LAST-RD STUDY – LITHIUM AND STANDARD THERAPY IN RESISTANT DEPRESSION. RANDOMIZED EVALUATION OF THE EFFECTIVENESS OF LITHIUM IN SUBJECTS WITH TREATMENT-RESISTANT DEPRESSION AND SUICIDE RISK. AN INDEPENDENT, PRAGMATIC, MULTICENTRE, PARALLEL-GROUP, SUPERIORITY TRIAL.

Background: In treatment-resistant depression (TRD), self-harm and suicide ideas represent alarming psychopathological symptoms. These may lead to self-harm and suicide attempts and, in up to 10% of cases, to completed suicides. The intervention following non-fatal suicidal behavior is relevant to suicide prevention, because the risk of suicide following deliberate self-harm is considerable. Objective: The primary aim of the LAST study is to assess whether lithium is effective in reducing the risk of suicidal behavior in subjects with TRD and suicide risk. Secondary aims of the study are to assess whether lithium is effective in improving depressive symptomatology and to evaluate the tolerability profile of lithium. Methods: LAST is a multicentre trial that aimed to include subjects affected by treatment-resistant depression with a history of attempted suicide or deliberate self-harm in the previous 12 months. Patients meeting eligibility criteria were allocated, through a centralized randomization procedure, to lithium plus usual pharmacological and non pharmacological treatment or to usual pharmacological and non pharmacological treatment. Results: Of 58 patients screened for inclusion, a total of 56 were enrolled in the study and randomly assigned to treatment. Of them, 29 subjects were allocated to lithium (experimental group) and 27 were assigned to standard therapy (control group). Survival curves highlighted that the number of events (considering first event only) occurred during the follow-up period was not significantly different between the two treatment groups (Chi2=0.12, p=0.726). The survival probability at 12 month was 75% and 65% in the lithium and standard therapy group, respectively. Conclusions: In this study lithium treatment was not associated with lower risk of completed suicide and deliberate self-harm in adults affected by treatment-resistant depression with suicide risk. Funding: LAST has been approved and financially supported by the Agenzia Italiana del Farmaco (AIFA), Cod: FARM77Z3BL.