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Lung Cancer (Amsterdam, Netherlands) Oct 2023Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of... (Meta-Analysis)
Meta-Analysis Review
Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis.
OBJECTIVE
Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of different ALK-TKIs to guide clinical decision making.
MATERIALS AND METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Data were analyzed using random effects and consistency models under the frequency framework.
RESULTS
Of 865 relevant studies, 13 RCTs (encompassing 3,353 patients) were finally included. A network meta-analysis of all-grade AEs, fatal AEs, and treatment discontinuation due to AEs revealed no significant differences among the six ALK-TKIs. The rates of grade 3-4 AEs were: alectinib (16.2%), crizotinib (46.4%), brigatinib (63.7%), ensartinib (75.6%), ceritinib (78.3%), and lorlatinib (91.6%). The toxicity spectra of ALK-TKIs were different. The most frequent AEs associated with crizotinib were gastrointestinal reactions, visual disorders, neutropenia, edema, fatigue, and elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, while those in the alectinib group were anemia and constipation. Diarrhea, hepatotoxicity, and increased serum creatinine were most common with ceritinib. The most frequent AEs in the brigatinib group were gastrointestinal reactions, hypertension, cough, headache, and elevated ALT or AST levels. The most significant toxicities of ensartinib were skin disorders, including pruritus and rash. Changes in lipid levels were the most frequent AEs associated with lorlatinib; weight gain, cognitive effects, and mood effects were lorlatinib-specific AEs.
CONCLUSIONS
The toxicity spectra of ALK-TKIs differed. Alectinib might be the safest ALK-TKI drug according to the combined evidence of grades 3-4 AEs and the combined incidence.
Topics: Humans; Anaplastic Lymphoma Kinase; Protein-Tyrosine Kinases; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Crizotinib; Network Meta-Analysis; Lung Neoplasms; Protein Kinase Inhibitors
PubMed: 37597303
DOI: 10.1016/j.lungcan.2023.107319 -
Sports Medicine (Auckland, N.Z.) Oct 2023Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in...
BACKGROUND
Menstrual cycle (MC) disorders and MC-related symptoms can have debilitating effects on the health and performance of female athletes. As the participation of women in sports continues to increase, understanding the prevalence of a range of MC disorders and MC-related symptoms may guide preventive strategies to protect the health and optimise the performance of female athletes.
OBJECTIVE
To examine the prevalence of MC disorders and MC-related symptoms among female athletes who are not using hormonal contraceptives and evaluate the assessment methods used to identify MC disorders and MC-related symptoms.
METHODS
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Six databases were searched until September 2022 for all original research that reported the prevalence of MC disorders and/or MC-related symptoms in athletes not using hormonal contraceptives, which included the definitions of the MC disorders examined, and the assessment methods used. MC disorders included amenorrhoea, anovulation, dysmenorrhoea, heavy menstrual bleeding (HMB), luteal phase deficiency (LPD), oligomenorrhoea, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). MC-related symptoms included any affective and physical symptoms related to the MC that do not cause significant personal, interpersonal or functional impairment. The prevalence data across eligible studies were combined, and all studies were qualitatively synthesised to evaluate the assessment methods and tools used to identify MC disorders and MC-related symptoms. The methodological quality of studies was assessed using a modified Downs and Black checklist.
RESULTS
Sixty studies involving 6380 athletes were included. A wide range of prevalence was observed for all types of MC disorders, with a dearth of data on anovulation and LPD. Based on pooled data, dysmenorrhoea (32.3%; range 7.8-85.6%) was the most prevalent MC disorder. Studies reporting MC-related symptoms mostly examined the premenstrual and menstruation phases, where affective symptoms appeared more prevalent than physical symptoms. A larger proportion of athletes reported symptoms during the initial days of menstruation compared with the premenstrual phase. MC disorders and MC-related symptoms were retrospectively assessed using self-report methods in 90.0% of studies. Most studies (76.7%) in this review were graded as moderate quality.
DISCUSSION
MC disorders and MC-related symptoms are commonplace among female athletes, warranting further research examining their impact on performance and preventive/management strategies to optimise athlete health. To increase the quality of future studies, researchers should adopt standardised definitions of MC disorders and assessment methods such as a combination of calendar counting, urinary ovulation tests and a mid-luteal phase serum progesterone measurement when assessing menstrual function. Similarly, standardised diagnostic criteria should be used when examining MC disorders such as HMB, PMS and PMDD. Practically, implementing prospective cycle monitoring that includes ovulation testing, mid-luteal blood sampling (where feasible) and symptom logging throughout the MC could support athletes and practitioners to promptly identify and manage MC disorders and/or MC-related symptoms.
TRIAL REGISTRATION
This review has been registered in the PROSPERO database (CRD42021268757).
Topics: Female; Humans; Dysmenorrhea; Prevalence; Prospective Studies; Anovulation; Retrospective Studies; Menstrual Cycle; Premenstrual Syndrome; Menstruation Disturbances; Premenstrual Dysphoric Disorder; Athletes; Contraceptive Agents
PubMed: 37389782
DOI: 10.1007/s40279-023-01871-8 -
Journal of Affective Disorders Aug 2023Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the... (Review)
Review
BACKGROUND
Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the disease and its consequences, self-stigma can impact people with bipolar disorder. This review investigates the current state of research in self-stigma in bipolar disorder.
METHODS
An electronic search was carried out until February 2022. Three academic databases were systematically searched, and best-evidence synthesis was made.
RESULTS
Sixty-six articles were related to self-stigma in bipolar disorder. Seven key themes were extracted from these studies: 1/ Comparison of self-stigma in bipolar disorder and other mental illnesses, 2/ Sociocultural context and self-stigma, 3/ Correlates and predictors of self-stigma, 4/ Consequences of self-stigma, 5/ Treatments and self-stigma, 6/ Management of self-stigma, and 7/ Self-stigma and recovery in bipolar disorder.
LIMITATIONS
Firstly, a meta-analysis could not be performed due to the heterogeneity of the studies. Secondly, limiting the search to self-stigma has excluded other forms of stigma that also have an impact. Thirdly, the under-reporting of negative or nonsignificant results due to publication bias and unpublished studies might have limited the accuracy of this reviews' synthesis.
CONCLUSION
Research on self-stigma in persons with bipolar disorder has been the focused on different aspects, and interventions to reduce self-stigmatization have been developed, but evidence of their effectiveness is still sparse. Clinicians need to be attentive to self-stigma, its assessment, and its empowerment in their daily clinical practice. Future work is required to establish valid strategies to fight self-stigma.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Social Stigma; Mania
PubMed: 37207946
DOI: 10.1016/j.jad.2023.05.041 -
Scientific Reports Aug 2023The objective of this study was to assess the benefits and potential risks associated with different physical exercise modalities for managing symptoms in adults with... (Meta-Analysis)
Meta-Analysis
The objective of this study was to assess the benefits and potential risks associated with different physical exercise modalities for managing symptoms in adults with major depressive disorder who were not receiving second-generation antidepressants or cognitive behavioral therapy. A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted. The search included multiple databases: Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycInfo, Web of Science, Clinical Trials repository, gray literature, and manual search. No language restrictions were applied. Eligible studies involved RCTs of adults with major depressive disorder who were not on antidepressants or receiving psychological therapy, comparing various exercise modalities with second-generation antidepressants or cognitive behavioral therapy, body-mind exercise, or no exercise interventions. Nine RCTs involving 678 adults were analyzed. The pooled results indicated a small clinical effect favoring exercise in reducing depressive symptoms, although the difference was not statistically significant (SMD = 0.27, 95% CI [- 0.58, 0.04], P = 0.09). Subgroup analyses suggested that intervention duration, frequency, intensity, supervision, age, overweight/obesity status, and diagnosis of depression could influence treatment outcomes. A sensitivity analysis was conducted for studies with controls without exercise interventions and a low risk of bias in the domains related to the randomization process and deviations from the intended interventions. The results showed that there are no statistically significant differences when interventions are compared with medication and body-mind exercise (p = 0.12, I = 78%). Furthermore, the analysis showed a moderate effect size favoring exercise, but no statistically significant difference between groups (p = 0.05), with high heterogeneity (I = 85%). The evidence quality was generally low to very low, and methodological limitations compromised the certainty of the findings. Adverse events associated with exercise were manageable. The study emphasizes the need for well-designed RCTs to provide clearer insights into the potential benefits of exercise in managing major depressive disorder symptoms. Caution is warranted in interpreting these results due to the limitations of the included studies.Systematic review registration: PROSPERO CRD42022356741.
Topics: Adult; Humans; Depressive Disorder, Major; Antidepressive Agents; Cognitive Behavioral Therapy; Antidepressive Agents, Second-Generation; Exercise
PubMed: 37580497
DOI: 10.1038/s41598-023-39783-2 -
The Lancet. Psychiatry Mar 2024There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression.
METHODS
In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926.
FINDINGS
Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes.
INTERPRETATION
According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies.
FUNDING
None.
Topics: Male; Female; Humans; Middle Aged; Depressive Disorder, Major; Fluoxetine; Perphenazine; Network Meta-Analysis; Bipolar Disorder; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Depression; Antipsychotic Agents; Olanzapine
PubMed: 38360024
DOI: 10.1016/S2215-0366(24)00006-3 -
Translational Psychiatry Dec 2023Studies investigating gut microbiota composition in depressive disorder have yielded mixed results. The aim of our study was to compare gut microbiome between people... (Meta-Analysis)
Meta-Analysis
Studies investigating gut microbiota composition in depressive disorder have yielded mixed results. The aim of our study was to compare gut microbiome between people with depressive disorder and healthy controls. We did a meta-analysis and meta-regression of studies by searching PubMed, Web of Science, Embase, Scopus, Ovid, Cochrane Library, ProQuest, and PsycINFO for articles published from database inception to March 07, 2022. Search strategies were then re-run on 12 March 2023 for an update. We undertook meta-analyses whenever values of alpha diversity and Firmicutes, Bacteroidetes (relative abundance) were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesize the effect size (assessed by standardized mean difference [SMD]) across studies. We identified 44 studies representing 2091 patients and 2792 controls. Our study found that there were no significant differences in patients with depressive disorder on alpha diversity indices, Firmicutes and Bacteroidetes compared with healthy controls. In subgroup analyses with regional variations(east/west) as a predictor, patients who were in the West had a lower Chao1 level (SMD -0.42[-0.74 to -0.10]). Subgroup meta-analysis showed Firmicutes level was decreased in patients with depressive disorder who were medication-free (SMD -1.54[-2.36 to -0.72]), but Bacteroidetes level was increased (SMD -0.90[0.07 to 1.72]). In the meta-regression analysis, six variables cannot explain the 100% heterogeneity of the studies assessing by Chao1, Shannon index, Firmicutes, and Bacteroidetes. Depleted levels of Butyricicoccus, Coprococcus, Faecalibacterium, Fusicatenibacter, Romboutsia, and enriched levels of Eggerthella, Enterococcus, Flavonifractor, Holdemania, Streptococcus were consistently shared in depressive disorder. This systematic review and meta-analysis found that psychotropic medication and dietary habit may influence microbiota. There is reliable evidence for differences in the phylogenetic relationship in depressive disorder compared with controls, however, method of measurement and method of patient classification (symptom vs diagnosis based) may affect findings. Depressive disorder is characterized by an increase of pro-inflammatory bacteria, while anti-inflammatory butyrate-producing genera are depleted.
Topics: Humans; Gastrointestinal Microbiome; Phylogeny; Microbiota; Bacteria; Depressive Disorder
PubMed: 38065935
DOI: 10.1038/s41398-023-02670-5 -
Human Psychopharmacology Sep 2023Lithium is widely used as treatment of acute mania and as prophylactic therapy for bipolar disorder. International and national guidelines also consider lithium as a... (Review)
Review
BACKGROUND
Lithium is widely used as treatment of acute mania and as prophylactic therapy for bipolar disorder. International and national guidelines also consider lithium as a possible treatment of acute bipolar depression. Research on the use of lithium in bipolar depression, however, seems to be limited compared to the data available for its efficacy in the other phases of bipolar disorder.
OBJECTIVE
To provide a systematic review of the evidence for lithium in the treatment of acute bipolar depression and provide directions for further research.
METHOD
A systematic review of clinical studies investigating the use of lithium in bipolar depression was performed using preferred reporting items for systematic reviews and meta-analyses guidelines in Pubmed, Embase and Psychinfo using the medical subjects headings and free text terms "lithium," "bipolar depression," "dosage," "serum concentration" and "bipolar disorders."
RESULTS
This review included 15 studies with a total of 1222 patients, between the age of 18 and 65, suffering from bipolar depression of which 464 were treated with lithium. There are currently only limited and low-quality data on the efficacy of lithium as a treatment of bipolar depression. It appears that there have been no placebo controlled randomized controlled trials with lithium concentrations that are considered to be therapeutic. The older studies suffered from limitations such as small sample sizes, insufficient treatment lengths, and insufficient monitoring of serum concentrations.
CONCLUSION
In contrast to data for the treatment of mania and prophylaxis, robust data on the efficacy of lithium in bipolar depression is currently lacking, making it impossible to make conclusions regarding efficacy or inefficacy, for which further research is needed.
Topics: Humans; Bipolar Disorder; Lithium; Mania; Lithium Compounds
PubMed: 37789577
DOI: 10.1002/hup.2881 -
Journal of Psychiatric Research Aug 2023Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this... (Review)
Review
Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on RC-BD and extracted associated definitions, prevalence, risk-factors, and clinical outcomes. We assessed study quality (NIH Quality Assessment Tool) and levels of evidence (Oxford criteria). Of 146 identified reviews, 22 fulfilling selection criteria were included, yielding 30 studies involving 13,698 BD patients, of whom 3777 (27.6% [CI: 26.8-28.3]) were considered RC-BD, as defined in 14 reports by ≥4 recurrences/year within the past 12 months or in any year, without considering responsiveness to treatment. Random-effects meta-analytically pooled one-year prevalence was 22.3% [CI: 14.4-32.9] in 12 reports and lifetime prevalence was 35.5% [27.6-44.3] in 18 heterogenous reports. Meta-regression indicated greater lifetime prevalence of RC-BD among women than men (p=0.003). Association of RC-BD with suicide attempts, and unsatisfactory response to mood-stabilizers was supported by strong evidence (Level 1); associations with childhood maltreatment, mixed-features, female sex, and type-II BD had moderate evidence (Level 2). Other factors: genetic predisposition, metabolic disturbances or hypothyroidism, antidepressant exposure, predominant depressive polarity (Level 3), along with greater illness duration and immune-inflammatory dysfunction (Level 4) require further study. RC-BD was consistently recognized as having high prevalence (22.3%-35.5% of BD cases) and inferior treatment response. Identified associated factors can inform clinical practice. Long-term illness-course, metabolic factors, and optimal treatment require further investigation.
Topics: Female; Humans; Male; Antidepressive Agents; Bipolar Disorder; Hypothyroidism; Prevalence; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37429185
DOI: 10.1016/j.jpsychires.2023.06.021 -
Social Psychiatry and Psychiatric... Nov 2023This systematic review of systematic reviews aims to provide the first global picture of the prevalence and correlates of perinatal depression, and to explore the... (Review)
Review
PURPOSE
This systematic review of systematic reviews aims to provide the first global picture of the prevalence and correlates of perinatal depression, and to explore the commonalities and discrepancies of the literature.
METHODS
Seven databases were searched from inception until April 2022. Full-text screening and data extraction were performed independently by two researchers and the AMSTAR tool was used to assess the methodological quality.
RESULTS
128 systematic reviews were included in the analysis. Mean overall prevalence of perinatal depression, antenatal depression and postnatal depression was 26.3%, 28.5% and 27.6%, respectively. Mean prevalence was significantly higher (27.4%; SD = 12.6) in studies using self-reported measures compared with structured interviews (17.0%, SD = 4.5; d = 1.0) and among potentially vulnerable populations (32.5%; SD = 16.7, e.g. HIV-infected African women) compared to the general population (24.5%; SD = 8.1; d = 0.6). Personal history of mental illness, experiencing stressful life events, lack of social support, lifetime history of abuse, marital conflicts, maternity blues, child care stress, chronic physical health conditions, preeclampsia, gestational diabetes mellitus, being exposed to second-hand smoke and sleep disturbance were among the major correlates of perinatal depression.
CONCLUSION
Although the included systematic reviews were all of medium-high quality, improvements in the quality of primary research in this area should be encouraged. The standardisation of perinatal depression assessment, diagnosis and measurement, the implementation of longitudinal designs in studies, inclusions of samples that better represent the population and better control of potentially confounding variables are encouraged.
Topics: Female; Humans; Pregnancy; Child; Depression; Prevalence; Systematic Reviews as Topic; Depression, Postpartum; Pregnancy Complications
PubMed: 36646936
DOI: 10.1007/s00127-022-02386-9 -
Acta Psychiatrica Scandinavica Aug 2023Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD could reduce variability and benefit research. Since BD has a robust genetic component, studies can investigate clinical traits that cluster in families to identify phenotypes with a probable genetic basis.
METHODS
We conducted a systematic review of the current literature on familial clinical traits of BD. Text screening and data extraction were performed independently by two reviewers, and random effects meta-analysis was used.
RESULTS
Of 1117 unique records, 16 studies met inclusion criteria. These studies indicated 14 potentially familial traits of BD: age of onset (OR: 4.50; 95% CI: [3.25, 6.22]), bipolar type (OR: 2.05 [1.50, 2.79]), lithium response (OR: 3.71 [1.28, 10.82]), polarity at onset (OR: 1.17 [1.03, 1.34]), psychotic features (OR: 2.20 [1.51, 3.20]), mood-incongruent psychosis (OR: 2.52 [1.66, 3.83]), puerperal psychosis (OR: 6.54 [2.55, 16.77]), rapid cycling (OR: 4.95 [0.96, 25.40]), suicide attempt (OR: 1.04 [0.65, 1.67]), alcoholism (OR: 1.53 [1.09, 2.16]), obsessive-compulsive disorder (OR: 3.10 [1.31; 7.09]), panic disorder (OR: 2.69 [1.12; 6.48]), social anxiety disorder (OR: 1.00 [0.39, 2.55]), and specific phobia (OR: 1.94 [0.95; 3.96]). For most traits, tests of heterogeneity were significant and publication bias was likely.
CONCLUSION
The results of our review and meta-analysis highlight the lack of studies investigating familial clinical traits of BD, despite the need to address heterogeneity. The large degree of variability between studies must be reduced for future research.
Topics: Humans; Bipolar Disorder; Phenotype; Psychotic Disorders; Obsessive-Compulsive Disorder; Panic Disorder
PubMed: 37190775
DOI: 10.1111/acps.13569