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Objectives: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address., Method: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion., Results: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options., Conclusion: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess clinical outcomes associated with the presence of a lifetime history of comorbid posttraumatic stress disorder in subjects with bipolar disorder., Methods: This cross-sectional study of 284 subjects with bipolar disorder (DSM-IV) assessed the association between lifetime comorbid posttraumatic stress disorder (DSM-IV) and clinical characteristics. Participants were included from January 2006 to June 2009. We assessed age at onset, number of mood episodes, presence of rapid cycling, first drug use, suicide attempts, hospitalizations, functional impairment, and quality of life. Diagnostic, clinical, and functional assessments were carried out using the Structured Clinical Interview for DSM-IV Axis I Disorders, patient edition (SCID-I/P), the Functioning Assessment Short Test, and the World Health Organization Quality of Life scale. The number of manic episodes as assessed by SCID-I/P was the primary outcome., Results: The prevalence of lifetime comorbid posttraumatic stress disorder was 19.7% (56 subjects). Subjects with bipolar disorder and posttraumatic stress disorder had an accelerated course of illness, with a lower age at onset of manic/hypomanic episodes (P = .009) and earlier initiation of illicit drug use (P = .008). In addition, they were more likely to be younger when they received the diagnosis of bipolar disorder (P = .036) and had a higher number of manic/hypomanic episodes (P = .01). Quality of life was worse in all domains among subjects who presented the comorbidity, and rates of functional impairment were higher., Conclusions: Comorbid posttraumatic stress disorder was associated with increased morbidity and accelerated illness progression among subjects with bipolar disorder., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objectives: Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD., Methods: One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV., Results: Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed., Conclusions: This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness.

Molecules that are involved in neuronal intercommunication and adaptability of neural networks, such as brain-derived neurotrophic factor (BDNF), are targets of pathophysiological investigation in bipolar disorder (BD). Quetiapine is an attested treatment in this disorder, used in acute mood episodes. The aim of this study was to report prospective changes in serum BDNF levels in drug-free patients in acute mood episodes of BD who received treatment with extended-release quetiapine along a 16 week follow-up. Assessments were performed at baseline and weeks 2, 4, 8 and 16 with the Young Mania Rating Scale, the Hamilton Depression Rating Scale and the Clinical Global Impression severity scale. In these visits, serum BDNF levels were measured. Mixed effect models were used to investigate longitudinal changes. Twenty-five patients were included for this analysis, seventeen in a current depressive episode and eight in a manic/mixed episode. A significant improvement from baseline to endpoint was displayed. In the mixed model, significant main effects for episode and time appeared, and a time versus episode interaction showing increasing BDNF levels with time in those with a depressive episode, but a decrease in BDNF levels with time in those with a manic/mixed episode. BDNF may be a biomarker with differential response according to the polarity of mood episodes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and neuroplasticity. Altered BDNF signaling is thought to contribute to the pathogenesis of schizophrenia (SZ) especially in relation to cognitive deficits. Clozapine (CLZ) has been shown a beneficial effect on cognition in SZ in some studies and a detrimental effect in others. To examine serum BDNF, two groups of chronically medicated DSM-IV SZ patients (n=44), on treatment with clozapine (n=31) and typical antipsychotics (n=13) had 5ml blood samples collected by venipuncture. Serum BDNF levels were significantly correlated with CLZ daily dose (r=0.394, p=0.028), but not with typical antipsychotic daily dose (r=0.208, p=0.496). This study suggests that serum BDNF levels are correlated with CLZ daily dose, and this may lead to the cognitive enhancement as seen in patients with SZ under CLZ. Despite the strong evidence that chronic administration of CLZ is effective for patients with SZ, it is still unknown whether atypical antipsychotic drugs regulate BDNF expression. Serum BDNF levels concentration in SZ merits further investigations with regard to the role of neurotrophins in the cognitive response to treatment with CLZ and other atypical antipsychotics., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Numerous studies have demonstrated an association between bipolar disorder (BD) and obesity. However, these reports are limited by retrospective or cross-sectional designs, and the assessment of patients with lengthy illnesses. Prospective data, and data on weight gain early in the course of BD, are lacking., Methods: We prospectively measured weight gain and laboratory metabolic indices over 12 months in 47 patients with BD receiving maintenance treatment following their first manic episode, and in 24 age- and gender-matched healthy subjects., Results: Although approximately two-thirds of patients had experienced previous depressive or hypomanic episodes, there was no difference between patients and healthy subjects in mean body mass index or rates of overweight or obesity at recovery from the first mania. Mean weight gain over 12 months was 4.76kg in patients and 1.50kg in healthy subjects (p=0.047). Combined rates of overweight and obesity at 6 months and 12 months exceeded 50% in patients, and were almost double those of healthy subjects. Logistic regression demonstrated that weight gain in the first 6 months was significantly associated with male gender and prescription of olanzapine or risperidone. Patients who were obese at 6 months and/or 12 months had significantly greater mean serum triglyceride levels and fasting glucose levels than non-obese patients., Limitations: This was a naturalistic study., Conclusions: Even in patients with previous depressions and hypomanias, clinically significant weight gain in BD begins following the first manic episode, suggesting that it is primarily related to treatment with mood stabilizers and second-generation antipsychotics. However, the very small number of patients in our sample who were medication-free precludes a meaningful analysis of the degree to which weight gain might be an inherent feature of post-manic BD.