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      Bipolar depression: a review of treatment options

      review-article
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      General Psychiatry
      BMJ Publishing Group
      Bipolar Disorder, Depression, Mood Disorders

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          Abstract

          Bipolar depression (BD-D) is both common and incredibly challenging to treat. Even treated individuals with BD-D experience depression approximately 19% of the time, and subsyndromal depression an additional 18%. This stands in clear contrast to the approximately 10% of time spent in hypomania and 1% of time spent in mania. Despite this high illness burden, there remain relatively few treatment options approved by the US Food and Drug Administration for BD-D. Of the approved medications, four are second-generation antipsychotics (SGAs) and one is an SGA combined with an antidepressant. However, particularly when used long-term, antipsychotics can pose a significant risk of adverse effects, raising the clinical conundrum of weighing the risks associated with long-term antipsychotic use versus the risk of relapse when patients are off medications. Here, we review commonly used treatments for BD-D, including antipsychotics, classic mood stabilisers, electroconvulsive therapy and psychotherapy. We then address the somewhat controversial topic of antidepressant use in BD-D. Finally, we summarise emerging treatment options and highlight ongoing clinical trials. We hope this review will help compare the risks and benefits of several common and novel options for the treatment of patients with BD-D. In doing so, we also hope this review will aid the individualised selection of treatments based on each patient’s history and treatment goals.

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          Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

          The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.
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            The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

            Objective Suicide is a public health crisis with limited treatment options. We conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. Method Individual participant data were obtained from 10 of 11 identified comparison intervention studies (using either saline or midazolam as control). The analysis included only participants with suicidal ideation at baseline (n=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D)) and self-reported scales (Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) or Beck Depression Inventory (BDI)), obtained for up to one week post-ketamine administration. Results Ketamine rapidly reduced (one day) suicidal ideation on both the clinician-administered (p<0.001) and self-reported outcome measures (p<0.001). Effect sizes were moderate-to-large (Cohen’s d=0.51–0.85) at all time points post-dose. Sensitivity analysis demonstrated that, compared to controls, ketamine had significant benefits on the individual suicide items of the MADRS, HAM-D, and QIDS-SR (all p<0.001) but not on the BDI (p=0.080). Ketamine’s effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms. Conclusions Ketamine rapidly reduced suicidal thoughts within one day and for up to one week in depressed patients with suicidal ideation. Ketamine’s effects on suicidal ideation were partially independent of its effects on mood, though subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine’s long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.
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              The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.

              The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.
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                Author and article information

                Journal
                Gen Psychiatr
                Gen Psychiatr
                gpsych
                gpsych
                General Psychiatry
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2517-729X
                2022
                4 August 2022
                : 35
                : 4
                : e100760
                Affiliations
                [1]departmentPsychiatry and Behavioral Sciences , Johns Hopkins School of Medicine , Baltimore, Maryland, USA
                Author notes
                [Correspondence to ] Dr Zachary A Cordner; zac@ 123456jhmi.edu
                Author information
                http://orcid.org/0000-0001-6000-567X
                Article
                gpsych-2022-100760
                10.1136/gpsych-2022-100760
                9358943
                36035376
                cfb1cb4b-8cf4-4b14-aadb-d949705ca995
                © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 31 January 2022
                : 13 July 2022
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                Review
                1506
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                bipolar disorder,depression,mood disorders
                bipolar disorder, depression, mood disorders

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