Mania Research Articles

The Immunoseasonal Theory of Psychiatric Disorders.

Although the influence of the weather on the well-being and mental health of psychiatric patients has been widely seen, the relationships between various seasonal weather factors and depressive, manic, anxiety, and psychotic states have not been systematized in the literature. The current article describes the seasonal changes in weather-related immune responses and their impact on the development of episodes of depression, mania, psychosis, and anxiety, highlighting the T-helper 1 (Th1) and Th2 immune balance as their potential trigger. In autumn-winter depression, the hyperactivation of the Th1 system, possibly by microbial/airborne pathogens, may lead to the inflammatory inhibition of prefrontal activity and the subcortical centers responsible for mood, drive, and motivation. Depressive mood periods are present in most people suffering from schizophrenia. In the spring and summertime, when the compensating anti-Th1 property of the Th2 immune system is activated, it decreases the Th1 response. In individuals immunogenetically susceptible to psychosis and mania, the inhibition of Th1 by the Th2 system may be excessive and lead to Th2-related frontal and subcortical hyperactivation and subsequent psychosis. In people suffering from bipolar disorder, hyperintense changes in white matter may be responsible for the partial activation of subcortical areas, preventing full paranoid psychosis. Thus, psychosis may be mood-congruent in affective disorders.

The Course Patterns and Diagnostic Shifts of Patients With Schizoaffective Disorder: A Retrospective Cohort Study.

Since its introduction, schizoaffective disorder (SAD) has been one of the most controversial diagnoses in psychiatry, both clinically and nosologically. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), SAD diagnostic criteria were changed, and instead of a cross-sectional diagnosis, a longitudinal approach covering the life course of the illness was adopted. In this study, the meaning of this conceptual shift in the diagnosis of SAD in clinical practice is investigated throughout the course of the illness for patients with SAD. Sixty-two inpatients diagnosed with SAD according to DSM-5 diagnostic criteria are included in this study. The course of the illness from its onset to the present is investigated retrospectively. The disease duration is 18.3 ± 9.1 years. The most common diagnoses in the first hospitalization are bipolar disorder (manic episodes) and psychotic disorder, not otherwise specified. Furthermore, the time that elapsed between the first psychiatric application of the patients and the diagnosis of SAD is 9.5 ± 7.3 years. Further, when the course of the illness is grouped according to the predominance of affective and psychotic disorders, recurrent affective disorders are observed most frequently (29.3%), followed by mixed-episode disorders and a shift from affective disorders to psychotic disorders (22.4%). It is found that SAD has a heterogeneous course, and affective disorder diagnoses are more dominant during the course of the illness. The clinical relevance of the longitudinal emphasis on the total duration of the illness in the DSM-5 is also demonstrated. The affective and psychotic dichotomy, based on Kraepelin, has failed to elucidate the course of the disease in clinical practice. Therefore, clinicians should meticulously evaluate the entire course of the illness for SAD and avoid conclusive judgments over a single episode.

Disability and its correlates among persons with bipolar disorder: Exploratory findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

This study aimed to evaluate the disability and its correlates in persons with Bipolar Disorder during the remission phase. As part of the multicentric study, 773 patients with bipolar disorder, currently in clinical remission, were evaluated for disability on the Indian Disability Assessment Evaluation Scale. About one-fifth of the participants had some level of disability in the domain of self-care, one-third had some level of disability in the interpersonal domain, one-fourth had some level of disability in communication and understanding, and a maximum proportion (43.7%) had some disability in the domain of work. Overall, about one-fifth (18.4%) were considered to have a benchmark disability (i.e., disability >40%). In terms of correlates, those with a disability had a short duration of current remission, a higher number of manic and mixed episodes, a higher mean number of total episodes, spent more time in the episodes, had lower severity of the depressive episodes, higher residual depressive and manic symptoms, had overall higher manic affective morbidity, had a higher level of cognitive deficits, and had poorer insight. A significant proportion of patients with bipolar disorder have disability in work domain, and the presence of residual symptoms of either polarity are associated with higher level of disability.

Efficacy of cognitive behavioural therapy for bipolar disorder: A systematic review

IntroductionBipolar disorder (BD) is a serious mental illness with a chronic course and significant morbidity and mortality. BD has a lifetime prevalence rate of 1%–1.5% and is characterised by recurrent episodes of mania and depression, or a mixture of both phases. Although it has harmacological and psychotherapeutic treatment, cognitive behavioural therapy (CBT) has shown beneficial effects, but there is not enough clinical information in the current literature. MethodsThe main aim was to determine the efficacy of CBT alone or as an adjunct to pharmacological treatment for BD. A systematic review of 17 articles was carried out. The inclusion criteria were: quantitative or qualitative research aimed at examining the efficacy of CBT in BD patients with/without medication; publications in English language; and) being 18–65 years of age. The exclusion criteria were: review and meta-analysis articles; articles that included patients with other diagnoses in addition to BD and that did not separate the results based on such diagnoses; and studies with patients who did not meet the DSM or ICD criteria for BD. The PubMed, PsycINFO and Web of Science databases were searched up to 5 January 2020. The search strategy was: “Bipolar Disorder” AND “Cognitive Behavioral Therapy”. ResultsA total of 1531 patients both sexes were included. The weighted mean age was 40.703 years. The number of sessions ranged from 8 to 30, with a total duration of 45–120 min. All the studies show variable results in improving the level of depression and the severity of mania, improving functionality, reducing relapses and recurrences, and reducing anxiety levels and the severity of insomnia. ConclusionsThe use of CBT alone or adjunctive therapy in BD patients is considered to show promising results after treatment and during follow-up. Benefits include reduced levels of depression and mania, fewer relapses and recurrences, and higher levels of psychosocial functioning. More studies are needed.

Insight in patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

There are limited number of studies evaluating insight among patients with bipolar disorder (BD). This study aimed to examine insight and its correlates in BD using the data from the multicenter BD course and outcome study from India (BiD-CoIN). The additional aim was to evaluate the insight in patients with BD using different scales and understand the correlates of insight. 773 BD patients presently in clinical remission were evaluated on the Insight Scale for Affective Disorders (ISAD), insight items of the Hamilton Depression Rating Scale (HDRS), and the Young Mania Rating Scale (YMRS). The assessment scales influenced the prevalence of poor insight. Poorer insight irrespective of the assessment scale was consistently associated with higher residual depressive and manic symptoms, and a higher level of cognitive impairment and disability. Poor insight as assessed by ISAD was associated with a higher number of episodes in the lifetime, shorter duration of current remission, a higher number of depressive episodes, a higher amount of time spent in depressive episodes, higher depressive affective morbidity, a higher number of manic episodes, and higher residual depressive and manic symptoms. Poor insight in BD is consistently associated with higher residual depressive and manic symptoms and a higher level of cognitive impairment and disability. However, in terms of course variables, the correlates vary depending on the assessment method.

Episod maniacal indus prin corticoterapie postalblaţie de meningiom spinal. Rolul realităţii virtuale în psihoterapia anxietăţii postoperatorii

Corticosteroids have been linked to various neuropsychiatric adverse effects, including mood disorders. This case study describes a post-surgical manic episode (spinal meningioma ablation D11-D12) in a 57-year-old female patient on corticosteroids. This presentation aims to highlight corticosteroids’ potential psychiatric adverse effects and to emphasize the importance of recognizing and treating such complications. In this case, the management strategy involved discontinuing corticosteroids, initiating mood-stabilizing medications, and closely monitoring the symptoms. A mood stabilizer and a second-generation antipsychotic were administered to the patient to treat transient manic symptoms and prevent relapse. After discontinuing corticosteroids and beginning therapy with mood stabilizers, the patient’s bipolar symptoms improved. Psychoeducation and therapeutic support were provided to aid the patient in managing acute symptoms and encourage adherence to the treatment plan. As anxiety persisted after manic symptoms were controlled, the case management involved a psychotherapy technique facilitated by virtual reality. Relaxation breathing techniques were emulated through a virtual reality Oculus Quest 2 headset, improving patient-physician trust, subjectively relieving correlated anxiety, and ensuring therapeutic compliance during the admission and at home. Healthcare professionals must be vigilant to identify and effectively treat these complications of steroid anti-inflammatory medication. Immediate cessation of corticosteroids, the initiation of mood stabilizers and psychoeducation are essential for managing these cases. By presenting this case report, we hope to increase healthcare professionals’ awareness on the psychiatric consequences of corticosteroid use, the necessity of a multidisciplinary therapeutic approach, and the role of add-on virtual reality as integrated, personalized patient care to alleviate anxiety.

Deficits in sustained attention in adolescents with bipolar disorder during their first manic episode

ObjectivesEvaluate differences in sustained attention (SAT) and associated neurofunctional profiles between bipolar disorder type I (BD), attention-deficit/hyperactivity disorder (ADHD), and healthy comparison (HC) youth. MethodsAdolescent participants, aged 12–17 years, with BD (n = 30) and ADHD (n = 28) and HC adolescents (n = 26) underwent structural and functional magnetic resonance imaging (fMRI) while completing a modified Continuous Performance Task-Identical Pairs task. Attentional load was modifying in this task using three levels of image distortion (0 %, 25 % and 50 % image distortion). Task related fMRI activation and performance measures: perceptual sensitivity index (PSI); response bias (RB) and response time (RT); were calculated and compared between groups. ResultsBD participants displayed lower perceptual sensitivity index (0 % p = 0.012; 25 % p = 0.015; 50 % p = 0.036) and higher values of response bias across levels of distortion (0 % p = 0.002, 25 % p = 0.001, and 50 % p = 0.008) as compared to HC. No statistically significant differences were observed for PSI and RB between BD and ADHD groups. No difference in RT were detected. Between-group and within-group differences in task related fMRI measures were detected in several clusters. In a region of interest (ROI) analysis of these clusters comparing BD and ADHD confirmed differences between these two groups. ConclusionsCompared with HC, BD participants displayed SAT deficits. Increased attentional load revealed that BD participants had lower activation in brain regions associated with performance and integration of neural processes in SAT. ROI analysis between BD and ADHD participants shows that the differences were likely not attributable to ADHD comorbidity, suggesting SAT deficits were distinct to the BD group.

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study

BackgroundBipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD.MethodsA total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes.ResultsIn overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634–0.747), not in females.ConclusionsWhile both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.

Revisiting the association between treatment with antidepressants and mania: A nationwide within-individual study of 3554 patients with bipolar disorder.

Antidepressants are commonly used "off-label" for bipolar depression, despite concerns over the risk of potential treatment-emergent mania (or "manic switch"). Treatment-emergent mania is difficult to study with adequate power in clinical trials as it requires a large group of participants and long follow-up. Therefore, naturalistic register-based studies have been applied to assess this phenomenon. Here, we aimed to replicate previous findings and address key methodological limitations that were not previously taken into account. We utilized data from nationwide Danish health registries to identify patients with bipolar disorder treated with an antidepressant, either with or without concomitant treatment with a mood stabilizer (drug treatment proxied via redeemed prescriptions). We plotted the incidence of manic and depressive episodes relative to the initiation of antidepressant treatment and compared the incidence of mania in the period prior to and following initiation of antidepressant treatment (within-individual design). In 3554 patients with bipolar disorder initiating treatment with an antidepressant, the number of manic episodes peaked approximately 3 months prior to initiation of antidepressant treatment, and the number of depressive episodes peaked around the initiation of antidepressant prescription. This temporal pattern suggests that antidepressants were used to treat post-manic depression. Within-individual designs do not control sufficiently for confounding by indication, when the treatment indication is time-varying. Thus, results from prior within-individual studies of antidepressant treatment in the context of bipolar disorder may be invalid due to time-varying confounding by indication.

Prolactin Level Changes according to Atypical Antipsychotics Use: A Study Based on Clinical Data Warehouse.

: Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia. This study aimed to investigate the levels of serum prolactin depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse (CDW). : We conducted a cohort search in the CDW application and got 260 patients' medical records diagnosed with schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders who were taking one of risperidone, blonanserin, amisulpride, and olanzapine. After that, we reviewed the medical data and used the ANCOVA analysis and the post hoc test to compare serum prolactin levels among four antipsychotic drug groups. : Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.6 ± 54.6 ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between sex in the subjects who took amisulpride. : This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.

Single-cell immune profiling reveals broad anti-inflammation response in bipolar disorder patients with quetiapine and valproate treatment

Bipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood. Using single-cell RNA sequencing, we observed that B cells exhibited downregulation of inflammation-related genes, while pro-inflammatory mast and eosinophil cells decreased following treatment. Ribosomal peptide production genes were found to be reduced in both B and Tcells after treatment. Additionally, our findings suggest that the combined therapy effectively alleviates inflammation by reducing myloid-mediated immune signaling pathways. This study provides valuable insights into the immune atlas and uncovers a potential mechanism for immune disorder alleviation in patients with BD treated with quetiapine and valproate.

Dynamic time warp analysis of individual symptom trajectories in individuals with bipolar disorder.

Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3-6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. The mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the "Lethargy" dimension showed the highest out-strength, and its changes preceded those of "somatic/suicidality," while changes in "core (hypo)mania" preceded those of "dysphoric mania." Dynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

Sleep and bipolar disorder

A growing international scientific literature demonstrates the existence of sleep abnormalities and sleep/wake (or circadian) rhythms in bipolar disorder. These abnormalities exist during the acute phases of the disease, with the classic presentation of insomnia or hypersomnia during depressive episodes and a reduced need for sleep without feeling tired during manic episodes. But these disturbances can also appear or persist during phases of mood stability. However, it has now been clearly demonstrated that these disturbances can precipitate a new depressive or manic episode.

Predominant polarity in bipolar affective disorder and its impact on cognition and quality of life.

Bipolar mood disorder or bipolar affective disorder (BPAD) is a chronic illness characterized by phases of mania/hypomania, depression, or mixed episodes. The course of bipolar mood disorder is relapsing in nature. It is associated with high comorbidity rates, a large number of premature deaths due to suicide, and a worse social and work performance. All of those characteristics entail a significant economic impact due to both direct and indirect costs and require an effective diagnostic and therapeutic approach. Lifetime prevalence of BPAD is approximately 4% worldwide. Various attempts have been made to define "predominance" of polarity in BPAD. Our study tries to highlight the existence of predominant polarity by comparing effects of the same on substance consumption, cognitive abilities, quality of life, and preponderance of specific polarity to specific gender. After Institutional Ethics Committee Approval and written informed consent, patients who were diagnosed with BPAD attending out-patient department of a tertiary care hospital in Mumbai were recruited. A total of 57 participants were enrolled. The World Health Organization Quality of Life - Brief Scale (WHOQOL BREF) and the Montréal Cognitive Assessment (MoCA) were both used to evaluate the patients' quality of life and cognitive ability, respectively. Men exhibited manic predominant polarity, while women had depressive predominant polarity, with P value of. 003. Regarding age, illness length, education, substance abuse, family history, and suicide attempts, there was no discernible difference in the polarities. The outcome of female bipolar patients may be improved if the clinician is mindful of the burden of depression, risk of misdiagnosis, and variable therapy response. Interestingly, our study found no significant difference between MoCA scores of those with depressive and manic polarity. Substantial MoCA score differences were found between the groups with depressive polarity and no polarity. Men were observed to experience more manic episodes. More women in the study experienced predominantly depressive polarity, highlighting the need to probe for a past history of hypomania or mixed episodes to avoid misdiagnosis as unipolar depression in them. Manic predominate polarity performed better in the physical and psychological domains of the post hoc test for quality-of-life BREF scale. There were substantial MoCA score differences between the groups with depressive polarity and no polarity, with the depressive polarity showing more cognitive decline.

Should borderline personality disorder be placed on the bipolar spectrum?

Bipolar disorder (BD) is a mood disorder characterized by changes in activity levels, mood, and energy. These categories can range from elation during manic episodes to depression during depressive episodes. BD affects 2-3% of the population. Borderline personality disorder (BPD) is the diagnostic label assigned to individuals who struggle with unstable personal relationships, hypersensitivity to rejection, or an unstable self-image. 1.6% of the general population has this disorder and 20 percent of those in the psychiatric population have BD. Given that BD and BPD share features, such as rapid mood swings, impulsive actions, and suicidal behavior it is sometimes difficult for practitioners to readily and accurately differentiate between these two disorders. These issues with diagnosis have led to the idea BPD should belong on the spectrum of bipolar disorders. The current paper compares the disorders, including their clinical presentation and symptoms, the effect of genetic and environmental factors on the development of these disorders, and treatments for each disorder. The aforementioned topics represent factors underlying the resolution to the question of whether BPD belongs on the bipolar spectrum. Answering this question would allow researchers and clinicians to better understand the relationship between these disorders and the best treatments for BPD and BD.&#x0D;

Deep exome sequencing identifies enrichment of deleterious mosaic variants in neurodevelopmental disorder genes and mitochondrial tRNA regions in bipolar disorder.

Bipolar disorder (BD) is a global medical issue, afflicting around 1% of the population with manic and depressive episodes. Despite various genetic studies, the genetic architecture and pathogenesis of BD have not been fully resolved. Besides germline variants, postzygotic mosaic variants are proposed as new candidate mechanisms contributing to BD. Here, we performed extensive deep exome sequencing (DES, ~300×) and validation experiments to investigate the roles of mosaic variants in BD with 235 BD cases (194 probands of trios and 41 single cases) and 39 controls. We found an enrichment of developmental disorder (DD) genes in the genes hit by deleterious mosaic variants in BD (P = 0.000552), including a ClinVar-registered pathogenic variant in ARID2. An enrichment of deleterious mosaic variants was also observed for autism spectrum disorder (ASD) genes (P = 0.000428). The proteins coded by the DD/ASD genes with non-synonymous mosaic variants in BD form more protein-protein interaction than expected, suggesting molecular mechanisms shared with DD/ASD but restricted to a subset of cells in BD. We also found significant enrichment of mitochondrial heteroplasmic variants, another class of mosaic variants, in mitochondrial tRNA genes in BD (P = 0.0102). Among them, recurrent m.3243 A > G variants known as causal for mitochondrial diseases were found in two unrelated BD probands with allele fractions of 5-12%, lower than in mitochondrial diseases. Despite the limitation of using peripheral tissues, our DES investigation supports the possible contribution of deleterious mosaic variants in the nuclear genome responsible for severer phenotypes, such as DD/ASD, to the risk of BD and further demonstrates that the same paradigm can be applied to the mitochondrial genome. These results, as well as the enrichment of heteroplasmic mitochondrial tRNA variants in BD, add a new piece to the understanding of the genetic architecture of BD and provide general insights into the pathological roles of mosaic variants in human diseases.

A pilot pharmacogenetic study of calcium channel blocker treatment of bipolar mania

Common genetic variants located in calcium channel genes are important markers of genetic susceptibility for bipolar disorder (BD). Previous clinical trials with Calcium Channel Blocker (CCB) medication improved mood stability for some BD patients. We hypothesize that manic patients who carried calcium channel risk variants would differentially benefit from treatment with CCBs. In this pilot study, 50 BD patients (Chinese: 39; US: 11) who were hospitalized for manic episodes were given add-on CCB treatment. We determined genotypes for each patient. There was a significant decrease in the Young Mania Rating Scale (YMRS) after add-on medication treatment. Of note, two intronic variants of the Calcium Voltage-Gated Channel Subunit Alpha1 B (CACNA1B) were associated with treatment outcomes for manic patients: rs2739258 and rs2739260. BD rs2739258/rs2739260 AG-allele carriers had a better treatment response with add-on CCB than those carrying the AA or GG genotypes by survival analysis. Although these findings did not pass multiple testing correction, this study suggests that single-nucleotide polymorphisms (SNPs) residing in calcium channel genes could be predictors for response to add-on CCB treatment of bipolar mania patients, and that calcium channel genes may be involved in treatment responses for BD.

0642 Effect of Iloperidone on Sleep Symptoms in Bipolar Patients with Manic and Mixed Episodes: A Randomized, Placebo Controlled Study

Abstract Introduction Iloperidone, a dopamine D2 receptor and serotonin 5HT2A receptor antagonist, was evaluated for the treatment of acute manic and mixed episodes associated with bipolar I disorder in adults in a phase 3 clinical trial. A core symptom of bipolar I disorder is disturbance in sleep. During manic episodes this commonly presents as reduced need for sleep with studies finding that 69%–99% of bipolar individuals report a lessened need for sleep or difficulties in falling and/or staying asleep. Here we present a post hoc analysis evaluating iloperidone effects on the sleep component of the Young Mania Rating Scale (YMRS) in patients with bipolar I disorder which addresses both sleep and the reduced need for sleep in that component. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of iloperidone in patients with acute manic or mixed episodes associated with bipolar I disorder. Patients received four weeks of double-blind treatment. The primary analysis demonstrating an overall improvement from baseline YMRS score in iloperidone assigned patients versus placebo assigned patients (p = 0.000008) at the end of the study (week 4). A YMRS item level analysis evaluated changes on YMRS single items including the sleep component in the intent-to-treat population (N = 392) using a mixed-effects model for repeated measures approach. Results The least squares mean difference (LSMD) in change from baseline to day 28 was statistically significant on the YMRS sleep component in favor of iloperidone versus placebo (iloperidone = -1.26, placebo = -0.95; p = 0.008). Conclusion In addition to improving overall mania symptoms as reported by the YMRS, improvements were also seen in iloperidone treated patients in the sleep component which at baseline included assessments of both decreased sleep and decreased need or denial of the need for sleep. Support (if any) This work was supported by Vanda Pharmaceuticals Inc.

Cariprazine (Vraylar) for adjunctive treatment of depression.

The FDA has approved the second-generation antipsychotic drug cariprazine (Vraylar — Abbvie) for adjunctive treatment of major depressive disorder (MDD) in adults. Cariprazine was previously approved for treatment of schizophrenia and bipolar depression, and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

Lifestyle in bipolar disorder: A cross-sectional study

BackgroundModifiable lifestyle behaviors are important factors for improving mental health, yet there has been a lack of research studying lifestyle as a multidimensional construct in bipolar disorder (BD). The aim of this cross-sectional study was to compare the lifestyle patterns of individuals with BD in a current mood episode with healthy controls (HCs) using the Short Multidimensional Inventory Lifestyle Evaluation (SMILE). Materials and methodsThe sample consisted of 46 individuals with BD currently experiencing a depressive or manic episode and 50 HC, assessed using the MINI International Neuropsychiatric Interview, Montgomery-Åsberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS). The SMILE scale assesses lifestyle across seven domains: diet and nutrition, substance abuse, physical activity, stress management, restorative sleep, social support, and environmental exposures. Between-groups comparisons were performed based on the presence of a psychiatric diagnosis and the type of BD episode. ResultsWe found significant differences in the total SMILE score (r=0.75, p<0.001) and in scores from each domain of the scale between BD and HC (p<0.05), where individuals with BD in a depressive or manic episode with or without mixed features reported worse lifestyle across all domains. Differences between individuals with BD in different mood episodes across domains on the SMILE scale were non-significant. ConclusionFindings from this study highlight the presence of unhealthy lifestyle patterns in people with BD regardless of the polarity of their mood episode. Implementation of multidimensional lifestyle assessments is an essential step toward detecting the clustering of unhealthy lifestyle patterns in BD.