-
The Cochrane Database of Systematic... Jun 2019Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective...
BACKGROUND
Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective maintenance treatment for bipolar disorder. It acts as mood stabiliser and reduces the risk of suicide. However, evidence assessing the efficacy of lithium in the treatment of acute mania is less robust. Current evidence-based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments: more definite evidence is needed to decide if lithium should be the first-line therapy.
OBJECTIVES
1. To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2. To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO. We also searched the World Health Organization trials portal (ICTRP) and ClinicalTrials.gov. We checked the reference lists of all included studies and relevant systematic reviews. We have incorporated studies from searches to 18 May 2018 into the current analyses.
SELECTION CRITERIA
Prospective randomised controlled studies comparing lithium with placebo or alternative drug treatment in treatment of acute mania. We included anyone with bipolar disorder, male and female, of any age.
DATA COLLECTION AND ANALYSIS
At least two review authors independently extracted data and assessed methodological quality. We used odds ratios (ORs) to analyse binary efficacy outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuously distributed outcomes. We used a fixed-effect model unless heterogeneity was moderate or substantial, in which case we used a random-effects model. We used Review Manager 5 to analyse data. We assessed the certainty of evidence for individual outcomes using the GRADE approach.
MAIN RESULTS
We found 36 randomised controlled studies comparing lithium with placebo, one of 12 drugs, or electroconvulsive therapy for treatment of acute mania. Studies included male and female participants (n = 4220), of all ages, who all fitted criteria for a manic episode within the context of a diagnosis of bipolar disorder.Risk of bias was variable; 12 studies had a high risk of bias in one domain and 27 gave inadequate information on randomisation leading to an 'unclear' rating for selection bias.Lithium versus placeboHigh-certainty evidence found that lithium was an effective treatment for acute mania and was more effective than placebo at inducing a response (OR 2.13, 95% confidence interval (CI) 1.73 to 2.63; participants = 1707; studies = 6; I = 16%; high-certainty evidence), or remission (OR 2.16, 95% CI 1.73 to 2.69; participants = 1597; studies = 5; I = 21%; high-certainty evidence).Lithium was more likely than placebo to cause tremor (OR 3.25, 95% CI 2.10 to 5.04; participants = 1241; studies = 6; I = 0%; high-certainty evidence), and somnolence (OR 2.28, 95% CI 1.46 to 3.58; participants = 1351; studies = 7; I = 0%; high-certainty evidence).There was insufficient evidence to determine the effect of lithium for all-cause dropouts (OR 0.76; 95% CI 0.46 to 1.25; participants = 1353; studies = 7; I = 75%; moderate-certainty evidence), and weight gain (OR 1.48, 95% CI 0.56 to 3.92; participants = 735, studies = 3; I= 51%; moderate-certainty evidence).Lithium versus antipsychotics or mood stabilisersFor the outcome of inducing a response, there was only very low-certainty evidence regarding lithium compared to haloperidol (MD -2.40, 95% CI -6.31 to 1.50; participants = 80; studies = 3; I = 95%), quetiapine (OR 0.66, 95% CI 0.28 to 1.55; participants = 335; studies = 2; I = 71%), and carbamazepine (SMD 0.21, 95% CI -0.18 to 0.60; participants = 102; studies = 3; I = 0%).Lithium was probably less likely to induce a response than olanzapine (OR 0.44, 95% CI 0.20 to 0.94; participants = 180; studies = 2; I = 0%; moderate-certainty evidence).Lithium may be less likely to induce a response than risperidone (MD 7.28, 95% CI 5.22 to 9.34; participants = 241; studies = 3; I = 49%; low-certainty evidence).There was no evidence of a difference between lithium and valproate (OR 1.22, 95% CI 0.87 to 1.70; participants = 607; studies = 5; I = 22%; moderate-certainty evidence).There was moderate-certainty evidence that lithium was more effective than topiramate at treating acute mania (OR 2.28, 95% CI 1.63 to 3.20; participants = 660; studies = 1).Data on adverse events for these comparisons contained too few studies to provide high-certainty evidence.
AUTHORS' CONCLUSIONS
This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor. Limited evidence suggests little or no difference between lithium and other mood stabilisers (valproate, carbamazepine) or antipsychotics (risperidone, quetiapine, haloperidol). Olanzapine may be an exception, as it is probably slightly more effective than lithium. There is uncertain evidence that risperidone may also be more effective than lithium. Lithium is probably more effective at treating acute mania than topiramate. When compared to placebo, lithium was more likely to cause adverse events. However, when compared to other drugs, too few studies provided data on adverse effects to provide high-certainty evidence. More, rigorously designed, large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania.
Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium Compounds; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 31152444
DOI: 10.1002/14651858.CD004048.pub4 -
Progress in Neuro-psychopharmacology &... Mar 2015Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity.... (Review)
Review
Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system - particularly the modulation of P1 and P2 receptor subtypes - plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.
Topics: Adenosine; Adenosine Triphosphate; Animals; Biomarkers; Guanosine; Humans; Models, Neurological; Molecular Targeted Therapy; Mood Disorders; Neuroimaging; Psychotropic Drugs; Receptors, Purinergic
PubMed: 25445063
DOI: 10.1016/j.pnpbp.2014.10.016 -
Brain Sciences Feb 2023Previous research suggests that there is a link between perfectionism and symptoms of depression. This study aimed to see if different types of perfectionism are linked... (Review)
Review
BACKGROUND
Previous research suggests that there is a link between perfectionism and symptoms of depression. This study aimed to see if different types of perfectionism are linked differently to symptoms of depression in mood disorders and if there is a relationship between perfectionism and symptoms of mania in bipolar disorder.
METHODS
A systematic search was conducted in the databases PsycINFO, EMBASE, Web of Science, and PubMed to find papers which examined the relationship in clinical depression and bipolar disorder. A meta-analysis pooled the correlation effect sizes for mood symptoms severity and the severity of the perfectionism subtype.
RESULTS
Twelve papers were included in the review, with five of these being included in the meta-analysis. The meta-analysis found statistically significant positive correlations between greater severity of depression symptoms and more severe perfectionism for the following subtypes: concern over mistakes, doubts about actions, other-oriented perfectionism, parental criticism, self-oriented perfectionism, and socially prescribed perfectionism. There was no significant relationship between depression symptoms and perfectionism subtypes of organisation and personal standards. There were not enough studies reporting data for manic symptoms for the meta-analysis or for any firm conclusions to be drawn.
CONCLUSIONS
The relationship between depression and perfectionism differs depending on the particular type of perfectionism examined. Most studies were cross-sectional and correlational, so causation cannot be inferred, and future longitudinal studies are needed.
PubMed: 36979187
DOI: 10.3390/brainsci13030377 -
BMJ Mental Health Feb 2023Are antipsychotic dose equivalents between acute mania and schizophrenia the same? (Meta-Analysis)
Meta-Analysis
QUESTION
Are antipsychotic dose equivalents between acute mania and schizophrenia the same?
STUDY SELECTION AND ANALYSIS
Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.
FINDINGS
We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%).
CONCLUSIONS
Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.
Topics: Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Haloperidol; Bipolar Disorder; Mania; Schizophrenia; Randomized Controlled Trials as Topic
PubMed: 36789916
DOI: 10.1136/bmjment-2022-300546 -
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 -
Brain and Behavior Jun 2023Bipolar disorder (BD) is a mood disorder that affects millions worldwide. Up to half of the diagnosed patients are reported to not receive adequate treatment. This study... (Review)
Review
BACKGROUND
Bipolar disorder (BD) is a mood disorder that affects millions worldwide. Up to half of the diagnosed patients are reported to not receive adequate treatment. This study aims to assess the relationship between the gut-brain axis and BD and to discuss and compare the efficacy of varying methods of balancing gut microbiotas in BD.
METHODS
Using PubMed, Embase, and Google Scholar from November 2021 to February 2022, we found 5310 studies on gut microbiota and its relation to BD. Using our inclusion criteria, 5283 studies were excluded. A total of 27 full-text articles were assessed for eligibility. Also, 12 articles that met our criteria and eligibility criteria reported on 613 BD patients.
RESULTS
Most studies analyzed found an overall difference in gut microbiota composition in bipolar patients compared to healthy controls, though the alterations found were not consistent. Differences in Lactobacillus, Faecalibacterium, and Ruminococcus abundance in BD compared to controls were found to be the most consistent across a few of the studies, but their effects on the gut-brain axis conflicted. Probiotic supplementation was found to lower patient rehospitalizations and significantly improve depressive symptoms and cognitive impairments among patients with BD.
CONCLUSIONS
Multiple studies included in this review point toward a possible link between BD and the gut microbiota. Probiotic supplements and other gut-balancing therapies could serve as effective adjunctive methods for the treatment of BD. Notable limitations of the studies included for analysis were small sample sizes and majority observational study designs. Furthermore, the microbiota aberrations found in patients with BD were not consistent across multiple studies. Despite these limitations, our findings demonstrate the need for further research regarding the relationship between aberrant gut microbiota profiles and BD, as well as the effectiveness of gut balancing methods as adjunctive treatments.
Topics: Humans; Bipolar Disorder; Gastrointestinal Microbiome; Brain-Gut Axis; Observational Studies as Topic
PubMed: 37127945
DOI: 10.1002/brb3.3037 -
Bipolar Disorders Jun 2022Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in... (Review)
Review
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.
BACKGROUND
Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.
METHODS
The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.
RESULTS
We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking.
CONCLUSIONS
Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.
Topics: Bipolar Disorder; Cognition; Cognitive Dysfunction; Humans; Lurasidone Hydrochloride; Mood Disorders
PubMed: 35174594
DOI: 10.1111/bdi.13193 -
The International Journal of Social... Mar 2023Schizoaffective psychosis is a severe and chronic psychiatric disorder defined by the presence of mood symptoms, like mania and/or depression and schizophrenia, such as... (Review)
Review
BACKGROUND
Schizoaffective psychosis is a severe and chronic psychiatric disorder defined by the presence of mood symptoms, like mania and/or depression and schizophrenia, such as hallucinations and/or delusions.
AIMS
We aim to find out whether there is a correlation between schizoaffective psychosis and being homeless.
METHOD
To do so, a literature search was carried out in the PubMed platform in April 2022, using the keywords 'schizoaffective' and 'homeless'.
RESULTS
In this review, 28 articles from this search were included. Intrinsic characteristics, rates of psychiatric readmission, prediction of homelessness, medication noncompliance, and substance use were explored, as they were the main themes of the results.
CONCLUSIONS
The homeless population suffers from great diagnostic variability and the diagnosis schizoaffective psychosis is still evolving contributing to such diagnostic and treatment difficulties. Their frequent visits to the healthcare services, especially emergency room leads to consequent interaction with multiple healthcare professionals, resulting in a myriad of diagnoses, with clinical remission and therapeutic goals not being attained. More studies are necessary for a better evaluation of this super difficult population.
Topics: Humans; Psychotic Disorders; Schizophrenia; Hallucinations; Ill-Housed Persons
PubMed: 36317594
DOI: 10.1177/00207640221131247 -
Frontiers in Immunology 2021Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.
METHODS
A systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.
RESULTS
Twenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; < 0.001), kynurenine (SMD = - 0.3; = 0.001) and kynurenic acid (SMD = -.45; = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.
CONCLUSION
The TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
Topics: Bipolar Disorder; Depression; Humans; Inflammation; Kynurenic Acid; Kynurenine; Tryptophan
PubMed: 34093561
DOI: 10.3389/fimmu.2021.667179 -
Cureus Aug 2022Bipolar disorder (BD) is a mood disorder characterized by severe mood swings and or periods of depression. This study examined the role that practicing yoga has on the... (Review)
Review
Bipolar disorder (BD) is a mood disorder characterized by severe mood swings and or periods of depression. This study examined the role that practicing yoga has on the symptoms of BD. One of the main goals was to identify if patients with BD believe that yoga is a viable treatment option. Six research databases were searched using the keywords "yoga" AND "therapy" AND "BD" AND "bipolar depression." Articles published in 2005 and later were included in the search. After duplicates were removed, and inclusion and exclusion criteria were applied, five articles were analyzed and included in this literature review. Results of this review indicate that yoga has been shown to be associated with both benefits and risks for the treatment of BD. Studies have shown that yoga might relieve some symptoms of BD and depression. However, due to the lack of research on the impact of yoga on BD and the small number of studies included in this review, results should be approached with caution. Overall, yoga was well-tolerated in the studies reviewed in this article. Yoga may relieve the symptoms of depression. Future research should analyze the long-term impact of yoga on bipolar depression. Yoga instructional standards should also be considered.
PubMed: 36072189
DOI: 10.7759/cureus.27688