title: Lithium and suicide prevention in bipolar disorder.
abstract: BACKGROUND
  Bipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations.
  
  
  METHODS
  We conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: "lithium" AND "suicide" OR "suicidality" OR "suicide attempt".
  
  
  RESULTS
  As confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The "impulsive-aggressive" endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/β (GSK3α and β; proteins inhibited by Li) seem to be associated with more impulsiveness in BD populations.
  
  
  CONCLUSIONS
  The anti-suicidal effect of Li has been very well demonstrated. By its specific action on the serotoninergic system, treatment with Li significantly reduces "impulsive-aggressive" behaviour which is a vulnerability factor common to suicide and BD. Long-term appropriately modulated treatment with Li seems to have considerable impact on the reduction of suicidal behaviours, suicidal ideation and death by suicide in the BD population.
authors.affiliation: Centre hospitalier universitaire de Lille (CHRU), 59000 Lille, France; Université de Lille, 59000 Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Benard
authors.affiliation: Centre hospitalier universitaire de Lille (CHRU), 59000 Lille, France; Université de Lille, 59000 Lille, France.
authors.forename: G
authors.initials: G
authors.lastname: Vaiva
authors.affiliation: Clinique médicale du Château-de-Garches, 92380 Garches, France; Service S.H.U., hôpital Sainte-Anne, 1, rue Cabanis, 75004 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Masson
authors.affiliation: Inserm, U1144, 75006 Paris, France; Université Paris Descartes, UMR-S 1144, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, 75013 Paris, France; Pôle de psychiatrie et de médecine addictologique, groupe hospitalier Saint-Louis-Lariboisière-F.-Widal, AP-HP, 75475 Paris cedex 10, France; Fondation FondaMental, 94000 Créteil, France. Electronic address: pierre.a.geoffroy@gmail.com.
authors.forename: P A
authors.initials: PA
authors.lastname: Geoffroy
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D059020:Suicidal Ideation; D013406:Suicide, Attempted / Q000523:psychology; D000092864:Suicide Prevention
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds
keywords: Bipolar disorder; Lithium carbonate; Lithium salts; Mood stabilizer treatment; Sels de lithium; Suicidal ideation; Suicidalité; Suicide; Suicide attempt; Tentative de suicide; Traitement stabilisateur de l’humeur; Trouble bipolaire