Psychosocial impairment represents an important treatment target in major depressive disorder (MDD). The majority of patients with MDD do not regain premorbid levels of psychosocial functioning ...despite the resolution of core depressive symptoms. This study aimed to investigate the respective effects of cognitive function and depression severity on impaired psychosocial function in MDD.
Adults aged 18–65 with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls participated in a cross-sectional study validating the THINC-integrated tool (THINC-it), a cognitive screening tool comprised of objective and subjective measures of cognitive function. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale and psychosocial function was assessed using the Sheehan Disability Scale (SDS).
Subjects with MDD reported greater impairment in psychosocial function than healthy controls, with significant differences in SDS total and domain scores (ps < .01) after controlling for age, sex, and education. Generalized linear models indicated that subjective cognitive function was most strongly associated with SDS total score (RR = .14, p = .01) and SDS domains of work/school (RR = .15, p = .03), family and home responsibilities (RR = .15, p = .02), and economic days lost (RR = .18, p =.03). Depression severity was most strongly associated with SDS social life (RR = .08, p < .01) and economic days underproductive (RR = .07, p < .01). Objective cognitive function was not significantly associated with any SDS outcomes.
The cross-sectional, observational study design limits temporal inferences. The self-report nature of measures included may have influenced associations observed. Potential medication effects are not noted.
Cognitive deficits, as measured by the THINC-it, are associated with significant psychosocial impairment in MDD. These results provide empirical support for the assessment of both subjective and objective measures of cognition, as they are not associated with each other and have differential effects on functional trajectory.
•Cognitive dysfunction is a core and persisting deficit in adults with MDD.•Cognitive impairment exerts independent effects on psychosocial outcomes.•Subjective cognition predicts functional outcome independent of depression severity.
Introduction:
Atypical antipsychotics provide broad-spectrum effectiveness for the acute and/or preventative treatment of disparate psychiatric disorders. Atypical antipsychotics offer improved ...efficacy in some psychopathological domains when compared with typical antipsychotics. Notwithstanding, atypicals are not a catholicon and are associated with clinically significant and treatment-limiting side effects (e.g., extrapyramidal symptoms and weight gain).
Areas covered:
This article reviews commonly encountered adverse events attributable to the use of atypical antipsychotic agents. This review aims to provide a current overview of common adverse events associated with atypical agents with a particular emphasis on adverse events that frequently lead to treatment discontinuation (e.g., changes in weight, metabolism, extrapyramidal side effects, neuroendocrine changes, blood dyscrasias, and cardiovascular toxicity).
Expert opinion:
Atypicals are not a catholicon and are associated with clinically significant and treatment-limiting side effects (e.g., extrapyramidal symptoms and weight gain). Improving the utility of these agents requires a familiarity and understanding of the heterogeneous tolerability and safety profiles of atypical agents as well as the therapeutic evidence for their efficacy.
Herein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized ...antidepressant therapy.
Adults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity
, Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20 were treated with open-label vortioxetine (10-20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB).
After 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (
, processing speed) (p = 0.031). A subdomain measure of working memory (
, symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively.
The THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB.
ClinicalTrials.gov, identifier NCT03053362.
Depressive episodes and symptoms of bipolar I disorder are commonly misdiagnosed as major depressive disorder (MDD) in primary care. The novel and pragmatic Rapid Mood Screener (RMS) was developed to ...screen for manic symptoms and bipolar I disorder features (e.g. age of depression onset) to address this unmet clinical need.
A targeted literature search was conducted to select concepts thought to differentiate bipolar I from MDD and screener tool items were drafted. Items were tested and refined in cognitive debriefing interviews with individuals with self-reported bipolar I or MDD (n = 12). An observational study was conducted to evaluate predictive validity. Participants with clinical interview-confirmed bipolar I or MDD diagnoses (n = 139) completed a draft 10-item screening tool and other questionnaires. Data were analyzed to identify the smallest possible subset of items with optimized sensitivity and specificity.
Adults with confirmed bipolar I (n = 67) or MDD (n = 72) participated in the observational study. Ten draft screening tool items were reduced to 6 final RMS items based on the item-level analysis. When 4 or more items of the RMS were endorsed ("yes"), sensitivity was 0.88 and specificity was 0.80; positive and negative predictive values were 0.80 and 0.88, respectively. These properties were an improvement over the Mood Disorder Questionnaire in the same analysis sample while using 60% fewer items.
The pragmatic 6-item RMS differentiates bipolar I disorder from MDD in patients with depressive symptoms, providing real-world guidance to primary care practitioners on whether a more comprehensive assessment for bipolar I disorder is warranted.
•Metabolic predictors of antidepressant response, like insulin resistance, may allow for more precise and personalized care of major depressive disorder.•Insulin resistance was a predictor of ...response to vortioxetine, even in the context of other factors including, but not limited, to obesity/BMI.•Higher baseline insulin resistance predicted decreased improvements of anhedonia early on in the course of treatment.•Higher baseline insulin resistance predicted poorer subjective assessments of cognition at the endpoint of treatment.•Higher baseline insulin resistance predicted decreased psychosocial functioning at the endpoint of treatment.
To assess the effect of insulin resistance (IR) on treatment response to the antidepressant, vortioxetine, in patients with Major Depressive Disorder (MDD).
This is a secondary analysis of an 8-week, open-label clinical trial. Ninety-five adults in a primary care setting experiencing a major depressive episode were included. Response to vortioxetine was measured using the THINC-integrated tool, Montgomery Åsberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Perceived Deficits Questionnaire (PDQ-5), and the Sheehan Disability Scale (SDS). Generalized estimating equation models were utilized for data analysis.
When adjusted for age, gender, dose, and BMI, there was a significant baseline IR by time interaction for SHAPS (p = 0.022), PDQ-5 (p = 0.037), and SDS (p = 0.013). Higher baseline IR predicted decreased early improvements in anhedonia. It also predicted poorer subjective assessments of cognition and increased functional impairment at the endpoint of treatment. For functional capacity (i.e. SDS) other covariates including severity of symptoms, illness course, other metabolic factors (e.g. cholesterol), and physical activity were included with no changes to the moderating effect of baseline IR.
This was a post-hoc analysis of a primarily non-diabetic sample. Also, only one agent was assessed.
IR was a predictor of response to vortioxetine. This persisted after controlling for other factors including, but not limited to, BMI. These findings strengthen the link between depression and IR and may point to another novel metabolic predictor of response. These findings should be replicated using other antidepressants.
Objectives
The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment ...recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided—a critical gap which the current update aims to address.
Method
Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high‐quality data and reliance on expert opinion.
Results
No agents met threshold for first‐line treatment of DSM‐5 manic or depressive episodes with mixed features. For mania + mixed features second‐line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second‐line options. For DSM‐IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first‐line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second‐line. Research on maintenance treatments following a DSM‐5 mixed presentation is extremely limited, with third‐line recommendations based on expert opinion. For maintenance treatment following a DSM‐IV mixed episode, quetiapine (monotherapy or combination) is first‐line, and lithium and olanzapine identified as second‐line options.
Conclusion
The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.
We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with schizophrenia.
In accordance with PRISMA ...guidelines, articles were systematically searched for in databases and clinical trial registries.
A total of 4 preclinical trials and 3 randomized controlled trials (RCTs) were included in this review. A 4-week RCT observed a difference of 24.0 points (SD 21.0) in the Positive and Negative Syndrome Scale (PANSS) total score between xanomeline and placebo groups (
= 0.039). A 5-week RCT observed PANSS total score changes from baseline to week 5, including -17.4 and -5.9 points in KarXT and placebo groups, respectively (LSMD -11.6 points; 95% CI -16.1 to -7.1;
< 0.001; d = 0.75). Another 5-week RCT observed PANSS total score changes from baseline to week 5, including -21.2 (SE 1.7) and -11.6 (SE 1.6) points in KarXT and placebo groups, respectively (LSMD -9.6; 95% CI -13.9 to -5.2;
< 0.0001; d = 0.61). Side effects include constipation, nausea, vomiting, dyspepsia, and dry mouth.
KarXT offers an innovative non-D2 blocking approach, representing a promising treatment avenue for schizophrenia.
An increasing body of evidence suggests that, in comparison to the general population, patients with severe mental illnesses such as schizophrenia or bipolar disorder have worse physical health and a ...far shorter life expectancy in developed countries, due primarily to premature cardiovascular disease.
This article is based on presentations and discussion on somatic comorbidity in psychiatric illnesses by a group of 37 international experts during 2 meetings held in 2006.
At the preparatory meeting in Paris, France, the group determined key topics for presentations and group discussions. During the meeting in Vienna, Austria, on day 1, each set of presentations was followed by discussions in small groups with the meeting participants. On day 2, conclusions reached by each discussion group were presented and used as a platform for a consensus view adopted by the meeting participants. The presentations and discussions were collated into a draft that was revised and approved by each of the bylined authors.
General health care needs are commonly neglected in patients with severe mental illness, with suboptimal integration of general somatic and psychiatric care services, current lack of consensus as to which health care professionals should be responsible for the prevention and management of comorbid somatic illnesses in patients with severe mental disorders, and, at least in some countries, a paucity of funding for general somatic care for patients with severe mental disorders, especially those in long-term psychiatric treatment.
The somatic health of patients with severe medical illnesses is too often neglected, thus contributing to an egregious health disparity. The reintegration of psychiatry and medicine, with an ultimate goal of providing optimal services to this vulnerable patient population, represents the most important challenge for psychiatry today, requiring urgent and comprehensive action from the profession toward achieving an optimal solution.
Background: Guidelines recommend selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) as first-line treatments for major depressive disorder (MDD) ...and emphasize the importance of early pharmacological treatment as key factors to treatment success.
Objectives: To compare the MDD-related healthcare resource utilization (HCRU) and cost among patients (1) with early vs late pharmacological treatment initiation and (2) achieving minimum therapeutic dose (MTD) early vs late.
Methods: The MarketScan database (2010-2015) was used. Adults who were newly-treated with SSRI/SNRI within 12 months after the initial MDD diagnosis (index) were included. Patients who initiated SSRI/SNRI within 2 weeks of the index date were defined as early initiators; those who reached MTD within 4 weeks of index date were defined as early MTD achievers. MDD-related HCRU and costs per year after the index date were compared between early and late initiators and between early and late achievers using propensity score matching and generalized linear models.
Results: Of the 55,539 patients, 60% were early initiators and 61% were early MTD achievers. The mean number of MDD-related outpatient visits per year were significantly higher for late initiator (6.7 vs 4.2, p < .001) and late MTD achievers (6.5 vs 4.5, p < .001) vs their early counterparts. Mean annual MDD-related outpatient, drug, and total cost were significantly higher for late initiators and MTD achievers vs the early groups.
Conclusions: There is an opportunity to improve outcomes by treating MDD patients with SSRI/SNRI within 2 weeks and at or above the MTD within 4 weeks of diagnosis or less.
Subjects with schizophrenia have high risks of metabolic abnormalities and bioenergetic dysfunction. Acyl-carnitines involved in bioenergetic pathways provide potential biomarker targets for ...identifying early changes and onset characteristics in subjects with schizophrenia. We measured 29 acyl-carnitine levels within well-characterized plasma samples of adults with schizophrenia and healthy controls using liquid chromatography-mass spectrometry (LC-MS). Subjects with schizophrenia were measured at baseline and after 8 weeks of treatment. A total of 225 subjects with schizophrenia and 175 age- and gender-matched healthy controls were enrolled and 156 subjects completed the 8-week follow-up. With respect to plasma acyl-carnitines, the individuals with schizophrenia at baseline showed significantly higher levels of C4-OH (C3-DC) and C16:1, but lower concentrations of C3, C8, C10, C10:1, C10:2, C12, C14:1-OH, C14:2, and C14:2-OH when compared with healthy controls after controlling for age, sex, body mass index (BMI), smoking, and drinking. For the comparison between pretreatment and posttreatment subjects, all detected acyl-carnitines were significantly different between the two groups. Only the concentration of C3 and C4 were increased after selection by variable importance in projection (VIP) value >1.0 and false discovery rate (FDR) q value <0.05. A panel of acyl-carnitines were selected for the ability to differentiate subjects of schizophrenia at baseline from controls, pre- from post-treatment, and posttreatment from controls. Our data implicated acyl-carnitines with abnormalities in cellular bioenergetics of schizophrenia. Therefore, acyl-carnitines can be potential targets for future investigations into their roles in the pathoetiology of schizophrenia.
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