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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Emotional blunting—inability to feel positive or negative emotions, detachment, or reduced emotional responsiveness—is common in people with depression. However, there is a paucity of studies comprehensively investigating this symptom and its functional impact. This study investigated the experience of emotional blunting, and its impact on overall functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the clinical presentation of emotional blunting in depression from the patient perspective. Methods: Cross-sectional, observational study conducted in Brazil, Canada, and Spain between April 15 and May 18, 2021. Data were collected via a self-completed online survey. Respondents were adults with depression (acute or remission phase), who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ; total score range 26–130, higher scores indicate greater emotional blunting). Results: In all, 752 patients completed the survey (62% female; mean age, 45 years). Overall, 44% of patients rated their emotional blunting as extremely severe (acute phase [n = 300], 72%; remission phase [n = 452], 25%; difference, p < 0.01). In all, 56% of patients considered their emotional blunting to be caused by their depression (acute phase, 62%; remission phase, 52%). Mean ODQ total score was 94.8 for patients in the acute phase of depression and 85.7 for those in remission (difference, p < 0.01). Mean score for the ODQ 'antidepressant as cause' domain (maximum possible score, 30) was 18.0 in patients in the acute phase and 17.6 in those in remission. Overall, 45% of patients believed that their antidepressant medication was blunting their emotions and 39% were considering stopping or had already stopped their antidepressant because of perceived emotion-related side effects. Conclusions: Almost three-quarters of patients in the acute phase of depression and one-quarter of those in remission reported severe emotional blunting. Approximately 56% of patients considered their emotional blunting to be caused by their depression, while 45% believed that their antidepressant medication was negatively affecting their emotions. Just over one-third of patients were considering stopping or had stopped their antidepressant as a result. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor of Acta Neuropsychiatrica written by Andrea Fagiolini. Fagiolini expresses concern that their study on the effectiveness of vortioxetine in treating emotional blunting in patients with major depressive disorder was not included in a recent systematic review on apathy associated with antidepressant drugs. Fagiolini argues that their study met the inclusion criteria and had relevant results, and requests that the authors consider including their study in the review. Fagiolini emphasizes the importance of their findings in improving emotional blunting symptoms and overall functioning in patients with major depressive disorder. [Extracted from the article]

Importance: Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established.Objective: To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant.Design, Setting, and Participants: In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase.Interventions: Patients who achieved stable remission and those who achieved stable response (without remission) were randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued in each group.Main Outcomes and Measures: Time to relapse was examined in patients who achieved stable remission, as assessed using a weighted combination log-rank test.Results: Among the 297 adults (mean age [SD], 46.3 [11.13] years; 197 [66.3%] female) who entered the randomized maintenance phase, 176 achieved stable remission; 24 (26.7%) in the esketamine and antidepressant group and 39 (45.3%) in the antidepressant and placebo group experienced relapse (log-rank P = .003, number needed to treat [NNT], 6). Among the 121 who achieved stable response, 16 (25.8%) in the esketamine and antidepressant group and 34 (57.6%) in the antidepressant and placebo group experienced relapse (log-rank P < .001, NNT, 4). Esketamine and antidepressant treatment decreased the risk of relapse by 51% (hazard ratio [HR], 0.49; 95% CI, 0.29-0.84) among patients who achieved stable remission and 70% (HR, 0.30; 95% CI, 0.16-0.55) among those who achieved stable response compared with antidepressant and placebo treatment. The most common adverse events reported for esketamine-treated patients after randomization were transient dysgeusia, vertigo, dissociation, somnolence, and dizziness (incidence, 20.4%-27.0%), each reported in fewer patients (<7%) treated with an antidepressant and placebo.Conclusions and Relevance: For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo.Trial Registration: ClinicalTrials.gov identifier: NCT02493868. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to describe the prescription pattern of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in an Italian setting, focusing on therapy duration, switching and adherence. Method: Historic cohort study, based on administrative databases of three Italian local health-units, was conducted. Patients with a prescription of antidepressants (ADs) in 2009 were enrolled and grouped into: (1) naïve, (2) already in treatment with the same drug and (3) already in treatment with a different drug. Therapy duration, switching and adherence [as medication possession ratio-(MPR)] were evaluated. A logistic regression model was performed to identify predictors of adherence. Results: There were 88,755 subjects recruited: 37 % naïve, 58 % already in treatment with the same drug and 4 % with different drug. A treatment duration of ≤3 months was found in 41 % of naïve patients, whereas the majority of patients already in treatment had a duration of ≥6 months. Switches occurred in 0.7 % of the whole cohort and mostly occurred between two different SSRIs. The 63 % of naïve patients had a low adherence (MPR < 60 %), whereas a good adherence (MPR ≥ 80 %) was found in 58 % of patients already in treatment with the same drug and in 39 % of those already in treatment with different drug. Predictors of adherence were: female gender, increasing comorbidity and pain absence. All ADs, except for fluoxetine and venlafaxine, showed a better adherence than paroxetine. Conclusion: Notwithstanding the difficulty to associate the AD prescription to the specific diagnosis of depression, this study highlighted a short duration and a low adherence of AD therapies, especially at the initiation of treatment. Physicians should carefully balance the need to prescribe these drugs, considering the great likelihood of a short duration of treatment and a very low level of adherence. [ABSTRACT FROM AUTHOR]

Approximately 40% of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with bipolar depression. Compared with bipolar patients without mixed features, patients with bipolar mixed states generally have more severe symptomatology, more lifetime episodes of illness, worse clinical outcomes and higher rates of comorbidities, and thus present a significant clinical challenge. Most clinical trials have investigated second-generation neuroleptic monotherapy, monotherapy with anticonvulsants or lithium, combination therapy, and electroconvulsive therapy (ECT). Neuroleptic drugs are often used alone or in combination with anticonvulsants or lithium for preventive treatment, and ECT is an effective treatment for mixed manic episodes in situations where medication fails or cannot be used. Common antidepressants have been shown to worsen mania symptoms during mixed episodes without necessarily improving depressive symptoms; thus, they are not recommended during mixed episodes. A greater understanding of pathophysiological processes in bipolar disorder is now required to provide a more accurate diagnosis and new personalised treatment approaches. Targeted, specific treatments developed through a greater understanding of bipolar disorder pathophysiology, capable of affecting the underlying disease processes, could well prove to be more effective, faster acting, and better tolerated than existing therapies, therefore providing better outcomes for individuals affected by bipolar disorder. Until such time as targeted agents are available, second-generation neuroleptics are emerging as the treatment of choice in the management of mixed states in bipolar disorder. [ABSTRACT FROM AUTHOR]

Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepi-nephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antide-pressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as OleptroTM; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the man-agement of patients with MDD. Although trazodone is approved for the treatment of depression, evidence sup-ports the use of low-dose trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as part of a combination strategy. Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. Methods: The study sample includes 225 patients who entered the 6-month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score ≥15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. Results: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. Conclusions: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a recurrent illness with high rates of chronicity, treatment-resistance, and significant economic impact. S-Adenosylmethionine (SAMe), a molecule that is formed naturally in the human body, has shown antidepressant effects and may expand the available options for treating MDD. This systematic review examines the evidence concerning the efficacy of SAMe as monotherapy or in combination with antidepressants. Methods: A systematic search in Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register was conducted for any reference recorded up to March 2020. Double-blind, randomised controlled trials, comparing the antidepressant efficacy of SAMe to placebo or/and to other antidepressants, were selected. Two authors evaluated each study independently and then, reconciled findings. Results: Eight trials, with a total of 11 arms and 1011 subjects, evaluating the efficacy of SAMe used as monotherapy or as adjunctive therapy (512 individuals), were included in this review. The study duration ranged between 2 and 12 weeks and the daily dose of SAMe varied from 200 to 3200 mg. Five comparisons evaluated the differences between SAMe and placebo and SAMe resulted significantly better than placebo in three of these studies. Four comparisons evaluated the differences between SAMe and other antidepressants (imipramine or escitalopram) and showed no significant difference. One study showed that SAMe was significantly better than placebo in accelerating the response to imipramine from day 4 to day 12, but the mean scores were not statistically different at the day 14 endpoint. One study showed that SAMe combined with serotonin reuptake inhibitors (SSRI) was better than PBO combined with SSRI. The studies reported only mild, transient or non-clinically relevant side effects. Conclusions: The existing trials of SAMe, used as monotherapy or add on to another antidepressants, have shown encouraging and generally positive results. However, more evidence is necessary before definitive conclusions can be drawn. Larger, double-blind randomised controlled studies are warranted to confirm the antidepressant effectiveness of SAMe. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of effective antidepressants, about half of patients with major depressive disorder (MDD) display an inadequate response to their initial treatment. A large patient survey recently reported that 29.8% of MDD patients experiencing an inadequate treatment response felt frustrated about their medication and 19.2% were frustrated with their healthcare provider. This survey and chart audit evaluated healthcare professionals' (HCP) views on the emotional impact of having an inadequate response to antidepressant medication. Methods: HCPs who frequently treat patients with MDD completed a survey and chart audit of their MDD patients currently experiencing an inadequate response to antidepressant treatment. Results: 287 HCPs completed 1336 chart audits. HCPs reported that 38% of their patients were trusting/accepting of their MDD medications and 41% of their patients trusted/felt confident with their healthcare provision. Conversely, HCPs reported that 11% of their patients were frustrated with their medication and 5% with their healthcare benefits. HCPs cited impact on daily life (53%) and treatment issues (lack of efficacy and side effects; 50%) as the main drivers for their patients' feelings of frustration. When HCPs recognized patients' feelings of frustration, the top concerns of the HCPs were worsening of symptoms (43%) and non-compliance (41%). Conclusions: This survey and chart audit highlights the emotional burden associated with inadequate responses to MDD treatment in addition to persistent symptoms. Differences between the views of the HCPs and patients are highlighted and suggest that HCPs may underestimate the full impact that having to try numerous medications has on their patients. [ABSTRACT FROM AUTHOR]

Abstract: Complicated grief (CG) is a debilitating syndrome that can be reliably identified, but there is a paucity of research examining treatment of CG. A targeted psychotherapy for complicated grief (CGT) was recently shown to be efficacious [Shear, K., Frank, E., Houck, P.R., Reynolds, C.F., 3rd, 2005. Treatment of complicated grief: a randomized controlled trial. Journal of the American Medical Association 293, 2601–2608]. We provide a detailed examination of the association of naturalistic pharmacotherapy use with treatment response and study completion in the psychotherapy study. Patients on an antidepressant medication were more likely to complete a full course of CGT (91% vs. 58% completed), while antidepressant use had no effect on completion rates for the comparator, interpersonal psychotherapy (70% vs. 77%). Our naturalistic data underscore the need for prospective, randomized controlled studies of CG pharmacotherapy and psychotherapy alone and in combination. [Copyright &y& Elsevier]

• 5-year retrospective follow-up on 93 remitters from a first major depressive episode. • Less depressive recurrences in remitters to brief dynamic therapy than in remitters to antidepressants. • Significantly higher rates of hypomanic/manic episodes in remitters to antidepressants. Short-term psychodynamic psychotherapy (STPP) both combined with medication and alone has been shown to be effective in major depressive disorder (MDD). However, few studies compared STTP and pharmacotherapy in monotherapy during acute phase and there is lack of data concerning the prevention of recurrences. The aim of this retrospective study was to evaluate the clinical course of patients who achieved remission from their first life-time major depressive episode after treatment with antidepressant (AD) therapy or brief dynamic therapy (BDT), a specific type of STPP, examining the recurrence rates during a 5-year treatment-free period. The analysis was conducted on 93 subjects (remitters to BDT n = 46; remitters to AD n = 47). Treatment with BDT was associated with a significantly higher proportion of patients without depressive recurrences during the observation period. Among patients who were remitters to BDT, 71.7% did not experience depressive recurrences at the end of the observation period, compared to 46.8% of those treated with pharmacotherapy. BDT may be more effective than AD pharmacotherapy in improving the long-term outcome of patients with a first major depressive episode; further studies comparing STPP and AD in terms of efficacy and cost-effectiveness are needed. [ABSTRACT FROM AUTHOR]