients were selected and followed for the length of their enrollment between January 1, 1998 and December 31, 2002. All costs associated with the patients' medical claims were adjusted to 2002 dollars using the medical component of Consumer Price Index. Patients were classified into three groups based on their drug regimen: atypical antipsychotics (ATYP), atypical antipsychotics plus mood stabilizers (ATYP + MS), and mood stabilizers only (MS). The Charlson comorbidity index was used to control for comorbid conditions. Using both Poisson and log-linear regression analyses, numbers of hospitalizations, emergency room (ER) visits, and outpatient visits, as well as treatment costs per enrolled month, were regressed on age, sex, medication regimen, and clinical comorbidities. RESULTS: The mean charge and reimbursement per patient-year were $12,797 and $6581, respectively. Of the treatment cost, 33% was BPD-related, and 67% was attributed to comorbidities. Compared to patients in the MS treatment regimen, higher treatment costs were associated with ATYP (Rate Ratio = 1.24, 95% CI 1.17-1.31) and ATYP + MS (RR = 1.52, 1.47-1.56). Moreover, higher costs were associated with key comorbidities like personality disorder (RR = 1.45, 1.37-1.53). Patients on the ATYP regimen had higher risks of hospitalization (RR = 1.44, 1.33-1.56) and ER visits (RR = 1.15, 1.04-1.27), but lower risk of outpatient visits (RR = 0.81, 0.76-0.86). CONCLUSIONS: Controlling treatment costs for BPD patients requires focusing on patients with key comorbidities and monitoring the association between treatment regimen and resource use.

A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder.

OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of pharmacological and/or psychosocial interventions for the prevention of relapse in people with bipolar disorder. DATA SOURCES: Major electronic databases were searched up to September 2005. REVIEW METHODS: Systematic reviews were undertaken on the clinical and economic effectiveness of treatments. An analysis was performed using the methods of mixed treatment comparison (MTC) to enable indirect comparisons to be made between the treatments. An economic model of treatments for the prevention of relapse in bipolar disorder was developed. RESULTS: Forty-five trials were included in the clinical effectiveness review; all but one studied adults. This review found that for the prevention of all relapses, lithium, valproate, lamotrigine and olanzapine performed better than placebo, with lithium and lamotrigine having the strongest evidence. For depressive relapse prevention, valproate, lamotrigine and imipramine performed better than placebo, with evidence strongest for lamotrigine and weakest for imipramine. For manic relapses, lithium and olanzapine performed significantly better than placebo. The MTC found that the best treatment for bipolar I patients with mainly depressive symptoms was valproate, followed by lithium plus imipramine. For bipolar I patients with mainly manic symptoms, olanzapine was the best treatment. From the studies investigating psychosocial interventions, there were few data for each comparison and outcome. The evidence suggests that cognitive behaviour therapy (CBT), in combination with usual treatment, is effective for the prevention of relapse. Group psychoeducation and possibly family therapy may also have roles as adjunctive therapy for preventing relapse. The results from the decision analytic model developed on the cost-effectiveness of long-term maintenance treatments of bipolar I patients suggest that the choice of treatment is dependent upon a number of factors: the previous episode history of a patient and the mortality benefit assumed for lithium strategies. The results from the base-case analysis for patients with a recent history of depression suggest that valproate, lithium and the combination of lithium and imipramine are potentially cost-effective depending upon the amount that a decision-maker is willing to pay for additional health gain. Using conventional amounts that the NHS is prepared to pay for health gain, then the lithium-based strategies appear to be potentially cost-effective for this group. For patients with a recent history of mania, the choice of pharmacological intervention appears to be between olanzapine and lithium monotherapy. Again using conventional threshold as a reference point, the results suggest that lithium is the most cost-effective therapy. Excluding the additional mortality benefit associated with lithium-based strategies resulted in all treatments for patients with a recent history of a depressive episode being dominated by valproate and, in the case of patients with a recent history of a manic episode, by olanzapine. CONCLUSIONS: Lithium, valproate, lamotrigine and olanzapine are effective as maintenance therapy for the prevention of relapse in bipolar disorder. Olanzapine and lithium are efficacious for the prevention of manic relapses and valproate, lamotrigine and imipramine for the prevention of depressive relapse. There is some evidence that CBT, group psychoeducation and family therapy might be beneficial as adjuncts to pharmacological maintenance treatments. Insufficient information is available regarding the relative tolerability of the treatments or their relative effects on suicide rate and mortality. For patients with a recent depressive episode, valproate, lithium monotherapy and the combination of lithium and imipramine are potentially cost-effective. For patients with a recent manic episode, olanzapine and lithium monotherapy are potentially cost-effective. The cost-effectiveness estimates in both groups of patients were shown to be sensitive to the assumption of a reduced suicidal risk associated with lithium-based strategies. Further research is needed into the adverse effects of all treatments and the differential effects of agents. Good-quality trials of valproate, of combination therapy, e.g. lithium plus a selective serotonin reuptake inhibitor antidepressant, of psychosocial interventions and of the disorder in children are also required.

Ensuring sustained ACT production and reliable artemisinin supply.

INTRODUCTION: This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. Production and cost data provided in this paper are based on an ongoing project (Artepal). Stability data are derived from a development project on rectal artesunate. DISCUSSION: The artemisinin raw material and its derivatives appear to be very stable compared to the finished products. Supply of artemisinin changed in May 2004 when the Global Fund shifted financial support to qualified countries from chloroquine or sulphadoxine-pyrimethamine to an ACT for treatment of malaria. First, there was a sudden shortage of the starting material, and short term scarcity led to a steep rise in API price: it increased dramatically in 2004, from $350 per kg to more than $1000. Second, there was a parallel increase in the number of companies extracting artemisinin from 10 to 80 between 2003 and 2005 in China, and from 3 to 20 in Vietnam. Commercial cultivation began also in East Africa and Madagascar.A steady and predictable demand for the crop can eliminate such wide fluctuations and indirectly contribute to price stability of the herb, the API and ACT. With appropriate mechanisms to reduce those fluctuations, the cost of artemisinin might decrease sustainably to US$ 250-300 per kg. CONCLUSION: Today the global health community is facing the risk of another cyclical swing with lower demand feeding into reduced planting of A. annua and, thereafter, a new shortage of the raw material and higher API prices. International donors, the largest purchasers for ACTs could better coordinate their activities, in order to guarantee purchase of ACTs and consequently of API with manufacturers. In parallel, the base of quality producers of APIs and finished ACT products needs to be broadened.While the ACT programme is still in its early stages, the consequences of another wave of artemisinin and ACT shortages would permanently discredit it and impede any progress in rolling malaria back.

Treatment costs related to bipolar disorder and comorbid conditions among Medicaid patients with bipolar disorder.

OBJECTIVE: This study assessed costs among patients with bipolar disorder for treatment related to bipolar disorder and to comorbid conditions. Risk factors associated with costs were also assessed. METHODS: Data (January 1998 to December 2002) were from a seven-state Medicaid managed care claims database for 13,471 patients who had received a diagnosis of bipolar disorder, most of whom received medications. Each medical claims cost was adjusted by the medical component of the Consumer Price Index as the dollar value in 2002. In a Poisson regression analysis, treatment costs per enrollment month were regressed on patient's age, gender, medications, and clinical comorbidities. RESULTS: Bipolar disorder treatment accounted for 30% of costs and comorbid disorders for 70%. Key cost components were inpatient care (35%), outpatient care (16%), prescriptions (13%), and physician encounters (11%). Patients with bipolar disorder received a variety of medications: lithium, 13%; anticonvulsants, 35%; second-generation antipsychotics, 24%; first-generation antipsychotics, 22%; and antidepressants, 42%. Compared with the costs for patients receiving antidepressants alone or no medication, the high costs for bipolar disorder treatment and overall treatment were associated with use of second-generation antipsychotics (rate ratio [RR]=1.71, 95% confidence interval [CI]=1.58-1.86 and RR=1.26, CI=1.18-1.34, respectively) and use of anticonvulsants (RR=1.37, CI=1.26-1.48 and RR=1.06, CI=1.00-1.12). Higher costs were significantly associated with key comorbidities, such as drug abuse (RR=1.58, CI=1.47-1.70), cerebral-vascular disease (RR=1.72, CI=1.51-1.94), ischemic heart disease (RR=1.47, CI=1.30-1.66), and hypertension (RR=1.44, CI=1.33-1.56). CONCLUSIONS: Cost-containment efforts may need to manage or prevent key comorbidities among patients with bipolar disorder and to evaluate the association between antipsychotic use and treatment outcomes and hospital services.

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.

The impact of unrecognized bipolar disorders among patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program: a 6-year retrospective analysis.

INTRODUCTION: The cost of unrecognized bipolar disorders over time is unknown. METHODS: Ten years of data from the California Medicaid program were used to identify depressed patients initiating new episodes of antidepressant therapy and with 6+ years of post-treatment data. Recognized bipolar (RBP) patients received a BP diagnosis or used mood stabilizers in the pre-index period. Unrecognized bipolar (UBP) patients received an initial BP diagnosis or used a mood stabilizer in the post-index period. Depression-only (MDD) patients had no BP diagnosis or mood stabilizer use. Three analyses were conducted: (1) regression models of cost per year, (2) a regression model of aggregate cost over 6 years and (3) a time trend analysis of the costs for UBP patients. RESULTS: 14,809 patients were identified: RBP 14.5%, UBP 28.2% and MDD 57.3%. The growth in costs per month for UBP patients over 6 years (171%) far exceeds the growth for RBP and MDD patients (82% and 95%, respectively). RBP and MDD patients cost 2316 dollars and 1681 dollars less per year in the 6th year relative to UBP patients (p<0.0001 for both estimates). The cost per month increased by 91 dollars for each month of delayed diagnosis (p=0.011). Costs for UBP patients increased by 10 dollars per month prior to their initial BP diagnosis (p<0.001) and by -1.01 dollars thereafter (p=0.006 for the change in slope). LIMITATIONS: Classification of patients based on diagnosis or mood stabilizer use using paid claims data is inexact. CONCLUSIONS: Early diagnosis of bipolar disorders may significantly reduce health care cost.

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.