Treatment Of Bipolar Disorder Patients Research Articles

Comparison of personality factors, adherence to medication and quality of life in bipolar disorder-I patients with or without substance use disorder

IntroductionSome specific personality factors in patients of bipolar disorder are potential risk factors for developing comorbid substance use disorder. Comorbid substance use disorder is one of the most common factors associated with non-adherence to treatment in bipolar disorder patients leading to poor quality of life. We compared all three variables in bipolar disorder-1patients with or without substance use disorder. MethodsIt is a cross-sectional study done on 90 patients of Bipolar disorder-1 diagnosed as per DSM-5, 45 without and 45 with comorbid substance use disorder. Personality factors, non-adherence to medication and quality of life were assessed and compared between both the groups using standardized tools and appropriate statistical analysis methods. ResultsThere was a significant difference between the groups in terms of distribution of socio-economic status (Bias Corrected Cramer'sV = 0.31 moderate association), gender (Bias Corrected Cramer'sV = 0.37 moderate association), distribution of 16 personality factor B (Cramer's V = 0.28) and factor G (χ2 = 6.222, p = 0.045) (Cramer's V = 0.26). LimitationsSmall sample size and a cross-sectional study design. ConclusionSUD and NSUD group differed on 16 PF factor B and G which are factors for reasoning and Rule-Consciousness respectively although on regression analysis this difference was not significant for factor G. In binary logistic regression multivariable model, an average score (as compared to low score) of personality factor B was found to significantly increase the ODDS of substance use. SUD group had more severity and greater number of episodes, had lower level of education, belonged to low socio-economic status.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study

BackgroundWe conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. MethodsSeventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. ResultsThe overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LimitationsThe small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. ConclusionThe results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

A Longitudinal Study of the Association between the LEPR Polymorphism and Treatment Response in Patients with Bipolar Disorder.

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.

Barriers and facilitators associated with pharmacological treatment in bipolar disorder patients

IntroductionThe main factors that are involved in a correct adherence to the therapeutic recommendations in Bipolar Disorder includes aspects related to age, sex, ethnicity, socioeconomic level and characteristics of the illness associated with the severity, comorbidity and adverse effects related to previous medicine.ObjectivesTo analyse the individual perception that the patient with Bipolar Disorder has regarding the positive and negative aspects of taking the recommended medication.MethodsDescriptive and interpretative observational study under the qualitative paradigm of research, extracting the data through the completion of four focus groups with ten patients everyone. To complete the codification of the content of the participant’s discourses, we rely on the QRS NVivo 10 computer program.ResultsIn the participant’s discourse concerning the main barriers to pharmacological treatment, for example “It’s because we live in a society and, because of that, we don’t go without medicine; if we didn’t live in society, we wouldn’t take medicine because we wouldn’t bother anyone”. Some examples of patient’s discourse, about perceived facilitators were: “I have to take medicine for my bipolar disorder, that’s it, I have a treatment, my illness has a name”.ConclusionsThe main facilitators regarding the use of pharmacological treatment in Bipolar Disorder are the perceived need for treatment in the acute phase and the recognition of the illness, the shared clinical decision and the causal biological attribution in the chronic phase. About perceived barriers, social control is identified in both phases, adverse effects in the acute cases and the absence of effective treatment in the chronic state.

Aripiprazole Augmentation to Mood Stabilizers for Obsessive-Compulsive Symptoms in Bipolar Disorder.

Background and Objectives: Aripiprazole is a first-line agent in the treatment of bipolar disorder (BD) and available data demonstrates its efficacy on clinical symptoms in serotonin reuptake inhibitors-resistant obsessive-compulsive disorder (OCD) patients. Therefore, aripiprazole augmentation to mood stabilizers could represent a promising treatment in BD patients with comorbid OCD. The study examined the efficacy and safety of aripiprazole added to lithium or valproate for the treatment of obsessive-compulsive (OC) symptoms in euthymic BD patients with comorbid OCD. Materials and Methods: This is a 12-week prospective observational study. The efficacy of aripiprazole on OC symptoms was assessed through the mean change of Yale–Brown Obsessive-Compulsive (YBOCS) total score. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Results: A total of 70 patients were included in the analyses. The withdrawal rate was 21.4%, mainly due to adverse events. Mean ± SD final aripiprazole dose was 15.2 ± 5.3 in the completer sample (N = 55). The Y-BOCS mean score decreased from 24.0 ± 4.1 at baseline to 17.1 ± 4.3 at 12 weeks. Treatment response rate (Y-BOCS reduction ≥ 35%) was 41.8%, while partial response rate (Y-BOCS reduction greater than 25% but less than 35% from baseline) accounted for the other 18.2% of patients. Overall, 91.4% of completers had at least 1 adverse effect (tremor, tension/inner unrest, reduced duration of sleep, akathisia). No significant differences emerged comparing aripiprazole efficacy and tolerability between patients treated with lithium or valproate. Conclusion: Our findings show that aripiprazole addition to lithium or valproate can reduce OC symptoms in real-world BD euthymic patients.

The efficacy and safety of sulforaphane as an adjuvant in the treatment of bipolar depressive disorder: Study protocol for a randomized, double-blinded, placebo-controlled, parallel-group clinical trial.

Background:Bipolar disorder (BD) is a chronic and disabling psychiatric disorder. The treatment of BD still remains a significant clinical challenge due to the complex nature of the disease. Nutraceutical therapy as adjunctive role is a promising therapy for BD. Sulforaphane (SFN), a broccoli extract, was reported to be effective for emotional problems and cognitive impairment. However, clinical research of SFN in the treatment of BD was rare. Therefore, this study is designed to evaluate the adjuvant role of SFN in the treatment of BD.Methods:This is a randomized, double-blinded, placebo-controlled, parallel-group clinical trial. A total of 100 patients who meet inclusion criteria will be assigned to receive quetiapine plus SFN or quetiapine plus placebo in a 1:1 ratio. The total duration of the study will be 12 weeks including 5 follow ups. The primary outcome is in the Montgomery–Asberg depression rating scale. The secondary outcomes are the quick inventory of depressive symptomatology—self report, Hamilton anxiety rating scale, young mania rating scale, cognitive function, inflammatory factors, and intestinal flora. Any adverse events will be recorded throughout the trial.Discussion:This trial will provide evidences to evaluate the efficacy and safety of SFN combined with quetiapine in the treatment of BD patients, as well as the adjuvant role of SFN in combination.Trial registration:This study protocol was registered at the Chinese clinical trial registry (ChiCTR2000028706).

Drug treatment for patients with bipolar disorders in psychiatric practices in Germany in 2009 and 2018

AimsThe aim of this study was to describe the treatment of bipolar disorder patients in psychiatric private practices in Germany in 2009 and 2018. MethodsThis retrospective study included patients with bipolar disorder who had received at least one prescription for antidepressants, antipsychotics, antiepileptic drugs or benzodiazepines in 93 neuropsychiatric private practices in Germany between January 2009 and December 2018. Outcomes of this study were the prevalence of prescriptions for defined mood stabilizers, antipsychotics, antidepressants, and benzodiazepines, and the prevalence of mono and combination therapy in 2009 and 2018. Results1,815 and 2,322 patients with bipolar disorder were examined in 2009 and 2018, respectively. Compared to 2009, there was a decrease in the proportion of prescriptions for mood stabilizers by 2018 (58.6% to 49.5%) especially for lithium (from 31.4% to 26.2%) and an increase in the prescription of antipsychotics (38.4% in 2009 and 53.1% in 2018) and antidepressants (32.6% in 2009 and 45.1% in 2018). The share of combination therapy increased moderately from 39.3% to 41%. ConclusionsQuetiapine has displaced lithium from the number one medication of the most commonly prescribed drugs in patients with bipolar disorders. The rate of patients in this study receiving monotherapy was surprisingly high.

Clinical Risk Factors for Therapeutic Lithium-Associated Electrocardiographic Changes in Patients With Bipolar Disorder.

Lithium, a common medication used in bipolar disorder treatment, can exert an inhibitory effect on sodium and potassium channels and potentially cause cardiac electrical conduction disturbance and corrected QT (QTc) prolongation. This study aimed to examine whether lithium at therapeutic levels can change electrocardiographic parameters in different groups of patients with bipolar disorder and to identify the potential clinical risk factors. Standard 12-lead electrocardiogram data before and after lithium treatment in bipolar disorder patients after at least 2-week dropout of psychotropic medications were analyzed. A total of 39 patients with bipolar disorder receiving lithium treatment were enrolled. Nineteen patients (48.7%) exhibited increased from P wave beginning to QRS complex beginning intervals after lithium treatment (mean serum level, 0.653 ± 0.247 mmol/L). Twenty-four patients (61.5%) exhibited increased a combination of Q, R, and S waves complex durations and increased QTc intervals. Twenty-three patients (59.0%) exhibited increased corrected JT (JTc) intervals. The patient group with increased QTc or JTc intervals exhibited a higher mean systolic blood pressure than did the patient group without increased QTc (134.7 ± 19.2 mm Hg vs 115.7 ± 11.8 mm Hg, P = 0.020) or JTc intervals (134.4 ± 19.6 mm Hg vs 117.6 ± 13.3 mm Hg, P = 0.054), respectively. Biochemical and hemodynamic parameters were comparable between patients with and without increased a combination of Q, R, and S waves complex durations or from P wave beginning to QRS complex beginning intervals. Elevated systolic blood pressure may be the risk factor for the ventricular conduction delay in bipolar disorder patients receiving lithium at therapeutic levels.

Patients With Drug-Naive Bipolar Disorder in Remission After 8 Weeks of Treatment Had Decreased Serum Uric Acid Concentrations.

Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD.Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age- and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group.Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients.Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.

Gut Microbiota Changes in Patients with Bipolar Depression.

This study aims to characterize the gut microbiota in depressed patients with bipolar disorder (BD) compared with healthy controls (HCs), to examine the effects of quetiapine treatment on the microbiota, and to explore the potential of microbiota as a biomarker for BD diagnosis and treatment outcome. Analysis of 16S‐ribosomal RNA gene sequences reveals that gut microbial composition and diversity are significantly different between BD patients and HCs. Phylum Bacteroidetes and Firmicutes are the predominant bacterial communities in BD patients and HCs, respectively. Lower levels of butyrate‐producing bacteria are observed in untreated patients. Microbial composition changes following quetiapine treatment in BD patients. Notably, 30 microbial markers are identified on a random forest model and achieve an area under the curve (AUC) of 0.81 between untreated patients and HCs. Ten microbial markers are identified with the AUC of 0.93 between responder and nonresponder patients. This study characterizes the gut microbiota in BD and is the first to evaluate microbial changes following quetiapine monotherapy. Gut microbiota‐based biomarkers may be helpful in BD diagnosis and predicting treatment outcome, which need further validations.

Effects of valproate on brain volumes in pediatric bipolar disorder: A preliminary study

Sodium valproate (VPA) has well-established neuroprotective effects and is recommended as treatment in bipolar disorder patients. The neural effects of VPA in pediatric bipolar disorder (PBD) have yet to be established. This preliminary study explored the effects of VPA on brain structure in PBD.Fourteen PBD patients (10 males; mean = 13.43 ± 3.05 years old) underwent a structural MRI before and after a 6-week VPA treatment period. Bayesian linear mixed modeling explored seven brain region volumes as a function of dichotomous pre/post time.Results showed a decrease in amygdala volume over time. These findings need to be confirmed by large-scale, longitudinal studies.

Successful treatment of bipolar disorder patients with transcranial magnetic stimulation

Successful treatment of bipolar disorder patients with transcranial magnetic stimulation

Unmet needs of bipolar disorder patients.

BackgroundBipolar disorder (BD) is a serious mental illness with adverse impact on the lives of the patients and their caregivers. BD is associated with many limitations in personal and interpersonal functioning and restricts the patients’ ability to use their potential capabilities fully. Bipolar patients long to live meaningful lives, but this goal is hard to achieve for those with poor insight. With progress and humanization of society, the issue of patients’ needs became an important topic. The objective of the paper is to provide the up-to-date data on the unmet needs of BD patients and their caregivers.MethodsA systematic computerized examination of MEDLINE publications from 1970 to 2015, via the keywords “bipolar disorder”, “mania”, “bipolar depression”, and “unmet needs”, was performed.ResultsPatients’ needs may differ in various stages of the disorder and may have different origin and goals. Thus, we divided them into five groups relating to their nature: those connected with symptoms, treatment, quality of life, family, and pharmacotherapy. We suggested several implications of these needs for pharmacotherapy and psychotherapy.ConclusionTrying to follow patients’ needs may be a crucial point in the treatment of BD patients. However, many needs remain unmet due to both medical and social factors.

Leukocyte telomere length positively correlates with duration of lithium treatment in bipolar disorder patients

Bipolar disorder (BD) has been suggested to be associated with accelerated aging and premature cell senescence. While findings on shorter telomeres in BD are controversial, a recent study showed that long-term lithium treatment correlates with longer telomeres in BD. In our study, we sought to investigate the correlation between leukocyte telomere length (LTL) and long-term lithium treatment in a sample of 200 BD patients characterized for lithium response. We also compared data from two different methods commonly used to measure telomere length, quantitative PCR (qPCR) and quantitative fluorescence in situ hybridization (Q-FISH). We also measured, for the first time, the effect of lithium in vitro on the expression of the telomerase gene in human-derived neural progenitor cells (NPCs). Our findings showed that LTL correlated negatively with age (p=0.0002) and was independent of sex, diagnosis, age at onset, suicidal behavior, number of mood episodes, response to lithium and use of other psychotropic medications. After correcting for age, LTL was positively correlated with lithium treatment duration in patients treated for more than two years (n=150, R=0.17, p=0.037). There was a significant correlation between data measured with qPCR and Q-FISH (p=0.012, R=0.826). Lithium treatment increased telomerase expression in NPCs, though this effect was not statistically significant.Our data support previous findings showing that long-term lithium treatment associates with longer telomeres in BD, though this effect appeared to be independent from clinical response to the treatment. Moreover, we suggested for the first time that lithium increases the expression of telomerase gene in human neural progenitor cells.

Optical analysis of lithium carbonate: towards the development of a portable lithium blood level analyzer for bipolar disorder patients.

Lithium medication is the gold standard of treatment in Bipolar Disorder patients, preventing and reducing mood swings and suicidality. However, despite its effectiveness, it is a potentially hazardous drug requiring regular monitoring of blood levels to ensure toxic levels are not reached. This paper describes the first steps towards developing a new portable device that can be used by Bipolar Disorder patients to facilitate the analysis of lithium blood levels at home. Solutions of lithium carbonate have been optically fingerprinted using a high-end spectrophotometer. Preliminary measurements indicate that while the visible to near infrared region of the absorption spectra fall heavily within the water band, measurements in the Ultraviolet region show a strong distinction between different lithium concentrations. The optical spectra of Lithium in the 220 nm to 230 nm region demonstrated the ability to differentiate between concentrations representing those found in patients.

Personalized medicine in bipolar disorder: how can we overcome the barriers to clinical translation?

Bipolar disorder (BD) is a complex mood disorder characterized by recurrent episodes of mania and depression, affecting 1–4% of the general population [1]. The phenotypic representation of BD is highly heterogeneous, a characteristic that is reflected in the variability in response to mood-stabilizing drugs observed in bipolar patients. Mood stabilizers are a class of drugs that includes anticonvulsants, second-generation antipsychotics and lithium, with the latter being the mainstay in BD treatment. In 1949, John Cade described, for the first time, lithium’s antimanic effect [2]. In the following years, many trials demonstrated lithium’s efficacy in shortterm and prophylactic treatment of BD [3]. The choice of lithium as the first treatment in BD patients has also been influenced by its welldescribed antisuicidal effect – suicide being one of the leading causes of death in BD patients [4]. For these reasons, the vast majority of studies on response to drugs used in BD have thus far been focused on lithium more than any other mood stabilizer. While a significant proportion of patients chronically treated with lithium show full remission with stabilization of mood alterations, approximately 70% of subjects present partial or complete nonresponse [5]. This significant rate of insufficient response, together with the potentially serious adverse effects of lithium treatment, has stimulated a growing body of research aimed at the identification of predicting factors and new drug targets. The first step for the design of targeted therapies should consist of the identification of predictive markers of response. Nevertheless, with the exception of clinical factors, findings have so far provided weak evidence for specific predictors of lithium response. The main barriers

Transtorno Bipolar: Avaliação de um Programa de Psicoeducação sob o Enfoque da Análise do Comportamento

A psicoeducação é uma das estratégias que deve ser inserida no tratamento de pacientes com diagnóstico de transtorno bipolar, e tem demonstrado eficácia para fomentar respostas relacionadas à adesão à medicação. O objetivo deste estudo foi avaliar a efetividade de um programa de psicoeducação, aplicado a 9 pacientes com diagnóstico de transtorno bipolar, os quais se encontravam em tratamento em um hospital público. Para avaliação foram aplicadas as escalas de depressão (Hamilton), de mania (Young) e de Qualidade de Vida (WHOQOL). Foram realizadas 16 sessões de atendimento em grupo. Os resultados mostram que houve redução significativa na mania do pré para o pós-teste e melhora no domínio “Físico” da escala de Qualidade de Vida. Além disso, a alta frequência de pacientes com depressão leve e os relatos de conflitos familiares apontam a necessidade de intervenção com a família e focadas no treino de habilidades sociais.

VEGF regulates antidepressant effects of lamotrigine

The anticonvulsant drug lamotrigine has been shown to produce strong antidepressant effects in the treatment of bipolar disorder patients. Our previous studies have demonstrated that brain derived neurotrophic factor (BDNF) signaling plays an important role in regulating its behavioral actions in several rodent models of depression. The current study extends earlier work on BDNF and explores the role of another important neurotrophin vascular endothelial growth factor (VEGF) in regulating the antidepressant actions of lamotrigine. The results showed that chronic administration of 30mg/kg lamotrigine (14days) normalized the down-regulated frontal and hippocampal VEGF protein expression as well as the behavioral deficits induced by chronic unpredictable stress. In addition, pharmacological inhibition of VEGF signaling by infusion of SU5416, a selective Flk-1 receptor inhibitor, blocks the antidepressant effects of lamotrigine in all behavioral paradigms. Taken together, this study provides further evidence that VEGF is also an essential regulator for the antidepressant effects of lamotrigine.

Towards long term monitoring of electrodermal activity in daily life

Manic depression, also known as bipolar disorder, is a common and severe form of mental disorder. The European research project MONARCA aims at developing and validating mobile technologies for multi-parametric, long term monitoring of physiological and behavioral information relevant to bipolar disorder. One aspect of MONARCA is to investigate the long term monitoring of Electrodermal activity (EDA) to support the diagnosis and treatment of bipolar disorder patients. EDA is known as an indicator of the emotional state and the stress level of a person. To realize a long-term monitoring of the EDA, the integration of the sensor system in the shoe or sock is a promising approach. This paper presents a first step towards such a sensor system. In a feasibility study including 8 subjects, we investigate the correlation between EDA measurements at the fingers, which is the most established sensing site, with measurements of the EDA at the feet. The results indicate that 88% of the evoked skin conductance responses (SCRs) occur at both sensing sites. When using an action movie as psychophysiologically activating stimulus, we have found weaker reactivity in the foot than in the hand EDA. The results also suggest that the influence of moderate physical activity on EDA measurements is low and has a similar effect for both recording sites. This suggests that the foot recording location is suitable for recordings in daily life even in the presence of moderate movement.