Arguments for the specificity of the antisuicidal effect of lithium

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Abstract

Affective disorders are characterized by first a high recurrence risk, second a 30–50 times increased suicide risk and third a 2- to 3 times increased overall mortality. In contrast to a populistic belief no scientific evidence exists that antidepressant treatment, particularly long-term treatment, could reduce the the risk of suicidal acts in depressive patients with a history of suicide attempts. Data, however, coming from international, systematic, retrospective analyses of well-documented long-term courses of illness in reliably diagnosed patients, and from a large national, prospective long-term trial on the prophylactic efficacy of lithium versus carbamazepine and amitriptyline has accumulated in the last 10–15 years strongly supporting a (possibly specific) antisuicidal effect of lithium. The large collaborative IGSLI study (International Group for the Study of Lithium-treated Patients) covering 5,616 patient years clearly showed that adequate long-term lithium treatment significantly reduces and even normalizes the excess mortality of patients with affective disorders. A metaanalysis on 17,000 patients pooled from 28 studies demonstrated that the rate of suicidal acts is 8.6 fold higher in patients without lithium as compared to those with regular lithium treatment.

A post-hoc analysis of a large multicenter, controlled long-term trial found no suicidal acts in 146 patients randomized to lithium compared to 9 suicidal acts in 139 patients randomized to carbamazepine.

Reanalysis of the data from the IGSLI study supports the concept of the specificity of lithium, i.e., evidence could be provided that lithium also reduces suicidal behavior in patients who do not benefit from the lithium treatment in terms of episode reduction.

Conclusion Lithium has to be considered as a first line mood stabilizer in affective disorders, particularly in patients with a history of suicide attempts. Extreme caution is required when lithium is discontinued or a patient is switched to another mood stabilizer, because such a patient might have been protected against suicidal impulses in spite of an incomplete response as to the number and quality of depressive/manic episodes.

Dedicated to Prof. Per Bech in appreciation and admiration for his continuous support and promotion of a rational and optimized pharmacotherapy in psychiatry.