Background The advantages of lithium in treating bipolar disorder (BD) are inconsistent with a declining trend in lithium prescriptions worldwide. Understanding lithium prescription patterns and serum concentrations could improve lithium clinical practices. Methods This multicentre study used latent variable analysis to explore lithium prescription patterns and changing trends in lithium serum concentrations. A regression model was used to identify their underlying associated factors. Results High- and low-dose prescription patterns were discovered in patients with mania and bipolar depression (BD-D), respectively. Patients with BD-D tended to receive lower lithium dosages. Lithium combination therapy was mainstream for BD. Factors associated with prescription patterns differed between patients with mania and BD-D. The lithium concentration-to-dose (C/D) ratio initially decreased but then increased. The final lithium serum concentration was mainly associated with dose titration. Conclusions In this study, lower lithium dosage combined with second-generation antipsychotics is commonly used in the treatment of BD, and lithium prescription patterns fail to follow the guideline recommendations for BD. There are episode-specific factors associated with lithium prescriptions. A non-linear trend in the C/D ratio appears to be one of the factors contributing to lithium delay effects. Adjusting the lithium dosage is a direct way to change its serum concentration. Key Points Lower lithium dosage combined with SGAs is commonly used in the treatment of BD, and lithium prescription patterns fail to follow the guideline recommendations for BD. Factors associated with lithium prescription patterns differed between patients with mania and BD-D. In the context of a standardised lithium dosage (1 g), lithium plasma levels initially decrease before gradually increasing, which appears to be one of the factors contributing to lithium delay effects.

Bipolar disorder (BD) is commonly misdiagnosed as major depressive disorder (MDD) due to depression often preceding manic symptoms. Yet, neurobiological mechanisms underlying emotional states transition in depressed patients remain largely unexplored. Leveraging a lifespan normative model from a large healthy cohort (N = 1262), we quantified the structural or functional brain variability for 389 depressed patients (179 MDD, 138 BD, 72 transition to BD [tBD]). The MDD and tBD patients were followed up for 6~13 years. A dimensional approach was employed to dissect the neuroimaging variability across different clinical dimensions in MDD and BD patients, represented as the transdiagnostic covariation modes between clinical risk factors for emotional states transition and brain structural or functional variability. Two covariation modes were identified: Mode 1, tied to earlier age of onset, exhibited reduced activity in limbic/subcortical networks and increased activity in dorsal attention, executive control networks, which facilitated differentiating BD from MDD; Mode 2, associated with the retardation symptom, revealed gray matter atrophy in default mode, limbic and subcortical networks, whose structural pattern identified tBD from MDD. Multifaceted genetic landscape underpinning the structural pattern in Mode 2 suggested dopamine (specifically DRD2-related genetic risk) showed a significant association with the structural deficits in reward circuit, covary with the changes of retardation symptom. Our findings aid in better understanding the underlying neurobiological mechanisms of emotional states transition and clinically subtle symptom changes in early-stage BD patients who have never experienced a mania/hypomania episode, providing important target information for early intervention in BD.

ABSTRACTBackgroundThis was a 4‐year mirror‐image study of adult patients diagnosed with bipolar disorder (BD) assessing the effects on treatment continuation and hospitalisation between aripiprazole 1‐month (A1M), risperidone‐LAI (R‐LAI) and the monthly and 3‐monthly formulations of paliperidone palmitate (PP1M, PP3M). We aimed to evaluate and compare the use of A1M, R‐LAI, and the monthly and 3‐monthly formulations of paliperidone palmitate (PP1M, PP3M) by using the change of number and length of hospitalisations 2 years before compared to 2 years after initiation of LAIs for continuers and discontinuers. Secondary outcomes were: (1) discontinuation rates at 2 years and reasons per LAI, (2) time to discontinuation per LAI, and (3) time to first hospitalisation per LAI.ResultsA total of 122 BD were included; 74 continued LAI treatment at two years. Reasons for discontinuation were poor compliance (50%), ineffectiveness (43.2%), and tolerability issues (13.6%). Both time to individual LAI discontinuation and time to first hospital admission were significantly lower in the R‐LAI group. There was a significant overall reduction in the number and length of hospitalisations two years before and after LAI initiation, although multivariate logistic regression analysis showed that A1M, PP1M and R‐LAI were associated with an increased risk (OR = 1.89, 95% CI = 1.54–3.68, p = 0.015; OR = 1.63, 95% CI = 1.29–2.77, p = 0.022; OR = 3.08, 95% CI = 1.48–6.05, p = 0.008, respectively) of bed usage compared to PP3M. Last, study completers showed a considerable drop of 79% in number of hospital admissions and 83% in bed days (p = 0.001) as opposed to non‐completers.ConclusionsStudy findings suggest that long‐acting antipsychotics such as A1M, PP1M, and particularly PP3M are associated with high retention and lower hospitalisation rates after 2 years of treatment in patients with BD.

Psilocybin use in bipolar disorder: A comprehensive review.

BACKGROUNDAnxiety disorders are highly prevalent in patients with bipolar disorder (BD) and are associated with a more severe illness course and poorer outcomes. A significant clinical challenge is the frequent initial misdiagnosis of BD as anxiety, leading to prolonged diagnostic delays and suboptimal treatment. Growing evidence suggests that early intervention in individuals at high risk for BD can improve prognosis. Established clinical high-risk factors include early onset, family history of BD, and subthreshold manic symptoms. This creates a clinical dilemma whereby the administration of first-line antidepressants (e.g., sertraline) for anxiety is debated in patients with a bipolar diathesis, given the associated risk of mood destabilization. Conversely, mood stabilizers like lithium are foundational in BD treatment, but their role in treating anxiety in high-risk populations is unproven. Therefore, we conducted this randomized controlled trial to evaluate whether early intervention with a combination of sertraline and lithium is more effective than sertraline monotherapy for anxiety disorder patients with clinical high-risk factors for BD.AIMTo investigate whether early intervention has a more positive outcome for anxiety disorders in patients who present with clinical high risk factors for BD.METHODSA total of 66 patients were enrolled in this study from January 2021 and December 2022 in Huzhou Third Municipal Hospital. They were randomly assigned to two groups to receive either an antidepressant (sertraline, n = 32) or a combination therapy (sertraline and lithium, n = 34). The main variables included alterations in Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores from the initial assessment to the final evaluation. A thorough combined Wald test was conducted to examine the intention-to-treat differences in scale assessment across treatment and time conditions.RESULTSSignificant differences in the change of Hamilton Anxiety Rating Scale scores were observed between the two groups at week 1, week 2, and week 4 (P < 0.05). However, after 8 weeks and 12 weeks of treatment, there were no significant different (P = 0.485 and P = 0.206). There was no significant difference in the change over time in Hamilton Depression Rating Scale scores between the treatment groups (P = 0.2), except at week 12 (P = 0.034). No significant differences were observed in the adverse effects reported between patients treated with sertraline alone (18%) and those treated with the combination therapy (21%).CONCLUSIONThis current double-blind, case-controlled study assessed the effectiveness and tolerability of combined therapy vs monotherapy for anxiety disorder in patients with clinical high-risk factors for BD. In light of the constraints associated with this initial study, the results imply that the combination of sertraline and lithium may provide a more favorable prognosis.

Chronic renal impairment can be caused by prolonged exposure to lithium (Li), which is considered a prototype medication for the treatment of bipolar disorders (BDs). The current study aimed to enhance the biological efficacy of biosynthesized gold nanoparticles (Au-NPs) using an algal extract from Nannochloropsis oculata to mitigate the neurotoxicity and kidney damage induced by Li in rats. The kidney and brain tissues were analyzed using conventional biochemical tests to assess oxidative stress and inflammatory responses. Electrophoretic techniques were used to examine native protein and isoenzyme patterns. Histopathological analysis was conducted on both tissues. mRNA expression levels of inflammatory markers (NF-κB, IL-6, and IL-1β) and antioxidant enzymes (SOD1, CAT, and GPx1) were also measured. The study found that the gold N. oculata nano-extract restored normal hematological and biochemical parameters that were affected by an injection of lithium carbonate (Li2CO3). It improved antioxidant indicators, reduced inflammatory markers, and enhanced the antioxidant state of kidney and brain tissues. The gold nano-extract also reduced histopathological damage to the brain and kidney caused by Li2CO3. Furthermore, it alleviated the differences in electrophoretic patterns between the Li2CO3-injected group and the control group. The nano-extract also restored mRNA expression of inflammatory markers and antioxidant enzymes that were altered by Li2CO3 intoxication. The study found that the gold N. oculata nano-extract reduced kidney and brain toxicity at various levels, including biochemical, histopathological, physiological, and molecular.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-33835-5.

This study aimed to explore and understand the experiences of patients with bipolar disorder type I who underwent magnetic resonance imaging (MRI) brain scans as part of lithium treatment assessment in the European R-LiNK study. All participants underwent brain imaging at baseline and three months after starting lithium treatment. 1H-MRI scans (structural, diffusion-weighted, and single voxel proton spectroscopy) were conducted on both occasions, with 7Li-MRI at the second visit, all at 3T. The study used a qualitative, inductive approach to explore patients' subjective experiences. Eight participants were included, four males and four females, aged 22 to 52 years. This group was selected from the R-LiNK study based on s having completed the imaging component before and after lithium treatment initiation. Seven themes were identified: Motivations for Participation, Experiences with MRI Scans, Psychological Impact of MRI Scans, Patient Reflections on Lithium Use, Integration of Technology in Treatment, Evaluating Combined Treatment Strategies, and Implications for Future Research. Participants commonly described lithium as contributing to mood stabilisation, while the MRI scans provided several individuals with a tangible sense of the biological underpinnings of their illness. Conversely, some participants reported anxiety and discomfort with the MRI procedure and particularly in relation to lithium's side effects, emphasizing the importance of supportive and empathetic communication throughout the treatment process to encourage trust and understanding. This qualitative study revealed that adding 7Li-MRI scans to the early stages of lithium treatment subjectively validated the diagnosis, increased participants' confidence in the treatment process, and highlighted the importance of integrating patient experiences when incorporating advanced technology to monitor treatment response.

Exploring temperamental and clinical predictors of lithium treatment outcomes in bipolar disorder using diverse machine learning approaches.

Epigenetic markers of lithium response in bipolar disorder: optimization of a Methylation-Sensitive High-Resolution Melting assay (MS-HRM) and relevance in combination with clinical factors.

Bipolar disorder (BD) often begins in adolescence, a period marked by dynamic neurodevelopment. However, the neurobiological basis from genetic risk and subthreshold symptoms to diagnosed BD remains unclear. We conducted a cross-sectional analysis using data from the Recognition and Early Intervention of Prodromal Bipolar Disorders cohort (NCT01863628), including 392 participants aged 12-25 years with a balanced sexual distribution, stratified into five groups: offspring of patients with BD with (OBDs, n=48) or without (OBDns, n=62) subthreshold symptoms, individuals without BD family history but with subthreshold symptoms (nOBDs, n=63), patients diagnosed with BD (n=133) and healthy controls (HCs, n=86). Cortical thickness relative to HC was assessed using high-resolution T1-weighted images and FreeSurfer V.7.3.2. Gene expression patterns were derived from the Allen Human Brain Atlas, and partial least squares regression, along with gene enrichment analyses, were applied to link cortical alterations with underlying transcriptomic profiles. Cross-sectional analyses revealed graded cortical thickness differences across the BD risk spectrum, with patients with BD showing the most pronounced deviations and high-risk individuals with subthreshold symptoms displaying intermediate features relative to HCs. Cortical changes were significantly associated with spatial gene expression patterns, particularly in genes involved in mitochondrial ATP production, oxidative phosphorylation and synaptic signalling. Gene set enrichment revealed that BD-specific cortical thinning correlated with downregulation of excitatory synaptic pathways and excitatory neuron-related gene expression. Conversely, high-risk individuals exhibited upregulation of both excitatory and inhibitory neuronal markers. Developmental transcriptomic enrichment further linked significant genes to mid-childhood and adolescence. By identifying distinct transcriptomic signatures associated with cortical thinning at different stages, our findings underscore the potential of transcriptomic markers for early detection and intervention in BD. The findings highlight the potential for using transcriptomic markers for early detection and intervention, suggesting that identifying these markers could lead to improved outcomes for at-risk adolescents. This research has the potential to inform clinical practices and policies aimed at early screening and preventive strategies for BD.

Simple lithium measurement in capillary dried plasma microsamples collected with the HealthID PSD device.

Aripiperazole is an atypical antipsychotic belongs to BCS Class IV, hygroscopic drug used in the treatment of schizophrenia, bipolar disorder, and major depressive disorder also helps to balance dopamine and serotonin levels in the brain with potentially fewer side effects like weight gain. So It has low risk of hyperprolactemia and lower incidence of sedation, Due to this reason doctors and patients often prefer it This comprehensive preformulation study aims to investigate the physicochemical properties of aripiprazole and evaluate its behavior under various conditions relevant to pharmaceutical formulation development. To understand its physical and chemical properties to develop a safe effective and stable dosage form using this drug aripiperazole. Its preformulation study is require. The preformulation study encompasses solubility analysis, stability assessment, particle size distribution, polymorphism, hygroscopicity, and compatibility with common excipients e.g Magnesium stearate, Polyvinyl pyrollidone K30, Lactose monohydrate, Microcrystalline cellulose. Results indicate that aripiprazole exhibits poor aqueous solubility, with pH-dependent solubility profiles. Stability studies reveal sensitivity to light and elevated temperatures. Particle size analysis shows a tendency for agglomeration, while polymorphic studies confirm the existence of multiple crystal forms. Hygroscopicity tests demonstrate minimal moisture uptake under standard conditions. Excipient compatibility studies identify potential interactions with certain additives like Magnesium stearate and Polyvinyl pyrollidone K30 exhibiting a conclusion that during formulation aripiperazole needs special attention and care as well standard optimization studies which can be proved as useful side effect reduction. These findings provide crucial insights for the development of stable, effective formulations of aripiprazole, paving the way for improved drug delivery systems and therapeutic outcomes.

Medication adherence is crucial for long-term outcomes in bipolar disorder. Despite the rising use of aripiprazole, a longacting injectable for bipolar disorder, once monthly to improve adherence and manage side effects, research on its effects in South Korean patients with bipolar disorder is limited. In this non-interventional, retrospective study, medical records were used to analyze aripiprazole once monthly treatment from its initiation in routine clinical settings. The data were collected at 1, 3, 6, 9, and 12 months. Functional level and symptom severity were measured using the Global Assessment of Functioning (GAF), Clinical Global Impression-Bipolar-Severity (CGI-BP-S), Young Mania Rating Scale (YMRS), Korean version of the Montgomery-Åsberg Depression Rating Scale (K-MADRS), and Hamilton Anxiety Rating Scale (HAM-A). Additionally, the dosages and number of pills of mood stabilizers and antipsychotics, and the total number of medications, were recorded. Among 24 patients with bipolar disorder, significant functional improvement and symptom relief were observed over 1 year, with a significant reduction in total pill count and dosages of mood stabilizers and antipsychotics. Specifically, the GAF score increased by 25.7% (p=0.001), while CGI-BP-S, YMRS, K-MADRS, and HAM-A scores decreased by 24.4% (p=0.001), 81.2% (p=0.001), 36.2% (p=0.002), and 36.1% (p=0.003), respectively. Six patients reported side effects such as akathisia, tremors, weight gain, and headache, but no severe adverse effects were noted. This study showed significant improvement in functional outcomes and mood symptoms with monthly aripiprazole treatment in bipolar disorder. Mood stabilizer and antipsychotic dosages were also reduced. The results highlight the proactive role of longacting injectable antipsychotics in enhancing functioning, symptoms, and quality of life in bipolar disorder.

ABSTRACT Disruption of social and circadian rhythms (SCRs) is linked to the pathophysiology and course of bipolar disorder (BD). Valproate response in BD is variable and may be influenced by SCRs and genetic polymorphisms. This study investigated the relationship of valproate response with COMT (rs4680), CLOCK (rs1801260), GSK3-ß (rs334558) polymorphisms, SCRs, and chronotype. Ninety-four subjects with BD in remission and under valproate treatment were enrolled. Rhythm was evaluated with the Social Rhythm Metric-5 (SRM-5), the Biological Rhythm Interview for Assessment in Neuropsychiatry (BRIAN), and the Morningness Eveningness Questionnaire. Valproate response was measured with the Alda Scale. Genotyping was detected using PCR-RFLP, and serum valproate levels were measured 12 h after the last dose. In GSK3-ß, the C/T genotype showed lower partial response rate (p = 0.02), and C allele was present in all evening chronotypes (p = 0.06). In COMT, A allele carriers had greater deviation in first social interaction (p = 0.04), and the A/A genotype had higher complete response rates than the A/G (p = 0.03). In CLOCK, C allele carriers had a later age of onset (p = 0.01), fewer previous depressive (p = 0.05) and manic/hypomanic (p = 0.02) episodes, lower BRIAN total (p = 0.01) and social subscale scores (p = 0.01), and lower SRM-5 weekly mood swing score (MSS) (p = 0.03). All evening chronotypes were non-C allele carriers (p = 0.06). Valproate response was predicted by a model including duration of illness, HDRS total score, number of previous manic/hypomanic episodes, SRM-5 weekly MSS, duration of valproate exposure, and presence of the A allele in COMT polymorphism (R 2 = 0.31, p < 0.001). These results highlight the value of integrating genetic and SCRs factors into personalized BD treatment.

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are a common treatment for depression and anxiety in adolescents but are associated with an increased incidence of bipolar disorder (BD). Whether this relationship is causal remains unclear.ObjectiveWe applied a quasi-experimental design to national registry data, using an instrumental variable (IV) approach (regional variation in prescribing practice) to investigate for a causal relationship between adolescent SSRI treatment and subsequent risk of BD.MethodsWe used national electronic health register data on individuals born 1991–1998 followed to maximum age 32 years, looking at individuals diagnosed with unipolar depression in adolescence. Using regional variation in prescribing practice as an IV, we compared risk of BD in adolescents prescribed vs not prescribed SSRIs (fluoxetine, sertraline or citalopram).FindingsIn non-IV analyses, adolescents who were prescribed SSRIs had an increased risk of BD, in keeping with previous research. Subsequent IV analyses, however, did not support a causal relationship between SSRI treatment and BD risk, either in the short or long term.Clinical implicationsThese findings do not support a causal relationship between SSRI treatment and risk of BD. Rather, they suggest that the apparent relationship between SSRI treatment and later BD may be a result of unmeasured confounding.

A case report on treatment of bipolar disorder in Late Onset Tay-Sachs disease

Aripiprazole, brexpiprazole, and cariprazine have a unique pharmacology as demonstrated by their high affinity to the dopamine type-2 receptor (ie, D2 receptor). These agents may be preferred over others for the treatment of psychotic and bipolar disorders due to their lower incidence of movement disorders and sedation. When prescribed adjunctively to full antagonist agents, partial agonist antipsychotics can mitigate adverse effects such as hyperprolactinemia. However, their high affinity for the D2 receptor may interfere with the efficacy of full antagonist antipsychotics when used in combination. Some partial agonists may be less preferred in particular patient scenarios based on their demonstrated clinical efficacy. Three illustrative patient cases highlight clinical pearls related to the safe and effective use of antipsychotic polypharmacy involving partial agonist antipsychotics.

Patterns and trends of medication use among patients with bipolar disorder in Northeast China: A study from a large psychiatric center (2013-2022).

Bipolar disorder: Systematic review of approved psychiatric medications (2008-2024) and pipeline Phase-3 medications.

Lithium and lamotrigine are mood stabilizers approved for the treatment of bipolar disorder. Lithium's narrow therapeutic index and comparatively minor alterations in plasma concentrations can have significant clinical sequelae (McKnight et al., 2012). Several classes of drugs have been implicated in developing lithium toxicity, including diuretics and nonsteroidal anti-inflammatory compounds (Finley, 2016). Lithium is not metabolized and is eliminated almost entirely via the renal route (Rust et al., 2018). Consequently, plasma concentrations are exquisitely sensitive to physiological factors affecting renal function, such as age, dehydration, and sodium imbalance. Sodium depletion can cause increased lithium reabsorption in the kidneys, potentially leading to toxicity (Joshi et al., 2019). Lamotrigine is known to carry the risk of causing rash, which in severe cases can be fatal. The rash leads to cutaneous and extracutaneous involvement, with impaired alimentation leading to fluid and electrolyte imbalance. In this case report, we present a patient prescribed a combination of lamotrigine and lithium. The patient developed rash due to lamotrigine, leading to lithium toxicity and acute kidney injury, emphasising the importance of monitoring patients closely when using these medications in combination.