New pharmacotherapies to tackle the unmet needs in bipolar disorder: a focus on acute suicidality.

Suicidal behavior is common among people with bipolar disorder and is the leading cause of death in this group, with rates remaining high despite standard treatments like lithium, antidepressants, and psychotherapy. A review of PubMed identified few studies on acute suicidality and lithium or clozapine, but 14 studies on ketamine, esketamine, or glutamate-related treatments. Glutamatergic abnormalities are present in both bipolar disorder and suicide. The NMDA antagonist ketamine and its S-enantiomer esketamine appear to decrease acute suicidality, possibly by rapidly remodeling glutamate activity. Intranasal esketamine or subcutaneous ketamine, and possibly other glutamate receptor modulators, may improve suicidal behavior in unipolar and bipolar depression, suggesting glutamatergic modulators could reduce acute suicidality and mortality in bipolar disorder.

Study at a glance

Abstract

Suicidal behavior is relatively frequent in patients with bipolar disorder (BD) and constitutes their most frequent cause of death. Suicide rates remain high in patients with BD despite adherence to guidelines recommending lithium as first line, and/or antidepressants, antipsychotics, psychotherapy, psychosocial interventions, and electroconvulsive therapy. Hence the need to identify more effective and rapid anti-suicide interventions. To tackle the unmet needs of pharmacotherapy, we investigated the PubMed database on 24-25 January 2024 using strategies like ('acute suicid*'[ti] OR 'suicide crisis syndrome' OR 'acute suicidal affective disturbance') AND (lithium[ti] OR clozapine[ti]), which obtained 3 results, and ('acute suicid*'[ti] OR 'suicide crisis syndrome' OR 'acute suicidal affective disturbance') AND (ketamine[ti] OR esketamine[ti] OR NMDA[ti] OR glutamat*[ti]), which yielded 14 results. We explored glutamatergic abnormalities in BD and suicide and found alterations in both. The noncompetitive NMDS antagonist ketamine and its S-enantiomer esketamine reportedly decrease acute suicidality. Intranasal esketamine or subcutaneous ketamine, single-bolus or intravenous, and possibly other glutamate receptor modulators may improve suicidal behavior in patients with unipolar and bipolar depression. This may be achieved through prompt remodulation of glutamate activity. The correct use of glutamatergic modulators could reduce acute suicidality and mortality in patients with BD.