The Treatment of Bipolar Depression: Current Status and Future Perspectives

Abstract

Purpose of Review This paper aims to review current available treatment options and to consider future directions in the treatment of bipolar depression. Recent Findings There are a limited number of established treatments that have demonstrated varied efficacy in acute bipolar depression including modern antipsychotics (quetiapine, lurasidone, olanzapine ± fluoxetine and recently cariprazine) and mood stabilisers (lamotrigine and valproate). Lithium has a role in protecting against depressive relapses and suicide. Alternative and experimental treatments including pramipexole, modafinil/armodafinil, omega-3 fatty acids and thyroxine may be used to augment the treatment of bipolar depression. Ketamine represents a major breakthrough, producing rapid reductions in depressive symptoms even in cases of treatment-resistance, but challenges remain in how best to maintain response and reduce unwanted side effects. Summary There remains uncertainty with regard to the relative efficacy and safety of established and experimental treatments for bipolar depression. Further work using consistent and optimal trial designs and further investigation into novel compounds and treatment interventions are warranted.

“A sense of the bigger picture:” A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use

“…Currently available pharmacological treatments for BD-associated depression are inadequate with inconsistent efficacy, significant side effects, and the risk of possibly precipitating "affective switching" [10,11]. The cycling nature of BD poses particular challenges to clinicians and researchers [12] and controversy and lack of consensus continues regarding the use of serotonergic antidepressants for BD depression [10,[13][14][15]. While some have advised against it entirely [13], others have questioned the perceived causality of antidepressants and emergent hypo/mania given affective changes associated with this condition [10].…”

“…While some have advised against it entirely [13], others have questioned the perceived causality of antidepressants and emergent hypo/mania given affective changes associated with this condition [10]. Given the clinical need and limited established treatments for depression in BD, new treatment approaches are desperately needed [12,16].…”

“…TEAS characterizes what is typically a switch from a depressive episode to hypo/mania [33,34]. Whether this pattern of emergent hypo/mania following depression is due to antidepressant treatment is yet to be fully understood [12,34,35]. Furthermore, it remains unclear to what extent the non-static nature of depression in this population contributes to these unresolved dilemmas and thus treatment options [36].…”

“…A subsample of Phase I survey respondents were invited to participate in followup interviews designed to deepen understanding of the preliminary survey results, and elucidate specific contextual factors associated with adverse reactions in naturalistic settings. Considering the variability of lived experience and treatment options for individuals with bipolar depression [12], a qualitative phase of the study is crucial to understanding the benefits, risks, and contextual factors that will inform future research in the field of psychedelic science.…”

“…We have also provided evidence that adults living with BD have experienced mental health improvements following psilocybin use. Given the long history of excluding this population from psychedelic science, lack of clear evidence for these exclusions, [19,31,32] the significant burden of depression for individuals living with a BD diagnosis [5,[90][91][92], and limited treatment options available [12], more research is urgently needed. Findings from this study will guide the design of our upcoming clinical trial at the University of California, San Francisco aimed at identifying the safety and feasibility of psilocybinassisted psychotherapy as a novel treatment for symptoms of depression in adults aged 30-65 living with a diagnosis of BD-II.…”