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Human Psychopharmacology Apr 2024Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential... (Review)
Review
BACKGROUND
Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings.
METHODS
A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials.
RESULTS
The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000 mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment.
CONCLUSION
There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.
PubMed: 38683854
DOI: 10.1002/hup.2899 -
BMC Pregnancy and Childbirth Aug 2023Bipolar disorder (BD) is a mental disorder characterized by mood shifts from severe depression to mania. Pregnant women with BD may experience manic or depressive...
BACKGROUND
Bipolar disorder (BD) is a mental disorder characterized by mood shifts from severe depression to mania. Pregnant women with BD may experience manic or depressive episodes, so they are usually concerned about the effects of BD on their pregnancy. The aim of this systematic review is to determine the effects of BD on maternal health and fetal health, weight, and development. It also addresses how BD affects the probability of incidence of pregnancy complications in women with bipolar compared with healthy controls.
METHODS
Seven electronic databases (Ovid MEDLINE, Embase, MIDRIS, APA PsychINFO, Scopus, Web of Science, and ScienceOpen) were searched, and 1728 eligible studies were identified. After deduplication, screening, and manual search processes, we included only 15 studies. Descriptive analysis, and calculation of the probability of incidence for each pregnancy outcome were used to analyze the results.
RESULTS
The findings of the included studies suggest that BD during pregnancy may affect both fetal growth and maternal health by increasing the risk of giving birth to an infant with some birth defects such as microcephaly, CNS problems, small for gestational age, and other congenital anomalies, in addition to causing some obstetric complications such as gestational hypertension, preterm labor, need for assisted delivery, hospital readmission, and others.
CONCLUSION
Bipolar disorder during pregnancy negatively affects mothers and their fetuses and increases the probability of incidence of obstetrics complications.
Topics: Infant; Infant, Newborn; Female; Pregnancy; Humans; Bipolar Disorder; Prenatal Care; Fetus; Psychotic Disorders; Parturition
PubMed: 37641006
DOI: 10.1186/s12884-023-05924-8 -
Journal of Affective Disorders Apr 2024Bipolar disorder (BD) is a severe affective disorder characterized by recurrent episodes of depression or mania/hypomania, which significantly impair cognitive function,... (Review)
Review
Bipolar disorder (BD) is a severe affective disorder characterized by recurrent episodes of depression or mania/hypomania, which significantly impair cognitive function, life skills, and social abilities of patients. There is little understanding of the neurobiological mechanisms of BD. The diagnosis of BD is primarily based on clinical assessment and psychiatric examination, highlighting the urgent need for objective markers to facilitate the diagnosis of BD. Metabolomics can be used as a diagnostic tool for disease identification and evaluation. This study summarized the altered metabolites in BD and analyzed aberrant metabolic pathways, which might contribute to the diagnosis of BD. Search of PubMed and Web of science for human BD studies related to metabolism to identify articles published up to November 19, 2022 yielded 987 articles. After screening and applying the inclusion and exclusion criteria, 16 untargeted and 11 targeted metabolomics studies were included. Pathway analysis of the potential differential biometabolic markers was performed using the Kyoto encyclopedia of genes and genomes (KEGG). There were 72 upregulated and 134 downregulated biomarkers in the untargeted metabolomics studies using blood samples. Untargeted metabolomics studies utilizing urine specimens revealed the presence of 78 upregulated and 54 downregulated metabolites. The targeted metabolomics studies revealed abnormalities in the metabolism of glutamate and tryptophan. Enrichment analysis revealed that the differential metabolic pathways were mainly involved in the metabolism of glucose, amino acid and fatty acid. These findings suggested that certain metabolic biomarkers or metabolic biomarker panels might serve as a reference for the diagnosis of BD.
Topics: Humans; Bipolar Disorder; Metabolomics; Mood Disorders; Amino Acids; Biomarkers
PubMed: 38218254
DOI: 10.1016/j.jad.2024.01.033 -
Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
Frontiers in Neurology 2023Electroconvulsive therapy (ECT) is a widely used treatment for severe psychiatric disorders such as schizophrenia, depression, and mania. The procedure involves applying...
BACKGROUND
Electroconvulsive therapy (ECT) is a widely used treatment for severe psychiatric disorders such as schizophrenia, depression, and mania. The procedure involves applying brief electrical stimulation to induce a seizure, and anesthesia is used to ensure sedation and muscle relaxation. Finding the right anesthetic agent with minimal side effects, especially on seizure duration, is crucial for optimal outcomes because seizure duration is an important factor in the effectiveness of ECT, but the anesthetic agents used can affect it.
OBJECTIVE
This systematic review and meta-analysis aimed to pool the results of all relevant studies comparing the two induction agents, etomidate and propofol, for motor and electroencephalogram (EEG) seizure duration outcomes.
METHODS
A comprehensive literature search was conducted in the PubMed, Medline, and Cochrane Library databases to identify the relevant articles. The primary outcome measures were motor and EEG seizure durations. Statistical power was ensured by performing heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Standard mean difference and 95% confidence intervals were calculated for continuous outcomes, and a random-effects model was used.
RESULTS
A total of 16 studies were included in this meta-analysis, comprising 7 randomized control trials (RCTs), 7 crossover trials, and 2 cohorts. The overall motor seizure duration was statistically significantly longer with etomidate than with propofol. The overall result for EEG seizure duration was also longer with the use of etomidate over propofol and was statistically significant. In addition, subgrouping was performed based on the study design for both outcomes, which showed insignificant results in the cohort's subgroup for both outcomes, while the RCTs and crossover subgroups supported the overall results. Heterogeneity was assessed through subgrouping and sensitivity analysis.
CONCLUSION
Our meta-analysis found that etomidate is superior to propofol in terms of motor and EEG seizure duration in ECT, implying potentially better efficacy. Hence, etomidate should be considered the preferred induction agent in ECT, but larger studies are needed to further validate our findings.
PubMed: 37915381
DOI: 10.3389/fneur.2023.1251882 -
The British Journal of Clinical... Mar 2024Dysfunctional attitudes (DA) are higher in depression; however, less is understood about their role in bipolar disorder (BD). This paper aimed to explore the presence of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dysfunctional attitudes (DA) are higher in depression; however, less is understood about their role in bipolar disorder (BD). This paper aimed to explore the presence of DA in BD in comparison to clinical and non-clinical groups. Also explored were the associations between DA and mood states of depression, mania or euthymia in BD.
METHODS
A systematic review and meta-analysis were conducted. A total of 47 articles were included in the systematic review of which 23 were included in the meta-analysis. The quality of each study was rated.
RESULTS
The meta-analysis showed significantly higher DA in BD than healthy controls (d = .70). However, no difference was observed between BD and unipolar participants (d = -.16). When reviewing mood state within BD, a significant mean difference was found between DA scores for euthymic and depressed participants (d = -.71), with those who were depressed scoring higher. Three studies found that psychological therapies significantly reduce DA in BD (d = -.38).
CONCLUSIONS
These findings imply not only that DA are both a characteristic of BD that is not as prevalent in healthy populations but also that a depressed mood state is associated with increased severity. This implies that DA could possibly go 'offline' when mood symptoms are not present. Psychological therapies appear to reduce DA in BD. Implications for future research as well as practice-based implications are expanded on in the discussion.
Topics: Humans; Bipolar Disorder; Affect; Depression
PubMed: 37807389
DOI: 10.1111/bjc.12442 -
Journal of Affective Disorders Sep 2024Bipolar disorder (BD) is a chronic and recurrent illness characterized by manic, mixed or depressive episodes, alternated with periods of euthymia. Several prognostic... (Review)
Review
INTRODUCTION
Bipolar disorder (BD) is a chronic and recurrent illness characterized by manic, mixed or depressive episodes, alternated with periods of euthymia. Several prognostic factors are associated with higher rates of relapse, which is crucial for the identification of high-risk individuals. This study aimed at systematically reviewing the existing literature regarding the impact of sociodemographic, clinical and environmental factors, in clinical relapses, recurrences and hospitalizations due to mood episodes in BD.
METHODS
A systematic search of electronic databases (PubMed, Cochrane library and Web of Science) was conducted to integrate current evidence about the impact of specific risk factors in these outcomes.
RESULTS
Fifty-eight articles met the inclusion criteria. Studies were grouped by the type of factors assessed. Family and personal psychiatric history, more severe previous episodes, earlier age of onset, and history of rapid cycling are associated with clinical relapses, along with lower global functioning and cognitive impairments. Unemployment, low educational status, poorer social adjustment and life events are also associated with higher frequency of episodes, and cannabis with a higher likelihood for rehospitalization.
LIMITATIONS
Small sample sizes, absence of randomized clinical trials, diverse follow-up periods, lack of control for some confounding factors, heterogeneous study designs and diverse clinical outcomes.
CONCLUSIONS
Although current evidence remains controversial, several factors have been associated with an impaired prognosis, which might allow clinicians to identify patients at higher risk for adverse clinical outcomes and find modifiable factors. Further research is needed to elucidate the impact of each risk factor in the mentioned outcomes.
Topics: Humans; Bipolar Disorder; Recurrence; Risk Factors; Prognosis; Hospitalization; Age of Onset; Sociodemographic Factors
PubMed: 38797389
DOI: 10.1016/j.jad.2024.05.064 -
Journal of Affective Disorders Aug 2024Bipolar disorder remains a disabling mental health condition despite the availability of effective treatments. Collaborative chronic care models (CCMs) represent an... (Review)
Review
BACKGROUND
Bipolar disorder remains a disabling mental health condition despite the availability of effective treatments. Collaborative chronic care models (CCMs) represent an evidence-based way to structure care for conditions like bipolar disorder. Life Goals Collaborative Care (LGCC) was designed specifically for bipolar disorder, featuring psychoeducation alongside collaborative components (e.g. nurse care management or expert psychiatric consultation). Despite the use of Life Goals across health systems, a systematic review summarizing its effectiveness has never been conducted.
METHODS
We conducted a systematic review of randomized controlled trials (RCTs) of LGCC through December 2023 to help guide the field in treating bipolar disorder (PROSPERO: #404581). We evaluated study quality and outcomes in several symptom and quality of life domains.
RESULTS
Ten articles describing eight studies met inclusion criteria. All studies featured group-based LGCC; most were compared to treatment as usual (TAU). Three of eight studies found LGCC to be associated with statistically significant effects for the prevention of manic episodes. Most studies finding positive effects featured additional collaborative care components beyond psychoeducation and were conducted in capitated healthcare systems.
LIMITATIONS
Limitations include: several types of potential bias in included studies; exclusion of observational studies of LGCC; lack of generalizability to pediatric populations; insufficient studies to conduct subgroup analyses; and low confidence in the quality of the evidence.
CONCLUSIONS
In this systematic review, group-based LGCC demonstrated some positive effects for reducing mania recurrence; results for other outcome domains were equivocal. Future studies should investigate one-on-one LGCC, both in person and virtually, to enhance well-being for people with bipolar disorder.
Topics: Humans; Bipolar Disorder; Quality of Life; Randomized Controlled Trials as Topic; Goals; Cooperative Behavior
PubMed: 38754598
DOI: 10.1016/j.jad.2024.05.058 -
The Cochrane Database of Systematic... Jun 2024Mental health problems contribute significantly to the overall disease burden worldwide and are major causes of disability, suicide, and ischaemic heart disease. People... (Review)
Review
BACKGROUND
Mental health problems contribute significantly to the overall disease burden worldwide and are major causes of disability, suicide, and ischaemic heart disease. People with bipolar disorder report lower levels of physical activity than the general population, and are at greater risk of chronic health conditions including cardiovascular disease and obesity. These contribute to poor health outcomes. Physical activity has the potential to improve quality of life and physical and mental well-being.
OBJECTIVES
To identify the factors that influence participation in physical activity for people diagnosed with bipolar disorder from the perspectives of service users, carers, service providers, and practitioners to help inform the design and implementation of interventions that promote physical activity.
SEARCH METHODS
We searched MEDLINE, PsycINFO, and eight other databases to March 2021. We also contacted experts in the field, searched the grey literature, and carried out reference checking and citation searching to identify additional studies. There were no language restrictions.
SELECTION CRITERIA
We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that focused on the experiences and attitudes of service users, carers, service providers, and healthcare professionals towards physical activity for bipolar disorder.
DATA COLLECTION AND ANALYSIS
We extracted data using a data extraction form designed for this review. We assessed methodological limitations using a list of predefined questions. We used the "best fit" framework synthesis based on a revised version of the Health Belief Model to analyse and present the evidence. We assessed methodological limitations using the CASP Qualitative Checklist. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) guidance to assess our confidence in each finding. We examined each finding to identify factors to inform the practice of health and care professionals and the design and development of physical activity interventions for people with bipolar disorder.
MAIN RESULTS
We included 12 studies involving a total of 592 participants (422 participants who contributed qualitative data to an online survey, 170 participants in qualitative research studies). Most studies explored the views and experiences of physical activity of people with experience of bipolar disorder. A number of studies also reported on personal experiences of physical activity components of lifestyle interventions. One study included views from family carers and clinicians. The majority of studies were from high-income countries, with only one study conducted in a middle-income country. Most participants were described as stable and had been living with a diagnosis of bipolar disorder for a number of years. We downgraded our confidence in several of the findings from high confidence to moderate or low confidence, as some findings were based on only small amounts of data, and the findings were based on studies from only a few countries, questioning the relevance of these findings to other settings. We also had very few perspectives of family members, other carers, or health professionals supporting people with bipolar disorder. The studies did not include any findings from service providers about their perspectives on supporting this aspect of care. There were a number of factors that limited people's ability to undertake physical activity. Shame and stigma about one's physical appearance and mental health diagnosis were discussed. Some people felt their sporting skills/competencies had been lost when they left school. Those who had been able to maintain exercise through the transition into adulthood appeared to be more likely to include physical activity in their regular routine. Physical health limits and comorbid health conditions limited activity. This included bipolar medication, being overweight, smoking, alcohol use, poor diet and sleep, and these barriers were linked to negative coping skills. Practical problems included affordability, accessibility, transport links, and the weather. Workplace or health schemes that offered discounts were viewed positively. The lack of opportunity for exercise within inpatient mental health settings was a problem. Facilitating factors included being psychologically stable and ready to adopt new lifestyle behaviours. There were positive benefits of being active outdoors and connecting with nature. Achieving balance, rhythm, and routine helped to support mood management. Fitting physical activity into a regular routine despite fluctuating mood or motivation appeared to be beneficial if practised at the right intensity and pace. Over- or under-exercising could be counterproductive and accelerate depressive or manic moods. Physical activity also helped to provide a structure to people's daily routines and could lead to other positive lifestyle benefits. Monitoring physical or other activities could be an effective way to identify potential triggers or early warning signs. Technology was helpful for some. People who had researched bipolar disorder and had developed a better understanding of the condition showed greater confidence in managing their care or providing care to others. Social support from friends/family or health professionals was an enabling factor, as was finding the right type of exercise, which for many people was walking. Other benefits included making social connections, weight loss, improved quality of life, and better mood regulation. Few people had been told of the benefits of physical activity. Better education and training of health professionals could support a more holistic approach to physical and mental well-being. Involving mental health professionals in the multidisciplinary delivery of physical activity interventions could be beneficial and improve care. Clear guidelines could help people to initiate and incorporate lifestyle changes.
AUTHORS' CONCLUSIONS
There is very little research focusing on factors that influence participation in physical activity in bipolar disorder. The studies we identified suggest that men and women with bipolar disorder face a range of obstacles and challenges to being active. The evidence also suggests that there are effective ways to promote managed physical activity. The research highlighted the important role that health and care settings, and professionals, can play in assessing individuals' physical health needs and how healthy lifestyles may be promoted. Based on these findings, we have provided a summary of key elements to consider for developing physical activity interventions for bipolar disorder.
Topics: Humans; Bias; Bipolar Disorder; Caregivers; Exercise; Health Personnel; Qualitative Research; Quality of Life; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38837220
DOI: 10.1002/14651858.CD013557.pub2 -
Psychological Medicine Nov 2023The diagnostic concept of unipolar mania (UM), i.e. the lifetime occurrence of mania without major depressive episodes, remains a topic of debate despite the evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The diagnostic concept of unipolar mania (UM), i.e. the lifetime occurrence of mania without major depressive episodes, remains a topic of debate despite the evidence accumulated in the last few years. We carried out a systematic review and meta-analysis of observational studies testing factors associated with UM as compared to bipolar disorder with a manic-depressive course (md-BD).
METHODS
Studies indexed up to July 2022 in main electronic databases were searched. Random-effects meta-analyses of the association between UM and relevant correlates yielded odds ratio (OR) or standardized mean difference (SMD), with 95% confidence intervals (CIs).
RESULTS
Based on data from 21 studies, factors positively or negatively associated with UM, as compared to md-BD, were: male gender (OR 1.47; 95% CI 1.11-1.94); age at onset (SMD -0.25; 95% CI -0.46 to -0.04); number of hospitalizations (SMD 0.53; 95% CI 0.21-0.84); family history of depression (OR 0.55; 95% CI 0.36-0.85); suicide attempts (OR 0.25; 95% CI 0.19-0.34); comorbid anxiety disorders (OR 0.35; 95% CI 0.26-0.49); psychotic features (OR 2.16; 95% CI 1.55-3.00); hyperthymic temperament (OR 1.99; 95% CI 1.17-3.40). The quality of evidence for the association with previous suicide attempts was high, moderate for anxiety disorders and psychotic features, and low or very low for other correlates.
CONCLUSIONS
Despite the heterogeneous quality of evidence, this work supports the hypothesis that UM might represent a distinctive diagnostic construct, with peculiar clinical correlates. Additional research is needed to better differentiate UM in the context of affective disorders, favouring personalized care approaches.
Topics: Humans; Male; Depressive Disorder, Major; Mania; Bipolar Disorder; Mood Disorders; Anxiety
PubMed: 37016793
DOI: 10.1017/S0033291723000831