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.

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.

A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder.

Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (-3.095 [-5.256, -0.935]; P = 0.0051) and the SDS total score (-2.632 [-4.193, -1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥ 5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales, reflecting symptomatic and functional improvement; treatment was generally well tolerated.

Sheehan Suicidality Tracking Scale (S-STS): reliability, convergent and discriminative validity in young Italian adults.

BACKGROUND AND PURPOSE: The Sheehan Suicidality Tracking Scale (S-STS) is a patient self-report or clinician-administered rating scale that tracks spontaneous and treatment-emergent suicidal ideation and behaviors. This study set out to evaluate the reliability, convergent and divergent validity of the S-STS in a sample of college students, a population with a high risk of completed and attempted suicide. METHODS: Cross-sectional, survey design. Participants (303 undergraduate students; males: 42%) completed several measures assessing psychological distress (General Health Questionnaire; GHQ); self-esteem (Rosenberg Self Esteem Scale; RSES); social support (Modified Social Support Survey; MOSSS); and suicidal behavior, including ideation and attempts (S-STS). RESULTS: Both internal consistency and test-retest stability were excellent for the S-STS-global score. The S-STS subscale on suicide ideation also showed good reliability, while the subscale on suicidal behavior showed some inconsistency at retest. Convergent and divergent validity of S-STS was confirmed. All S-STS items loaded on a single factor, which had an excellent fit for the unidimensional model, thus justifying the use of the S-STS as a screening tool. In a mediation model, self-esteem and social support explained 45% of the effects of psychological distress on suicide ideation and behavior as measured by the S-STS-global score. CONCLUSIONS: This study provided promising evidence on the convergent, divergent, internal consistency and test-retest stability of the Sheehan Suicidality Tracking Scale. The cross-sectional design and lack of measures of hopelessness and helplessness prevent any conclusion about the links of suicidal behavior with self-esteem and social support.

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.

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.

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.

Clinical and functional outcomes in patients with major depressive disorder and painful physical symptoms switched to treatment with duloxetine.

OBJECTIVE: This post hoc analysis of a multicenter, single-arm, open-label trial (the Attributes of Response in Depressed Patients Switched to Treatment with Duloxetine [ARDENT] study) assessed the relationship between functional improvement in the Sheehan Disability Scale (SDS) and clinical outcomes of mood, pain, and anxiety over 8 weeks after switching treatment to duloxetine in patients with major depressive disorder. METHODS: Analyses included all 195 patients who completed the study. Pearson's correlation and multivariate regression analyses were used to evaluate the relationship between change from baseline in SDS total score and 17-item Hamilton Rating Scale for Depression (HAMD(17)) Maier score (mood), Brief Pain Inventory-Short Form average pain score (pain), and Hamilton Anxiety Rating Scale total score (anxiety) at week 8. RESULTS: At week 8, change in SDS total score was positively correlated with change in mood (r = 0.49), anxiety (r = 0.44), and pain (r = 0.40). Multivariate linear regression coefficients for mood and pain were estimated at 1.21 (standard error [SE] = 0.184) and 1.16 (SE = 0.180), respectively (both p < 0.0001) compared with 0.02 (SE = 0.097; p = 0.82) for anxiety. Overall, 43% of patients achieved both HAMD(17) and SDS total remission. CONCLUSIONS: Functional improvement at 8 weeks was positively correlated with mood, pain, and anxiety in patients with major depressive disorder switched to duloxetine. Change in mood and pain exerted a relatively stronger joint effect on functioning than did anxiety in this patient population. Copyright © 2011 John Wiley & Sons, Ltd.

Evaluating functional disability in clinical trials of lisdexamfetamine dimesylate in binge eating disorder using the Sheehan Disability Scale.

OBJECTIVES: This study examined Sheehan Disability Scale (SDS) performance in binge eating disorder (BED) and explored relationships between SDS and BED outcomes using data from three placebo-controlled lisdexamfetamine (LDX) studies (two short-term, dose-optimized studies and one double-blind, randomized-withdrawal study) in adults with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR)-defined BED. METHODS: Analyses evaluated the psychometric properties of the SDS. RESULTS: Confirmatory factor analysis supported a unidimensional total score in the short-term studies, with internal consistency (Cronbach's α) being 0.878. Total score exhibited good construct validity, with moderate and statistically significant correlations observed with Yale-Brown Obsessive Compulsive Scale modified for binge eating, Binge Eating Scale (BES), and EuroQol Group 5-Dimension 5-Level health status index scores. Known-groups validity analysis for the short-term studies demonstrated a significantly lower total score at end of study in participants considered "not ill" versus "ill" based on Clinical Global Impressions-Severity scores. SDS total score changes in the short-term studies were greater in responders than nonresponders based on binge eating abstinence or BES score. In the randomized-withdrawal study, SDS scores increased relative to baseline to a greater extent in participants randomized to placebo than LDX. CONCLUSIONS: These analyses support the reliability, validity, and responsiveness to change of the SDS in individuals with BED.

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.

Pilot Mental Health Survey, Nepal: Lessons Learned for Survey Design and Instrumentation.

Objective: Learning from pilot studies is crucial for the successful implementation of large-scale surveys. In this manuscript, we present the lessons learned for instrumentation and survey methods from a pilot national mental health survey conducted in Nepal. Design: We conducted a cross-sectional study among 1,647 participants aged 13 years and older in three districts of Nepal. We used the Nepali translated standard adult and adolescent versions of the Mini International Neuropsychiatric Interview (MINI) 7.0.2 for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) to do face-to-face structured diagnostic interviews. In addition, we included questionnaires on help-seeking behavior and barriers in accessing care. Results: We used a six-step procedure to translate and fit the tools in the context of Nepal. We conducted pretesting to evaluate the Nepali translated tools and adaptations, such as the addition of bridging sentences at the start of different modules. We identified different challenges during the tools administration and the ways to minimize reporting bias during data collection. Conclusion: The pilot survey identified the areas for improvement in survey tools, techniques, and methodology. The lessons learned from the pilot survey and the resulting corrective recommendations helped in more successful implementation of the Nepal national mental health survey.

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.

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.

Assessing treatment effects in clinical trials with the discan metric of the Sheehan Disability Scale.

The Sheehan Disability Scale (SDS) is a patient-rated, discretized analog measure of functional disability in work, social, and family life. Its increasing use in clinical trials in psychiatry suggests a need to assess its responsiveness and interpretability. In this paper we identify and review studies in which the SDS was used as a treatment outcome measure. Our objectives are (i) to evaluate the sensitivity of the SDS to treatment effects and (ii) to examine potential thresholds or cutoff scores for remission and response. Studies for the review were retrieved from the National Library of Medicine's PubMed database (1966 to 21 March 2007) and other sources. All studies had to use the SDS, be double-blind, controlled or large open-label trials in English. Studies assessing nonpharmacological treatments, long-term trials (>12 weeks), small n trials (less than 20 patients per treatment arm) and trials for conditions other than one of the anxiety disorders, depression, or premenstrual dysphoric disorder were excluded. Extracted data included the diagnostic target of treatment, n, study design, and method of analysis. Initial, endpoint and/or mean change scores were extracted from tables, text, or extrapolated from figures. In all, 37 studies meeting the inclusion criteria were retrieved and reviewed. All of the studies treated the SDS as a numeric scale and analyzed mean change or endpoint differences with parametric statistics. Three provided additional outcome data using nonparametric response or remission criteria. Overall, the SDS performed well in discriminating between active and inactive treatments. The results indicate that the SDS is sensitive to treatment effects. To establish reliable and valid cutoff scores for remission and response, there is a need to supplement parametric analyses using mean change and endpoint differences with nonparametric analyses showing the percentage meeting specified response and remission criteria. In addition, the percentages with endpoint scores of zero should be reported.

Effects of Lisdexamfetamine Dimesylate on Functional Impairment Measured on the Sheehan Disability Scale in Adults With Moderate-to-severe Binge Eating Disorder: Results from Two Randomized, Placebo-controlled Trials.

Objective: In two Phase III, randomized, placebo-controlled trials (NCT01718483 and NCT01718509 at ClinicalTrials.gov), lisdexamfetamine dimesylate (LDX) reduced binge eating days/week in adults with moderate-to-severe binge eating disorder (BED). We describe the effects of LDX (50mg and 70mg) on the Sheehan Disability Scale (SDS; exploratory endpoint) from both studies. Design: The SDS was assessed at baseline, Week 6, and Week 12/early termination. Analyses included mixed-effects models for repeated measures for the examination of SDS total and domain score changes and a generalized estimating equation model to assess dichotomized remission status (remission [total score ≤6] versus nonremission [total score >6]). Results: Least squares (95% confidence interval [CI]) mean treatment differences for SDS total score change from baseline at Week 12 were -2.80 (-3.98, -1.61) in Study 1 and -3.70 (-4.81, -2.58) in Study 2 (both p<0.001). Least squares (95% CI) mean treatment differences across SDS domains favored LDX over placebo in both studies for the change from baseline at Week 12 (work/school: -0.8 [-1.2, -0.4] and -1.1 [-1.5, -0.7], both p<0.001; social life/leisure activities: -1.0 [-1.4, -0.5] and -1.4 [-1.8, -1.0], both p<0.001; and family life/home responsibilities: -1.0 [-1.4, -0.5] and -1.3 [-1.7, -0.9], both p<0.001). Odds ratios (95% CI) for SDS remission versus nonremission favored LDX over placebo at Week 12 (Study 1: 2.39 [1.44, 3.96]; p<0.001 and Study 2: 5.12 [2.80, 9.33]; p<0.001). Conclusion: These findings indicate that LDX treatment is associated with improvement on the SDS in adults with moderate-to-severe BED.

Perceived stress in anxiety disorders and the general population: a study of the Sheehan stress vulnerability scale.

The objectives of this study were to (1) validate and establish normative values for a single-item, self-rated measure of perceived stress, the Stress Vulnerability Scale (SVS); and (2) compare levels of perceived stress in patients with anxiety disorders with the general population. The sample was drawn from the general population (n=630) and from participants in pharmacotherapy trials of anxiety disorders (social phobia, n=127; posttraumatic stress disorder, n=116). The SVS was administered at baseline in all groups and following treatment in the placebo-controlled clinical trial samples. The SVS demonstrated good reliability and validity. Pretreatment scores in the anxiety disorders were significantly greater than in the general population. Perceptions of vulnerability to the effects of daily stress are considerably greater in anxiety disorders compared to the general population and also differ within the anxiety disorders.

Restoring function in major depressive disorder: A systematic review.

BACKGROUND: Functional impairment contributes to significant disability and economic burden in major depressive disorder (MDD). Treatment response is measured by improvement in depressive symptoms, but functional improvement often lags behind symptomatic improvement. Residual deficits are associated with relapse of depressive symptoms. METHODS: A literature search was conducted using the following terms: "major depressive disorder," "functional impairment," "functional outcomes," "recovery of function," "treatment outcome," "outcome assessment," "social functioning," "presenteeism," "absenteeism," "psychiatric status rating scales," and "quality of life." Search limits included publication date (January 1, 1995 to August 31, 2016), English language, and human clinical trials. Controlled, acute-phase, nonrecurrent MDD treatment studies in adults were included if a functional outcome was measured at baseline and endpoint. RESULTS: The qualitative analysis included 35 controlled studies. The Sheehan Disability Scale was the most commonly used functional assessment. Antidepressant treatments significantly improved functional outcomes. Early treatment response predicted functional improvement, while baseline disease severity did not. LIMITATIONS: Clinical studies utilized various methodologies and assessments for functional impairment, and were not standardized or adequately powered. CONCLUSIONS: The lack of synchronicity between symptomatic and functional improvement highlights an unmet need for MDD. Treatment guided by routine monitoring of symptoms and functionality may minimize residual functional impairments.

The effect of vortioxetine on overall patient functioning in patients with major depressive disorder.

BACKGROUND: The objectives of this meta-analysis of data from randomized, placebo-controlled studies were to assess the effect of vortioxetine on overall functioning (primary) and functional remission (secondary) using the Sheehan Disability Scale (SDS) in adults with major depressive disorder (MDD). METHODS: Data from nine short-term (6/8 weeks) pivotal studies that included patient functioning assessments were included in this random-effects meta-analysis, which used aggregated study-level data for all therapeutic vortioxetine doses and a mixed-effect model for repeated measures using the full analysis set. RESULTS: A total of 4,216 patients received ≥1 dose of study treatment (1,522 placebo, 2,694 vortioxetine 5-20 mg/day). At study end, the meta-analysis showed improvement for vortioxetine versus placebo (n = 911) in SDS total score (vortioxetine 5 mg, n = 564, change from baseline versus placebo [Δ] -0.24, p = NS; 10 mg, n = 445, Δ -1.68, p ≤ .001; 15 mg, n = 204, Δ -0.91, p = NS; 20 mg, n = 340, Δ -1.94, p ≤ .01). Functional remission (SDS total score ≤6) was observed with vortioxetine 10 mg (n = 170/573; odds ratio [OR] relative to placebo 1.7, p < .001) and 20 mg (n = 144/447; OR 1.6, p < .05), but not 5 mg (n = 207/757; OR 1.1, p = NS) or 15 mg (n = 92/295; OR 1.3, p = NS). CONCLUSION: Vortioxetine 5-20 mg for 6/8 weeks improved overall patient functioning in patients with MDD. Relative to placebo, vortioxetine 10 and 20 mg demonstrated significant improvement in SDS total score and functional remission.

Importance of Restoring Function in Patients With Major Depressive Disorder.

Patients with depression experience symptoms that hinder their ability to function at home, at work, and in social settings. Even when mood symptoms improve, patients' function may not return to normal. Clinicians must make restoration of function a treatment goal along with symptom remission. Rating scales that assess function can help clinicians monitor areas such as work performance, role fulfillment, social activities, and more. The process of treating functional impairments will take time and may require specific interventions, but patients will feel "recovered" only when these areas are restored.