SIBAT-A Computerized Assessment Tool for Suicide Ideation and Behavior: Development and Psychometric Properties.

Objective: Most assessments of suicidal ideation and behavior (SIB) are limited by reliance on a single assessor, typically a clinician or patient, with scant detail on patient-related drivers of SIB and inability to detect rapid change in SIB. Furthermore, many techniques do not include a semistructured interview, increasing rater variability. The Suicide Ideation and Behavior Assessment Tool (SIBAT) addresses these limitations. Design: More than 30 experts in scale development, statistics, and clinical management of suicidal patients collaborated over a greater than four-year period to develop the SIBAT. Input for content and validity was received from patients, clinicians, and regulatory authorities in the United States (US) and Europe. Psychometric properties of the SIBAT were evaluated in validation studies. Results: The SIBAT is organized into eight independent patient- or clinician-rated modules with branching logic and scoring algorithms, which necessitates computerization. Patient-reported information is first captured in Modules 1 to 5. Thereafter, an experienced clinician reviews the patient's report, conducts a semistructured interview (Module 6), and assesses the patient's suicide risk (Module 7) and optimal antisuicide management (Module 8). Input from cognitive interviews of diverse adult, adolescent, and clinician participants was incorporated into the final version of the SIBAT. Psychometric testing demonstrated good inter-rater reliability (intraclass coefficient range: 0.68-0.82), intra-rater reliability (weighted-kappa range: 0.64-0.76), and concurrent validity with other instruments for assessing SIB. Conclusion: Patient- and clinician-based assessments and the psychometric studies summarized in this report support the validity and reliability of the SIBAT for capturing critical information related to assessment of SIB in adolescents and adults at risk for suicide.

THE DEPRESSION INVENTORY DEVELOPMENT SCALE: Assessment of Psychometric Properties Using Classical and Modern Measurement Theory in a CAN-BIND Trial.

Objective: The goal of the Depression Inventory Development (DID) project is to develop a comprehensive and psychometrically sound rating scale for major depressive disorder (MDD) that reflects current diagnostic criteria and conceptualizations of depression. We report here the evaluation of the current DID item bank using Classical Test Theory (CTT), Item Response Theory (IRT) and Rasch Measurement Theory (RMT). Methods: The present study was part of a larger multisite, open-label study conducted by the Canadian Biomarker Integration Network in Depression (ClinicalTrials.gov: NCT01655706). Trained raters administered the 32 DID items at each of two visits (MDD: baseline, n=211 and Week 8, n=177; healthy participants: baseline, n=112 and Week 8, n=104). The DID's "grid" structure operationalizes intensity and frequency of each item, with clear symptom definitions and a structured interview guide, with the current iteration assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain, and appetite. Participants were also administered the Montgomery- Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) that allowed DID items to be evaluated against existing "benchmark" items. CTT was used to assess data quality/reliability (i.e., missing data, skewness, scoring frequency, internal consistency), IRT to assess individual item performance by modelling an item's ability to discriminate levels of depressive severity (as assessed by the MADRS), and RMT to assess how the items perform together as a scale to capture a range of depressive severity (item targeting). These analyses together provided empirical evidence to base decisions on which DID items to remove, modify, or advance. Results: Of the 32 DID items evaluated, eight items were identified by CTT as problematic, displaying low variability in the range of responses, floor effects, and/or skewness; and four items were identified by IRT to show poor discriminative properties that would limit their clinical utility. Five additional items were deemed to be redundant. The remaining 15 DID items all fit the Rasch model, with person and item difficulty estimates indicating satisfactory item targeting, with lower precision in participants with mild levels of depression. These 15 DID items also showed good internal consistency (alpha=0.95 and inter-item correlations ranging from r=0.49 to r=0.84) and all items were sensitive to change following antidepressant treatment (baseline vs. Week 8). RMT revealed problematic item targeting for the MADRS and QIDSSR, including an absence of MADRS items targeting participants with mild/moderate depression and an absence of QIDS-SR items targeting participants with mild or severe depression. Conclusion: The present study applied CTT, IRT, and RMT to assess the measurement properties of the DID items and identify those that should be advanced, modified, or removed. Of the 32 items evaluated, 15 items showed good measurement properties. These items (along with previously evaluated items) will provide the basis for validation of a penultimate DID scale assessing anhedonia, cognitive slowing, concentration, executive function, recent memory, drive, emotional fatigue, guilt, self-esteem, hopelessness, tension, rumination, irritability, reduced appetite, insomnia, sadness, worry, suicidality, and depressed mood. The strategies adopted by the DID process provide a framework for rating scale development and validation.

The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.

A systematic review of the health-related quality of life and economic burdens of anorexia nervosa, bulimia nervosa, and binge eating disorder.

PURPOSE: To perform a systematic review of the health-related quality of life (HRQoL) and economic burdens of anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). METHODS: A systematic literature search of English-language studies was performed in Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier, and Cochrane Library. Cost data were converted to 2014 Euro. RESULTS: Sixty-nine studies were included. Data on HRQoL were reported in 41 studies (18 for AN, 17 for BN, and 18 for BED), on healthcare utilization in 20 studies (14 for AN, 12 for BN, and 8 for BED), and on healthcare costs in 17 studies (9 for AN, 11 for BN, and only 2 for BED). Patients' HRQoL was significantly worse with AN, BN, and BED compared with healthy populations. AN, BN, and BED were associated with a high rate of hospitalization, outpatient care, and emergency department visits. However, patients rarely received specific treatment for their eating disorder. The annual healthcare costs for AN, BN, and BED were €2993 to €55,270, €888 to €18,823, and €1762 to €2902, respectively. CONCLUSIONS: AN, BN, and BED have a serious impact on patient's HRQoL and are also associated with increased healthcare utilization and healthcare costs. The burden of BED should be examined separately from that of BN. The limited evidence suggests that further research is warranted to better understand the differences in long-term HRQoL and economic burdens of AN, BN, and BED.

Assessment of functional outcomes by Sheehan Disability Scale in patients with major depressive disorder treated with duloxetine versus selective serotonin reuptake inhibitors.

OBJECTIVE: We compared functional impairment outcomes assessed with Sheehan Disability Scale (SDS) after treatment with duloxetine versus selective serotonin reuptake inhibitors (SSRIs) in patients with major depressive disorder. METHODS: Data were pooled from four randomized studies comparing treatment with duloxetine and SSRIs (three double blind and one open label). Analysis of covariance, with last-observation-carried-forward approach for missing data, explored treatment differences between duloxetine and SSRIs on SDS changes during 8 to 12 weeks of acute treatment for the intent-to-treat population. Logistic regression analysis examined the predictive capacity of baseline patient characteristics for remission in functional impairment (SDS total score ≤ 6 and SDS item scores ≤ 2) at endpoint. RESULTS: Included were 2193 patients (duloxetine n = 1029; SSRIs n = 835; placebo n = 329). Treatment with duloxetine and SSRIs resulted in significantly (p < 0.01) greater improvements in the SDS total score versus treatment with placebo. Higher SDS (p < 0.0001) or 17-item Hamilton Depression Rating Scale baseline scores (p < 0.01) predicted lower probability of functional improvement after treatment with duloxetine or SSRIs. Female gender (p ≤ 0.05) predicted higher probability of functional improvement after treatment with duloxetine or SSRIs. CONCLUSIONS: Treatment with SSRIs and duloxetine improved functional impairment in patients with major depressive disorder. Higher SDS or 17-item Hamilton Depression Rating Scale baseline scores predicted less probability of SDS improvement; female gender predicted better improvement in functional impairment at endpoint.

Current Assessment and Classification of Suicidal Phenomena using the FDA 2012 Draft Guidance Document on Suicide Assessment: A Critical Review.

OBJECTIVE: Standard international classification criteria require that classification categories be comprehensive to avoid type II error. Categories should be mutually exclusive and definitions should be clear and unambiguous (to avoid type I and type II errors). In addition, the classification system should be robust enough to last over time and provide comparability between data collections. This article was designed to evaluate the extent to which the classification system contained in the United States Food and Drug Administration 2012 Draft Guidance for the prospective assessment and classification of suicidal ideation and behavior in clinical trials meets these criteria. METHOD: A critical review is used to assess the extent to which the proposed categories contained in the Food and Drug Administration 2012 Draft Guidance are comprehensive, unambiguous, and robust. Assumptions that underlie the classification system are also explored. RESULTS: The Food and Drug Administration classification system contained in the 2012 Draft Guidance does not capture the full range of suicidal ideation and behavior (type II error). Definitions, moreover, are frequently ambiguous (susceptible to multiple interpretations), and the potential for misclassification (type I and type II errors) is compounded by frequent mismatches in category titles and definitions. These issues have the potential to compromise data comparability within clinical trial sites, across sites, and over time. CONCLUSION: These problems need to be remedied because of the potential for flawed data output and consequent threats to public health, to research on the safety of medications, and to the search for effective medication treatments for suicidality.

Humanistic and economic burden of generalized anxiety disorder in North America and Europe.

BACKGROUND: To review the humanistic and economic burden of generalized anxiety disorder (GAD). METHODS: MEDLINE, EMBASE and the Cochrane Library, limited to articles published in English, between 1987 and 2010, in North America, Europe and Australia. The key focus was humanistic or functional outcomes, cost of illness and economic outcomes. Ninety articles fitting criteria on (a) GAD study population, (b) United States, Europe or Australia, and (c) humanistic burden or economic burden were reviewed. Methods and findings were summarized by two researchers; inconsistencies were resolved by a third reviewer. RESULTS: GAD was associated with increased impairments in psychosocial functioning, role functioning, work productivity and health-related quality of life (HRQL). The HRQL impairments were comparable with those associated with depression or panic disorder. Patients with GAD and co-morbid depression reported significantly greater impairment in HRQL than did those with either disorder alone. GAD patients had significantly higher median medical costs than primary care patients without GAD (US $2375 versus $1448). The mean annual medical cost of GAD was $2138 higher than for other anxiety disorders (mean $6475). Finally, GAD was frequently under-recognized in primary care, and available studies reported that only 20% to 32% of patients were adequately treated. LIMITATIONS: The review was limited to pharmacologic treatments for GAD and to publications in English. CONCLUSIONS: GAD is associated with significant burden on patient functioning and well-being, leading to increased health care utilization and medical costs. Patients with GAD are often suboptimally treated, which adds to the HRQL burden of this disorder.

Patients with obsessive-compulsive disorder vs depression have comparable health care costs: a retrospective claims analysis of Florida Medicaid enrollees.

BACKGROUND: The health care burden of obsessive-compulsive disorder (OCD) is relatively unknown. OBJECTIVE: To compare the health care burden of patients with OCD vs depression. METHODS: This retrospective claims analysis compared the 2-year median per-patient health care claims and costs for Florida Medicaid adult enrollees (1997 to 2006) newly diagnosed with "pure OCD" (P-OCD; OCD without comorbid major depression, bipolar disorder, psychosis, organic mental disorder, pervasive developmental disorder, nonpsychotic brain damage, developmental delay, or mental retardation) with matched patients newly diagnosed with "pure depression" (P-D; similar to P-OCD but excluding OCD instead of depression). RESULTS: Eighty-five newly diagnosed P-OCD patients were matched with 14,906 P-D patients. Although median per-patient total health care costs were comparable across groups, patients with P-D incurred significantly higher median outpatient medical costs ($1,928 vs $363, P = .003), while those with P-OCD incurred almost three-fold greater psychiatric costs ($2,028 vs $759, P < .0001). The latter was due primarily to significantly higher costs of psychotropic medications among those with P-OCD ($4,307 vs $2,317, P = .0006) rather than to psychiatric outpatient care. CONCLUSIONS: Patients with P-D and P-OCD carry a similar burden in overall health care costs. However, the burden of those with P-D was largely attributable to outpatient medical costs while that of those with P-OCD was due to higher costs of psychotropic medications.

Antidepressant use in geriatric populations: the burden of side effects and interactions and their impact on adherence and costs.

OBJECTIVES: The study aimed to determine the prevalence of documented side effects and drug­drug interactions in older adults using antidepressants and their implications for adherence. DESIGN: Data were from the MarketScan Medicare Database,which comprises insurance claims from retirees with employer-sponsored Medicare supplemental insurance. Subjects were aged 65 years or older, new antidepressant users, and had a depression diagnosis between July 1, 2001, and December 31, 2006.Twelve commonly reported antidepressant side effects were identified in the month after drug initiation through International Classification of Diseases, Ninth Revision,Clinical Modification diagnoses. Potential drug- drug interactions involving an antidepressant and another drug were identified during the 1 year after antidepressant initiation using MicroMedex DRUG-REAX software. Multinomial logistic regression was used to determine the association of side effects and potential interactions with refills rates, switching, and discontinuation. RESULTS: The presence of a side effect was associated with a 4.7 percentage point increase in the probability of switching (from 16.5% to 21.7%) and a 3.7 percentage point increase in the discontinuation rate (from 22% to 25.7%). Among the 39,512 treatment-naive antidepressants users, 25.4% hadpotential contraindicated or major interactions, 36.1% had moderate interactions,and 38.5% had minor or no interactions. The presence of potential contraindicated or potential major interactions increased the probability of switching by 19.5 percentage points and had a minimal effect on discontinuation. CONCLUSION: Although antidepressant medications have been demonstrated to be effective in treatment of geriatric depression, this study highlights the complexity of antidepressant prescribing in this population and the need for clinicians to be aware of potential drug- drug interactions and side effects.

Expenditures associated with dose titration at initiation of therapy in patients with major depressive disorder: a retrospective analysis of a large managed care claims database.

OBJECTIVE.: Although selective serotonin reuptake inhibitors (SSRIs) are considered cost-effective medications for patients with major depressive disorder (MDD), significant dosage adjustments are often necessary when treatment is initiated. Our study was conducted to examine whether dose titration for SSRIs at initiation of therapy was associated with a greater use of health care resources and higher costs. STUDY DESIGN.: A retrospective database analysis was conducted. METHODS.: A nationally representative cohort of individuals with MDD was identified in a large managed care claims database between January 1, 2004, and December 31, 2006. A study-specific titration algorithm was used to identify patients who underwent dose titration, compared with those who did not, within the first eight weeks of initiating SSRI therapy. We calculated propensity scores and identified a 1:1 matched cohort of titration versus non-titration patients. We used univariate and multivariate statistical tests to compare the mean number of therapeutic days, health care service utilization, and expenditures between the two groups during the first eight weeks (56 days) of treatment and six months (180 days) after treatment began. RESULTS.: Over the first eight weeks, the titration cohort had a 32% decrease in the adjusted mean number of therapeutic days (38 vs. 56, respectively; P < 0.001), a 50% increase in depression-related outpatient visits (1.8 vs. 1.2; P < 0.001), a 38% increase in depression-related outpatient costs ($137 vs. $81; P ≤ 0.001), an increase in antidepressant pharmacy costs ($139 vs. $61; P < 0.001), and a 64% increase in psychiatric visits (0.69 vs. 0.42; P = 0.001), compared with the matched non-titration cohort. These differences were consistent among individual SSRI groups as well as during the six-month period. CONCLUSION.: Patients undergoing dose titration of SSRIs at the beginning of therapy consumed more medical resources and spent more days receiving a subtherapeutic dose than a comparable control group without dose titration. Differences in the utilization of resources were consistent with increased patient monitoring in the titration group; however, the added benefit of titration could not be assessed with this database.

Adequacy of pharmacotherapy among medicaid-enrolled patients newly diagnosed with obsessive-compulsive disorder.

OBJECTIVE: To determine the adequacy of pharmacotherapy received by patients with newly-diagnosed obsessive-compulsive disorder (OCD), based on current practice guidelines. METHODS: A 9 year (1997-2006) retrospective claims analysis of adults enrolled in Florida Medicaid for at least 3 continuous years was conducted to determine the percentage who received both a minimally effective duration (> 8 continuous weeks) and dose of first-line OCD pharmacotherapy during the year following their first ("index") OCD diagnosis. RESULTS: Among 2,960,421 adult (> 18 years of age) enrollees, 2,921 (0.1%) were diagnosed with OCD. Among the 2,825 OCD patients without comorbid Asperger syndrome or autism, 843 had newly-diagnosed OCD and at least 12 months of follow-up data after their index diagnosis. Among these 843 patients, 588 (69.7%) received first-line OCD pharmacotherapy but only 323 (38.3%) received a minimally effective pharmacotherapy trial in the year following their index diagnosis. CONCLUSIONS: Among clinically-diagnosed persons with OCD (<10% of those with the disorder), a minority of newly-diagnosed patients receive a minimally effective pharmacotherapy trial consistent with current standards of care. Reasons such as limited patient adherence and/or physician awareness of guidelines must be identified and redressed to ameliorate the patient, healthcare system, and economic burdens associated with OCD.

Differences in medication adherence and healthcare resource utilization patterns: older versus newer antidepressant agents in patients with depression and/or anxiety disorders.

BACKGROUND: Given the number of antidepressants available and their rising costs, healthcare payers have initiated restrictive reimbursement policies for newer antidepressants, without consideration for differences in their effectiveness or tolerability. OBJECTIVE: The objective of this study was to comprehensively compare medication adherence rates and associated healthcare utilization costs for patients using later-generation versus earlier-generation antidepressants in a managed care setting. Antidepressants launched after 2002 were deemed third-generation antidepressants, while antidepressants available prior to 2002 were deemed first-generation (TCAs and MAOIs) and second-generation (serotonin and noradrenaline [norepinephrine]-dopamine reuptake inhibitors). STUDY DESIGN: Retrospective database analysis using medical and pharmacy data from over 75 managed care plans covering 55 million lives. SETTING/PATIENTS: All patients receiving an antidepressant between 1 January 2002 and 30 September 2004 were identified. The index date for patients was the date of their first antidepressant prescription within this time period. Patients had to (i) have a diagnosis of depression or anxiety disorder, or depression and anxiety disorder within 6 months prior to or 30 days after their index prescription; (ii) be at least 18 years of age, without having taken antidepressant therapy for 6 months prior to their index date; and (iii) be continuously eligible for 6 months prior to their index date and during their 6-month follow-up period. Patients were excluded if they had a diagnosis of psychosis-related disease, Alzheimer's or Parkinson's disease, or were initiated on psychosis-related medications. INTERVENTION/MAIN OUTCOME MEASURE: Patients meeting selection criteria were followed for 6 months to assess rates of antidepressant adherence, therapy change rates and medical healthcare costs. STUDY POPULATION: A total of 266 665 patients met the study criteria. Approximately 66% were female, with a mean age of 39 years. About 63% had a diagnosis of depression, 31% had an anxiety disorder diagnosis and 6% had diagnoses for both an anxiety disorder and depression. Therapy change: Therapy change within 6 months occurred in 18% of patients receiving third-generation agents compared with 21% and 40% for second- and first-generation agents, respectively. The odds of a therapy change were significantly lower with third-generation antidepressants compared with both older agent cohorts. Adherence: Of patients receiving third-generation antidepressants, 33.6% were adherent compared with 29.3% and 12.4% of patients receiving second- and first-generation antidepressants, respectively. Newer agents also had better adherence rates across all diagnostic cohorts. After adjusting for baseline differences, the odds of being adherent to therapy were significantly lower for those taking second- and first-generation agents versus newer antidepressants. Among the newer agents, the proportion of patients adherent to their therapy was: venlafaxine extended release 38%, paroxetine controlled release (CR) 35%, escitalopram 34%, duloxetine 32% and bupropion extended release (XL) 31%. Healthcare utilization: Of the patients taking older antidepressants, 13% (second generation) and 21% (first generation) were hospitalized at least once for any reason compared with 12% of patients taking newer agents. Overall, the odds of all-cause hospitalization within 6 months of therapy initiation were significantly higher for patients taking older antidepressants. Among the newer agents, hospitalization rates ranged from 15.9% for duloxetine to 12.5% for paroxetine CR and bupropion XL. The unadjusted 6-month total medical costs (not including pharmacy costs) per patient were $US 3514 for second-generation, $US 5744 for first-generation and $US 3284 for newer antidepressants. After controlling for baseline differences, patients receiving second- and first-generation antidepressants incurred 12% and 44% higher costs, respectively. The unadjusted 6-month medical costs for the newer agents ranged from $US 2715 for paroxetine CR to $US 6042 for duloxetine. CONCLUSION: The results of this study provide essential information for healthcare decision makers about the potential advantages of newer generation antidepressants versus older generation antidepressants, as well as the differences between the specific newer agents, with respect to improved rates of adherence and therapy change, reduced hospitalizations and healthcare costs.

Differences in total medical costs across the SSRIs for the treatment of depression and anxiety.

There is growing evidence that adherence to the recommended duration of antidepressant therapy results in reduced medical costs compared with nonadherence, and that the likelihood of adhering to therapy is not equivalent across the selective serotonin reuptake inhibitors (SSRIs). As such, the purpose of this study was to assess differences in 6-month medical costs between paroxetine controlled-release (CR) and immediate-release (IR) SSRI agents in a retrospective analysis of patients initiating SSRI therapy identified from the Integrated Healthcare Information Services National Managed Care Benchmark Database during a 2.5-year time frame. Inferential analyses were performed to evaluate differences in 6-month medical costs, controlling for differences in age, sex, utilization of psychiatric specialty care services, titration, pre-period costs, and comorbidity measures. Of the 146 075 patients included in this study, approximately 7% received paroxetine CR. Approximately 29.5% of patients had an anxiety disorder diagnosis; 26.0% had a depression-only diagnosis; and 13.2% had comorbid anxiety and depression. The 6-month medical costs were 244 US dollars lower for patients initiating with paroxetine CR compared with the average medical costs for patients receiving IR SSRIs. Paroxetine CR also had the lowest medical costs compared with each individual SSRI evaluated. After log transformation of costs and adjustment for baseline covariates, the aggregated IR SSRIs were associated with 8.7% higher 6-month medical costs than paroxetine CR (P <.001) and even greater costs after stratifying by diagnosis: 12.5% higher costs in patients with anxiety, 14.3% higher costs in patients with depression, and 15.9% higher costs in patients with comorbid anxiety and depression (P <.001 for all). Each individual IR SSRI was also associated with significantly higher medical costs than paroxetine CR, irrespective of diagnosis. As demonstrated, medical costs over a 6-month time frame were significantly greater for IR SSRIs versus paroxetine CR, even after adjusting for background characteristics and stratifying by diagnosis. Future studies should measure rates of adherence in relation to medical outcomes over an expanded time frame.

Evaluating the economic consequences of early antidepressant treatment discontinuation: a comparison between controlled-release and immediate-release paroxetine.

INTRODUCTION: Early antidepressant discontinuation has been linked to significant clinical and economic consequences. Clinical practice guidelines suggest that treatment should last for at least 3 to 9 months into the continuation phase; however, 30% of patients discontinue therapy within 30 days, and over 40% discontinue therapy within 90 days of initiation, primarily due to adverse events. Clinical trials have shown that controlled-release (CR) paroxetine has a favorable tolerability profile when compared to immediate-release (IR) paroxetine, which may result in lower discontinuation rates and improved economic outcomes. This is the first study to directly compare treatment discontinuation rates and health care expenditures of a CR selective serotonin reuptake inhibitors with its IR counterpart. METHODS: This matched retrospective study used claims from a national managed care database to assess differences in discontinuation rates and health care expenditures between paroxetine CR and IR for treating depression and/or anxiety. Discontinuation was assessed by survival analysis, and health care expenditure was assessed using average monthly medical and pharmacy charges. RESULTS: There were 1275 paroxetine CR patients and 2550 paroxetine IR patients matched in the analysis. At 90 days, 62% of paroxetine CR patients continued therapy versus 56% of paroxetine IR patients. At 180 days, 51% of paroxetine CR patients continued therapy versus 42% of paroxetine IR patients. When evaluating all medical charges, paroxetine CR patients incurred US 119 dollars less per month than paroxetine IR patients (P = 0.054). CONCLUSIONS: Patients receiving paroxetine CR remained on therapy longer than patients on paroxetine IR, which resulted in lower total monthly medical costs for patients receiving paroxetine CR. Differences in costs were primarily driven by reduction in hospitalization expenditures.

Impact of formulary restrictions on the cost-effectiveness of antidepressant treatment.

Newer antidepressants are associated with higher costs of treatment of anxiety and depression. Managed care organizations are challenged to control treatment costs by implementing restricted formularies based on price and perceived medical value. Despite unfavorable side effects of efficacious tricyclic antidepressants, the low acquisition cost rationalizes the inclusion of this older class of agents on a formulary. On the other hand, cost-containment approaches have been taken toward more expensive drug classes (e.g., selective serotonin reuptake inhibitors) despite a superior safety profile of these drug classes over tricyclics. There is compelling evidence that dual reuptake inhibitors (e.g., venlafaxine extended-release), which have acquisition costs similar to serotonin reuptake inhibitors, have a broad spectrum of efficacy and thus added value, contributing to the cost-effectiveness of including this agent in the managed care formulary. Assessment of overall cost-effectiveness should not be limited by acquisition costs but should take total healthcare costs into consideration.

Generalized anxiety disorder: raising the expectations of treatment.

Anxiety disorders are prevalent and associated with an increase in morbidity and mortality, particularly when present with additional psychiatric disorders. They represent a public health and economic burden, yet they are commonly underrecognized and undertreated. Benzodiazepines are effective anxiolytics, but they primarily treat the somatic symptoms of generalized anxiety disorder (GAD), and are not effective in treating the depressive symptoms that are often comorbid in chronic anxiety disorders like GAD. Some antidepressants may therefore offer the best choice of therapy. Their benefit in the treatment of GAD has been demonstrated using the tricyclic antidepressant, imipramine, and some selective serotonin reuptake inhibitors. The serotonin and norepinephrine reuptake inhibitor venlafaxine extended release (XR), has been indicated for GAD and has proven to be effective in both the short- and long-term treatment of patients with this disorder. Many patients treated with venlafaxine XR achieve and sustain remission from the symptoms of GAD, which is the goal of treatment.