• Bipolar disorder
• Endophenotype
• Neurobiology
• Polarity index
• Predominant polarity
• Subphenotype

• Humans
• Bipolar Disorder/therapy
• Bipolar Disorder/physiopathology
• Bipolar Disorder/diagnosis
• Bipolar Disorder/drug therapy
• Precision Medicine/methods
• Phenotype

• Universitat de Barcelona

• Bipolar disorder
• Cognitive impairment
• Depression
• Lithium
• Suicide

• Depression
• Depression & mood disorders
• PSYCHIATRY

• Lurasidone Hydrochloride/therapeutic use
• Lurasidone Hydrochloride/administration & dosage
• Humans
• Bipolar Disorder/drug therapy
• Antipsychotic Agents/administration & dosage
• Antipsychotic Agents/therapeutic use
• Antipsychotic Agents/adverse effects
• Dose-Response Relationship, Drug
• Randomized Controlled Trials as Topic
• Treatment Outcome

• Bipolar disorder
• Lithium
• Lithium genetics
• Lithium response
• Mechanisms of action

• Humans
• Bipolar Disorder/drug therapy
• Lithium Compounds/pharmacology
• Antimanic Agents/adverse effects
• Antidepressive Agents/pharmacology
• Depressive Disorder, Treatment-Resistant/drug therapy
• Lithium/therapeutic use

• Bipolar disorder
• Childbearing age
• Major depressive disorder
• Mood disorders
• Post-partum pharmacotherapy
• Pregnancy

• Humans
• Female
• Pregnancy
• Pregnancy Complications/drug therapy
• Mood Disorders/drug therapy
• France
• Psychotropic Drugs/therapeutic use
• Bipolar Disorder/drug therapy
• Depressive Disorder, Major/drug therapy
• Adult
• Societies, Medical
• Biological Psychiatry
• Psychopharmacology
• Practice Guidelines as Topic

• bipolar depression
• bipolar disorder
• drug-drug interactions
• guidelines
• pharmacotherapy
• polypharmacy
• prescription rate

• Humans
• Animals
• Lithium Compounds/pharmacology
• Lithium Compounds/therapeutic use
• Antimanic Agents/pharmacology
• Antimanic Agents/therapeutic use
• Bipolar Disorder/drug therapy
• Neuronal Plasticity/drug effects
• Glycogen Synthase Kinase 3/metabolism
• Glycogen Synthase Kinase 3/antagonists & inhibitors

• Antipsychotic depots
• antipsychotic long‐acting injection
• bipolar disorder
• maintenance treatment
• rehospitalization
• relapse

• Humans
• Bipolar Disorder/drug therapy
• Antipsychotic Agents/administration & dosage
• Antipsychotic Agents/therapeutic use
• Female
• Male
• Adult
• Retrospective Studies
• Administration, Oral
• Middle Aged
• Injections
• Delayed-Action Preparations/administration & dosage
• Treatment Outcome
• Medication Adherence/statistics & numerical data
• Follow-Up Studies

• Humans
• Algorithms
• Hospitalization
• Mania/drug therapy
• Antipsychotic Agents/therapeutic use
• Antimanic Agents/therapeutic use
• Bipolar Disorder/drug therapy
• Bipolar Disorder/therapy

• emergency medicine
• hypothyroidism
• intoxication
• lithium
• sinus node dysfunction

• Cariprazine
• I
• I1
• I11
• I12
• I15
• atypical antipsychotic
• bipolar I disorder
• claims-based analysis
• healthcare costs
• healthcare resource utilization
• treatment patterns

• Humans
• Bipolar Disorder/drug therapy
• Bipolar Disorder/economics
• Female
• Male
• Adult
• Middle Aged
• Antipsychotic Agents/therapeutic use
• Antipsychotic Agents/economics
• Piperazines/therapeutic use
• Piperazines/economics
• United States
• Insurance Claim Review
• Hospitalization/economics
• Hospitalization/statistics & numerical data
• Patient Acceptance of Health Care/statistics & numerical data
• Health Resources/statistics & numerical data
• Health Resources/economics
• Emergency Service, Hospital/statistics & numerical data
• Young Adult
• Adolescent
• Retrospective Studies
• Health Expenditures/statistics & numerical data
• Health Services/statistics & numerical data
• Health Services/economics

• AutoML
• Biosignature
• Bipolar disorder
• KREMEN2
• Learning
• Machine
• Psychiatry
• RNU6–576 P
• VEPH1

• Adverse drug reaction (ADR)
• Case–control study
• Drug safety
• Lithium
• Mood stabilizer
• Pharmacovigilance
• Weight gain

• Universitätsklinik München (6933)

• anticonvulsants
• antipsychotic agents
• bipolar disorder
• diabetes mellitus
• lamotrigine
• lithium
• valproic acid

• Humans
• Bipolar Disorder/drug therapy
• Bipolar Disorder/epidemiology
• Bipolar Disorder/diagnosis
• Antipsychotic Agents/adverse effects
• Lamotrigine/adverse effects
• Valproic Acid/adverse effects
• Lithium/therapeutic use
• Anticonvulsants/adverse effects
• Diabetes Mellitus/chemically induced
• Diabetes Mellitus/epidemiology
• Diabetes Mellitus/drug therapy
• Antimanic Agents/adverse effects

• electronic health record
• lithium
• mood disorders
• quality of health care
• randomized controlled trial

• Adult
• Humans
• Electronic Health Records
• Lithium/therapeutic use
• Mood Disorders/drug therapy
• Antipsychotic Agents

• Psychoanalysis
• bipolar disorder
• manic depression
• psychoanalytic psychotherapy

• Humans
• Bipolar Disorder/drug therapy
• Psychoanalytic Therapy
• Psychoanalysis
• Health Promotion
• Object Attachment

• bipolar disorder
• cohort study
• lithium
• mood stabilizer
• standardized mortality ratio

• Algorithm
• Bipolar disorder
• Guideline
• KMAP-BP 2022
• Pharmacotherapy

• Humans
• Female
• Adult
• Smartphone
• Self-Management
• Quality of Life
• Bipolar Disorder/therapy
• Chronic Disease

• UL1 TR001422 NCATS NIH HHS
• R01 MH110626 NIMH NIH HHS

• Bipolar disorder
• Expert consensus
• KMAP-BP 2022
• Pharmacotherapy

• Antipsychotic drug
• Bipolar depression
• Lamotrigine
• Lithium
• Treatment-resistant depression

Background: An important aspect of managing chronic disorders like bipolar disorder is to have access to relevant health information. This study investigates and compares the quality of information on the treatments of bipolar disorder that is available on English websites, as an international language, and on Italian websites, as a popular local language. Methods: A systematic review search was obtained from four search engines. We excluded unrelated materials, scientific papers, and duplicates. We analyzed popularity with PageRank; technological quality with Nibbler; readability with the Flesh Reading Ease test and Gulpease index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and on the extent of adherence to the HONCode. Results: 35 English and 31 Italian websites were included. The English websites were found to have a higher level of quality information and technological quality than the Italian ones. Overall, the websites were found to be difficult to read, requiring a high level of education. Conclusions: These results can be important to inform guidelines for the improvement of health information and help users to reach a higher level of evidence on the websites. Users should find the benefits of treatment, support for shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing treatment.

• bipolar disorder
• mental health
• repetitive transcranial magnetic stimulation
• treatment

• N/A Alberta Mental Health Foundation.

Evidence suggests that inhibition of protein kinase C (PKC) signalling may have a contributing role in the treatment of bipolar affective disorder (BPAD). Endoxifen, an active metabolite of tamoxifen, is a potent direct PKC inhibitor. This report presents a severe case of a BPAD patient with a baseline Young Mania Rating Scale (YMRS) score of 49, associated family history and addiction to psychostimulants, with no improvement by the first and second-generation antipsychotics. Treatment with endoxifen 8 mg once a day showed improvement in manic symptoms with a YMRS score of 4 and a reduction in the use of psychostimulants as well as other antipsychotic concomitant medications. No adverse effects were noted up to 8-month follow-up. Long-term treatment with endoxifen is safe and effective in severe BPAD.

• antidepressants
• bipolar II disorder
• bipolar depression
• meta-analysis

• Antidepressive Agents, Second-Generation
• Bipolar Disorder/drug therapy
• Depression/drug therapy
• Humans
• Lithium/therapeutic use
• Randomized Controlled Trials as Topic
• Sertraline/therapeutic use
• Venlafaxine Hydrochloride/therapeutic use

• T32 GM008685 NIGMS NIH HHS

To investigate the association between polypharmacy, anxiety, and depression among Chinese older adults.

The data used in this study were from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the 2018 wave. Polypharmacy status was measured by the accumulation of self-reported medications. Anxiety and depression were assessed by the Generalized Anxiety Disorder (GAD-7) scale and the Center for Epidemiologic Studies Depression Scale (CES-D-10), respectively. Logistic regression models were performed.

A total of 2484 Chinese older adults (female: 1321, 53.2%) aged from 60 to 117 years old were included in the analysis. Regression analysis showed that polypharmacy was associated with depression after controlling for the covariates. No association was observed between polypharmacy and anxiety.

There was a suggestive link between polypharmacy and depression among Chinese older adults. Having polypharmacy might be an indicator for the possible depression among this population, but a comprehensive assessment of polypharmacy is necessary.

• Aged
• Aged, 80 and over
• Anxiety/drug therapy
• Anxiety/epidemiology
• Anxiety Disorders/drug therapy
• Anxiety Disorders/epidemiology
• China/epidemiology
• Depression/drug therapy
• Depression/epidemiology
• Female
• Humans
• Polypharmacy

• is no funding

• Antipsychotics
• Bipolar disorder
• Mood stabilizers
• Polypharmacy
• Psychotropic drug load

Bipolar disorder is a severe mental illness with high morbidity and mortality rates. Even with pharmacological treatment, frequent recurrence of episodes, long episode durations, and persistent interepisode symptoms are common and disruptive. Combining psychotherapy with pharmacotherapy improves outcomes; however, many individuals with bipolar disorder do not receive psychotherapy. Mental health technologies can increase access to self-management strategies derived from empirically supported bipolar disorder psychotherapies while also enhancing treatment by delivering real-time assessments, personalized feedback, and provider alerts. In addition, mental health technologies provide a platform for self-report, app use, and behavioral data collection to advance understanding of the longitudinal course of bipolar disorder, which can then be used to support ongoing improvement of treatment.

A description of the theoretical and empirically supported framework, design, and protocol for a randomized controlled trial (RCT) of LiveWell, a smartphone-based self-management intervention for individuals with bipolar disorder, is provided to facilitate the ability to replicate, improve, implement, and disseminate effective interventions for bipolar disorder. The goal of the trial is to determine the effectiveness of LiveWell for reducing relapse risk and symptom burden as well as improving quality of life (QOL) while simultaneously clarifying behavioral targets involved in staying well and better characterizing the course of bipolar disorder and treatment response.

The study is a single-blind RCT (n=205; 2:3 ratio of usual care vs usual care plus LiveWell). The primary outcome is the time to relapse. Secondary outcomes are percentage time symptomatic, symptom severity, and QOL. Longitudinal changes in target behaviors proposed to mediate the primary and secondary outcomes will also be determined, and their relationships with the outcomes will be assessed. A database of clinical status, symptom severity, real-time self-report, behavioral sensor, app use, and personalized content will be created to better predict treatment response and relapse risk.

Recruitment and screening began in March 2017 and ended in April 2019. Follow-up ended in April 2020. The results of this study are expected to be published in 2022.

This study will examine whether LiveWell reduces relapse risk and symptom burden and improves QOL for individuals with bipolar disorder by increasing access to empirically supported self-management strategies. The role of selected target behaviors (medication adherence, sleep duration, routine, and management of signs and symptoms) in these outcomes will also be examined. Simultaneously, a database will be created to initiate the development of algorithms to personalize and improve treatment for bipolar disorder. In addition, we hope that this description of the theoretical and empirically supported framework, intervention design, and study protocol for the RCT of LiveWell will facilitate the ability to replicate, improve, implement, and disseminate effective interventions for bipolar and other mental health disorders.

ClinicalTrials.gov NCT03088462; https://www.clinicaltrials.gov/ct2/show/NCT03088462

DERR1-10.2196/30710

• bipolar disorder
• eHealth
• mHealth
• mental health
• mobile health
• mobile phone
• self-management
• smartphone

Background and Objectives: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. Materials and Methods: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. Results: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. Conclusions: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine’s side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine–lamotrigine combination in bipolar patients.

Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

• Antipsychotic Agents/pharmacology
• Antipsychotic Agents/therapeutic use
• Bipolar Disorder/metabolism
• Bipolar Disorder/therapy
• Cognitive Behavioral Therapy
• Combined Modality Therapy/methods
• Dietary Supplements
• Dopamine/metabolism
• Humans
• Mitochondria/drug effects
• Mitochondria/metabolism
• Oxidative Stress/drug effects
• Treatment Outcome

• Koukopoulos
• bipolar disorder
• mixed depression
• mixed states
• mood
• psychomotor agitation
• review

• adaptive
• behavioral intervention technology
• bipolar disorder
• depression
• mHealth
• mania
• personalized
• self-management
• smartphone

• R01 MH110626 NIMH NIH HHS

Routine monitoring of lithium levels is common clinical practice. This is because the lithium prediction strategies available developed by previous studies are still limited due to insufficient prediction performance. Thus, we used machine learning approaches to predict lithium concentration in a large real-world dataset. Real-world data from multicenter electronic medical records were used in different machine learning algorithms to predict: (1) whether the serum level was 0.6–1.2 mmol/L or 0.0–0.6 mmol/L (binary prediction), and (2) its concentration value (continuous prediction). We developed models from 1505 samples through 5-fold cross-validation and used 204 independent samples to test their performance by evaluating their accuracy. Moreover, we ranked the most important clinical features in different models and reconstructed three reduced models with fewer clinical features. For binary and continuous predictions, the average accuracy of these models was 0.70–0.73 and 0.68–0.75, respectively. Seven features were listed as important features related to serum lithium levels of 0.6–1.2 mmol/L or higher lithium concentration, namely older age, lower systolic blood pressure, higher daily and last doses of lithium prescription, concomitant psychotropic drugs with valproic acid and -pine drugs, and comorbid substance-related disorders. After reducing the features in the three new predictive models, the binary or continuous models still had an average accuracy of 0.67–0.74. Machine learning processes complex clinical data and provides a potential tool for predicting lithium concentration. This may help in clinical decision-making and reduce the frequency of serum level monitoring.

• XGBoost
• bipolar disorder
• lithium
• machine learning
• random forest
• support vector machine
• therapeutic drug monitoring

• Mania
• bipolar disorder
• treatment resistance

Most treatment guidelines emphasize the use of psychotropic drugs for both the acute and maintenance treatment of bipolar disorder (BD). However, relying only on psychotropics without adjunctive psychosocial interventions may be insufficient in treating patients with BD. Given its unique view in the explanation of psychopathological states, metacognitive therapy (MCT) might be helpful for BD. Metacognitive theory posits that psychopathology is a result of the cognitive attentional syndrome (CAS) and that it is influenced and maintained by dysfunctional metacognitive beliefs, perseverative thinking, attentional biases, and dysfunctional coping strategies. In this review, literature data regarding these areas in BD are examined. Studies suggest that perseverative thinking might be among the emotion regulation strategies endorsed in individuals with BD. Regarding attentional biases, literature data show that state-dependent, mood-changing attentional biases and a ruminative self-focused attention are present. Studies also suggest that cognitive self-consciousness is higher in BD compared to controls. It is seen that maladaptive coping strategies are frequently reported in BD, and that these strategies are associated with depression severity, negative affect and relapse risk. Studies focusing on dysfunctional metacognitive beliefs in BD reported that individuals with BD had higher scores for negative metacognitive beliefs, self-consciousness, need to control thoughts, and a lack of cognitive confidence. Also, dysfunctional metacognitive beliefs were associated with depressive symptomatology. These findings suggest that the components of CAS and dysfunctional metacognitive beliefs are evident in BD. For a subgroup of patients with BD who fail to respond to evidence-based psychopharmacological and adjunctive psychotherapeutic interventions, MCT might be an alternative way to consider as a treatment option. In conclusion, taken the available data together, we propose a sequential treatment protocol for BD, mainly based on the MCT treatment plan of depressive disorders.

• Attentional biases
• Bipolar disorder
• Dysfunctional coping
• Metacognition
• Metacognitive therapy
• Perseverative thinking
• Threat monitoring

Lithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.

To estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.

Data from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately.

Lithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately.

The advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.

The online version contains supplementary material available at 10.1186/s40345-021-00223-7.

• Bipolar disorder
• Drug therapy
• Health care quality assessment
• Lithium
• Outcome assessment

• anxiety
• bipolar disorder
• depression
• gut microbiota
• mania
• mood

• Adolescence onset
• Adverse effects
• Bipolar disorder
• Dosing schedule
• First episode
• Lithium
• Psychiatrists’ attitude
• Survey