Economic burden and antidepressant treatment patterns among patients with major depressive disorder in the United States.

BACKGROUND: The prevalence of major depressive disorder (MDD) continues to rise year over year, resulting in significant economic implications. However, when patients are treated with contemporary standard-of-care antidepressant pharmacotherapies, a suboptimal response is often attained, resulting in frequent treatment changes. OBJECTIVE: To compare health care resource utilization (HCRU) and all-cause medical and pharmacy costs between commercially insured patients with an MDD diagnosis and matched non-MDD patients and explore treatment patterns among patients with MDD initiating antidepressant pharmacotherapy. METHODS: This was a retrospective, observational analysis of IBM MarketScan US commercial claims data. Adults aged 18 years and older with continuous enrollment 12 or more months before and after the patient's first MDD diagnosis from 2017 to 2018 were included in the analysis. HCRU and all-cause medical and pharmacy costs were compared among patients with MDD and a 1:1 exact-matched cohort of non-MDD patients during the same period (Objective 1). Treatment patterns (persistence, discontinuation, switch, combination, and augmentation) were analyzed for patients with MDD starting first-line antidepressant monotherapy for up to 12 months following their antidepressant initiation index date (Objective 2). Time to first treatment change or discontinuation was calculated and treatment patterns were graphically displayed in Sankey diagrams. RESULTS: 625,272 patients with MDD were matched 1:1 to a cohort of non-MDD patients in Objective 1. Patients with MDD had statistically significantly greater all-cause medical (20.4 vs 9.4; P < 0.0001), outpatient (19.5 vs 9.0; P < 0.0001), emergency department (0.51 vs 0.23; P < 0.0001), inpatient (0.35 vs 0.11; P < 0.0001), and any mental health-related (7.7 vs 0.58; P < 0.0001) visits compared with non-MDD patients. Mean all-cause medical costs were $6,809 (P < 0.0001) higher among patients with MDD than among patients without MDD ($13,183 vs $6,374, respectively). In Objective 2, 44,485 patients with MDD who received antidepressant monotherapy as their first-line MDD treatment were examined. Among the first treatment patterns observed following initiation, 19.3% of patients persisted with their first-line therapy, 56.2% discontinued antidepressant therapy, 24.5% experienced a treatment change (switching, adding a second antidepressant, or augmenting their existing therapy). The median days until first treatment change were 65 days for those discontinuing and 47 days for those switching antidepressants. Among the 24.5% of patients with a treatment change, 50.0% experienced another change in therapy within 30 days. CONCLUSIONS: The HCRU and costs accrued for patients with MDD is significantly greater than those for non-MDD patients. A large proportion of patients with MDD experienced treatment changes shortly after initiating their first-line antidepressant therapy. The results of this study highlight the need for reevaluation of the current MDD treatment paradigm. DISCLOSURES: Drs Zhu and Namjoshi are employees of Biogen Inc. and may hold stock. Dr Ferries and Ms Suthoff are employees of Sage Therapeutics, Inc., and may hold stock and/or stock options. Dr Bera has no potential conflicts of interest to disclose. This research was funded by Sage Therapeutics and Biogen. Manuscript editorial services were provided by Boston Strategic Partners, Inc., funded by Sage Therapeutics and Biogen. This work was supported by Sage Therapeutics, Inc., and Biogen. The authors had full editorial control of the manuscript and provided final approval on all content.

Relationship between incidence of fracture and health-related quality-of-life in metastatic breast cancer patients with bone metastases.

OBJECTIVE: This retrospective observational study describes treatment patterns and longitudinal health-related quality-of-life (HRQoL) among metastatic breast cancer patients with bone metastasis from nine community oncology clinics. METHODS: For description of treatment patterns, patients were classified as treated if they started zoledronic acid within 60 days of diagnosis of bone metastasis, were considered untreated if they had not, and were considered unclassified if they died or experienced fracture before 60 days had elapsed. Medical record review provided demographic and disease characteristics as well as history of treatment. Patients completed Patient Care Monitor (PCM) assessments of patient reported outcomes during routine care for up to 2 years from the date of bone metastasis diagnosis. RESULTS: The overall rate of fracture in the sample was 17.4%. Of the 321 patients enrolled, 160 were treated as of 60 days after diagnosis of bone metastasis, 147 were untreated, and 14 were unclassified. Of the 147 untreated as of 60 days, 82 did eventually receive zoledronic acid. More than half of all patients treated with zoledronic acid delayed the start of treatment by more than 30 days after diagnosis of bone metastasis. Patients who had a fracture showed decreased mobility and increased pain and anxiety at fracture, with recovery taking ~16 months. LIMITATIONS: Key limitations included: convenience sample with information limited to medical record content, low rate of observed fractures possibly due to limited 2-year follow-up, and exclusion of non-zoledronic acid bisphosphonate use. CONCLUSIONS: Whereas the proportion of patients experiencing a fracture was small, the impact of fracture on HRQoL was significant and was more prominently seen to impact specific dimensions of HRQoL.

Characterization of clinical course and usual care patterns in female metastatic breast cancer patients treated with zoledronic acid.

PURPOSE: To describe usual care received by women with bony metastatic breast cancer (ICD-9: 174.xx and 198.5) treated in a United States specialty cancer hospital, an Electronic Medical Record (EMR)-based retrospective review identified 111 deceased female breast cancer patients ≥18 years of age treated with zoledronic acid (ZOL). RESULTS: Baseline symptoms included bone pain/fracture (58.6%), breathing difficulties (24.3%), or mental status changes (11.7%). ZOL was started at/after metastatic diagnosis for 75.7% of women (N = 84), with average administration of 15.9 months (median 11.3). Nearly 20% required reduced ZOL doses, most (54.5%) due to impaired renal function; 61.3% discontinued ZOL due to patient death/disease progression. Adverse events were reported in 10.8%, while 0.9% (N = 1) had a documented osteonecrosis of the jaw. CONCLUSIONS: Initiation of palliative care should be considered early in patients with a history of metastatic breast cancer who report bone pain or other skeletal-related events.

Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

OBJECTIVE: To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). METHODS: Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. RESULTS: In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. LIMITATIONS: Assumptions about some model input parameters were necessary and may impact results. CONCLUSIONS: Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total budget increases were modest.

Cost-effectiveness of denosumab compared with zoledronic acid in patients with breast cancer and bone metastases.

BACKGROUND: Results from a phase III clinical trial showed that denosumab significantly reduced the risk of first on-study and subsequent skeletal-related events (SREs) compared with zoledronic acid. This study aims to assess the cost-effectiveness of denosumab vs. zoledronic acid in the prevention of SREs in patients with advanced breast cancer and bone metastases. MATERIALS AND METHODS: A Markov model was developed with 4-week model cycles and a 1-year time horizon. The health states were defined by SRE status (no SRE, first on-study SRE, subsequent SRE, no SRE but history of SRE) and SRE type (pathologic fracture, radiation to the bone, surgery to the bone, spinal cord compression). Costs (in 2011 US dollars) included drug, SRE treatment, and adverse event (AE) costs and were assessed from a third-party payer perspective. The primary outcome was incremental total cost per SRE avoided; the secondary outcome was incremental total cost per pathologic fracture avoided. One-way and probabilistic sensitivity analyses were used to assess the robustness of the model. RESULTS: During the 1-year treatment period, denosumab incurred $7522 higher costs ($30,033 for denosumab and $23,511 for zoledronic acid), 0.06 fewer SREs, and 0.02 fewer pathologic fractures per patient, which led to an incremental total cost per SRE and pathologic fracture avoided of $114,628 and $290,136, respectively, compared with zoledronic acid. Results were robust to 1-way and probabilistic sensitivity analyses. CONCLUSION: Although denosumab demonstrated superiority in preventing SREs in the phase III trial, it may not be cost-effective compared with zoledronic acid because of its high cost.

Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases.

BACKGROUND: Bone metastases are common in patients with hormone-refractory prostate cancer. In a study of autopsies of patients with prostate cancer, 65%-75% had bone metastases. Bone metastases place a substantial economic burden on payers with estimated total annual costs of $1.9 billion in the United States. Skeletal-related events (SREs), including pathologic fractures, spinal cord compression, surgery to bone, and radiation to bone, affect approximately 50% of patients with bone metastases. They are associated with a decreased quality of life and increased health care costs. Zoledronic acid is an effective treatment in preventing SREs in solid tumors and multiple myeloma. Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. A Phase 3 clinical trial (NCT00321620) demonstrated that denosumab had superior efficacy in delaying first and subsequent SREs compared with zoledronic acid. However, the economic value of denosumab has not been assessed in patients with hormone-refractory prostate cancer. OBJECTIVE: To compare the cost-effectiveness of denosumab with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer. METHODS: An Excel-based Markov model was developed to assess costs and effectiveness associated with the 2 treatments over a 1- and 3-year time horizon. Because the evaluation was conducted from the perspective of a U.S. third-party payer, only direct costs were included. Consistent with the primary outcome in the Phase 3 trial, effectiveness was assessed based on the number of SREs. The model consisted of 9 health states defined by SRE occurrence, SRE history, disease progression, and death. A hypothetical cohort of patients with hormone-refractory prostate cancer received either denosumab 120 mg or zoledronic acid 4 mg at the model entry and transitioned among the 9 health states at the beginning of each 13-week cycle. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase 3 clinical trial and were supplemented with published literature. The model assumed that a maximum of 1 SRE could occur in each cycle. Drug costs included wholesale acquisition cost, health care professional costs associated with drug administration, and drug monitoring costs, if applicable. Nondrug costs included incremental costs associated with disease progression, costs associated with SREs, and terminal care costs, which were derived from the literature. Adverse event (AE) costs were estimated based on the incidence rates reported in the Phase 3 trial. Resource utilization associated with AEs was estimated based on consultation with a senior medical director employed by the study sponsor. All costs were presented in 2010 dollars. The base case estimated the incremental total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time horizon were also estimated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the model. RESULTS: In the base case, the total per patient costs incurred over 1 year were estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for denosumab and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for zoledronic acid, with an incremental total direct cost of $7,813 for denosumab. The estimated numbers of SREs per patient during the 1-year period were 0.49 for denosumab and 0.60 for zoledronic acid, resulting in an incremental number of SREs of -0.11 in the denosumab arm. The estimated incremental total direct costs per SRE avoided with the use of denosumab instead of zoledronic acid were $71,027 for 1 year and $51,319 for 3 years. The 1-way sensitivity analysis indicated that the results were sensitive to the drug costs, median time to first SRE, and increased risk of SRE associated with disease progression. Results of the PSA showed that based on willingness-to-pay thresholds of $70,000, $50,000, and $30,000 per SRE avoided, respectively, denosumab was cost-effective compared with zoledronic acid in 49.5%, 17.5%, and 0.3% of the cases at 1 year, respectively, and 79.0%, 49.8%, and 4.1% of the cases at 3 years, respectively. CONCLUSIONS: Although denosumab has demonstrated benefits over zoledronic acid in preventing or delaying SREs in a Phase 3 trial, it may be a costly alternative to zoledronic acid from a U.S. payer perspective.

Comparison of skeletal complications and treatment patterns associated with early vs. delayed zoledronic acid therapy in multiple myeloma.

BACKGROUND: This study retrospectively compared the risks of skeletal-related events (SREs) and zoledronic acid (ZOL) treatment discontinuation associated with early vs. delayed ZOL therapy for patients with symptomatic multiple myeloma (MM). PATIENTS AND METHODS: Data were collected from a physician-administered medical chart review among US patients with a confirmed diagnosis of symptomatic MM treated after 01/01/2002. Early and delayed ZOL therapy were defined, respectively, as initiating ZOL ≤ 60 days (N = 126) vs. > 60 days (N = 186) after the first symptomatic MM diagnosis. Kaplan-Meier analysis with a log-rank test was performed to compare the risk of SREs between the cohorts. Cox proportional hazard modeling compared the risk of SREs associated with early vs. delayed ZOL treatment, controlling for demographic factors, stage of MM, bone health status, and presence of major comorbidities at diagnosis. Time to ZOL discontinuation was evaluated using the Kaplan-Meier method, following patients from the date of ZOL initiation. RESULTS: Time to the first SRE was significantly longer for patients who received early treatment with ZOL (P = .005). At 2 years after diagnosis, the SRE-free rate was 74.6% vs. 56.5% in the early vs. delayed treatment group, respectively. Early ZOL therapy was associated with a significantly lower risk of any SRE (hazard rate [HR] = .625 vs. delayed ZOL therapy; P = .029). At 2 years from ZOL therapy initiation, rates of ZOL discontinuation were 9.6% vs. 16.4% among patients with early vs. delayed therapy, respectively (P < .05). CONCLUSION: Early treatment with ZOL was associated with significantly reduced risks of SREs and with better treatment persistence compared with delayed treatment.

Health care costs for schizophrenia patients started on olanzapine versus risperidone.

PURPOSE: The change in direct medical costs for schizophrenia patients who were started on olanzapine or risperidone and who were privately insured was studied. METHODS: A retrospective analysis of 1996-1999 data from the databases representing the health care experiences of individuals employed by large organizations and their dependents was performed. The sample included all individuals with a drug claim for olanzapine or risperidone, a claim with a schizophrenia diagnosis within 90 days of the drug claim, no claim for the same drug in the prior six months, and continuous health-plan enrollment for 12 months before and after the prescription. RESULTS: The sample included 162 patients initiated on olanzapine and 119 patients initiated on risperidone. Demographic and clinical profiles were not significantly different between groups. Annual schizophrenia-related prescription and outpatient costs increased following initiation on olanzapine or risperidone compared with the pre-initiation period. This was partially offset by a decrease in inpatient expenditures. Olanzapine initiators had higher outpatient drug expenditures than risperidone initiators in the 12 months following initiation (adjusted means, $2105 versus $1934) (p < 0.05), but there was no significant difference between groups in total schizophrenia-related payments ($5251 versus $4950). CONCLUSION: The total health care expenditure related to treating schizophrenia was similar between privately insured patients who were initiated on olanzapine and patients who were started on risperidone.

Quality of life assessment in patients with bipolar disorder treated with olanzapine added to lithium or valproic acid.

BACKGROUND: The objective of this study was to determine the clinical and quality of life outcomes associated with adjunctive treatment of olanzapine added to either lithium or valproic acid/divalproex sodium in patients with bipolar disorder. METHODS: Patients with bipolar I disorder, were randomized to receive either olanzapine (5-20 mg) added to mood stabilizer therapy (n=224), or placebo added to mood stabilizer therapy (n=112) for 6 weeks. Changes in clinical outcomes over 6 weeks were measured by the Young Mania Rating Scale (Y-MRS) and the Hamilton Rating Scale for Depression (HAM-D). Quality of life was measured by the Lehman Brief Quality of Life Interview (QLI). RESULTS: Patients treated with olanzapine added to mood stabilizers, experienced significantly greater mean clinical improvements from baseline on both the Y-MRS and the HAM-D compared to those treated with placebo added to mood stabilizers. Over 6 weeks, patients treated with olanzapine added to mood stabilizers had significantly greater mean improvements from baseline on five of the nine subjective scales on the QLI, compared to patients treated with placebo added to mood stabilizers. Changes in scores on the subjective scales of the QLI were more strongly correlated to changes in depressive symptomatology measured by the HAM-D, than to changes in symptoms of mania measured by the Y-MRS. CONCLUSION: The results of this study demonstrate that patients receiving adjunctive treatment have significantly greater improvements in both clinical and quality of life outcomes compared to monotherapy with mood stabilizers.

Improvement of Positive and Negative Syndrome Scale cognitive score associated with olanzapine treatment of acute mania.

OBJECTIVE: This study analyzed the effect of olanzapine on a psychopathology-based scale assessing abnormal thought processes and examined the relationship between improvement on this scale and mania and depression improvement in acutely manic patients. METHODS: The study sample (N = 254) was pooled from two double-blind, randomized, placebo-controlled clinical trials. Disturbance in thought processes was measured by the Positive and Negative Symptom Scale cognitive component (PANSS-Cognitive) score. Mood severity was measured by the Young-Mania Rating Scale (Y-MRS) and Hamilton Depression Inventory (HAM-D). Last-observation-carried-forward (LOCF) changes from baseline to endpoint (Week 3) were presented for patients who had at least one post-baseline assessment. RESULTS: Olanzapine-treated patients experienced modest but significant improvement in PANSS-Cognitive score (olanzapine: -4.25 n = 124; placebo: -1.69 n = 120, p < 01), regardless of age, gender, mania subtype (pure, mixed), course (rapid or non-rapid cycling), or the presence or absence of psychotic features. PANSS-Cognitive improvement was more highly correlated with mania than depression improvement. CONCLUSION: Olanzapine improved abnormal thought processes measured by the PANSS-Cognitive score in patients with acute mania. This improvement in thought processes was significantly associated with improvement in acute mania. More sensitive and specific neuropsychological testing could help clarify whether improvement in thought processes on olanzapine was independent of mania reduction.

Effects of olanzapine alone and olanzapine/fluoxetine combination on health-related quality of life in patients with bipolar depression: secondary analyses of a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Improving patients' health-related quality of life (HRQOL) could be a treatment goal for bipolar depression. OBJECTIVES: The objectives of these secondary analyses of a previous report were to determine the benefits of olanzapine alone and olanzapine-fluoxetine combination (OFC) for improving HRQOL in patients with bipolar depression using both a generic and a depression-specific HRQOL instrument, and to examine the association between the 2 HRQOL instruments and the construct validity of the depression-specific HRQOL instrument. METHODS: This was a double-blind, placebo-controlled, 83-site, international, randomized trial. Adults with bipolar I disorder, most recent episode depressed (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), were randomly assigned to receive olanzapine (6-20 mg/d), OFC (6/25, 12/25, or 12/50 mg/d), or placebo for 8 weeks. HRQOL improvement was calculated as last-observation-carried-forward changes in dimension and component summary scores on Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and total score on the Quality of Life in Depression Scale (QLDS). RESULTS: Patients were assigned to receive olanzapine (n = 370), [corrected] OFC (n = 86), or placebo (n = 377) [corrected] for 8 weeks. Of 833 enrolled patients, 454 discontinued (olanzapine, 191/370 [51.6%] [corrected]OFC, 31/86 [36.0%]; and placebo, 232/377 [61.6%]) [corrected] Compared with placebo, olanzapine-treated patients exhibited greater improvements on SF-36 mental component summary (MCS) score ( P=0.002) and 3 of 8 SF-36 dimension scores (mental health [P=0.015], role-emotional [P=0.046], and social functioning [P=0.006). OFC-treated patients exhibited greater improvements on MCS score ( P<0.001) vs both placebo and olanzapine), 5 SF-36 dimension scores (general health perception (P<0.001) vs placebo; (P<0.001) vs olanzapinel, mental health [ P=0.001] vs both placebo and olanzapine], role-emotional [ P<0.001] vs placebo; [P=0.007] vs olanzapine], social functioning [ P=0.001] vs placebo; [P=0.032] vs olanzapine], and vitality [P=0.002] vs placebo; [P=0.011] vs olanzapine]), and QLDS total score ( P<0.001] vs both placebo and olanzapine). Changes in SF-36 scores of mental health, social functioning, role-emotional, and vitality were highly correlated to changes in the QLDS total score (all p < -0.5). CONCLUSIONS: Based on these analyses, patients with bipolar depression receiving olanzapine or OFC for 8 weeks had greater improvement in HRQOL than those receiving placebo. OFC treatment was associated with greater improvement in HRQOL than olanzapine alone. The correlation results support the construct validity of the QLDS.

Economic outcomes associated with switching individuals with schizophrenia between risperidone and olanzapine: findings from a large US claims database.

OBJECTIVES: To assess the impact of switching atypical antipsychotic treatment [from (i) risperidone to olanzapine or (ii) olanzapine to risperidone] on medication use patterns and treatment costs for individuals with schizophrenia. METHODS: Using a large, integrated medical service and pharmacy claims database, 244 individuals diagnosed with schizophrenia (International Classification of Diseases [9th revision]: 295.xx) who switched treatment from risperidone to olanzapine (n = 202) or from olanzapine to risperidone (n = 42) were identified. Changes in medication use patterns and treatment costs (1999 values) per patient from the pre- to the post-switch period were evaluated. McNemar's tests were used to compare changes in use of antiparkinsonian, antidiabetic and antihyperlipidaemic agents and typical antipsychotics, while the Wilcoxon signed rank tests were applied to examine changes in treatment costs. RESULTS: After switching from risperidone to olanzapine, the percentage of patients using concomitant antiparkinsonian agents and typical antipsychotics decreased significantly from 30.20% to 21.29% (p = 0.0094) and from 30.69% to 18.32% (p = 0.0006), respectively. There was no significant change in the use of antidiabetic or antihyperlipidaemic drugs. For mental health-related treatment, annualised pharmaceutical costs increased by $US1761 (from $US1829 to $US3590, p < 0.0001) but medical service costs decreased by $US3511 (from $US11 292 to $US7781, p = 0.0036), driven primarily by significantly lower emergency room care and hospital outpatient costs. This resulted in no significant change in overall mental healthcare costs. Similar results were observed with total healthcare costs. In contrast, after switching from olanzapine to risperidone there was no significant change in treatment patterns for any of the medications assessed or in healthcare costs (mental healthcare-related or total), despite a significant decrease in mental health-related pharmaceutical costs. CONCLUSIONS: Switching from risperidone to olanzapine was associated with improved medication use patterns for antiparkinsonian and typical antipsychotic agents. While both mental health and total healthcare pharmaceutical costs increased significantly, this was not associated with a significant increase in overall mental health and total healthcare costs. These outcomes, however, were not evidenced in patients switched from olanzapine to risperidone.

A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania.

BACKGROUND: This randomized controlled trial compares the efficacy and safety of olanzapine vs haloperidol, as well as the quality of life of patients taking these drugs, in patients with bipolar mania. METHODS: The design consisted of 2 successive, 6-week, double-blind periods and compared flexible dosing of olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219). RESULTS: Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup of patients whose index episode did not include psychotic features, rates of remission were significantly greater for the olanzapine group compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques (P =.04), and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms, as indicated by several measures. Weight gain was significantly greater in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group. CONCLUSIONS: These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania. However, haloperidol carries a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with weight gain.

Economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in mania. Results from a randomized controlled trial.

INTRODUCTION: The objectives of this study were to determine the economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in patients diagnosed with mania. METHODS: Patients with a diagnosis of bipolar I disorder with manic or mixed episodes were enrolled in a randomized controlled trial. The study design comprised a 3-week acute phase followed by a 49-week open label extension. In the open label extension, the use of lithium and fluoxetine was permitted for patients who experienced breakthrough symptoms. Clinical, economic, and quality-of-life outcomes of treatment were assessed. RESULTS: During the acute phase, olanzapine patients experienced a statistically significant greater mean improvement from baseline on the Y-MRS total score compared to the placebo patients. In the open label extension, patients experienced a statistically significant mean change of 11.8 units on the Y-MRS from the end of the acute phase. When compared to costs incurred in the previous 12 months of therapy, patients experienced savings of almost $900 per month during the 49 weeks of olanzapine therapy. These cost savings were largely driven by reductions in in-patient costs during the open label extension. Health-related quality of life improvements measured by the SF-36 were seen on several dimensions both in the 3-week acute phase as well as in the 49-week open label extension. CONCLUSION: From a clinical, economic, and quality-of-life outcomes standpoint, olanzapine had a significant impact in the treatment of mania, and could be considered a cost-effective treatment option for use in this population if these findings are extrapolated to non-clinical trial populations.

Pharmacotherapy patterns in the treatment of bipolar disorder.

OBJECTIVES: To assess medication use patterns of patients with bipolar disorder, and, through multivariate analysis, to elucidate the role of selected demographic and clinical factors on medication choice and use patterns. METHODS: Patients were privately insured individuals aged 18-64, continuously enrolled in a health plan for 15 months or longer during the years 1994-1998, and either diagnosed with bipolar disorder or prescribed lithium or valproate at least 90 days after the start of the study period. Medical and pharmacy claims data were used to analyze medication therapy over a 12-month period. RESULTS: First-generation antipsychotics were used by 16.4% of patients and second-generation agents by 12.4%. Patients starting on antipsychotics tended to stay with them for 12 months or longer, while patients starting on anticonvulsants or antidepressants were more likely to stop therapy or to switch to another medication class. Patients treated with olanzapine appeared to have more psychiatric comorbidities and more psychiatric hospitalizations than users of first-generation agents. CONCLUSIONS: Although mood stabilizers and anticonvulsant agents are widely used to treat bipolar disorder, antipsychotic agents are also present in the treatment regimens of bipolar patients. Demographic and clinical factors were significant predictors of the choice of initial medication therapy and subsequent use patterns. In particular, patient gender and the number of psychiatric and physical comorbidities were significantly related to the course of medication therapy.