Treatment Of Bipolar Disorder Research Articles

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.

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.

Lithium response in bipolar disorder: Epigenome-wide DNA methylation signatures and epigenetic aging

Lithium (Li) is the first-line treatment for bipolar disorder (BD) even though only 30 % of BD patients are considered excellent responders. The mechanisms by which Li exerts its action are not clearly understood, but it has been suggested that specific epigenetic mechanisms, such as methylation processes, may play a role. In this regard, DNA methylation patterns can be used to estimate epigenetic age (EpiAge), which is accelerated in BD patients and reversed by Li treatment. Our first aim was to compare the DNA methylation profile in peripheral blood between BD patients categorized as excellent responders to Li (Ex-Rp) and non-responders (N-Rp). Secondly, EpiAge was estimated to detect differential age acceleration between the two groups.A total of 130 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) between Ex-Rp (n = 26) and N-Rp (n = 37) were identified (FDR adjusted p-value < 0.05). We found 122 genes mapping the DMPs and DMRs, nine of which (HOXB6, HOXB3, HOXB-AS3, TENM2, CACNA1B, ANK3, EEF2K, CYP1A1, and SORCS2) had previously been linked to Li response. We found genes related to the GSK3β pathway to be highly represented. Using FUMA, we found enrichment in Gene Ontology Cell Component for the synapse. Gene network analysis highlighted functions related to the cell cycle, nervous system development and function, and gene expression. No significant differences in age acceleration were found between Ex-Rp and N-Rp for any of the epigenetic clocks analysed.Our findings indicate that a specific methylation pattern could determine the response to Li in BD patients. We also found that a significant portion of the differentially methylated genes are closely associated with the GSK3β pathway, reinforcing the role of this system in Li response. Future longitudinal studies with larger samples will help to elucidate the epigenetic mechanisms underlying Li response.

Study of the different sleep disturbances during the prodromal phase of depression and mania in bipolar disorders.

One of the challenges in bipolar disorder (BD) lies in early detection of the illness and its recurrences, to improve prognosis. Sleep disturbances (SD) have been proposed as reliable predictive markers of conversion. While preliminary studies have explored the relationship between SD and the onset of mood episodes, the results remain heterogeneous and a few have specifically examined patients' perception of prodromal symptoms and their progression until the episode occurs. Identifying prodromes represents a crucial clinical challenge, as it enables early intervention, thereby reducing the severity of BD. Therefore, the objective of this study is to better characterize and evaluate the progressive nature of SD as prodromal symptoms of mood episodes, and patients' perception of it. Patients diagnosed with BD, either hospitalized or seeking treatment for a (hypo)manic or depressive episode benefited from standardized questionnaires, structured interviews, and self-report questionnaires to evaluate SD prior to the current episode, as well as sociodemographic and clinical information. Out of the 41 patients included, 59% spontaneously reported SD prior to the episode, appearing 90 days before depression and 35 days before mania (pre-indexed/spontaneous reports: 51.22% insomnia complaints, 4.88% hypersomnolence complaints, 7.32% parasomnias, 2.44% sleep movements). After inquiry about specific SD, the percentage of patients reporting prodromal SD increased significantly to 83%, appearing 210 days before depression and 112.5 days before mania (post-indexed reports: 75.61% presented with insomnia complaints appearing 150 days before depression and 20 days before mania, 46.34% had hypersomnolence complaints appearing 60 days before depression, 43.9% had parasomnias appearing 210 days before depression and 22.5 days before mania, 36.59% had sleep movements appearing 120 days before depression and 150 days before mania). Of note, bruxism appeared in 35% of patients before mania, and restless legs syndrome in 20% of patients before depression. This study highlights the very high prevalence of SD prior to a mood episode in patients with BD with differences between depressive and manic episodes. The more systematic screening of sleep alterations of the prodromal phase improved the recognition and characterization of different symptoms onset by patients. This underscores the need for precise questioning regarding sleep patterns in patients, to better identify the moment of transition toward a mood episode, referred to as "Chronos syndrome". The study emphasizes the importance of educating patients about the disorder and its sleep prodromal symptoms to facilitate early intervention and prevent recurrences.

Prior psychiatric morbidity and differential psychopharmacological treatment patterns: Exploring the heterogeneity of bipolar disorder in a nationwide study of 9594 patients.

Individuals with bipolar disorders (BD) have heterogenic pre-onset illness courses and responses to treatment. The pattern of illness preceding the diagnosis of BD may be a marker of future treatment response. Here, we examined associations between psychiatric morbidity preceding the diagnosis of BD and pharmacological treatment patterns in the 2 years following diagnosis. In this register-based study, we included all patients with a diagnosis of BD attending Danish Psychiatric Services between January 1, 2012 and December 31, 2016. We examined the association between a diagnosis of substance use disorder, psychosis (other than schizophrenia or schizoaffective disorder), unipolar depression, anxiety/OCD, PTSD, personality disorder, or ADHD preceding BD and pharmacological treatment patterns following the diagnosis of BD (lithium, valproate, lamotrigine, antidepressants, olanzapine, risperidone, and quetiapine) via multivariable Cox proportional hazards regression adjusted for age, sex, and year of BD diagnosis. We included 9594 patients with a median age of 39 years, 58% of whom were female. Antidepressants, quetiapine, and lamotrigine were the most commonly used medications in BD and were all linked to prior depressive illness and female sex. Lithium was used among patients with less diagnostic heterogeneity preceding BD, while valproate was more likely to be used for patients with prior substance use disorder or ADHD. The pharmacological treatment of BD is linked to psychiatric morbidity preceding its diagnosis. Assuming that these associations reflect well-informed clinical decisions, this knowledge may inform future clinical trials by taking participants' prior morbidity into account in treatment allocation.

Case study: bipolar disorder and catatonia in an adult autistic male with intellectual disability and Phelan-McDermid syndrome (22q13.33 deletion syndrome): psychopharmacological treatment and symptom trajectories

Objectives Individuals with Phelan-McDermid syndrome (PHMDS) appear to be at increased risk of bipolar disorder and catatonia. While previous research indicates that standard pharmacological treatment of both conditions may be effective in individuals with PHMDS, there is limited knowledge concerning treatment when bipolar disorder and catatonia co-occur. Moreover, symptom trajectories during treatment of bipolar disorder and catatonia in this population have been sparsely described. Methods Case study describing treatment choices, sequence of interventions, and treatment outcome using standardised checklists, for co-occurring bipolar disorder and catatonia in an adult autistic man with intellectual disabilities. Results The current patient was initially diagnosed with a depressive disorder and catatonia. Treatment of catatonia appeared to trigger mania, indicating that catatonia was associated with, and possibly secondary to, affective symptomatology. The successful treatment of catatonia required the discontinuation of antidepressants and the introduction of a mood stabilising drug, in addition to standard catatonia treatment. Conclusions The current case demonstrates the importance of considering the treatment of catatonia in the context of co-occurring affective disorder, and vice versa, in individuals with PHMDS. The symptom trajectories and outcomes described add to the current evidence base concerning the treatment of bipolar disorder/catatonia in PHMDS.

COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors.

Recently, a growing number of adolescents have been afflicted with mental disorders, with annual morbidity rates on the rise. This trend has been exacerbated by the global coronavirus disease 2019 (COVID-19) pandemic, leading to a surge in suicide and self-harm rates among this demographic. To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder (BD), along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents. A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians. Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders, international classification of diseases-11, and the National institute of mental health research domain criteria. Statistical analyses were performed using SPSS 26.0 software, with significance set at P < 0.05. A cohort of 171 adolescents diagnosed with BD between January 1, 2018, and December 31, 2022, was included in the analysis. The gender distribution was 2.8:1 (female to male), with ages ranging from 11 to 18 years old. Major factors contributing to adolescent BDs included familial influences, academic stress, genetic predisposition and exposure to school-related violence. Notably, a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic. Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress, thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents. The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD. This study underscores the urgent need for societal, familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention, diagnosis and treatment of adolescent BDs.

Evidence-based Psychopharmacological Treatments for Pediatric Bipolar Disorder

Evidence-based Psychopharmacological Treatments for Pediatric Bipolar Disorder

BI-REAL: A 12-session DBT skills group intervention adapted for bipolar disorder – A feasibility randomised pilot trial

International guidelines endorse psychological treatment for Bipolar Disorder (BD); however, the absence of a recognised gold-standard intervention requires further research. A Dialectical Behaviour Therapy (DBT) skills group intervention with 12 sessions was developed. This pilot randomised controlled trial (RCT) aims to evaluate the feasibility, acceptability, and outcomes variance of Bi-REAL – Respond Effectively, Assertively, and Live mindfully, tailored for individuals with BD, in preparation for a future RCT. Methods52 participants (female = 62.7 %; mean age = 43.2 ± 11.1) with BD were randomised by blocks to either the experimental group (EG; n = 26; Bi-REAL + Treatment as Usual, TAU) receiving 12 weekly 90-minutes sessions, or the control group (CG; n = 26, TAU). Feasibility and acceptability were assessed with a multimethod approach (qualitative interviews, semi-structured clinical interviews and a battery of self-report questionnaires – candidate main outcomes Bipolar Recovery Questionnaire (BRQ) and brief Quality of Life for Bipolar Disorder (QoL.BD)). All participants were evaluated at baseline (T0), post-intervention (T1) and 3-month follow-up (T2). ResultsAcceptability was supported by participants' positive feedback and ratings of the sessions and programme overall, as well as the treatment attendance (86.25 % of sessions attended). The trial overall retention rate was 74.5 %, with CG having a higher dropout rate across the 3-timepoints (42.31 %). A significant Time × Group interaction effect was found for BRQ and QoL.BD favouring the intervention group (p < .05). LimitationsThe assessors were not blind at T1 (only at T2). Recruitment plan was impacted due to COVID-19 restrictions and replication is questionable. High attrition rates in the CG. ConclusionsThe acceptability of Bi-REAL was sustained, and subsequent feasibility testing will be necessary to establish whether the retention rates of the overall trial improve and if feasibility is confirmed, before progressing to a definitive trial.

Global perspectives on bipolar disorder treatment: in-depth comparative analysis of international guidelines for medication selection.

Bipolar disorder, a chronic mental health condition characterised by fluctuations in mood, energy and functionality, affects millions of individuals worldwide. Its management requires a comprehensive approach, and, as such, treatment guidelines have a pivotal role in guiding clinicians to alleviate symptoms, prevent relapse and enhance overall patient well-being. However, the treatment landscape is far from homogenous, with significant variations existing across different countries. This study aimed to explore and compare treatment guidelines for bipolar disorder in various regions, shedding light on the factors that influence therapeutic approaches and thus offering insights that could contribute to the ongoing refinement of evidence-based practices in management. The study explores various international treatment guidelines for bipolar disorder that have been updated after 2014. Guidelines from the UK, Canada, Australia/New Zealand, South Korea and the International College of Neuropsychopharmacology are scrutinised to identify factors contributing to the observed differences among them. The variations in recommended drugs across guidelines arise from the approaches employed in guideline development - whether relying on expert consensus or meta-analysis results. Timing disparities in conducting these analyses and the selection of studies also exert influence. Moreover, differences in metabolic enzymes among diverse races and the health policies implemented by individual nations play a significant part in shaping these differences. The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.

Lithium carbonate-induced confusional state in patients with bipolar disorder: identification of case reports and review of the evidence

Objective: Lithium carbonate is a mood stabilizer used in the treatment of bipolar disorder. However, its narrow therapeutic index (normal = 0.6-1.2 mmol/L) predisposes patients to toxic effects. This study aimed to identify case reports and review the evidence on the frequency, mechanism, risk factors and guidelines associated with a lithium-induced confusional state in patients with bipolar disorder. Methods: All Databases from the National Center for Biotechnology Information (NCBI) were used to search for lithium AND “confusional state” AND “case report” published in English between 2015 and 2020. This search engine was also used to search for lithium AND “confusional state” AND frequency OR mechanism OR “risk factor” OR guideline published in English. Results: Case reports showed (1) all patients were treated with lithium for bipolar disorder and hospitalized for a confusional state, (2) most patients took concomitant therapies and recovered after lithium withdrawal, (3) some patients were female and old-aged (65+ years old), and (4) no ethnicities, causality assessments and dose patterns were reported. Other scientific literature showed (1) frequencies of a lithium-induced confusional state varied from very common (&gt;10%) to rare (&lt;0.01%), (2) inhibition of inositol phosphate-phosphatase (IMPase) and glycogen synthase kinase-3 (GSK3) might result in a lithium-induced confusional state, (3) ageing, diseases and concomitant therapies increased the risk of a lithium-induced confusional state, and (4) patients should complete lab tests and diagnostic procedures to monitor and/or prevent a lithium-induced confusional state. Conclusion: Case reports and other scientific literature elucidated the relationship between lithium and a confusional state.

Study on the Correlation between Hcy and Hs-CRP Levels and Cognitive Function in Patients with Bipolar Disorder and Borderline Personality Disorder.

This study aims to explore the correlation and clinical significance of homocysteine and high-sensitivity C-reactive protein levels with cognitive function in patients with bipolar disorder (BD) and borderline personality disorder (BPD). Patients with BD admitted to our hospital from January 2022 to December 2022 were chosen retrospectively. BPD patients were categorized into comorbidity groups, while those without BPD were assigned to non-comorbidity groups, each consisting of 60 cases. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess serum levels of homocysteine (Hcy) and high-sensitivity C-reactive protein (hs-CRP) in both patient groups. Clinical symptoms were evaluated by the Hamilton Depression Rating Scale (HAMD) and the Young Mania Rating Scale (YMRS). Cognitive function was evaluated and compared using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pearson correlation analysis was performed on the correlation between patients' serum Hcy and hs-CRP levels and HAMD, YMRS, and RBANS scores. In the comorbidity group, patients exhibited significantly elevated serum Hcy and hs-CRP levels compared to the non-comorbidity group (p < 0.05). Patients in the comorbidity group displayed higher HAMD and YMRS scores than those in the non-comorbidity group (p < 0.05). Additionally, attention, speech, visual span, immediate memory, and delayed memory in the comorbidity group were notably lower than in the non-comorbidity group (p < 0.05). The speech, visual span, and immediate memory of RBANS in bipolar depressive patients with comorbid BPD were lower than those in bipolar depressive patients without comorbid BPD (p < 0.05), the speech of RBANS in bipolar manic patients with comorbid BPD was lower than those in bipolar manic patients without comorbid BPD (p < 0.05). Pearson correlation analysis showed that the expression of Hcy and hs-CRP in the comorbid group was positively correlated with HAMD and YMRS scores, and negatively correlated with attention, speech, visual span, immediate memory, and delayed memory, and these differences were statistically significant (p < 0.05). High serum Hcy and hs-CRP expression levels may regulate inflammatory responses, aggravating cognitive impairment in patients with BD and BPD. Serum Hcy and hs-CRP expression levels are significantly related to cognitive dysfunction. They are expected to guide the prevention and treatment of BD comorbid BPD patients.

Effect of antipsychotics and mood stabilisers on metabolism in bipolar disorder: a network meta-analysis of randomised-controlled trials

Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA=90.7%) and serum insulin (SUCRA=96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA=82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA=93.3%), TG (SUCRA=89.6%), and LDL (SUCRA=94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA=82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA=100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).

Oxcarbazepine for the treatment of bipolar and depressive disorders in the outpatient setting: A retrospective chart review

Oxcarbazepine is often utilized off-label for bipolar and depressive disorders in outpatient settings despite limited evidence. We performed a retrospective chart review on 38 adult outpatients diagnosed with bipolar and depressive disorders (ICD-10 codes F30-39), treated with oxcarbazepine by psychiatrists and psychiatric nurse practitioners between 2015 and 2021. Primary outcomes were Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores, assigned retrospectively from clinical documentation. Patients were predominantly female (70%), aged 20–76 (mean 36), with a mean of 1.8 DSM diagnoses (range 1–4) and 1.7 (range 0–5) concurrent psychotropic medications. A starting mean oxcarbazepine dose of 489 mg/day, titrated to a mean final dose of 663 mg/day, was associated with a CGI-I of 2.5 [2.25, 2.75] and a pre-to-post treatment decrease in CGI-S from 3.4 to 2.4. Overall response and remission rates were 52% and 29%, respectively. Limitations of this study include potential sample bias, documentation bias and rater bias among other limitations inherent to retrospective study designs.

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study.

Mood stabilisers and other psychotropic drugs can lead to serious adverse drug events (ADEs). However, the incidence remains unknown. We aimed to (a) determine the incidence of serious ADEs in patients with bipolar or schizoaffective disorders, (b) explore the role of lithium exposure, and (c) describe the aetiology. This study is part of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Between 2001 and 2017, patients in the Swedish region of Norrbotten, with a diagnosis of bipolar or schizoaffective disorder, were screened for serious ADEs to psychotropic drugs, having resulted in critical, post-anaesthesia, or intensive care. We determined the incidence rate of serious ADEs/1,000 person-years (PY). In 1,521 patients, we identified 41 serious ADEs, yielding an incidence rate of 1.9 events per 1,000 PY. The incidence rate ratio (IRR) between ADEs with lithium present and causally implicated and ADEs without lithium exposure was significant at 2.59 (95% CI 1.20-5.51; p = 0.0094). The IRR of ADEs in patients <65 and ≥65 years was significant at 3.36 (95% CI 1.63-6.63; p = 0.0007). The most common ADEs were chronic lithium intoxication, oversedation, and cardiac/blood pressure-related events. Serious ADEs related to treatment of bipolar (BD) or schizoaffective disorder (SZD) were uncommon but not rare. Older individuals were particularly at risk. The risk was higher in individuals exposed to lithium. Serum lithium concentration should always be checked when patients present with new or unclear somatic symptoms. However, severe ADEs also occurred with other mood stabilisers and other psychotropic drugs.

Preparation and characterization of injectable in-situ forming gel based on lipid liquid crystal for one month delivery of aripiprazole: In-vitro and in-vivo evaluations in rats

The present study developed a one-month sustained-release formulation of aripiprazole, used for the treatment of schizophrenia and bipolar disorder, based on lipid liquid crystal (LLC) using phosphatidylcholine (PC) and N-methyl-2-pyrrolidone (NMP) solvent with sorbitan monooleate (SMO) or derivative glycerol oleate (glycerol monooleate (GMO), glycerol di-oleate (GDO), and glycerol trioleate (GTO)). The best formulation was selected based on the minimum initial burst release and the highest release of aripiprazole during the 30-day period. So, the formulations containing GMO and SMO exhibited the best initial slow release, while the other two formulations showed a burst release within 24 h. Furthermore, the GMO formulation did not release the drug completely during the 30-day study period, and the formulation containing GTO released the drug completely in less than a month. Therefore, the two formulations containing SMO and GDO were selected for further tests. The prepared liquid crystals had a hexagonal structure, indicating the creation of a suitable formulation structure with slow and controlled release. The area under the curve for the LLC-SMO formulation was higher than for other formulations, supporting the sustained release of aripiprazole and improving the long-term bioavailability of the drug. Moreover, this formulation was found to be safe and did not cause any damage to the skin at the injection site or vital organs such as the spleen, kidney, brain, heart, and liver. Hence, it can be considered a suitable option for developing an extended-release LLC formulation of aripiprazole.

The Dilemma of Lithium Discontinuation in Bipolar Disorder During Pregnancy Planning: A Case Report and Literature Review

IntroductionLithium is considered the gold standard mood stabiliser for bipolar disorder, yet its use during pregnancy remains controversial, demanding careful consideration of potential risks and benefits. Classically, it has been associated with an increased risk in congenital heart defects, however, recent studies point towards a much lower absolute risk than was previously believed. Furthermore, discontinuation of lithium before or during pregnancy poses a high risk of destabilisation and lithium has been shown to reduce the risk of relapse both in pregnancy and in the postpartum period. Hence, treatment planning is of the upmost importance in this patient group and individual risk stratification should be undertaken for patients to make informed decisions about their treatment.ObjectivesTo describe the case of a patient with bipolar disorder who discontinued lithium treatment while attempting to conceive and subsequently presented with a manic episode and to expand the scientific knowledge on this topic.MethodsCase report and brief literature review.Results A 41-year-old patient with a diagnosis of bipolar disorder, previously on lithium 900mg/day, was admitted to the emergency department with symptoms suggestive of a manic episode. One month prior, the patient had discontinued treatment with lithium due to her desire to pursue pregnancy and interrupt treatment while trying to conceive. The patient had a history of postpartum psychosis followed by various depressive and manic episodes with psychotic symptoms, leading to a bipolar disorder diagnosis and commencing treatment with lithium. Her consultant psychiatrist had informed her of the individualised risks of interrupting treatment with lithium and had advised to continue treatment alongside frequent follow-up due to the high-risk of relapse. Despite her consultant’s recommendation, she decided to interrupt treatment and hence a personalised lithium tapering regime and advice to continue treatment with quetiapine 200mg/day was given. During the ED stay, treatment with olanzapine was introduced which helped to stabilise her symptoms. Lithium levels were subtherapeutic (lithium serum level 0.11 mmol/L). Inpatient psychiatric admission was avoided due to rapid symptom improvement, strong social support in the community and her preference for ambulatory care. Lithium was gradually reintroduced and antipsychotic treatment was adjusted at follow up appointments, which ultimately led to the resolution of symptoms and stabilisation.ConclusionsThis case highlights the significance of considering continuing lithium treatment in bipolar disorder during pregnancy planning. Decisions about medication in pregnancy are multifaceted, making appropriate risk stratification imperative in order to inform individualised care plans to minimise the risk of relapse in these patients.Disclosure of InterestNone Declared

Methylomic signature of lithium response in bipolar disorder

Introduction Bipolar disorder (BD) is a chronic and severe psychiatric disorder, characterized by the alternance of episodes of (hypo)-mania and major depression. Lithium (Li) is the first-line treatment for BD but unfortunately response to Li is highly variable: after at least two consecutive years of treatment, only a fraction of patients receiving Li will display significant improvement in the frequency and/or severity of mood recurrences. This interindividual variability of treatment response is difficult to predict, in the bipolar disorder context. This could be determined by genetic factors still misidentified by available genetic studies. In addition, no clinical or biological markers are available to reliably define eligibility criteria for a lithium treatment in bipolar disorder. A consequence is a long process of therapeutic trials (18-24 months) to phenotype Li response, delaying the stabilization.ObjectivesTo identify objective biomarkers of the prophylactic response to lithium in order to improve patient care and propose therapeutic alternatives to patients who do not respond to lithium.Methods Using a genome-wide methylomic approach, and then logistic regressions incorporating as covariates the different types of treatments, we were able to identify differentially methylated regions (DMRs) whose methylation difference between responders and non-responders was not impacted by co-prescribed treatments. Then, we used Methylation Specific High-Resolution Melting (MS-HRM), a PCR based method than can be implemented in any medical laboratory at low cost and with minimal equipment, to estimate methylation proportion of 9 DMRs in 61 samples of bipolar patients.Results In the sample of 61 individuals with BD, the 9 MS-HRM-measured DMRs combined with clinical variables (age, sex, cigarette smoking status, lifetime number of hospitalizations, age at onset of BD, polarity at onset, psychotic symptoms at onset, family history of BD, lifetime alcohol/cannabis misuse, panic disorders, Li prescribed as the first mood stabilizer (vs 2nd or 3rd choice)) correctly classified 83,6% of individuals as good or non-responders (n=61, prophylactic response phenotype defined using the “Alda” scale). Excluding the partial responders, the percentage of correctly classified individuals is as high as 100% (n=43, 18 non responders and 25 responders). The AUC are respectively AUC=0.913 and AUC=1.0.ConclusionsThe MS-HMR method allow to identify the response status of individuals with BD with 9 DMR. These DMRs discriminate good from non-responders and can be used in combination with clinical variables.Disclosure of InterestNone Declared

Relationship between changing cognitive domains and atypical antipsychotic treatment in bipolar disorders: a three-year observational study in a psychiatric rehabilitation center during COVID-19 pandemic

IntroductionBipolar Disorders have been consistently associated with cognitive dysfunction across a broad range of cognitive domains (patients, who usually took psychiatric drugs, sometimes presented changes of cognitive disorders). Many studies have focused on improving the illness severity of patients with MDD or BD by combining mood-stabilizing drugs with atypical antipsychotics (AA). However, the results are contradictory and have not confirmed the certain superiority of AA to other therapeutic strategies. Among these, the cognitive remedy has demonstrated important effectiveness on cognitive variations in this group of patients.ObjectivesIn our study, we tried to evaluate some changes in cognitive function in patients with BD treated with antipsychotics related to critical problems with typical cognitive tests.MethodsIn our observational study, we recruited forty-three inpatients (20 females, 23 males) affected by Bipolar Disorder (DSM-5 criteria; particularly 78.5% affected by BD-I), in a psychiatric rehabilitation center. All patients were included in the ordinary rehabilitation treatment. All patients were treated with mood stabilizers (lithium n. 14; valproate n. 29), and at least one AA. The AAs have been the following: quetiapine, aripiprazole, and olanzapine (authorized in Italy)(Table 1). The observation period lasted three years, during three significant waves of the COVID-19 pandemic.All patients at baseline (T0) (March-April 2020), T1 (Maj-June 2021), T2 (April-Maj 2022), and T3 (April – June 2023) were administered the following rating scales: BPRS, YMRS, GAF, and HAM-DThe data were statistically analyzed with the EZAnalyze 3.0 software for the Excel platform.ResultsIn Table 2 and Graphic the results obtained with the rating scales and statistical analysis are shown. In BRPS the data shows a statistically significant reduction in the total score in all periods analyzed. Similar results were found in the GAF and YRMS scales. However, with the HAM-D Scale, there was evidence of an increase in T2, although the differences were not statistically demonstrated. The differences in mean scores are more evident for quetiapine and olanzapine.Image:Image 2:Image 3:ConclusionsOur observational study showed that the atypical antipsychotics used in our work allowed a significant improvement of the symptoms in BD. However, the pandemic waves have no correlation with the treatment performed. New studies are necessary to highlight the relationship of the pharmacological treatment of BD with the progress of the COVID-19 pandemic.Disclosure of InterestNone Declared