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

Expert Opin Pharmacother. 2024 Mar;25(4):435-446. doi: 10.1080/14656566.2024.2334425. Epub 2024 Mar 25.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Suicide, completed; bipolar disorder; drug design; drug treatment; glutamatergic transmission; suicidal ideation; suicidality; suicide attempt.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use
  • Antimanic Agents / administration & dosage
  • Antimanic Agents / therapeutic use
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder* / drug therapy
  • Humans
  • Ketamine / administration & dosage
  • Ketamine / therapeutic use
  • Suicidal Ideation
  • Suicide Prevention*
  • Suicide* / psychology

Substances

  • Ketamine
  • Antidepressive Agents
  • Antipsychotic Agents
  • Antimanic Agents