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Lithium, suicide prevention and unipolar depression?

Australia’s suicide rate continues to rise, which is of significant concern, while lithium use has been in decline. The release of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) mood disorder guidelines (Malhi et al., 2015) comprehensively addresses most aspects of mood disorder management, including the important role of lithium. However, the role of lithium’s anti-suicidal effect specifically for unipolar depression is not described. In a recent conceptual overview of suicide in the Lancet (Turecki and Brent, 2016), the role of lithium in reducing suicide was specifically mentioned for both unipolar and bipolar depression. A recent systematic review and meta-analysis of randomized trials (Cipriani et al., 2013) found that in unipolar depression, lithium was associated with a significantly reduced risk of suicide (odds ratio: 0.36, 95% confidence interval [CI] = [0.13, 0.98]). The new metaanalytic findings (Cipriani et al., 2013) in relation to lithium’s specific antisuicidal effects for unipolar depression are an important addition to current clinical knowledge and practice. It is generally known that lithium’s anti-suicidal effect likely relates to more than just its prophylactic benefits for mood disorder relapse. It is thought that lithium may also decrease aggression and impulsivity, which are both mediating factors associated with increased rates of suicide (Cipriani et al., 2013; Turecki and Brent, 2016). The adverse effect profile of lithium is well known including renal insufficiency and thyroid dysfunction (Malhi et al., 2015), which when accompanied by the requirement for regular blood-level monitoring may limit its widespread use by clinicians. The medical risks associated with lithium overdose may also lead to clinical concerns about its safety in potentially suicidal patients. However, from an overall evidence-based perspective, we think lithium should now be considered beyond the acute phase of depression treatment but also as a specific indication for the maintenance treatment of unipolar depressed patients at longitudinal risk of self-harm or suicide (Cipriani et al., 2013). This will require clinician education that lithium may well have effects beyond mood stabilization (Cipriani et al., 2013; Turecki and Brent, 2016), which may include independent anti-suicidal, anti-aggressive, anti-impulsive and possible neuroprotective effects. Further research is required to both confirm the evidence that lithium can prevent suicide in unipolar depression and elucidate its mechanism of action to prevent suicide. This research will help in formulating targeted public health strategies for suicide prevention, as well as providing a better understanding about the neurobiology of suicide.