Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142934/1/bdi12609.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142934/2/bdi12609_am.pd

Executive function deficits in bipolar I disorder : association with brain structure, illness progression, and antipsychotic medication

Executive function impairments are a core feature of Bipolar I Disorder (BDI), present not only during acute episodes but also persisting following remission of mood symptoms. Despite advances in knowledge regarding the neural basis of executive functions (EF) in healthy subjects, particularly in regards to the role of the dorsolateral prefrontal cortex (DLPFC) and caudate; research into how changes within these regions contribute to the deficits in BDI is lacking. This thesis explores EF in patients early in the course of illness, examining how impairments evolve with illness progression and how this may relate to neuromorphological changes and naturalistic pharmacological treatment regimes. The first analysis demonstrates that EF is moderate-severely impaired in patients with BDI even following sustained symptomatic recovery from their first manic episode. Both larger caudate size and treatment with a higher relative dose of an antipsychotic drug predicted the severity of deficits. Despite receiving ongoing clinical care, half of patients experienced a subsequent hypo/manic and/or depressive episode within one year. While those who remained well did show significant improvements in EF compared to those whose illness progressed, both patient groups still maintained moderate deficits compared to healthy subjects at follow-up. Although not directly associated with cognitive changes, sustained recovery during this time was also associated with reduced grey matter loss (including the left DLPFC) when compared affective recurrence, even after accounting for other clinical or treatment factors. Maintenance pharmacological treatment with an antipsychotic is commonly used to prevent episode recurrence in BDI. Drugs within this class each show varying affinity to the dopamine D₂ receptor (D₂R), which plays an important modulatory role in DLPFC and caudate function. Differences in D₂R binding have a likely impact on EF, as patients receiving an antipsychotic with high D₂R affinity (risperidone) showed larger impairments when compared to those treated with a low affinity drug (quetiapine) or no antipsychotic. These results demonstrate that illness related structural changes in the DLPFC and caudate are associated with the presence and evolution of executive function deficits in BDI; although the potential confounding effects of antipsychotics which influence functioning in these regions must also be considered.Medicine, Faculty ofGraduat

FcRn is a CD32a coreceptor that determines susceptibility to IgG immune complex-driven autoimmunity.

IgG immune complexes (ICs) promote autoimmunity through binding fragment crystallizable (Fc) γ-receptors (FcγRs). Of these, the highly prevalent FcγRIIa (CD32a) histidine (H)-131 variant (CD32aH) is strongly linked to human autoimmune diseases through unclear mechanisms. We show that, relative to the CD32a arginine (R)-131 (CD32aR) variant, CD32aH more avidly bound human (h) IgG1 IC and formed a ternary complex with the neonatal Fc receptor (FcRn) under acidic conditions. In primary human and mouse cells, both CD32a variants required FcRn to induce innate and adaptive immune responses to hIgG1 ICs, which were augmented in the setting of CD32aH. Conversely, FcRn induced responses to IgG IC independently of classical FcγR, but optimal responses required FcRn and FcγR. Finally, FcRn blockade decreased inflammation in a rheumatoid arthritis model without reducing circulating autoantibody levels, providing support for FcRn\u27s direct role in IgG IC-associated inflammation. Thus, CD32a and FcRn coregulate IgG IC-mediated immunity in a manner favoring the CD32aH variant, providing a novel mechanism for its disease association

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations

ObjectivesThe 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.MethodOverview 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.ResultsNo 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.ConclusionThe 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171126/1/bdi13135.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171126/2/bdi13135_am.pd