Objectives
To aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus‐based ...guidance paper for the methodology and design of cognition trials in bipolar disorder.
Methods
The task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face‐to‐face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.
Results
Key methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non‐study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.
Conclusions
This ISBD task force guidance paper provides the first consensus‐based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.
Objectives
Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) ...Targeting Cognition Task Force aimed to develop consensus‐based clinical recommendations on whether, when and how to assess and address cognitive impairment.
Methods
The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face‐to‐face meeting, telephone conference call and email exchanges. Consensus‐based recommendations were achieved through these exchanges with no need for formal consensus methods.
Results
The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy‐to‐administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence‐based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments.
Conclusions
This task force paper provides the first consensus‐based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients’ functional recovery and improve their quality of life.
Background:
Management of cognitive deficits in Major Depressive Disorder (MDD) remains an important unmet need. This meta-analysis evaluated the effects of vortioxetine on cognition in patients with ...MDD.
Methods:
Random effects meta-analysis was applied to three randomized, double-blind, placebo-controlled 8-week trials of vortioxetine (5–20mg/day) in MDD, and separately to two duloxetine-referenced trials. The primary outcome measure was change in Digit Symbol Substitution Test (DSST) score. Standardized effect sizes (SES) versus placebo (Cohen’s d) were used as input. Path analysis was employed to determine the extent to which changes in DSST were mediated independently of a change in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Meta-analysis was applied to MADRS-adjusted and -unadjusted SES values. Changes on additional cognitive tests were evaluated (source studies only).
Results:
Before adjustment for MADRS, vortioxetine separated from placebo on DSST score (SES 0.25–0.48; nominal p < 0.05) in all individual trials, and statistically improved DSST performance versus placebo in meta-analyses of the three trials (SES = 0.35; p < 0.0001) and two duloxetine-referenced trials (SES = 0.26; p = 0.001). After adjustment for MADRS, vortioxetine maintained DSST improvement in one individual trial (p = 0.001) and separation from placebo was maintained in meta-analyses of all three trials (SES = 0.24; p < 0.0001) and both duloxetine-referenced trials (SES 0.19; p = 0.01). Change in DSST with duloxetine failed to separate from placebo in individual trials and both meta-analyses. Change in DSST statistically favored vortioxetine versus duloxetine after MADRS adjustment (SES = 0.16; p = 0.04).
Conclusions:
Vortioxetine, but not duloxetine, significantly improved cognition, independent of depressive symptoms. Vortioxetine represents an important treatment for MDD-related cognitive dysfunction.
Anhedonia is a core symptom of major depressive disorder (MDD), which has important functional consequences for the patient. This post hoc analysis investigated the relationship between anhedonia and ...functioning in patients with MDD treated with vortioxetine.
We conducted a pooled analysis of all 11 short-term, double-blind, randomized, placebo-controlled studies of vortioxetine (fixed dose, 5-20 mg/day) in patients with MDD which included Montgomery-Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS) assessments. A short-term, randomized, active-controlled trial of flexible-dose treatment with vortioxetine (10-20 mg/day) versus agomelatine (25-50 mg/day) was also analyzed. Mean changes from baseline to study endpoint in MADRS total, MADRS anhedonia subscale, SDS total, and SDS social-functioning scores were analyzed by a mixed model for repeated measures. The relationship between treatment effects on anhedonia and functioning was investigated using path analysis.
A total of 4988 patients with MDD were included in the placebo-controlled studies and 495 in the active-comparator study. Significant dose-dependent improvements in overall depressive symptoms, anhedonia, and measures of functioning were seen in vortioxetine-treated patients compared with those who received placebo or agomelatine. Results of the path analysis for the placebo-controlled studies suggested that the effect on functioning was mostly driven by the effect of treatment on MADRS anhedonia factors.
Vortioxetine showed significant short-term efficacy against anhedonia in this large population of patients with MDD. In the placebo-controlled studies, improvements in functioning associated with vortioxetine appeared to be mostly driven by the effect of treatment on MADRS anhedonia factors.
Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe ...the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t(10) = 2.761, P = 0.023; t(9) = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.
Background
The clinical effects of smartphone‐based interventions for bipolar disorder (BD) have yet to be established.
Objectives
To examine the efficacy of smartphone‐based interventions in BD and ...how the included studies reported user‐engagement indicators.
Methods
We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random‐effects meta‐analysis to calculate the standardized difference (Hedges’ g) in pre‐post change scores between smartphone intervention and control conditions. The study was pre‐registered with PROSPERO (CRD42021226668).
Results
The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta‐analyses comparing the pre‐post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta‐analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user‐engagement indicators.
Conclusion
We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.
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.
Although many branded and generic antidepressants are approved for the treatment of major depressive disorder (MDD) in Canada, efficacy and tolerability differ among patients, and new treatment ...options are needed. Symptom types (eg, fatigue, energy/motivation, cognition, and functioning), medication type, treatment duration, and the need for maintenance therapy are factors that may influence treatment effectiveness. Three antidepressants, vortioxetine, levomilnacipran extended-release (ER), and vilazodone have recently become available in Canada. The aim of this review is to contextualize differences in their mechanistic and clinical profiles, thereby providing practitioners with knowledge to support treatment decisions. In trials versus placebo, each drug improved depressive symptoms in adult patients with MDD. The antidepressant effect of vortioxetine may be related to enhanced serotonergic activity via reuptake inhibition and agonism and/or antagonism of various serotonin receptors. Vortioxetine may also improve cognitive functioning in MDD, and has proven efficacious in relapse prevention. Nausea was the most commonly reported adverse event (AE); rates of sexual dysfunction were low and abrupt discontinuation was well tolerated. Levomilnacipran ER, a serotonin norepinephrine reuptake inhibitor, demonstrated greater improvement versus placebo in functional impairment as well as depressive symptoms; in post hoc analyses, improvement in symptoms of motivation and energy were observed. Nausea was the most commonly reported AE; gradual discontinuation is recommended to avoid discontinuation syndrome. Vilazodone is a serotonin reuptake inhibitor and partial serotonergic 5-HT
receptor agonist. In addition to improvement in depressive symptoms, evidence suggests that vilazodone may be particularly well suited for depressed patients with high anxiety levels. Diarrhea, nausea, and headache were the most common AEs; low rates of sexual dysfunction were reported. The 2016 Canadian Network for Mood and Anxiety Treatments guidelines for MDD includes vortioxetine as a first-line treatment; levomilnacipran ER and vilazodone are considered as second-line treatments due to lack of relapse prevention data at the time of approval.
Maj Vinberg,1,2 Roger S McIntyre,3,4 Annamaria Giraldi,2,5,* Klara Coello6,* 1Mental Health Centre Northern Zealand, the Early Multimodular Prevention, and Intervention Research Institution (EMPIRI) ...– Mental Health Services CPH, Copenhagen, Denmark; 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 3Mood Disorders Psychopharmacology Unit, Toronto Western Hospital, University Health Network, Toronto, ON, Canada; 4Institute of Medical Science, University of Toronto, Toronto, ON, Canada; 5Sexological Clinic, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; 6Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Frederiksberg, Denmark*These authors contributed equally to this workCorrespondence: Maj Vinberg, Dyrehavevej 48, Hillerød, 3400, Denmark, Tel +453864 3227, Email maj.vinberg@regionh.dkAbstract: The link between childhood maltreatment and mood disorders is complex and involves multiple bio-psycho-social factors that affect multiple molecular pathways. The present narrative review aims to clarify the current understanding of the impact of childhood maltreatment on biomarkers in patients with mood disorders and their first-degree relatives. Neurotransmitters, such as serotonin, dopamine, norepinephrine, and hormones (eg the stress hormone cortisol), play a crucial role in regulating mood and emotion. Childhood maltreatment can alter and affect the levels and functioning of these neurotransmitters in the brain; further, childhood maltreatment can lead to structural and connectivity changes in the brain, hence contributing to the development of mood disorders and moderating illness presentation and modifying response to treatments. Childhood maltreatment information, therefore, appears mandatory in treatment planning and is a critical factor in therapeutic algorithms. Further research is needed to fully understand these pathways and develop new treatment modalities for individuals with mood disorders who have experienced childhood maltreatment and effective preventive interventions for individuals at risk of developing mood disorders.Keywords: biomarkers, childhood maltreatment, mood disorders, biosignatures, biotype
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