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Bipolar Disorders May 2024Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder... (Review)
Review
Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.
BACKGROUND
Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD.
METHODS
We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials.
RESULTS
Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias.
CONCLUSIONS
Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Cognitive Dysfunction; Central Nervous System Stimulants; Off-Label Use; Methylphenidate
PubMed: 38433530
DOI: 10.1111/bdi.13414 -
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 -
Journal of Affective Disorders Mar 2024The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence of treatment options' efficacy on acute bipolar manic episodes is relatively less in youths than adults. We aimed to compare and rank the drug's efficacy, acceptability, tolerability, and safety for acute mania in children and adolescents.
METHOD
We systematically reviewed the double-blinded, randomized controlled trials (RCTs) comparing drugs or placebo for acute manic episodes of bipolar disorder in children and adolescents using PRISMA guidelines. We searched PubMed/MEDLINE, EMBASE, Web of Science, EBSCO, Scopus, the Cochrane Central Register of Controlled Trials, and https://clinicaltrials.gov from inception until November 20, 2022. Response to treatment was the primary outcome, and random-effects network meta-analyses were conducted (PROSPERO 2022: CRD42022367455).
RESULTS
Of 10,134 citations, we included 15 RCTs, including 2372 patients (47 % female), 15 psychotropic drugs, and the placebo. Risperidone 0.5-2.5 mg/day, aripiprazole 30 mg/day olanzapine, quetiapine 400 mg/day, quetiapine 600 mg/day, asenapine 5 mg/day, asenapine 10 mg, ziprasidone, and aripiprazole 10 mg were found to be effective (in comparison with placebo) in children and adolescents, respectively (τ = 0.0072, I = 10.2 %). The tolerability of aripiprazole 30 mg/day was lower than risperidone 0.5-2.5 mg/day and olanzapine. Oxcarbazepine had the highest discontinuation due to the adverse effects risk ratio.
LIMITATIONS
Efficacy ranking of the treatments could be performed by evaluating relatively few RCT results, and only monotherapies were considered.
CONCLUSIONS
Efficacy, acceptability, tolerability, and safety are changing with the doses of antipsychotics for children and adolescents with acute bipolar manic episodes. Drug selection and optimum dosage should be carefully adjusted in children and adolescents.
Topics: Humans; Adolescent; Adult; Child; Risperidone; Olanzapine; Aripiprazole; Bipolar Disorder; Quetiapine Fumarate; Mania; Network Meta-Analysis; Antipsychotic Agents; Dibenzocycloheptenes
PubMed: 38211745
DOI: 10.1016/j.jad.2024.01.067 -
Journal of Attention Disorders Mar 2024To explore outcomes of stimulant treatment for ADHD in pediatric populations with particular attention to bipolar disorder (BPD).
OBJECTIVE
To explore outcomes of stimulant treatment for ADHD in pediatric populations with particular attention to bipolar disorder (BPD).
METHOD
We conducted a literature search of PubMed articles published prior to August 25, 2022 that focused on BPD, mania, and psychosis prior to, or as result of, stimulant treatment. We excluded studies: (1) unrelated to stimulants, (2) general stimulant research, (3) articles older than 40 years, (4) study protocols, or (5) case reports.
RESULTS
A total of 11 articles met all inclusion/exclusion criteria. Some reports found stimulant treatment safe and well-tolerated in children with comorbid BPD and ADHD. Others found evidence of treatment-emergent mania (TEM), discontinuation, and other adverse events with stimulant treatment.
CONCLUSION
Poor outcomes associated with stimulant treatment in pediatric populations with BPD necessitate work to identify patients at risk of serious stimulant-related adverse events. Our results were limited by automated search filters and a pediatric, primarily male sample.
Topics: Humans; Child; Male; Bipolar Disorder; Attention Deficit Disorder with Hyperactivity; Mania; Central Nervous System Stimulants
PubMed: 38156605
DOI: 10.1177/10870547231218045 -
Psychiatry Research Feb 2024Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.
Topics: Humans; Antipsychotic Agents; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia
PubMed: 38150810
DOI: 10.1016/j.psychres.2023.115637 -
The Journal of Clinical Endocrinology... May 2024Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric... (Meta-Analysis)
Meta-Analysis
CONTEXT
Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects.
OBJECTIVE
This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.
METHODS
Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.
RESULTS
We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.
CONCLUSION
The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.
Topics: Humans; Glucocorticoids; Mental Disorders
PubMed: 38038629
DOI: 10.1210/clinem/dgad701 -
Nutritional Neuroscience Aug 2024Available evidence points to a possible role of Short Chain Fatty Acids (SCFAs) in mood disorders. This is the first systematic review to map the associations between... (Review)
Review
Available evidence points to a possible role of Short Chain Fatty Acids (SCFAs) in mood disorders. This is the first systematic review to map the associations between SCFA levels and mood disorder symptoms. Following the PRISMA guidelines, the databases PubMed, Embase, and PsycINFO were searched for studies that assessed SCFA levels in human populations with mood disorder symptoms, or animal models of mood disorder. Risk of bias was assessed by the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) checklist. 19 studies were included and could be divided into animal (=8) and human studies (=11), with the animal studies including 166 animals and 100 controls, and the human studies including 662 participants and 330 controls. The studies were characterized by heterogeneity and methodological challenges on multiple parameters, limiting the validity and transferability of findings. Notably, only two of the clinical studies assessed the presence of mood disorder with diagnostic criteria, and no studies of mania or bipolar disorder met the inclusion criteria. Despite significant methodological limitations, associations between SCFA levels and depressive symptoms were reported in most of the studies. However, the direction of these associations and the specific SCFAs identified varied. The quantification of SCFA levels in mood disorders is an emerging yet sparsely studied research field. Although there is some evidence suggesting a link between SCFAs and depressive symptoms, the directionality of effects and mechanisms are unclear and the relation to manic symptoms is uninvestigated.
Topics: Fatty Acids, Volatile; Humans; Mood Disorders; Animals
PubMed: 37976103
DOI: 10.1080/1028415X.2023.2277970 -
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 -
Therapeutic Advances in... 2023The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD)...
BACKGROUND
The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD) remains uncertain.
OBJECTIVE
This systematic review aimed to summarize findings on the use of ketamine for the treatment of BD by assessing its efficacy, safety, and tolerability.
DESIGN
Systematic review.
METHODS
We conducted a systematic review of studies that investigated the use of ketamine for adults with BD. We searched PubMed and Embase for relevant randomized-controlled trials, open-label trials, and retrospective chart analyses published from inception to 13 March 2023.
RESULTS
Eight studies were identified [pooled = 235; mean (SD) age: 45.55 (5.54)]. All participants who received intravenous (IV) ketamine were administered a dose of 0.5-0.75 mg/kg as an adjunctive treatment to a mood-stabilizing agent, whereas participants who received esketamine were administered a dosage ranging from 28 to 84 mg. Flexible dosing was used in real-world analyses. A total of 48% of participants receiving ketamine achieved a response (defined as ⩾50% reduction in baseline depression severity), whereas only 5% achieved a response with a placebo. Real-world studies demonstrated lower rates of response (30%) compared to the average across clinical trials (63%). Reductions in suicidal ideation were noted in some studies, although not all findings were statistically significant. Ketamine and esketamine were well tolerated in most participants; however, six participants (2% of the overall sample pool, 5 receiving ketamine) developed hypomanic/manic symptoms after infusions. Significant dissociative symptoms were observed at the 40-min mark in some trials.
CONCLUSION
Preliminary evidence suggests IV ketamine as being safe and effective for the treatment of BD. Future studies should focus on investigating the effects of repeated acute and maintenance infusions using a randomized study design.
PubMed: 37771417
DOI: 10.1177/20451253231202723