Goal setting and goal attainment in patients with major depressive disorder: a narrative review on shared decision making in clinical practice.

OBJECTIVE: Narrative review of the processes of goal setting and goal attainment scaling, as practical approaches to operationalizing and implementing the principles of shared decision making (SDM) in the routine care of people living with major depressive disorder (MDD). METHODS: We searched electronic databases for clinical studies published in English using key terms related to MDD and goal setting or goal attainment scaling. Two clinical studies of goal setting in MDD are considered in detail to exemplify the practicalities of the goal setting approach. RESULTS: While SDM is widely recommended for people living with mental health problems, there is general agreement that it has thus far been implemented variably. In other areas of medicine, the process of goal setting is an established way to engage the patient, facilitate motivation, and assist the recovery process. For people living with MDD, the concept of goal setting is in its infancy, and only few studies have evaluated its clinical utility. Two clinical studies of vortioxetine for MDD demonstrate the utility of goal attainment scaling as an appropriate outcome for assessing functional improvement in ways that matter to the patient. CONCLUSIONS: Goal setting is a pragmatic approach to turning the principles of SDM into realities of clinical practice and aligns with the principles of recovery that encompasses the notions of self-determination, self-management, personal growth, empowerment, and choice. Accumulating evidence supports the use of goal attainment scaling as an appropriate personalized outcome measure for use in clinical trials.

Shared decision making is a structured approach in which a doctor assists their patient in making informed choices about treatment that consider the patient's own preferences. However, while acknowledged as the ideal approach, many doctors working in the mental health area say it can be difficult to apply in their daily clinical practice. In other areas of medicine, such as physical rehabilitation, the structured process of patients setting treatment goals in dialogue with their doctor has been recommended as a practical way to put the principles of shared decision making into practice.In this paper, we reviewed the medical literature to better understand how goal setting can be used to improve the care of people with major depressive disorder. The available evidence supports goal setting as a powerful way to engage patients in healthcare decisions, and ultimately improve health-related outcomes. The goal setting process provides patients the opportunity to verbalize their own, tangible goals for treatment; and following some negotiation, receive endorsement of their goals from their doctor. Patients feel supported and are better motivated to continue with their treatment.While still in its infancy, the growing evidence base supporting goal setting for people with major depressive disorder is encouraging. For example, the Goal Attainment Scaling (GAS) method of evaluating treatment success has been suitably adapted for use in people living with depression (GAS-D) and provides an easy, structured format for discussing personal treatment goals, as well as a method for tracking success, both in clinical practice and research studies.

Clinical benefits and bioequivalence of vortioxetine oral drop solution versus oral tablets.

BACKGROUND: Vortioxetine is efficacious and well tolerated in patients with major depressive disorder (MDD) and is available as an immediate-release tablet and oral drop solution. The oral drop solution may offer clinical benefits versus a tablet, such as the reduced risk of nausea, personalised dosing and ease of administration. AIMS: To investigate the bioequivalence of vortioxetine 20 mg/mL oral drop solution versus a 20 mg immediate-release tablet. METHODS: Healthy adults were randomised 1:1 to receive vortioxetine 20 mg oral drop solution or immediate-release 20 mg tablet after fasting on days 1 and 29 in an open-label, single-centre, single-dose crossover study. The area under the plasma concentration-time curve from 0 to 72 h (AUC0-72h) and maximum plasma concentration (Cmax) were analysed. Bioequivalence was concluded if the 90% CI for the oral drop solution-to-immediate-release tablet ratio for AUC0-72h and Cmax were contained within a range of 0.80-1.25. RESULTS: Vortioxetine oral drop solution was bioequivalent to the tablet (n = 26; estimated AUC0-72h ratio 1.06 (90% CI: 1.03-1.10); Cmax ratio 1.01 (90% CI: 0.97-1.05)). A similar proportion of participants reported adverse events in each study arm but more headache events (7 vs 1) were reported with the oral drop solution versus tablet. The most common adverse event was nausea (16-23% of participants; all mild intensity). CONCLUSIONS: Vortioxetine oral drop solution is bioequivalent to immediate-release tablets. Oral drop solution provides an alternative to tablets and facilitates clinical benefit through individualised treatment, including gradual dose up-titration, for patients with MDD.

Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder.

BACKGROUND: Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. METHODS: Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). RESULTS: After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. CONCLUSION: Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability.

BACKGROUND: Patients with major depressive disorder (MDD) often experience comorbid anxiety symptoms. Vortioxetine has demonstrated efficacy in treating anxiety symptoms in patients with MDD; however, efficacy and tolerability have not been assessed across the entire approved dosage range. METHODS: The efficacy and tolerability of vortioxetine 5-20 mg/day were assessed in patients with MDD and high levels of anxiety symptoms (Hamilton Anxiety Rating Scale [HAM-A] total score ≥ 20) using pooled data from four randomized, fixed-dose, placebo-controlled studies (n = 842). Data from a randomized, double-blind study of vortioxetine 10-20 mg/day versus agomelatine 25-50 mg/day in patients with an inadequate response to prior therapy (n = 299) were analyzed separately. Mean changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), HAM-A, and Sheehan Disability Scale (SDS) total scores were analyzed by vortioxetine dosage. RESULTS: The pooled analysis of fixed-dose studies demonstrated a clear dose-response relationship for vortioxetine 5-20 mg/day for improvements in MADRS, HAM-A, and SDS total scores. Vortioxetine 20 mg/day demonstrated significant effects versus placebo from week 4 onwards. In the post-hoc analysis of the active-controlled study in patients with an inadequate response to prior therapy, vortioxetine 10-20 mg/day was superior to agomelatine across all outcome measures from week 4 onwards. Up-titration of vortioxetine to 20 mg/day was not associated with an increase in adverse events. LIMITATIONS: Short-term trials. CONCLUSIONS: Vortioxetine is efficacious and well tolerated in patients with MDD and high levels of anxiety symptoms, including those with an inadequate response to prior therapy. The greatest therapeutic benefits were observed with vortioxetine 20 mg/day. TRIAL REGISTRATION: NCT01140906, NCT01153009, NCT01163266, NCT01255787, NCT01488071.

Effectiveness of vortioxetine in patients with major depressive disorder and co-morbid generalized anxiety disorder in routine clinical practice: A subgroup analysis of the RELIEVE study.

BACKGROUND: Generalized anxiety disorder (GAD) is commonly co-morbid with major depressive disorder (MDD) and is associated with greater functional impairment and poorer treatment outcomes than MDD alone. However, studies on treatment with drugs for depression in patients with MDD and co-morbid GAD are limited. AIMS: To examine the effectiveness of vortioxetine treatment in patients with MDD and co-morbid GAD in a subgroup analysis of the real-world RELIEVE study. METHODS: The analysis included outpatients diagnosed with MDD and co-morbid GAD who initiated vortioxetine treatment at their physician's discretion in the 24-week, observational RELIEVE study. Primary outcome was patient functioning (Sheehan Disability Scale (SDS)) after 12 and 24 weeks of vortioxetine treatment; secondary outcomes included depression severity (9-item Patient Health Questionnaire (PHQ-9)), cognitive symptoms (5-item Perceived Deficits Questionnaire - Depression (PDQ-D-5)) and cognitive performance (Digit Symbol Substitution Test (DSST)). RESULTS: Overall, 180 patients with MDD and co-morbid GAD were included in the analysis. Following vortioxetine initiation, clinically significant improvements in patient functioning (SDS total score) were observed at week 12 (least-squares (LS) mean reduction from baseline, 7.5 points), sustained through week 24 (9.2 points) (both p < 0.0001). LS mean PHQ-9, PDQ-D-5 and DSST scores improved by 7.9, 4.8 and 7.4 points at week 24, respectively (all p < 0.0001 vs baseline). Adverse events were reported by 33.9% of patients (most commonly nausea, 13.3%). CONCLUSIONS: In routine clinical practice, vortioxetine was associated with clinically meaningful, sustained improvements in functioning, and depressive and cognitive symptoms, in patients with MDD and co-morbid GAD. CLINICAL TRIALS REGISTRY NAME AND IDENTIFIER: Real-life Effectiveness of Vortioxetine in Depression (RELIEVE) (NCT03555136) https://clinicaltrials.gov/ct2/show/NCT03555136.

The Motivation and Energy Inventory (MEI): Analysis of the clinically relevant response threshold in patients with major depressive disorder and emotional blunting using data from the COMPLETE study.

BACKGROUND: The Motivation and Energy Inventory (MEI) is a patient-reported scale for assessment of the impact of mental/cognitive energy, social motivation, and physical energy on daily functioning in patients with major depressive disorder (MDD). This analysis was undertaken to establish the clinically relevant response threshold for the MEI in patients with MDD receiving antidepressant treatment. METHODS: Patients with MDD experiencing inadequate response and emotional blunting on selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor monotherapy (adequate dose for ≥6 weeks) were switched to vortioxetine 10-20 mg/day for 8 weeks. Anchor- and distribution-based methods were used to determine the minimal clinically important difference (MCID) in MEI total score. RESULTS: After 8 weeks of vortioxetine treatment, mean (standard deviation) change in MEI total score from baseline was 33.0 (27.3) points. At week 8, mean change in MEI total score from baseline was 37.5 (27.8) points in patients no longer reporting emotional blunting and 28.3 (26.2) points in those still experiencing emotional blunting. In patients considered minimally improved (i.e. Clinical Global Impression-Improvement [CGI-I] score of 3 after 8 weeks of vortioxetine), mean change in MEI total score from baseline was 14.7 (19.1) points. In patients defined as responders (CGI-I score of 2 at 8 weeks), mean change in MEI total score was 33.0 (24.7) points. LIMITATIONS: Short study duration. CONCLUSIONS: These results provide further validation of the clinical utility of the MEI for assessing treatment response in patients with MDD. The suggested MCID for MEI total score is 15 points. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03835715.

Effectiveness of vortioxetine in patients with major depressive disorder and comorbid Alzheimer's disease in routine clinical practice: An analysis of a post-marketing surveillance study in South Korea.

Background: Vortioxetine has demonstrated procognitive effects in patients with major depressive disorder (MDD). We assessed the effectiveness and safety of vortioxetine in a cohort of patients with MDD and comorbid Alzheimer's disease participating in a large post-marketing surveillance study in South Korea. Methods: Subgroup analysis of a 6-month, prospective, multicenter, non-interventional cohort study in outpatients with MDD with a pre-baseline diagnosis of Alzheimer's disease receiving vortioxetine in routine care settings (n = 207). Patients were assessed at baseline and after 8 weeks; a subset of patients was also assessed after 24 weeks. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale, cognitive symptoms using the Perceived Deficits Questionnaire-Depression, Korean version (PDQ-K), and cognitive performance using the Digit Symbol Substitution Test (DSST). Results: Most patients were receiving a mean daily vortioxetine dose of 5 mg/day (174/190 patients; 91.6%). After 24 weeks of vortioxetine treatment, 71.4% of patients (40/56) had experienced overall clinical improvement (i.e., CGI-Improvement score ≤3) and 51.9% (28/54) had achieved remission from depressive symptoms (i.e., MADRS total score ≤10 points). Respective mean changes in MADRS, PDQ-K, and DSST total scores from baseline to week 24 were -11.5 (p < 0.0001), -5.1 (p = 0.03), and +3.8 points (p = 0.0524). Adverse events were reported by 27 patients (13.0%) and were mostly mild (89.2%). Conclusion: Patients with MDD and comorbid Alzheimer's disease receiving vortioxetine in routine care settings in South Korea demonstrated clinically meaningful improvements in depressive symptoms, cognitive symptoms, and objective cognitive performance over the 6-month treatment period. Treatment with vortioxetine was well tolerated in this patient cohort, with reported adverse events consistent with the established tolerability profile of vortioxetine.

Predicting time to relapse in patients with schizophrenia according to patients' relapse history: a historical cohort study using real-world data in Sweden.

BACKGROUND: For patients with schizophrenia, relapse is a recurring feature of disease progression, often resulting in substantial negative impacts for the individual. Although a patient's relapse history (specifically the number of prior relapses) has been identified as a strong risk factor for future relapse, this relationship has not yet been meticulously quantified. The objective of this study was to use real-world data from Sweden to quantify the relationship of time to relapse in schizophrenia with a patient's history of prior relapses. METHODS: Data from the Swedish National Patient Register and Swedish Prescribed Drug Register were used to study relapse in patients with schizophrenia with a first diagnosis recorded from 2006-2015, using proxy definitions of relapse. The primary proxy defined relapse as a psychiatric hospitalisation of ≥7 days' duration. Hazard ratios (HRs) were calculated for risk of each subsequent relapse, and Aalen-Johansen estimators were used to estimate time to next relapse. RESULTS: 2,994 patients were included, and 5,820 relapse episodes were identified using the primary proxy. As the number of previous relapses increased, there was a general trend of decreasing estimated time between relapses. Within 1.52 years of follow-up, 50% of patients with no history of relapse were estimated to have suffered their first relapse episode. 50% of patients with one prior relapse were estimated to have a second relapse within 1.23 years (HR: 1.84 [1.71-1.99]) and time to next relapse further decreased to 0.89 years (HR: 2.77 [2.53-3.03]) and 0.22 years (HR: 18.65 [15.42-22.56]) for 50% of patients with two or ten prior relapses, respectively. Supplementary analyses using different inclusion/exclusion criteria for the study population and redefined proxies of relapse reflected the pattern observed with the primary analyses of a higher number of prior relapses linked with increased risk of/reduced estimated time to the next relapse. CONCLUSIONS: The results suggested a trend of accelerating disease progression in schizophrenia, each relapse episode predisposing an individual to the next within a shorter time period. These results emphasise the importance of providing early, effective, and tolerable treatments that better meet a patient's individual needs.

Transcriptome-wide comparison of selenium hyperaccumulator and nonaccumulator Stanleya species provides new insight into key processes mediating the hyperaccumulation syndrome.

To obtain better insight into the mechanisms of selenium hyperaccumulation in Stanleya pinnata, transcriptome-wide differences in root and shoot gene expression levels were investigated in S. pinnata and related nonaccumulator Stanleya elata grown with or without 20 µm selenate. Genes predicted to be involved in sulphate/selenate transport and assimilation or in oxidative stress resistance (glutathione-related genes and peroxidases) were among the most differentially expressed between species; many showed constitutively elevated expression in S. pinnata. A number of defence-related genes predicted to mediate synthesis and signalling of defence hormones jasmonic acid (JA, reported to induce sulphur assimilatory and glutathione biosynthesis genes), salicylic acid (SA) and ethylene were also more expressed in S. pinnata than S. elata. Several upstream signalling genes that up-regulate defence hormone synthesis showed higher expression in S. pinnata than S. elata and might trigger these selenium-mediated defence responses. Thus, selenium hyperaccumulation and hypertolerance in S. pinnata may be mediated by constitutive, up-regulated JA, SA and ethylene-mediated defence systems, associated with elevated expression of genes involved in sulphate/selenate uptake and assimilation or in antioxidant activity. Genes pinpointed in this study may be targets of genetic engineering of plants that may be employed in biofortification or phytoremediation.