Maintenance Treatment Of Bipolar Disorder Research Articles

Management of bipolar disorder in South Africa: National Department of Health essential medicine selection and treatment algorithms

Background. Bipolar disorder (BD) is a severe mental illness associated with multimorbidity, psychosocial disability and significant public health issues. However, guideline heterogeneity clouds therapeutic decisions, particularly in relapse prevention. Polypharmacy and poor health outcomes are common. For low- and middle-income countries, deciding which medicines to procure and how to treat BD in an integrated manner remains elusive. Although South Africa (SA) is committed to universal health coverage, the estimated treatment gap for mental disorders in the public health sector is 91%. An Essential Medicines List (EML) enables equitable access to medicines, while Standard Treatment Guidelines (STGs) facilitate rational prescribing and quality care. Objectives. To describe the medicine selection process for the treatment of BD in the SA public health sector, and the treatment algorithms developed to guide integrated care. Methods. Evidence-based medicine principles, stakeholder consultation and consensus decision-making were used. The existing (2015) BD guideline and stakeholder comments were reviewed by a ministerially appointed expert review committee, following which a research question with eligibility criteria was formed, and rapid systematic evidence synthesis conducted. PubMed and Cochrane databases were searched for systematic reviews of randomised controlled trials and observational studies of acute and maintenance treatment in BD, with an additional PubMed search for primary research. Quality of the systematic reviews was appraised using the 11-item assessment of multiple systematic reviews. After costing to ensure affordability, final recommendations were made to the National EML Committee (NEMLC) using the strength of recommendation taxonomy classification. Following approval by the NEMLC, proposed medicines were incorporated into the 2019 National Department of Health Adult Hospital STGs. As the STGs are updated every 3 years, stakeholder input was sought in 2021 and 2023, with no changes to the medicine selection. Results. Seven systematic reviews and one observational study were included in the evidence synthesis. Six medicines were selected as essential for maintenance treatment: lithium, valproate, lamotrigine, olanzapine, quetiapine and clozapine. While risperidone and benzodiazepines were retained for acute mania, carbamazepine and fluoxetine were removed from acute depression. Treatment algorithms for predominantly manic and depressive courses of illness were constructed to encourage person-centred care, aiming for euthymia, individual functioning and relapse prevention. Conclusion. Evidence-based medicine principles enabled the NEMLC to select a range of essential medicines for the management of BD in a middle-income country. Local monitoring and evaluation are needed to inform future editions of the STGs and EML.

A comparison of recurrence rates after discontinuation of second-generation antipsychotic long-acting injectable versus corresponding oral antipsychotic in the maintenance treatment of bipolar disorder: A systematic review

It has been previously reported that among patients with schizophrenia that long-acting injectable (LAI) antipsychotic formulations can delay time to relapse longer when compared to their oral equivalents when patients discontinue therapy. Unanswered is whether this same pattern would be observed for patients with bipolar disorder receiving maintenance treatment. A systematic review was undertaken to identify relevant studies of LAI antipsychotics in maintenance treatment of bipolar disorder, employing a placebo-controlled randomized withdrawal design, and where equivalent studies using the corresponding oral formulation were also available. We found five studies [one aripiprazole monohydrate once monthly (AOM) study, one oral aripiprazole (OARI) study, two 2 weeks risperidone-LAI (RIS-LAI) studies, and one oral paliperidone (OPAL) study]. Numerically lower recurrence rates at 2, 4, 6, 8, 12, 16, 20, and 26 weeks were observed when AOM was discontinued when compared with discontinuation from OARI. Numerically lower recurrence rates at 2, 4, 6, 8, and 16 weeks were observed when RIS-LAI was discontinued when compared with discontinuation from OPAL. These results can be interpreted as a substantial delay in time to recurrence with a LAI antipsychotics formulation compared to the oral equivalent when medication is discontinued in patients with mania who had been stabilized on LAI antipsychotics or corresponding oral antipsychotics.

Clinicians’ preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders around the world: a survey from the ISBD Lithium task force

BackgroundLithium has long been considered the gold-standard pharmacological treatment for the maintenance treatment of bipolar disorders (BD) which is supported by a wide body of evidence. Prior research has shown a steady decline in lithium prescriptions during the last two decades. We aim to identify potential factors explaining this decline across the world with an anonymous worldwide survey developed by the International Society for Bipolar Disorders (ISBD) Task Force “Role of Lithium in Bipolar Disorders” and distributed by diverse academic and professional international channels.ResultsA total of 886 responses were received of which 606 completed the entire questionnaire while 206 completed it partially. Respondents were from 43 different countries comprising all continents. Lithium was the most preferred treatment option for the maintenance of BD patients (59%). The most relevant clinical circumstances in which lithium was the preferred option were in patients with BD I (53%), a family history of response (18%), and a prior response during acute treatment (17%). In contrast, Lithium was not the preferred option in case of patients´ negative beliefs and/or attitudes towards lithium (13%), acute side-effects or tolerability problems (10%) and intoxication risk (8%). Clinicians were less likely to prefer lithium as a first option in BD maintenance phase when practising in developing economy countries [X2 (1, N = 430) = 9465, p = 0.002) ] and private sectors [X2 (1, N = 434) = 8191, p = 0.004)].ConclusionsClinicians’ preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders appear to be affected by both the patients’ beliefs and the professional contexts where clinicians provide their services. More research involving patients is needed for identifying their attitudes toward lithium and factors affecting its use, particularly in developing economies.

Prevention of mania in a primigravida at ultra-high risk of postpartum recurrence.

Prevention of mania in a primigravida at ultra-high risk of postpartum recurrence.

Differences In Antipsychotic Prescriptions In Relationship To Physician Demographics And In-patient Setting At An Inner-city hospital – A Prospective Cohort Study

IntroductionAntipsychotics are medications with an array of FDA approved indications in the field of psychiatry including Schizophrenia, Bipolar Mania, Bipolar Depression, Maintenance treatment for Bipolar Disorder, Schizoaffective Disorder, as well as an Adjunct treatment in Unipolar Depression and Tic disorders, among other indications for non-adult patients. Antipsychotics are widely used in psychiatric inpatient units throughout the United States, and globally. We observed trends of antipsychotic use in 3 different adult inpatient units with the same patient demographics located within one inner city hospital in the Bronx over a period of 4 months. We correlated the choice of antipsychotic to the prescribing physician’s period of training/date of graduation from psychiatry residency and reported the results.ObjectivesIdentify the choice of antipsychotics used by different psychiatrists.Correlate the dates of each psychiatrists residency training to the antipsychotics they chose.Identify whether the psychiatry residency training accuried in different decades has influenced psychiatrics to pick certain antipsychotics.MethodsWe obtained the dates of psychiatric residency training for each of 3 psychiatrists (Physicians 1, 2 and 3) assigned to one of 3 different inpatient psychiatric units which share the same patient demographics in an inner-city hospital in the Bronx. We obtained a record of total psychiatric inpatient hospitalizations from February 10th 2022 to June 10th 2022 in all 3 psychiatric inpatient units. The principal diagnoses for the total hospitalizations (300 patients) were reviewed and patients with diagnoses that do not have FDA approval for antipsychotic use were excluded. Among the remaining patients (267) we compared antipsychotic prescription trends and grouped patients according to antipsychotic of choice. We then correlated the antipsychotic of choice groups to one of three units/prescribing physician and the years of psychiatry residency training. The trends for antipsychotic of choice were compared to training dates and presented in a table.ResultsPhysician 1 who trained from 1980 to 1984 prescribed: 87% HALDOL and 13 % Chlorpromazine. Physician 2 who trained from 1992 to 1996 prescribed: 91 % PALIPERIDONE and 9% Risperidone. Physician 3 who trained from 2003 to 2007 prescribed: 60 % ABILIFY and 40% Olanzapine.ConclusionsThe physician with the earliest graduation date used mainly HALDOL, a first-generation antipsychotic, to treat disorders with FDA approval for antipsychotic use. The physician with the most recent graduation date, used mainly ARIPIPRAZOLE, a third-generation antipsychotic, to treat disorder with FDA approval for their use. The physician with a graduation date between them, used mainly (PALIPERIDONE), a second-generation antipsychotic to treat the disorders.Disclosure of InterestNone Declared

Long-acting new generation antipsychotics in the maintenance treatment of bipolar disorders

IntroductionMaintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.ObjectivesWe aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.MethodsClinical records of 56 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated. Descriptive statistical analysis was performed with Statistical Package for the Social Sciences (SPSS).ResultsNearly half of the patients were male (n:29, 52%). 49,1% of the patients were married. The mean age was 37.1±12.2 years and the mean duration of education was 11.1±4.2 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (64,7%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. We found a significant reduction in the number of manic episodes after long-acting treatment (p<0.001), but we could not find any difference for depression. Ten of the patients discontinued the treatment due to the side effects, extrapyramidal side effects were the most common side effects. Eight of the patients were switched from paliperidone treatment to aripiprazole treatment due to side effects, especially hyperprolactinemia. Relapse was observed in 46,4% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.ConclusionsLAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.Disclosure of InterestNone Declared

Application of Antipsychotic Drugs in Mood Disorders.

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders.

Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study

BackgroundLithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD).MethodsWe conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient’s medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization.ResultsA total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at − 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function.ConclusionThis study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.

A paper-based colorimetric method for monitoring of lithium therapeutic levels.

Lithium remains the "gold standard" for both acute and maintenance treatment of bipolar disorder (BD), a serious life-long condition characterised by recurrent episodes of depressed and manic mood states. However, lithium has a very narrow therapeutic range (0.4-1.2 mmol L-1) and despite its effectiveness in preventing and reducing mood swings and suicidality, it is a potentially hazardous drug. While it is crucial to carefully monitor lithium plasma levels, the current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Therefore, development of low-cost and facile lithium detection techniques that can be translated into point-of-care devices for personal monitoring will be a major advance in the management of BD. In the current study, we present colorimetric determination of lithium therapeutic levels utilizing test paper strips, based on its reaction with the chromogenic agent Quinizarin. Exposure of Quinizarin-dipped test papers to samples of interstitial fluid (ISF) or dH2O spiked with therapeutic concentrations of lithium resulted in colour changes that were monitored using optical spectroscopy. The acquired spectra from the test papers show spectral variations which are related to lithium concentrations in spiked samples of dh2O and artificial ISF with a coefficient of determination (R2) of 0.9 and 0.8, respectively. Altogether, the spectrophotometric and colorimetric analyses demonstrated strong correlations between the observed colour changes and the concentrations of lithium present in the sample. Therefore, this study has demonstrated that Quinizarin-treated cellulose-based papers are suitable for the precise detection of changes in lithium therapeutic levels. This method is simple and very convenient and serves as a foundation for the future development of a paper-based colorimetric sensor for monitoring of lithium therapeutic levels in ISF and other non-invasive biological fluids.

Studies on candidate genes for lithium prophylaxis performed at the Poznan University of Medical Sciences

Lithium is a drug of choice as a mood-stabilizer for the maintenance treatment of bipolar disorder. The prophylactic efficacy of lithium can be determined by genetic factors, partially related to a predisposition to bipolar disorder. In the field of psychiatric genetics, the first decade of the 21st century was dominated by the "candidate gene" research. In this paper, the studies on candidate genes connected with lithium prophylaxis performed at the Poznań University of Medical Sciences in 2005-2018 are presented. During this time, the polymorphisms of multiple genes have been investigated, many of which are also connected with a predisposition to bipolar illness. The associations with lithium prophylactic efficacy were found for the polymorphisms in 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1, and TIM, genes, but not those in 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GRIN2B, GSK-3β, MMP-9, and NTRK2 genes. The polymorphism of the GSK-3β gene was found to be associated with the kidney side-effects occurring during lithium therapy. Possible roles for these genes in both the mechanism of lithium prophylactic activity and pathogenesis of bipolar mood disorder were discussed.

An individualized medication model of sodium valproate for patients with bipolar disorder based on machine learning and deep learning techniques.

Valproic acid/sodium valproate (VPA) is a widely used anticonvulsant drug for maintenance treatment of bipolar disorders. In order to balance the efficacy and adverse events of VPA treatment, an individualized dose regimen is necessary. This study aimed to establish an individualized medication model of VPA for patients with bipolar disorder based on machine learning and deep learning techniques. The sequential forward selection (SFS) algorithm was applied for selecting a feature subset, and random forest was used for interpolating missing values. Then, we compared nine models using XGBoost, LightGBM, CatBoost, random forest, GBDT, SVM, logistic regression, ANN, and TabNet, and CatBoost was chosen to establish the individualized medication model with the best performance (accuracy = 0.85, AUC = 0.91, sensitivity = 0.85, and specificity = 0.83). Three important variables that correlated with VPA daily dose included VPA TDM value, antipsychotics, and indirect bilirubin. SHapley Additive exPlanations was applied to visually interpret their impacts on VPA daily dose. Last, the confusion matrix presented that predicting a daily dose of 0.5g VPA had a precision of 55.56% and recall rate of 83.33%, and predicting a daily dose of 1g VPA had a precision of 95.83% and a recall rate of 85.19%. In conclusion, the individualized medication model of VPA for patients with bipolar disorder based on CatBoost had a good prediction ability, which provides guidance for clinicians to propose the optimal medication regimen.

Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: A retrospective cohort study using target trial emulation framework.

SummaryBackgroundThere is a lack of consensus on the optimal serum valproic acid (VPA) concentration for maintenance therapy in bipolar disorder (BD). We aimed to investigate the association between serum VPA levels and risk of mood episode recurrence.MethodsWe enrolled patients with BD from multiple medical institutions in Taiwan between January 1, 2001 and December 31, 2019. Patients were divided into three groups according to their serum VPA concentrations (< 50 μg/ml, 50–74 μg/ml, and 75–104 μg/ml). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) compared times to mood episode recurrence using the < 50 μg/ml group as reference. A systematic review found relevant articles published before February 2022 (PROSPERO: CRD42022309661), and corresponding results were compared.FindingsThis cohort included 896 patients for an intention-to-treat analysis. Compared with the < 50 μg/ml group, a non-significantly lower risk of mood episode recurrence was found in the 50–74 μg/ml (aHR, 95% CI: 0·86, 0·71–1·05) and 75–104 μg/ml (0·91, 0·71–1·18) groups. A per-protocol analysis of 481 patients found a significant risk reduction in the 50–74 μg/ml group (0·76, 0·60–0·97), with inconclusive results in the ≥ 75 μg/ml group (1·03, 0·73–1·46). A meta-analysis including two studies (254 patients) and our cohort found a similar significantly lower risk of mood episode recurrence in the 50–74 μg/ml group (HR, 95% CI: 0·83, 0·69–0·99), while risk reduction in the 75–99 μg/ml group (0·62, 0·26–1·48) did not differ significantly from that in the < 50 μg/ml group or the 50–74 μg/ml group.InterpretationThe combined results of this cohort and previous studies suggest that VPA between 50–74 μg/ml may be a more effective concentration to prevent acute mood episodes during maintenance therapy in patients with BD compared with VPA < 50 μg/ml.FundingMinistry of Science and Technology, Taiwan, and Chang Gung Medical Research Project.

What are the effects of taking 300 pills of sodium valproate? - case report

INTRODUCTION: Sodium valproate is one of the most important antiepileptic drugs. It can be effective as a preventive treatment for migraine, it has also found use in the maintenance treatment of bipolar disorder and acute mania,it is sometimes used in the treatment of chronic neuropathic pain and fibromyalgia, in the treatment of schizophrenia borderline personality disorder and acquired brain injury, this drug is used off-label. Its overdose can be fatal.&#x0D; MATERIALS AND METHOD: Patient information was collected from hospital records available in the clinical toxicology department. In addition, we conducted a literature review on sodium valproate treatment, its toxicity, side effects and pharmacokinetics using PubMed.&#x0D; CASE REPORT: A 57-year-old patient with a history of depressive disorders was admitted to the Clinical Department of Toxicology and Cardiology in Lublin for intentional intoxication with the drug Absenor (sodium valproate). The patient had taken 3 packages of Absenor 500 mg (300 tablets in total) for suicidal purposes. The determined concentration of valproic acid was 841 µg/ml, and the patient's condition was very severe. Despite the treatment administered-multiple attempts at gastric lavage, administration of activated charcoal, performance of hemodialysis procedures, administration of infusion of catecholamines, the patient died on the fifth day of hospitalization.&#x0D; CONCLUSION: An overdose of sodium valproate can be fatal. Keep this in mind when ordering this drug for patients with a positive history of suicide attempts.

Long-acting new generation antipsychotics in the maintenance treatment of bipolar disorders

IntroductionMaintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.ObjectivesWe aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.MethodsClinical records of 44 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated.ResultsNearly half of the patients were male (n:24, 54%). 43,2% of the patients were married. The mean age was 36.6±11.9 years and the mean duration of education was 11.5±3.9 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (65.9%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. Ten of the patients discontinued the treatment due to the side effects and extrapyramidal side effects was the most common side effect. Relapse was observed in 25% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.ConclusionsLAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.DisclosureNo significant relationships.

How does lamotrigine compare with lithium for maintenance treatment of bipolar disorder?

How does lamotrigine compare with lithium for maintenance treatment of bipolar disorder?

Relationship of free thyroxine and triiodothyronine on recurrence in maintenance therapy for bipolar depression.

To examine whether thyroid function in the normal range is associated with recurrence of depressive or mania in bipolar disorder patients. 104 patients with bipolar disorder in maintenance therapy phase were assigned randomly to mood stabilizer combined with antidepressant group or mood stabilizer group. There were 52 patients in both groups respectively. Clinical symptoms were assessed at baseline, 3rd month, 6th month, 9th month, and 12th month using HAMD-17 and YMRS. Blood samples were analyzed for thyroid function. There was no statistically significant difference of recurrence rate of depressive episode and mania episode at the end of the 12-months between mood stabilizer combined with antidepressant group and mood stabilizer group. There was significant relation of baseline TT4 (P=0.020, HR = 0.948), FT3 (P=0.035, HR = 2.055), and FT4 (P=0.047, OR=0.769) with the recurrence of depressive episode in mood stabilizer group. The area under curve (AUC) of TT4, FT3, FT4 were 0.685, 0.613, 0.544, respectively. There was significant relation of baseline FT3 (P=0.044，HR = 4.493) with the recurrence of mania episode for mood stabilizer combined with antidepressants group. The AUC of FT3 was 0.806. Low level of TT4, FT4 and high level of FT3 within normal-range were related with the recurrence of depressive episode in the maintenance treatment with mood stabilizer of bipolar disorder. High level of FT3 within normal-range were related with recurrence of mania when mood stabilizer combined with antidepressants were used in the maintenance treatment of bipolar disorder.

Antiviral, immunomodulatory, and neuroprotective effect of lithium.

Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most important psychiatric use of lithium is probably increasing the efficacy of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts antisuicidal, antiviral, immunomodulatory, and neuroprotective effects. The goal of the review is to describe the experimental and clinical studies on the last three properties of lithium. Antiviral effects of lithium pertain mostly to DNA viruses, especially herpes viruses. The therapeutic effects of lithium in systemic and topical administration on labial and genital herpes were demonstrated in clinical studies. There is also some evidence, mostly in experimental studies, that lithium possesses antiviral activity against RNA viruses, including coronaviruses. The immunomodulatory effect of lithium can mitigate "low-grade inflammatory" conditions in bipolar illness. The neuroprotective properties of lithium make this ion a plausible candidate for the prevention and treatment of neurodegenerative disorders. A favorable effect of lithium was shown in experimental models of neurodegenerative disorders. On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed. Despite promising results of lithium obtained in animal models of Huntington's disease and amyotrophic lateral sclerosis, they have not been confirmed in clinical studies. A suggestion for common mechanisms of antiviral, immunomodulatory, and neuroprotective effects of lithium is advanced.

A pilot trial of quetiapine, lithium, or placebo added to divalproex sodium for hypomanic or manic episodes in ambulatory adults with bipolar I disorder

BackgroundMany patients with bipolar I disorder do not respond to monotherapy treatment with mood-stabilizing medications, and combination regimens are commonly used in both inpatient and outpatient settings for the acute and maintenance treatment of bipolar disorder. We studied whether combination therapy is more effective than monotherapy for the acute treatment of subjects with bipolar I disorder currently experiencing manic symptoms. The primary hypothesis was that combination treatments would be associated with greater reductions in symptoms of mania and hypomania than monotherapy alone. The secondary hypothesis was that combination therapies would be associated with lower depression levels than monotherapy alone. Last, a post-hoc exploratory aim was used to examine whether the effect of side effect severity on risk-of-dropout would be greater in combination therapies than in monotherapy alone.ResultsIn this 12-week, double-blind, placebo-controlled ambulatory pilot trial, participants (n = 75) with bipolar I disorder were randomly assigned to: (1) monotherapy divalproex plus placebo (DVP + PBO), (2) combination therapy of divalproex plus blinded lithium (DVP + Li) or (3) divalproex plus blinded quetiapine (DVP + QTP). Combination therapies (vs. monotherapy) were not associated with improved symptoms of mania, hypomania or depression. The effect of side effect severity on study retention did not differ between combination therapies and monotherapy. However, the risk-of-dropout was significantly greater in the DVP + Li arm versus the DVP + PBO arm.ConclusionsNo longitudinal differences in mania, hypomania or depression were found between combination therapies and monotherapy. The effect of side effect severity on study retention did not differ between groups. Due to the small sample size and differential rates of attrition between treatment arms, results of this pilot trial must be interpreted with caution.Trial registration ClinicalTrials.gov identifier: NCT00183443

Association of Social Determinants of Health With Adherence to Second-generation Antipsychotics for People With Bipolar Disorders in a Medicaid Population.

About 7 million people, 2.8% of US adults, have bipolar disorder (BD). While second-generation antipsychotics (SGA) are indicated as acute and maintenance treatments for BD, therapeutic success requires medication adherence and reported nonadherence estimates to range as high as 60%. Identifying patient risk factors for nonadherence is important for reducing it. The objective of this study was to quantify the associations of risk factors, including social determinants of health, with SGA nonadherence among patients with BD. In this cross-sectional study of 2015-2017 MassHealth Medicaid data, we examined several definitions of adherence and used logistic regression to identify risk factors for nonadherence (medication possession ratio <0.8) among all adults aged 18-64 diagnosed with BD who could be followed for 12 months following SGA initiation. Among 5197 patients, the mean (±SD) age was 37.7 (±11.4) years, and 42.3% were men. Almost half (47.7%) of patients were nonadherent to SGAs when measured by medication possession ratio. The prevalence of nonadherence peaked at middle age for men and younger for women. Nonadherence was less common among Massachusetts' Department of Mental Health clients (odds ratio=0.60, 95% confidence limit: 0.48-0.74) and among those who used other psychotropic medications (odds ratios between 0.45 and 0.81); in contrast, increase in neighborhood socioeconomic stress was associated with increased odds of nonadherence. Adherence to SGA treatment is suboptimal among people with BD. Recognizing risk factors, including those related to social determinants of health, can help target interventions to improve adherence for people at high risk and has implications for adherence-based quality measures.

Lamotrigine in the maintenance treatment of bipolar disorder.

Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall functioning and health-related quality of life. A worldwide prevalence rate of 2.4% has been reported. The risk of suicide is higher in people with bipolar disorder than those with other mental disorders. Therefore, effective management of bipolar disorder in the maintenance period is warranted to minimizethe risk of relapse or recurrence. Although lithium has been the standard treatment of bipolar disorder for many years, it is associated with adverse effects and teratogenicity. Lamotrigine is approved to be expected for prevention of recurrence for the maintenance treatment of bipolar disorder. In addition, lamotrigine is as effective as lithium. Therefore, we performed a systematic review to confirm the efficacy and safety of lamotrigine in the maintenance treatment of bipolar disorder. To assess the efficacy and tolerability of lamotrigine in the maintenance treatment of bipolar disorder. We searched Ovid MEDLINE, Embase, PsycINFO, the Cochrane Common Mental Disorders Group's Specialized Register (CCMDCTR) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 21 May 2021. We also searched international trial registries and contacted experts in the field. We included randomized controlled trials enrolling adults with bipolar disorder who were treated with lamotrigine, placebo or lithium. Two reviews authors independently checked the eligibility of studies and extracted data using a standardized form. Data extractedincluded study characteristics, participant characteristics, intervention details, settings, and outcome measures in the term of efficacy and tolerability. Study information were then entered into RevMan web. We included 11 studies with a total of 2314 participants in this review; 1146 were randomized to lamotrigine, 869 were randomized to placebo and, 299 to lithium. We rated all studies as having an unclear risk of bias in at least one domain of Cochrane's tool for assessing risk of bias, with the most commonly observed weaknessbeing selection bias (random sequence generation and allocation concealment). We judgedfive studies to be ata high risk of detection bias (blinding of outcome assessment). These potential biases pose as major threat to the validity of the included studies in this review. Outcomes of efficacy showed a possible advantage of lamotrigine over placebo. The estimated risk ratio (RR) for recurrence of manic symptom atoneyear as measured by the Young Mania Rating Scale (YMRS) was 0.67, (95% confidence interval (CI) 0.51 to 0.87; 3 studies, 663 participants; low-certaintyevidence) in favor of lamotrigine. The RR of clinical worsening with the need for additionalpsychotropic treatment(RR 0.82, 95% CI 0.70 to 0.98; 4 studies, 756 participants) based on moderate-certainty evidence. The possible benefits of lamotrigine were also seen for the outcome of treatment withdrawal due to any reason at 6-12 months after treatment(RR 0.88, 95% CI 0.78 to 0.99; 4 studies, 700 participants; moderate-certaintyevidence).Regarding tolerability, our analyses showed that the incidence rates of adverse effects were similar between the lamotrigine group and the placebo group(short-term effect: RR 1.07, 95% CI 0.81 to 1.42; 5 studies, 1138 participants; very low-certainty evidence;long-term effect: RR 0.97, 95% CI 0.77 to 1.23; 4 studies, 756 participants; moderate-certaintyevidence). In the comparison between lamotrigine and lithium, efficacy was similar between groups except for recurrence of mania episode at one year. Recurrence of manic symptoms was higher in the lamotrigine group than that of the lithium group (RR 2.13, 95% CI 1.32 to 3.44; 3 studies, 602 participants; moderate-certainty evidence). Analysis of adverse effects at 6-12 months showed that a lower proportion of participants experienced at least one adverse effect when treated with lamotrigine compared to lithium (RR 0.70, 95% CI 0.51 to 0.96; 4 studies, 691 participants; moderate-certainty evidence). Low- to moderate-certainty evidence collectively suggests that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder. In comparison to lithium, people with bipolar disorder seem to tolerate lamotrigine better in the long run; however, the demonstrated efficacy in the maintenance of bipolar disorder was similar between the two groups.