Exploring vortioxetine combination with intranasal esketamine: A feasible alternative to SSRI/SNRI? - Insights from the REAL-ESK study.

BACKGROUND: Treatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants. AIM: To assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS. METHODS: We conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2). RESULTS: The combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events. CONCLUSION: The combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings.

Effectiveness of Vortioxetine for the Treatment of Emotional Blunting in Patients with Major Depressive Disorder Experiencing Inadequate Response to SSRI/SNRI Monotherapy in Spain: Results from the COMPLETE Study.

Background: The multinational, open-label COMPLETE study (NCT03835715) investigated the effectiveness of vortioxetine in alleviating emotional blunting in patients with major depressive disorder (MDD) experiencing inadequate response and emotional blunting while being treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI). This paper presents results for the subgroup of patients enrolled in Spain. Methods: Patients with MDD (n = 67) experiencing partial response and emotional blunting during monotherapy with an SSRI or SNRI were switched to vortioxetine (10-20 mg/day) for 8 weeks. The primary study outcome was emotional blunting, assessed by the Oxford Depression Questionnaire (ODQ). Results: After 8 weeks of vortioxetine, the mean (SE) change in ODQ total score from baseline was -26.0 (2.9) (P < 0.001). Respective changes in Montgomery-Åsberg Depression Rating Scale (MADRS), Motivation and Energy Inventory, Digit Symbol Substitution Test, and Sheehan Disability Scale (SDS) total scores were -14.9 (0.8), +34.2 (4.5), +6.3 (1.6), and ‒9.0 (1.3) (all P < 0.001 vs baseline). At week 8, 70.4% of patients no longer reported emotional blunting and 53.7% had achieved remission from their depressive symptoms (defined as a MADRS total score ≤10). Mediation analysis showed 77.1% of the change in SDS total score to be a direct effect of the improvement in ODQ total score after switching to vortioxetine. Adverse events were reported by 35 patients (52.2%), most commonly nausea (14 patients, 20.9%). At week 8, 33/54 patients (61.1%) were receiving vortioxetine 20 mg/day. Conclusion: In this study investigating the effectiveness of vortioxetine in Spanish patients with MDD who experienced inadequate response and emotional blunting on SSRI/SNRI monotherapy, significant improvements in emotional blunting, core depressive symptoms (including anhedonia), sleep duration, motivation and energy, cognitive performance, and overall patient functioning were observed during the 8 weeks of treatment. Two-thirds of patients no longer reported emotional blunting and over half were in remission from their depressive symptoms at week 8.

Individualized strategies for depression: narrative review of clinical profiles responsive to vortioxetine.

BACKGROUND: Depression is a highly heterogeneous disorder, often resulting in suboptimal response and remission rates. This underscores the need for more nuanced clinical characterization of patients to tailor individualized treatment plans. Emerging evidence highlights the critical role of cognitive and emotional dysfunction in major depression, prompting the exploration of novel therapeutic interventions that target these specific symptom domains. MAIN TEXT: Vortioxetine, a multimodal antidepressant, enhances serotonergic activity while also modulating several other neurotransmitter systems involved in depressive symptoms such as emotional blunting, anhedonia, and cognitive dysfunction. Numerous randomized, placebo-controlled trials have demonstrated vortioxetine's efficacy and safety in treating depression, particularly in specific subgroups of depressed patients, including those with cognitive deficits and comorbid anxiety symptoms or disorders. Although not randomized or placebo-controlled, studies have also shown vortioxetine's efficacy in depressed patients with emotional blunting or anhedonia. Vortioxetine's ability to effectively treat a range of depressive symptoms, including anhedonia, emotional blunting, anxiety, and cognitive dysfunction, provides an individualized treatment solution for depressed individuals suffering from these symptoms. The purpose of this paper is to identify clinical profiles of patients who may benefit from vortioxetine, with the goal of optimizing therapeutic outcomes. CONCLUSION: Vortioxetine has been shown to be effective for patients with depression and symptoms such as anhedonia, emotional blunting, anxiety, and cognitive dysfunction. Tailoring treatment plans to individual needs and personalizing treatment choices based on the specific symptoms presented by depressed patients improve treatment outcomes.

A web-based survey on the occurrence of emotional blunting in patients with major depressive disorder in Japan: Patient perceptions and attitudes.

AIMS: To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. METHODS: Eligible patients in Japan (aged 18-59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self-reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9-item (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5-Dimension 5-Levels questionnaire (EQ-5D-5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. RESULTS: In total, 3376 patients were included in the analysis (56% male; 48% aged 50-59 years). Overall, 67.1% of patients self-reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ-9, GAD-7, WSAS, and EQ-5D-5L scores (correlation coefficients: 0.67, 0.55, 0.56, -0.51, respectively; all p < 0.0001). Descriptive analyses showed that one-third of patients reporting EB symptoms did not tell their physician, with two-thirds finding these symptoms distressing and likely to affect recovery. CONCLUSION: EB is an important clinical issue in Japan that needs to be considered alongside functional recovery when managing treatment of patients with MDD.

Perspectives on the impact of vortioxetine on the treatment armamentarium of major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a mental health issue that significantly affects patients' quality of life and functioning. Despite available treatments, many patients continue to suffer due to incomplete symptom resolution and side effects. AREAS COVERED: This manuscript examines Vortioxetine's role in Major Depressive Disorder (MDD) treatment, highlighting its potential to reshape therapeutic strategies due to its unique Multimodal action and proven broad-spectrum efficacy in multiple depressive domains. A detailed examination of Vortioxetine's pharmacological aspects, including indications, dosage, pharmacodynamics, and pharmacokinetics, is provided, emphasizing its safety and effectiveness. The discussion extends to Vortioxetine's role in acute-phase treatment and maintenance of MDD and its profound impact on specialized depression domains. EXPERT OPINION: Vortioxetine is distinguished for its novel multimodal serotonin modulation mechanism, showcasing significant promise as an innovative treatment for MDD. Its efficacy, which is dose-dependent, along with a commendable tolerability profile, positions it as a potential leading option for initial treatment strategies. The discourse on dosage titration, particularly the strategy of initiating treatment at lower doses followed by gradual escalation, underscores the approach toward minimizing initial adverse effects while optimizing therapeutic outcomes, aligning with the principles of personalized medicine in psychiatric care.

Emotional Blunting in Depression in the PREDDICT Clinical Trial: Inflammation-Stratified Augmentation of Vortioxetine With Celecoxib.

BACKGROUND: Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment. METHODS: The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments. RESULTS: In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group. CONCLUSIONS: This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p.

Efficacy of functional magnetic resonance imaging-guided personalized repetitive transcranial magnetic stimulation (fMRI-rTMS) in depressive patients with emotional blunting: study protocol for a randomized controlled trial.

BACKGROUND: Emotional blunting is a symptom that has always been present in depressed patients. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective supplementary therapy for treating depression. However, the effectiveness and brain imaging processes of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) in the treatment of depression with emotional blunting have not been observed in randomized controlled trials. METHODS: This study is a randomized, controlled, double-blind, and single-center clinical trial in which 80 eligible depressed patients with emotional blunting will be randomly assigned to two groups: a functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) group and a control group. Individuals in the fMRI-rTMS group (n = 40) will receive high-frequency rTMS (10 Hz, 120% MT). The main target of stimulation will be the area most relevant to the functional connectivity of the right medial prefrontal cortex (mPFC) and amygdala. The control group (n = 40) will receive sham stimulation, with a coil flipped to 90 degrees relative to the vertical scalp. All patients will receive 15 consecutive days of treatment, with each session lasting half an hour per day, followed by 8 weeks of follow-up. The primary outcome is the comparison of Oxford Depression Questionnaire (ODQ) scores between these two groups at different time points. The secondary outcomes include evaluating other clinical scales and assessing the differences in brain imaging changes between the two groups before and after treatment. DISCUSSION: This trial aims to examine the effects of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) intervention on depressed patients experiencing emotional blunting and to elucidate the potential mechanism behind it. The results will provide new evidence for using fMRI-rTMS in treating depression with emotional blunting in the future. TRIAL REGISTRATION: ClinicalTrials.gov INCT05555940. Registered on 13 September 2022 at http://clinicaltrials.gov .

Assessing Reliability and Validity of the Oxford Depression Questionnaire (ODQ) in a Japanese Clinical Population.

Purpose: Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ. Patients and methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: One hundred and sixteen patients initiated vortioxetine and had ≥1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach's α coefficient was 0.912, and the scale also showed good test-retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and Åsberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales. Conclusion: Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.

Embotional Blunting or apathy by SSRI? A sistematic review about their emotional effects / ¿Apatía o embotamiento emocional por ISRS? Una revisión de la literatura.

Introduction: Selective Serotonin Reuptake Inhibitors (SSRIs) are a group of antidepressants that have revolutionized the psychopharmacological therapeutic field since their appearance. They are in the first line of recommendation for the treatment of anxiety disorders and major depressive disorder. And although they are better tolerated and have a better side effect profile than the classic ones, they are not exempt from them. Among the adverse effects of SSRIs little considered by health professionals, are apathy or mental dullness. Restrictions of the range of emotions that are related to normal life, such as the ability to cry or feel pleasure, have been reported. This phenomenon has been called variously in the literature, such as emotional blunting, apathy, emotional indifference, or decreased sensitivity or emotional response. Objectives: The aim of this review is to analyze the emotional effects of SSRI that are described in the literature. Methods: A bibliographic review of the literature published in Pubmed from 2006 to 2021 was carried out, with the words Mesh "SSRI" and "Apathy" and "emotional blunting". Results: Literature reports indicate that the mental dullness produced by SSRIs is generated in at least 50 % of the patients who receive them, with different intensities between them. Conclusions: Although effects of emotional blunting or apathy have been reported with various groups of antidepressants, all reports agree that it occurs more frequently in patients taking SSRIs than with other antidepressants.

Introducción: Los Inhibidores Selectivos de la Recaptación de Serotonina (ISRS) son un grupo de antidepresivos que revolucionaron desde su surgimiento, el campo de la terapéutica psicofarmacológica, y se encuentran en la primera línea de recomendación para el tratamiento de los trastornos de ansiedad y del trastorno depresivo mayor. Si bien son mejor tolerados y presentan un mejor perfil de efectos adversos que los clásicos, no están exentos de ellos. Dentro de los efectos adversos de los ISRS poco considerados por los profesionales de la salud, se encuentran la apatía o el embotamiento mental. Se han reportado en la literatura restricciones del rango de las emociones que están relacionadas con la vida normal, como la capacidad de llorar o de sentir placer. Este fenómeno ha sido designado de varias maneras, como embotamiento emocional, apatía, indiferencia emocional,  disminución de sensibilidad o de la respuesta emocional. Objetivos: El objetivo del trabajo es analizar los efectos a nivel emocional de los ISRS, descriptos en la literatura. Metodología: Se realizó una revisión bibliográfica de la literatura publicada en Pubmed desde 2006 hasta 2021, con las palabras Mesh "SSRI" and "Apathy" and  "emotional blunting". Resultados: Según reportes de la literatura, el embotamiento emocional producido por los ISRS se genera en al menos un 50 % de los pacientes que lo reciben, con diferentes intensidades entre ellos. Conclusión: Si bien se han reportado efectos de embotamiento emocional o apatía con varios grupos de antidepresivos, todos los reportes concuerdan que se produce con más frecuencia en pacientes medicados con ISRS que con otros antidepresivos.

Can antidepressant use be associated with emotional blunting in a subset of patients with depression? A scoping review of available literature.

INTRODUCTION: Despite frequent recognition of emotional blunting in the published literature, either as a primary symptom of depression or as an adverse effect of antidepressants, there is no systematic synthesis on this topic to our knowledge. We undertook this scoping review to assess the prevalence, clinical features, implicated causes and management of emotional blunting, outlining the phenomenological and clinical gaps in research. METHOD: A systematic search was done until March 15, 2022, to include all original studies (i.e., interventional trials, cohort & cross-sectional studies, case reports, and case series). All reviewed data were delineated to answer pertinent clinical, phenomenological, and management questions related to the phenomenon of emotional blunting. RESULTS: A total of 25 original studies were included in our scoping review. Emotional blunting was described as a persistent diminution in both positive and negative feelings in depressed patients, who could subjectively differentiate it from their acute symptoms. However, the literature lacked the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants. Common clinical strategies to manage antidepressant-induced emotional blunting included dose reduction or switching to a different antidepressant. CONCLUSION: Emotional blunting was a significant patient-reported concern with antidepressants. Future research should clarify phenomenological and neurobiological constructs underlying emotional blunting to improve diagnostic and management skills.

The Chinese Version of Oxford Depression Questionnaire: A Validation Study in Patients with Mood Disorders.

Background: Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders. Methods: 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity. Results: A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p<0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p<0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p<0.01). The differences in the ODQ scores between the patient and control groups were statistically significant. Conclusion: The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.

Does partial blockade of dopamine D2 receptors with Amisulpride cause anhedonia? An experimental study in healthy volunteers.

BACKGROUND: Anhedonia is a frequent cause of functional impairment in psychosis. Although it is plausible that medication-induced D2 receptor blockade could diminish hedonic responding, there is little experimental research testing this hypothesis in humans. METHODS: To inspect possible effects of partial D2 blockade on hedonic experiences, we administered 300 mg of Amisulpride or placebo to 85 participants in a randomized, double-blind, placebo-controlled trial. Participants were then subjected to an emotional evocation task utilizing standardized pictorial pleasant, neutral, and unpleasant stimuli. RESULTS: We observed lower positivity ratings in the Amisulpride group compared to placebo across all stimulus categories (p = .026, f = 0.25) and no group differences in negativity or arousal ratings. The Amisulpride group also showed lower electrodermal responses across all stimulus categories compared to placebo (p = .017, f = 0.27). The electrodermal response was especially diminished for pleasant stimuli. CONCLUSION: We interpret our findings as evidence that D2 blockade via Amisulpride can reduce at-the-moment hedonic responsivity in healthy volunteers. If these results can be confirmed in drug-naïve clinical samples, this would indicate that antipsychotic medication contributes to clinical anhedonia, probably via antagonistic effects at the dopamine D2 receptor.

Apathy associated with antidepressant drugs: a systematic review.

OBJECTIVES: Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports. METHODS: We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI). RESULTS: According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants - usually SSRIs - can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate-modafinil-olanzapine combination. CONCLUSION: Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.

Are all antidepressants the same? The consumer has a point.

BACKGROUND: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. METHOD: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. RESULT: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. CONCLUSION: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.

Reliability and validity of the Chinese version of the Oxford Depression Questionnaire (ODQ-Chinese).

BACKGROUNDS: Emotional blunting is regularly reported in depressed patients on antidepressant treatment. It is uncertain whether this phenomenon represents residual symptoms of depression or side-effects of antidepressant treatment. At present, there is no adequate instrument to measure this phenomenon in China. This study aimed to test the reliability and validity of the Chinese version of The Oxford Depression Questionnaire (ODQ-Chinese). METHODS: The study sample comprised of 312 patients with major depressive disorder. All participants were assessed with the ODQ-Chinese, the Beck Depression Inventory-13 (BDI-13), the UKU side effects rating scale (UKU-SERS), and the 'gold standard' question related to the participant's experience of emotional side-effects. 20 % of the participants completed the ODQ-Chinese and BDI-13 within 1 or 2 weeks after the initial assessment. RESULTS: The Cronbach α statistic was 0.91 for the ODQ-Chinese. It had good split-half reliability. The scale showed excellent test-retest reliability and demonstrated significant correlation with the BDI-13. The sensitivity and specificity for detecting emotional side-effects according to patients' responses to the "gold standard" question were 69 % and 67 % for a cutoff point ≥ 13 of Antidepressant as the cause (AC) domain, AUCs was 0.74 (95 % CI: 0.68-0.79). CONCLUSION: In conclusion, the results of this study indicate that the Chinese version of the ODQ has good validity and reliability. It is an effective self-report measure of emotional blunting symptoms of depression.

Patient-reported outcome measures for life engagement in mental health: a systematic review.

BACKGROUND: Life engagement in the context of mental health is a broad term that describes positive health aspects relating to cognition, vitality, motivation and reward, and the ability to feel pleasure-concepts that are meaningful to patients. The aim of this systematic literature review was to identify validated patient-reported outcomes (PROs) that can assess any aspect of life engagement in adults, in the field of general mental health. METHODS: This was a systematic literature review of articles in English from the MEDLINE database (date of search: September 9, 2020). The search strategy had three components: (1) terms to capture PROs; (2) terms to capture mental health; and (3) terms to capture aspects of life engagement. Articles were eligible if they included a PRO that: (1) is named; (2) can be used across mental health disorders; (3) is used to assess any aspect of life engagement; and (4) has undergone psychometric validation and/or qualitative content validation. A list of PROs was extracted. RESULTS: A total of 1585 records were screened and 233 articles were eligible for inclusion. Within these 233 articles, 49 distinct PROs were identified, two of which specifically captured their authors' interpretation of life engagement: the Engaged Living Scale (ELS) and the Life Engagement Test (LET). However, while the ELS and LET covered motivation and reward, life fulfillment, and value-based living, neither scale captured the cognitive or vitality aspects of life engagement. The remaining identified PROs generally captured single aspects of life engagement, most commonly motivation/reward/energy-apathy, pleasure-anhedonia, and mental/psychological well-being. CONCLUSION: Numerous PROs are available that may capture aspects of life engagement. However, a need remains for a new PRO that can be used in clinical trials to provide a more comprehensive description of the improvements in life engagement that patients with mental health disorders may experience with successful treatment.

Emotional blunting in patients with depression. Part IV: differences between patient and physician perceptions.

BACKGROUND: Emotional blunting is common in patients with depression. An online survey was undertaken to assess the experience of emotional blunting, and its impact on functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the level of concordance between patient and HCP perspectives. METHODS: This was a cross-sectional, observational study. Patient respondents were adults with a diagnosis of depression, who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. HCPs completed the survey for the last two eligible patients they had seen, one in each phase of depression. Assessments included the Oxford Depression Questionnaire (ODQ) 'antidepressant as cause' domain and the Functioning Assessment Short Test (FAST). RESULTS: Mean ODQ 'antidepressant as cause' domain scores were significantly higher in the patient-reported cohort (n = 752) than in the HCP-assessed cohort (n = 766) in both the acute (18.0 vs 12.5, respectively; p < 0.01) and remission phases (17.6 vs 12.6; p < 0.01). Overall, 45% of patients believed that their antidepressant medication was negatively affecting their emotions and 39% were considering stopping or had stopped their antidepressant because of perceived emotion-related side effects. In the HCP-assessed cohort, the antidepressant was considered responsible for emotional blunting in 30% of patients and only 18% of patients were believed to be considering stopping their medication due to emotional blunting. Patients reported a greater impact of emotional blunting on activities of daily living than HCPs. Mean FAST score was significantly higher in each phase of depression in the patient-reported cohort than in the HCP-assessed cohort (acute phase, 47.0 vs 39.1; remission phase, 33.5 vs 19.4; both p < 0.01). CONCLUSIONS: Compared with previous studies, our results suggest that HCPs may underestimate the prevalence of emotional blunting in patients with depression. HCPs also appear to underestimate the severity and impact of emotional blunting on patient functioning and treatment adherence compared with patients' own perspectives. Differences between patient and HCP perspectives were most pronounced during the acute phase of the disease.

Emotional blunting in patients with depression. Part II: relationship with functioning, well-being, and quality of life.

BACKGROUND: Emotional blunting is a common symptom in people with depression and an important factor preventing full functional recovery. This international survey investigated the experience of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the impact of emotional blunting on overall functioning and health-related quality of life from the patient perspective. METHODS: Respondents were adults diagnosed with depression by a physician, currently prescribed an antidepressant, and reporting emotional blunting during the past 6 weeks. Assessments included the Oxford Depression Questionnaire (ODQ), the Functioning Assessment Short Test (FAST), and the World Health Organization-Five Well-being Index (WHO-5). Pearson correlation and multivariate regression analyses were applied to examine the relationship between ODQ and FAST scores. RESULTS: Data are available for 752 patients (62% female; mean age, 45 years). Mean ODQ total score was 94.8 in patients in the acute phase of depression (n = 300) and 85.7 in those in remission (n = 452; possible maximum, 130). Mean FAST total scores were 47.0 and 33.5, respectively (possible maximum, 72). Patients in the acute phase of depression had significantly greater impairment in functioning across all FAST domains than those in the remission phase (all differences, p < 0.01). Mean WHO-5 scores were 6.4 and 9.8 in the acute and remission phases, respectively (lower scores indicate poorer well-being). Overall, 65% of patients in the acute phase and 36% of those in remission reported that emotional blunting had a significant impact on their quality of life. Pearson correlation analysis showed a moderate positive correlation between ODQ and FAST total scores (r = 0.52) and a weak negative correlation between ODQ total score and WHO-5 score (r = - 0.26; both p < 0.01). In multivariate regression analysis, ODQ total score (in combination with other covariates) was the strongest significant predictor of poor patient functioning. CONCLUSIONS: Emotional blunting has a substantial negative impact on patients' daily functioning, well-being, and quality of life in both the acute and remission phases of depression. These findings highlight the importance of recognizing and treating emotional blunting in patients with major depressive disorder in order to achieve full functional recovery.