Treatment Of Bipolar Disorder Research Articles

N-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels.

Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical antipsychotic serotonin2A (5-HT2A) receptor antagonists, such as quetiapine and olanzapine, and mood-stabilizing voltage-gated sodium channel (VGSC) blockers, such as lamotrigine, carbamazepine, and valproate, show therapeutic synergy and are often prescribed in combination for the treatment of bipolar disorder. Combination therapy is a complex task for clinicians and patients, often resulting in unexpected difficulties with dosing, drug tolerances, and decreased patient compliance. Thus, an unmet need for bipolar disorder treatment is to develop a therapeutic agent that targets both 5-HT2A receptors and VGSCs. Toward this goal, we developed a novel small molecule that simultaneously antagonizes 5-HT2A receptors and blocks sodium current. The new compound, N-(4-bromo-2,5-dimethoxyphenethyl)-6-(4-phenylbutoxy)hexan-1-amine (XOB) antagonizes 5-HT-stimulated, Gq-mediated, calcium flux at 5-HT2A receptors at low micromolar concentrations while displaying negligible affinity and activity at 5-HT1A, 5-HT2B, and 5-HT2C receptors. At similar concentrations, XOB administration inhibits sodium current in heterologous cells and results in reduced action potential (AP) firing and VGSC-related AP properties in mouse prefrontal cortex layer V pyramidal neurons. Thus, XOB represents a new, proof-of-principle tool that can be used for future preclinical investigations and therapeutic development. This polypharmacology approach of developing a single molecule to act upon two targets, which are currently independently targeted by combination therapies, may lead to safer alternatives for the treatment of psychiatric disorders that are increasingly being found to benefit from the simultaneous targeting of multiple receptors. SIGNIFICANCE STATEMENT: The authors synthesized a novel small molecule (XOB) that simultaneously antagonizes two key therapeutic targets of bipolar disorder, 5-HT2A receptors and voltage-gated sodium channels, in heterologous cells, and inhibits the intrinsic excitability of mouse prefrontal cortex layer V pyramidal neurons in brain slices. XOB represents a valuable new proof-of-principle tool for future preclinical investigations and provides a novel molecular approach to the pharmacological treatment of complex neuropsychiatric disease, which often requires a combination of therapeutics for sufficient patient benefit.

Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project.

Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials shouldbeconducted in the future to prospectively investigate different implementation strategies.

Improving Quality of Life in Bipolar Disorders with an Immersive Virtual Reality Remediation Training Randomized Controlled Trial (RCT).

Background: Health-related quality of life (H-QoL) is a critical measure in bipolar disorder (BD). Recent trials using virtual reality (VR) have shown potential in improving H-QoL. However, VR's effect on the H-QoL of people with BD needs to be further explored. Methods: This study involved a secondary analysis of a feasibility randomized controlled trial, focusing on "quality of life". Participants (aged 18-75) diagnosed with bipolar disorder were randomized into two groups. The experimental group used the CEREBRUM VR app, while the control group received the usual care. Quality of life was assessed using the Short-Form Health Survey (SF-12). Results: A total of 39 individuals in the experimental group and 25 in the control group represent the final samples. The results showed a greater improvement in the SF-12 total score in the experimental group (8.7%) compared to the control group (F = 66.851 p < 0.0001), specifically in the dimension of physical activity limitation, emotional impact, concentration, pain, calmness, energy levels, discouragement, and social activities. Conclusions: This study demonstrated an improvement in QoL for individuals with BD following a VR intervention. As a feasibility study, this secondary outcome needs to be confirmed by further phase III studies. If confirmed, VR could offer valuable rehabilitation tools and insights into the pathogenesis and treatment of BD.

Psychotherapies for the Treatment of Bipolar Disorder

Bipolar disorder is one of the major mental disorders leading to disability. This review aims to highlight the most effective psychotherapies used in the treatment of bipolar disorder. Across diverse schools of psychology, five psychotherapeutic approaches have emerged as both highly utilized and effective. These are interpersonal social rhythm therapy, psychoeducation, cognitive-behavioral therapy, family-focused therapy and mindfulness therapy. Multiple randomized controlled trials focusing on these psychotherapeutic interventions have provided strong evidence of their effectiveness when delivered alongside standard care. The results suggest that these approaches have a constructive role to play as adjunctive models of psychotherapy in the management of bipolar disorder. While the available evidence is robust, further randomized clinical trials are needed. Expanding these studies to sub-areas such as geriatrics and adolescents would provide more detailed information on the feasibility and efficacy of these psychotherapies among different demographic groups.

Measurement of lithium response in patients with bipolar disorder using the Retrospective Assessment of Response to Lithium Scale (Alda scale)

Lithium is the first-line medication for the treatment of bipolar disorder (BD), but its exact biological mechanisms have not been identified. One of the major obstacles in lithium-related research is the difficulty in precisely and reliably measuring the response to lithium. The Alda scale was developed to retrospectively measure lithium response in a standardized way. However, several aspects should be considered in understanding previous studies that used the Alda scale. In this narrative review, we aim to review previous studies and present the limitations of prior findings. Additionally, we suggest future strategies for applying the Alda scale in measuring lithium response. Initial studies using the Alda scale mainly included patients who were on lithium monotherapy for a long-term period. However, lithium monotherapy is relatively rare in clinical practice. More importantly, in clinical practice, if patients do not respond well to lithium, clinicians do not prescribe it for a long-term period. Thus, a modified approach to include diverse patients is necessary to identify true poor responders. Most previous studies also mainly included European populations, and ancestrally diverse populations should be included in the research. Furthermore, applying the same scale to explore the effects of other medications would also enhance our understanding of the neurobiological mechanisms of psychiatric medications in BD. Applying electronic health record data in evaluating lithium response would soon facilitate large-scale studies. Future studies that include diverse clinical populations reflecting the clinical practice are necessary to advance precision psychiatry.

Improving Social and Personal Rhythm Dysregulation in Young and Old Adults with Bipolar Disorder: Post-Hoc Analysis of a Feasibility Randomized Controlled Trial Using Virtual Reality-Based Intervention.

Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18-75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p < 0.0001), both in young (18-45 years) (APC = 5.5%; F = 70.46; p < 0.0001) and, to a lesser extent, older (>46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population.

Pharmacological treatment for mental health illnesses in adults receiving dialysis: A scoping review.

Pharmacologic management of mental health illnesses in patients receiving dialysis is complex and lacking data. Our objective was to synthesize published data for the treatment of depression, bipolar and related disorders, schizophrenia or psychotic disorders, and anxiety disorders in adults receiving hemodialysis or peritoneal dialysis. We undertook a scoping review, searching the following databases: Medline, Embase, CINAHL, PsycINFO, Cochrane Library, Scopus, and Web of Science. Data on patients who received only short-term dialysis, a kidney transplant, or non-pharmacologic treatments were excluded. Seventy-three articles were included: 41 focused on depression, 16 on bipolar disorder, 13 on schizophrenia and psychotic disorders, 1 on anxiety disorders, and 2 addressing multiple mental health illnesses. The majority of depression studies reported on selective serotonin reuptake inhibitors (SSRIs) as a treatment. Sertraline had the most supporting data with use of doses from 25 to 200 mg daily. Among the remaining SSRIs, escitalopram, citalopram, and fluoxetine were studied in controlled trials, whereas paroxetine and fluvoxamine were described in smaller reports and observational trials. There are limited published data on other classes of antidepressants and on pharmacological management of anxiety. Data on treatment for patients with bipolar disorder or schizophrenia and related disorders are limited to case reports. Over half of the studies included were case reports, thus limiting conclusions. More robust data are required to establish effect sizes of pharmacological treatments prior to providing specific recommendations for their use in treating mental health illnesses in patients receiving dialysis.

Evidence-based group therapy for mood disorders: Treatment for depression and bipolar disorders.

Evidence-based group therapy for mood disorders: Treatment for depression and bipolar disorders.

Early specialised treatment for bipolar disorder: Long-term follow-up from the early intervention in affective disorders (EIA) randomised controlled trial.

It is unclear whether treatment early after onset in bipolar disorder may improve the long-term illness course. The early intervention in affective disorders (EIA) randomised controlled trial found that 2-years treatment in a specialised mood disorder clinic combining evidence-based pharmacological treatment with group psychoeducation improved clinical outcomes compared with standard treatment in patients with bipolar disorder discharged after their 1st, 2nd, or 3rd hospital admission. We aimed to assess the 16 years long-term outcomes after randomisation of the participants in the EIA trial. Data were obtained by linking nation-wide Danish population-based registers. All 158 participants of the EIA trial (Trial Registration Number NCT00253071) were followed from time of randomisation (2005-2009) to end of study (31 December 2021). The primary outcome was risk of psychiatric readmission. Secondary outcomes were total admissions and costs, medication use, intentional self-harm or suicide attempt or suicide, and socio-economic measures. The absolute mean risk of psychiatric readmission was 49.3% in the intervention group and 59.8% in the control group, with no statistically significant difference between the groups (b = -0.10, 95% CI: -0.26 to 0.047, p = 0.18). Compared with the control group, patients in the intervention group had numerically fewer total admission days (mean (SD) 44 (77) versus 62 (109)), lower total cost of psychiatric hospital admissions and hospital-based outpatient visits (mean (SD) 22,001 (36793) euros versus 29,822 (52671) euros) and higher use of lithium and antipsychotics, but the differences were not statistically significant. Fewer patients in the intervention group had an event of intentional self-harm or suicide attempt or suicide during follow-up (OR 0.25, 95% CI: 0.15-0.40, p < 0.001) compared with the control group and more patients in the intervention group used antiepileptics (OR 2.21, 95% CI: 1.08-4.60, p = 0.031). Analyses of very long-term outcomes of the EIA trial may potentially indicate a beneficial effect of the intervention at the long term but were likely underpowered to detect a more subtle effect and for most outcomes the differences between groups were not statistically significant.

An Retrospective Study of Commonly Prescribed Antiepileptic Drugs and it’s Interaction with Other Drugs which are Already in use Respect to Other Disease

Antiepileptic drugs (AED) are increasingly used in the treatment of some non-epileptic neurological diseases and psychiatric diseases. Most of the available data on the use of these agents in clinical conditions other than epilepsy are from case series, uncontrolled studies, or small randomized clinical trials, and their apparent efficacy requires confirmation in well-designed large phase III trials. Interactions between antiepileptic drugs or between antiepileptic drugs and other drugs can be pharmacokinetic or pharmacodynamic. Pharmacokinetic interactions include changes in absorption, distribution ,or eliminate , while pharmacodynamic interactions include synergism and antagonism at the site ,of action. Most clinically significant antiepileptic drug interactions are due to induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronide enzymes (as well as P-glycoprotein) and may reduce the effectiveness of concomitantly administered drugs such as oral anticoagulants, calcium antagonists, antimicrobial steroids. Mechanism Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties and less tendency to produce interactions mediated by enzyme induction. In contrast to enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, which can increase serum concentrations leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include valproic-induced increases in serum concentrations of phenobarbital and lamotrigine. There are also interactions where other drugs induce or inhibit the metabolism of antiepileptic drugs. Examples include an increase in serum carbamazepine concentration due to erythromycin and a decrease in serum lamotrigine concentration due to estrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the combined therapeutic synergy of valproic acid and lamotrigine, or adverse effects, such as the mutual potentiation of neurotoxicity in patients treated with a combination of sodium channel blocking antiepileptic drugs. AEDs are also used to treat psychiatric conditions, particularly bipolar disorder. To date, the AEDs most commonly used to treat this disorder have been carbamazepine and valproic acid, which have shown manic efficacy and likely long-term mood-stabilizing effects in many bipolar patients, including those who are lithium-intolerant. . The availability of new generation AEDs has expanded treatment options for bipolar disorder. Lamotrigine, oxcarbazepine, gabapentin, and topiramate appear to show promise in the treatment of bipolar disorder, both as monotherapy and in combination with traditional mood stabilizers. In addition, newer AEDs appear to have a more favorable tolerability and drug interaction profile than older compounds, thus improving compliance

Integrated proteomic and genomic analysis to identify predictive biomarkers for valproate response in bipolar disorder: a 6-month follow-up study

BackgroundSeveral genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip.ResultsThe markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression.ConclusionsThe markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment.

LiFT (a Lithium Fiber-Based Test): An At-Home Companion Diagnostics for a Safer Lithium Therapy in Bipolar Disorder.

This work presents LiFT (a lithium fiber-based test), a low-cost electrochemical sensor that can measure lithium in human saliva and urine with FDA-required accuracy. Lithium is used for the treatment of bipolar disorder, and has a narrow therapeutic window. Close monitoring of lithium concentration in biofluids and adjustment of drug dosage can minimize the devastating side effects. LiFT is an inexpensive, yet accurate and simple-to-operate lithium sensor for frequent at-home testing for early identification of lithium toxicity. The low cost and high accuracy of LiFT are enabled through an innovative design and the use of ubiquitous materials such as yarn and carbon black for fabrication. LiFT measures Li+ through potentiometric recognition using a lithium selective sensing membrane that is deposited on the ink-coated yarn. A detection limit of 0.97 µM is obtained with a sensitivity of 59.07±1.25 mV/decade for the Li+ sensor in deionized water. Moreover, the sodium correction extended LiFT's linear range in urine and saliva to 0.5 mM. The LiFT platform sends the test results to the patient's smartphone, which subsequently can be shared with the patient's healthcare provider to expedite diagnosis and prevention of acute lithiumtoxicity.

New perspectives in the treatment of bipolar affective disorder using transcranial magnetic stimulation

New perspectives in the treatment of bipolar affective disorder using transcranial magnetic stimulation

The role of Omega-3 Polyunsaturated Fatty Acids in the treatment of Bipolar Disorder – a narrative review

The role of Omega-3 Polyunsaturated Fatty Acids in the treatment of Bipolar Disorder – a narrative review

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

Introduction and purposeCariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use.Methods and materialsA review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist.ConclusionsCariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

Combining predominant polarity and affective spectrum concepts in bipolar disorder: towards a novel theoretical and clinical perspective

This is an overview of recent advances on predominant polarity conceptualization in bipolar disorder (BD). Current evidence on its operationalized definitions, possible contextualization within the affective spectrum, along with its epidemiological impact, and treatment implications, are summarized. Predominant polarity identifies three subgroups of patients with BD according to their mood recurrencies: (i) those with depressive or (ii) manic predominance as well as (iii) patients without any preponderance (‘nuclear’ type). A predominant polarity can be identified in approximately half of patients, with similar rates for depressive and manic predominance. Different factors may influence the predominant polarity, including affective temperaments. More generally, affective disorders should be considered as existing on a spectrum ranging from depressive to manic features, also accounting for disorders with ‘ultrapredominant’ polarity, i.e., unipolar depression and mania. While mixed findings emerge on its utility in clinical practice, it is likely that the construct of predominant polarity, in place of conventional differentiation between BD-I and BD-II, may be useful to clarify the natural history of the disorder and select the most appropriate interventions. The conceptualization of predominant polarity seems to reconcile previous theoretical views of both BD and affective spectrum into a novel perspective. It may provide useful information to clinicians for the early identification of possible trajectories of BD and thus guide them when selecting interventions for maintenance treatment. However, further research is needed to clarify the specific role of predominant polarity as a key determinant of BD course, outcome, and treatment response.

8. The Relationship Between Treatment, Symptom Severity, and Brain Connectivity in Bipolar Disorder: An International Study Across 16 Enigma-Bipolar Sites

8. The Relationship Between Treatment, Symptom Severity, and Brain Connectivity in Bipolar Disorder: An International Study Across 16 Enigma-Bipolar Sites

Post-marketing surveillance of quetiapine fumarate extended-release tablets in patients with bipolar depression.

This study aimed to verify the real-world efficacy and safety of quetiapine fumarate extended-release tablets (Bipresso® 50 mg and 150 mg; marketing authorization holder is KYOWA Pharmaceutical Industry Co., Ltd., Osaka, Japan) in patients with bipolar depression. We performed a post-marketing surveillance with an observation period of 12 weeks. In the safety analysis group (n = 345), adverse drug reactions (ADRs) occurred in 111 patients (32.17%). The most common ADRs (>1%) were somnolence in 55 patients (15.94%), akathisia in 11 (3.19%), dizziness in 10 (2.90%), weight increase in 6 (1.74%), thirst in 5 (1.45%), and hypersomnia, constipation, and nausea in 4 patients each (1.16%). The only severe ADR was one patient of suicidal ideation, and "longer time since the onset of the first episode" (p = 0.011) and "presence of complications" (p < 0.001) were identified as significant risk factors for the occurrence of ADRs. In the efficacy analysis group (n = 265), the average changes from baseline in the total Montgomery-Åsberg Depression Rating Scale (MADRS) score were -7.3 ± 8.8, -12.2 ± 10.7, -16.8 ± 12.7, and -13.2 ± 12.7 points after 4, 8, and 12 weeks, and at the last evaluation, respectively. The mean MADRS total score decrease had no significant association with maximum daily dose, diagnosis, and presence or absence of prior or concomitant treatment for bipolar disorder with mood stabilizers/antipsychotics/antidepressants. The efficacy of quetiapine fumarate extended-release tablets was confirmed in clinical practice, and no new safety concerns or risks were identified.

Efficacy and safety of endoxifen in bipolar disorder: A systematic review.

Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings. A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials. The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment. There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.

Dried Blood Spots and Miniaturized Ultrasonic Nebulization Microplasma Optical Emission Spectrometry for Point-of-Care Testing of Blood Lithium.

Despite the significant importance of blood lithium (Li) detection in the treatment of bipolar disorder (BD), its point-of-care testing (POCT) remains a great challenge due to tedious sample preparation and the use of large-footprint atomic spectrometers. Herein, a system coupling dried blood spots (DBS) with a point discharge optical emission spectrometer equipped with a miniaturized ultrasonic nebulizer (MUN-μPD-OES) was developed for POCT of blood Li. Three microliters of whole blood were used to prepare a dried blood spot on a piece of filter paper to which 10 μL of eluent (1% (v/v) formic acid and 0.05% (v/v) Triton-X) was added. Subsequently, the paper was placed onto the vibrating steel membrane of the ultrasonic nebulizer and powered on to generate aerosol. The aerosol was directly introduced to the μPD-OES for quantification of Li by monitoring its atomic emission line at 670.8 nm. The proposed method minimized matrix interference caused by high levels of salts and protein. It is worth noting that the MUN suitably matches the needs of DBS sampling and can provide aerosolized introduction of Li into the assembled μPD-OES, thus eliminating all tedious sample preparation and the need for a commercial atomic spectrometer. Calibration response is linear in the therapeutic range and a limit of detection (LOD) of 1.3 μg L-1 is well below the Li minimum therapeutic concentration (2800 μg L-1). Li in mouse blood was successfully detected in real-time using MUN-μPD-OES after intraperitoneal injection of lithium carbonate, confirming that the system holds great potential for POCT of blood Li for patients with BD.