Effects of N-Acetyl cysteine on suicidal ideation in bipolar depression.

To the Editor: Suicide is the leading cause of death in young adults, and the lifetime risk of suicide for people with bipolar disorder is 15%. A meta-analysis of 15 studies1 determined prevalence rates of attempted suicide as high as 36.3% in bipolar I disorder and 32.4% in bipolar II disorder. A recent review2 on suicide in bipolar disorder emphasized the need for further research into how suicidality is generated and how to avert this outcome. Of the available psychotropic agents, only lithium has an evidence base for efficacy in suicide prevention. Effective therapies, including novel therapies, for suicide prevention in bipolar disorder are therefore a clinical imperative. N-Acetyl cysteine (NAC) has a diversity of actions, including on glutamate, glutathione, oxidative stress, inflammation, and mitochondrial dysfunction, that as a group represent dysregulated pathways in bipolar disorder.3 Glutamate dysregulation in particular has been implicated in suicide attempts. A recent study4 reported increased levels of quinolinic acid (an agonist of the glutamatergic N-methyl-d-aspartate receptor) in the cerebrospinal fluid of 64 medication-free suicide attempters compared to 36 controls. This study emphasized the importance of inflammation and glutamate neurotransmission in the pathophysiology of suicidal behavior, which has implications for the detection and treatment of suicidal patients. However, no studies have been reported on the reduction of suicidality by NAC to date. NAC is a relatively safe, available, and well-tolerated agent, with efficacy signals in a number of neuropsychiatric disorders.5