Adjunctive Brexpiprazole for Patient Life Engagement in Major Depressive Disorder: A Canadian, Phase 4, Open-Label, Interventional Study: Brexpiprazole d'appoint pour l'engagement dans la vie des patients souffrant de trouble dépressif majeur: une étude interventionnelle canadienne ouverte de phase 4.

OBJECTIVES: To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. METHODS: An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1-2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5-2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. RESULTS: Of 122 enrolled patients, 120 (98.4%) were treated (mean [SD] dose: 1.2 [0.4] mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR10 Life Engagement subscale score (baseline mean [SD]: 16.1 [4.7]; change [95% confidence interval]: -8.11 [-9.34, -6.88]; p < 0.001) and IDS-SR total score (baseline mean [SD]: 41.3 [9.8]; change [95% confidence interval]: -17.38 [-20.08, -14.68]; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue (n = 13, 10.8%), headache (n = 13, 10.8%), insomnia (n = 12, 10.0%), nausea (n = 9, 7.5%), tremor (n = 8, 6.7%), and weight increase (n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean (SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. CONCLUSIONS: Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04830215.

Practical pathway for the management of depression in the workplace: a Canadian perspective.

Major depressive disorder (MDD) and other mental health issues pose a substantial burden on the workforce. Approximately half a million Canadians will not be at work in any week because of a mental health disorder, and more than twice that number will work at a reduced level of productivity (presenteeism). Although it is important to determine whether work plays a role in a mental health condition, at initial presentation, patients should be diagnosed and treated per appropriate clinical guidelines. However, it is also important for patient care to determine the various causes or triggers including work-related factors. Clearly identifying the stressors associated with the mental health disorder can help clinicians to assess functional limitations, develop an appropriate care plan, and interact more effectively with worker's compensation and disability programs, as well as employers. There is currently no widely accepted tool to definitively identify MDD as work-related, but the presence of certain patient and work characteristics may help. This paper seeks to review the evidence specific to depression in the workplace, and provide practical tips to help clinicians to identify and treat work-related MDD, as well as navigate disability issues.

Screening for Adulthood ADHD and Comorbidities in a Tertiary Mental Health Center Using EarlyDetect: A Machine Learning-Based Pilot Study.

Screening for adult Attention-Deficit/Hyperactivity Disorder (ADHD) and differentiating ADHD from comorbid mental health disorders remains to be clinically challenging. A screening tool for ADHD and comorbid mental health disorders is essential, as most adult ADHD is comorbid with several mental health disorders. The current pilot study enrolled 955 consecutive patients attending a tertiary mental health center in Canada and who completed EarlyDetect assessment, with 45.2% of patients diagnosed with ADHD. The best ADHD classification model using composite scoring achieved a balanced accuracy of 0.788, showing a 2.1% increase compared to standalone ADHD screening, detecting four more patients with ADHD per 100 patients. The classification model including ADHD with comorbidity was also successful (balanced accuracy = 0.712). The results suggest the novel screening method can improve ADHD detection accuracy and inform the risk of ADHD with comorbidity, and may further inform specific comorbidity including MDD and BD.

Individualized identification of sexual dysfunction of psychiatric patients with machine-learning.

Sexual dysfunction (SD) is prevalent in patients with mental health disorders and can significantly impair their quality of life. Early recognition of SD in a clinical setting may help patients and clinicians to optimize treatment options of SD and/or other primary diagnoses taking SD risk into account and may facilitate treatment compliance. SD identification is often overlooked in clinical practice; we seek to explore whether patients with a high risk of SD can be identified at the individual level by assessing known risk factors via a machine learning (ML) model. We assessed 135 subjects referred to a tertiary mental health clinic in a Western Canadian city using health records data, including age, sex, physician's diagnoses, drug treatment, and the Arizona Sexual Experiences Scale (ASEX). A ML model was fitted to the data, with SD status derived from the ASEX as target outcomes and all other variables as predicting variables. Our ML model was able to identify individual SD cases-achieving a balanced accuracy of 0.736, with a sensitivity of 0.750 and a specificity of 0.721-and identified major depressive disorder and female sex as risk factors, and attention deficit hyperactivity disorder as a potential protective factor. This study highlights the utility of SD screening in a psychiatric clinical setting, demonstrating a proof-of-concept ML approach for SD screening in psychiatric patients, which has marked potential to improve their quality of life.

Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing.

Intravenous (IV) ketamine is increasingly used off-label at subanesthetic doses for its rapid antidepressant effect, and intranasal (IN) esketamine has been recently approved in several countries for treating depression. The clinical utility of these treatments is limited by a paucity of publicly funded IV ketamine and IN esketamine programs and cost barriers to private treatment programs, as well as the drug cost for IN esketamine itself, which makes generic ketamine alternatives an attractive option. Though evidence is limited, use of non-parenteral racemic ketamine formulations (oral, sublingual, and IN) may offer more realistic access in less rigidly supervised settings, both for acute and maintenance treatment in select cases. However, the psychiatric literature has repeatedly cautioned on the addictive potential of ketamine and raised caution for both less supervised and longer-term use of ketamine. To date, these concerns have not been discussed in view of available evidence, nor have they been discussed within a broader clinical context. This paper examines the available relevant literature and suggests that ketamine misuse risks appear not dissimilar to those of other well-established and commonly prescribed agents with abuse potential, such as stimulants or benzodiazepines. As such, ketamine prescribing should be considered in a similar risk/benefit context to balance patient access and need for treatment with concern for potential substance misuse. Our consortium of mood disorder specialists with significant ketamine prescribing experience considers prescribing of non-parenteral ketamine a reasonable clinical treatment option in select cases of treatment-resistant depression. This paper outlines where this may be appropriate and makes practical recommendations for clinicians in judicious prescribing of non-parenteral ketamine.

Anxiety symptoms in working patients with major depressive disorder treated with vortioxetine: associations with clinical and treatment outcomes in the AtWoRC study.

BACKGROUND: Anxiety symptoms are common in patients with major depressive disorder (MDD) and usually confer worse treatment outcomes. The long-term, open-label AtWoRC study in working patients with MDD treated with vortioxetine demonstrated a significant correlation between severity of anxiety symptoms and impaired work productivity. This analysis was undertaken to further explore clinical characteristics and treatment outcomes in patients with different levels of severity of anxiety symptoms at baseline. METHODS: Post hoc analysis in 199 working patients with MDD treated with vortioxetine (10-20 mg/day), stratified by Generalized Anxiety Disorder 7-item (GAD-7) score at baseline [mild/moderate anxiety (GAD-7 ⩽14), n = 83; severe anxiety (GAD-7 ⩾15), n = 116]. Associations were examined between GAD-7 and other outcome assessment scores at baseline. Observed mean changes from baseline to week 52 were compared between groups. RESULTS: Patients with severe anxiety had significantly worse depressive and cognitive symptoms, functioning, and work productivity at baseline than those with mild/moderate anxiety, but similar cognitive performance. Statistically significant improvements from baseline were seen for all outcomes after 52 weeks of vortioxetine treatment, with no significant differences observed between the two groups after adjustment for baseline anxiety scores. CONCLUSION: Treatment with vortioxetine was associated with long-term improvement in clinical symptoms and measures of work productivity in patients with MDD in a real-world setting, irrespective of severity of anxiety symptoms at the start of treatment.

Improvements in Workplace Productivity in Working Patients With Major Depressive Disorder: Results From the AtWoRC Study.

OBJECTIVE: To assess changes in workplace productivity and functioning in an open-label study in working patients receiving vortioxetine (10 to 20 mg/d) for major depressive disorder (MDD). METHODS: Associations between items in the Work Limitations Questionnaire (WLQ), the Sheehan Disability Scale (SDS), and the Work Productivity and Activity Impairment (WPAI) questionnaire were assessed at 12 and 52 weeks by Pearson correlation coefficients. RESULTS: Significant improvements were observed across all domains of workplace productivity and functioning after 12 and 52 weeks' vortioxetine treatment. Strong correlations were seen between improvements in WLQ mental domains and WPAI presenteeism and SDS work/school items. Presenteeism showed stronger correlations with other workplace productivity measures than absenteeism. CONCLUSIONS: Presenteeism and absenteeism impact productivity in working patients with MDD. Vortioxetine confers long-term benefits across all workplace functioning domains.

Canadian economic impact of improved workplace productivity in patients with major depressive disorder treated with vortioxetine.

OBJECTIVE: The AtWoRC study is an interventional, open-label Canadian study that demonstrated significant improvements in cognitive function and workplace productivity in patients with major depressive disorder (MDD) treated with vortioxetine for a current major depressive episode. The objective of the present analysis was to assess the Canadian economic impact of improved workplace productivity based on the AtWoRC study results. METHODS: The economic impact of improved productivity in patients with MDD treated with vortioxetine was assessed over a 52-week period considering productivity loss due to absenteeism and presenteeism using the standard human capital approach and an employer's perspective. Absenteeism was measured with the Work Productivity and Activity Impairment questionnaire; and presenteeism with the Work Limitation Questionnaire. Productivity gains following treatment initiation with vortioxetine were estimated using the difference from baseline. RESULTS: In the AtWoRC study, patients at baseline reportedly missed, in the past 7 days, an average of 8.1 h due to absenteeism and 3.0 h due to presenteeism. Following 52 weeks of treatment with vortioxetine, patients reportedly missed an average of 4.9 h due to absenteeism and 2.0 h due to presenteeism. This improved workplace productivity translated into savings of C$110.64 for 1 week of work following 52 weeks of treatment. The cumulative 52-week economic impact showed potential savings of C$4,550 when factoring in the cost of therapy. CONCLUSION: This study suggested that workplace productivity gain due to an improvement in symptoms of MDD following treatment with vortioxetine will lead to substantial cost savings for the Canadian economy.

Esketamine for treatment resistant depression.

Introduction: Treatment Resistant Depression (TRD) is a common and burdensome condition with poor outcomes and few treatment options. Esketamine is the S-enantiomer of ketamine and has recently been FDA approved in the United States for treating depression that has failed to respond to trials of two or more antidepressants. Areas covered: This review will briefly discuss current treatment options for TRD, then review esketamine. Relevant literature was identified through online database searches, and clinical trial data were provided by Janssen Pharmaceuticals. Pharmacology, including kinetics and dynamics, is discussed, then clinical data regarding efficacy and safety for esketamine from Phase 2-3 trials are reviewed. Expert opinion: In the expert opinion, the authors discuss multiple factors including patient, physician, and social factors that will influence the use of esketamine. While the efficacy of esketamine compared to off-label use of racemic ketamine remains unclear, both esketamine's approval for use in TRD and longer-term safety data may position it preferentially above racemic ketamine, although factors such as cost and monitoring requirements may limit its use. While questions remain regarding duration and frequency of treatment, as well as addictive potential, esketamine is a novel treatment option offering new hope for TRD.

Long-term functioning outcomes are predicted by cognitive symptoms in working patients with major depressive disorder treated with vortioxetine: results from the AtWoRC study.

OBJECTIVE: AtWoRC (Assessment in Work productivity and the Relationship with Cognitive symptoms) was an interventional, open-label, Canadian study (NCT02332954) designed to assess the association between cognitive symptoms and workplace productivity in working patients with major depressive disorder (MDD) receiving vortioxetine. METHODS: Eligible patients with MDD received vortioxetine (10-20 mg/day) and were assessed over 52 weeks at visits emulating a real-life setting (n = 199). Partial correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire-Depression; PDQ-D-20) and workplace productivity (Work Limitations Questionnaire; WLQ) was assessed at 12 and 52 weeks. Additional assessments included depression severity, cognitive performance, and patient-reported functioning. Structural equations model (SEM) analyses assessed causal relationships between changes in measures of cognition and functioning over time, adjusted for improvements in depressive symptoms. RESULTS: Statistically significant improvements in all outcomes from baseline to week 52 were seen in the overall population and both subgroups (first treatment and switch). Response and remission rates were 77% and 56%, respectively. Improvements in PDQ-D-20 and WLQ productivity loss scores at weeks 12 and 52 were significantly correlated. SEM analyses found patient-rated cognitive symptoms (PDQ-D-20) at weeks 12 and 26 were significantly predictive (p < 0.05) of patient-reported functioning (Sheehan Disability Scale) at the subsequent visit. Depression severity and objectively measured cognitive performance did not significantly predict functional outcomes at any timepoint. CONCLUSION: These results demonstrate the long-term benefits of vortioxetine treatment in working patients with MDD and emphasize the strong association between cognitive symptoms and functioning in a real-world setting.

Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC): primary analysis from a Canadian open-label study of vortioxetine in patients with major depressive disorder (MDD).

OBJECTIVE: The Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC) study aimed to assess the association between cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a major depressive episode (MDE). METHODS: Patients diagnosed with major depressive disorder (MDD) and treated with vortioxetine independently of study enrollment were assessed over 52 weeks at visits that emulated a real-life setting. Patients were classified as those receiving vortioxetine as the first treatment for their current MDE (first treatment) or having shown inadequate response to a previous antidepressant (switch). The primary endpoint was the correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire [PDQ-D-20]) and changes in work productivity loss (Work Limitations Questionnaire [WLQ]) at week 12. Additional assessments included changes in symptom and disease severity, cognitive performance, functioning, work loss, and safety. RESULTS: In the week 12 primary analysis, 196 eligible patients at 26 Canadian sites were enrolled, received at least one treatment dose, and attended at least one postbaseline study visit. This analysis demonstrated a significant, strong correlation between PDQ-D-20 and WLQ productivity loss scores (r=0.634; p<0.001), and this correlation was significant in both first treatment and switch patients (p<0.001). A weaker correlation between Digit Symbol Substitution Test and WLQ scores was found (r=-0.244; p=0.003). CONCLUSION: At 12 weeks, improvements in cognitive dysfunction were significantly associated with improvements in workplace productivity in patients with MDD, suggesting a role for vortioxetine in functional recovery in MDD.

Assessment and management of sexual dysfunction in the context of depression.

Sexual dysfunction (SD) is pervasive and underreported, and its effects on quality of life are underestimated. Due in part to its bidirectional relationship with depression, SD can be difficult to diagnose; it is also a common side effect of many antidepressants, leading to treatment noncompliance. While physicians often count on patients to spontaneously report SD, treatment is optimized when the clinician instead performs a thorough assessment of sexual functioning before and during drug therapy using a standardized questionnaire such as the Arizona Sexual Experiences Scale (ASEX). Separating the effects of the disorder from those of medications is challenging; we present a concise, evidence-based schematic to assist physicians in minimizing treatment-emergent sexual dysfunction (TESD) while treating depression. Vascular, hormonal, neurogenic, and pharmacological factors should be considered when a patient presents with SD. We also recommend that physicians obtain patient information about baseline and historical sexual functioning before prescribing a drug that may lead to SD and follow up accordingly. When the goal is to treat depression while attenuating the risk of sexual symptoms, physicians may wish to consider agomelatine, bupropion, desvenlafaxine, moclobemide, trazodone, vilazodone, and vortioxetine.

Adult ADHD and comorbid disorders: clinical implications of a dimensional approach.

Attention-deficit/hyperactivity disorder (ADHD) in the adult population is frequently associated with comorbid psychiatric diseases that complicate its recognition, diagnosis and management.The prevalence of ADHD in the general adult population is 2.5% and it is associated with substantial personal and individual burden. The most frequent comorbid psychopathologies include mood and anxiety disorders, substance use disorders, and personality disorders. There are strong familial links and neurobiological similarities between ADHD and the various associated psychiatric comorbidities. The overlapping symptoms between ADHD and comorbid psychopathologies represent challenges for diagnosis and treatment. Guidelines recommend that when ADHD coexists with other psychopathologies in adults, the most impairing condition should generally be treated first.Early recognition and treatment of ADHD and its comorbidities has the potential to change the trajectory of psychiatric morbidity later in life. The use of validated assessment scales and high-yield clinical questions can help identify adults with ADHD who could potentially benefit from evidence-based management strategies.

Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment.

OBJECTIVE: This article presents the case that a more rapid, individualized approach to treating major depressive disorder (MDD) may increase the likelihood of achieving full symptomatic and functional recovery for individual patients and that studies show it is possible to make earlier decisions about appropriateness of treatment in order to rapidly optimize that treatment. DATA SOURCES: A PubMed search was conducted using terms including major depressive disorder, early improvement, predictor, duration of untreated illness, and function. English-language articles published before September 2015 were included. Additional studies were found within identified research articles and reviews. STUDY SELECTION: Thirty antidepressant studies reporting predictor criteria and outcome measures are included in this review. DATA EXTRACTION: Studies were reviewed to extract definitions of predictors, outcome measures, and results of the predictor analysis. Results were summarized separately for studies reporting effects of early improvement, baseline characteristics, and duration of untreated depression. RESULTS: Shorter duration of the current depressive episode and duration of untreated depression are associated with better symptomatic and functional outcomes in MDD. Early improvement of depressive symptoms predicts positive symptomatic outcomes (response and remission), and early functional improvement predicts an increased likelihood of functional remission. CONCLUSIONS: The approach to treatment of depression that exhibits the greatest potential for achieving full symptomatic and functional recovery is early optimized treatment: early diagnosis followed by rapid individualized treatment. Monitoring symptoms and function early in treatment is crucial to ensuring that patients do not remain on ineffective or poorly tolerated treatment, which may delay recovery and heighten the risk of residual functional deficits.

Food for thought: understanding the value, variety and usage of management algorithms for major depressive disorder.

By 2020, depression is projected to be among the most important contributors to the global burden of disease. A plethora of data confirms that despite the availability of effective therapies, major depressive disorder continues to exact an enormous toll; this, in part, is due to difficulties reaching complete remission, as well as the specific associated costs of both the disorder's morbidity and mortality. The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. The use of management algorithms has been shown to improve treatment outcomes in major depressive disorder and may be less costly than "usual care" practices. Nevertheless, many patients with depression remain untreated. As well, even those who are treated often continue to experience suboptimal quality of life. As such, the treatment algorithms in this article may improve outcomes for patients suffering with depression. This paper introduces some of the principal reasons underlying these treatment gaps and examines measures or recommendations that might be changed or strengthened in future practice guidelines to bridge them.

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders.

BACKGROUND: Anxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated. METHODS: These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980-2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. RESULTS: These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. CONCLUSIONS: Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments.

Comorbid attention deficit/hyperactivity disorder and substance use disorder: treatment considerations.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is predominantly a diagnosis of childhood and adolescence but has also been recognized in adults. It is associated with high rates of comorbid psychiatric conditions, particularly substance use disorders (SUD). METHODS: A review of the literature was conducted with a focus on ADHD, SUD, their comorbidity, and treatment considerations. RESULTS: Literature suggests that the use of methylphenidate (MPH) in children does not increase SUD later in life, and may in fact reduce substance use and abuse in adolescence and adulthood. Concurrent treatment of ADHD-SUD, which may be supported theoretically, has yielded inconsistent data on clinical trials. While MPH use in adults with ADHDSUD may be effective in alleviating ADHD symptoms, the benefits on SUD are not clear and remain controversial. Studies suggest that adults with comorbid ADHD-SUD do not misuse or divert their medication, but MPH does not consistently improve substance use. However, data are lacking for substances other than cocaine and stimulants other than MPH. While the risk of stimulant abuse should not be ignored, it may be minimized by selecting medications that are not readily crushed and solubilized for parenteral administration, or by utilizing non-stimulant medications and/or psychotherapy. CONCLUSION: While there are a lack of evidence-based guidelines for the concurrent treatment of ADHD and SUD, evidence to date suggests that stimulant medications should not necessarily be avoided for patients with comorbid ADHDSUD and that concurrent treatment may be a successful approach to improve ADHD outcomes without worsening SUD symptoms.

Prevalence of Bipolar Disorder symptoms in Primary Care (ProBiD-PC): A Canadian study.

Objective To describe the prevalence of patients who screen positive for symptoms of bipolar disorder in primary care practice using the validated Mood Disorders Questionnaire (MDQ). Design Prevalence survey. Setting Fifty-four primary care practices across Canada. Participants Adult patients presenting to their primary care practitioners for any cause and reporting, during the course of their visits, current or previous symptoms of depression, anxiety, substance use disorders, or attention deficit hyperactivity disorder. Main outcome measures Subjects were screened for symptoms suggestive of bipolar disorder using the MDQ. Health-related quality of life, functional impairment, and work productivity were evaluated using the 12-Item Short-Form Health Survey and Sheehan Disability Scale. Results A total of 1416 patients were approached to participate in this study, and 1304 completed the survey. Of these, 27.9% screened positive for symptoms of bipolar disorder. All 13 items of the MDQ were significantly associated with screening positive for bipolar disorder (P < .05). Patients screening positive were significantly more likely to report depression, anxiety, substance use, attention deficit hyperactivity disorder, family history of bipolar disorder, or suicide attempts than patients screening negative were (P < .001). Health-related quality of life, work or school productivity, and social and family functioning were all significantly worse in patients who screened positive (P < .001). Conclusion This prevalence survey suggests that more than a quarter of patients presenting to primary care with past or current psychiatric indices are at risk of bipolar disorder. Patients exhibiting a cluster of these symptoms should be further questioned on family history of bipolar disorder and suicide attempts, and selectively screened for symptoms suggestive of bipolar disorder using the quick and high-yielding MDQ.

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.