Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial

Abstract

BackgroundData on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH.Methods/DesignWe will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events.DiscussionThe results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide.Trial registrationClinicalTrials.gov identifier: NCT00927550

Generalizability of pharmacological and psychotherapy clinical trial results for borderline personality disorder to community samples.

“…Specification a priori of the goals of the study and estimation of the proportion of individuals ineligible for the trial due to the individually application of each exclusion criterion to the target population would assist study design. For example, effectiveness studies could place a larger emphasis on the generalizability of their findings whereas efficacy studies may benefit from relatively stringent eligibility criteria to maximize detection of drug-placebo differences (Blanco, Olfson, Goodwin, et al, 2008; Cipriani et al, 2013; Sani et al, 2013). …”

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

“…The Ethics Committee in Verona (coordinating centre) approved the study on May 6th 2009 (Study code: LAST-RD - FARM77Z3BL5.101-03-2009; Approval number 1675). A detailed description of the study methods has already been published [ 5 ]. Patients with a diagnosis of TRD and history of DSH were randomly allocated to (i) add lithium to usual care or (ii) usual care without lithium.…”

“…Acts of DSH and suicide during the 12 months of follow-up constituted the composite primary outcome. A sample size calculation [ 5 ] revealed that 210 patients would have 80% power to show a clinically significant advantage associated with lithium treatment. All phases of the trial were recorded following the CONSORT statement [ 6 , 7 ].…”

“…On these grounds, we designed a pragmatic randomised trial to assess whether adding lithium to usual care is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. As reported in the study protocol [ 5 ], we initially planned to include more than 200 participants, but we managed to randomise 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.…”

Adolescent self‐harm and risk factors

“…Now, multisystemic therapy versus psychiatric hospitalization was associated with a reduction of SH attempts in a sample of adolescents. Some research suggests that lithium and clozapine may have specific anti‐suicidal properties (Meltzer et al ., ; Cipriani et al ., ). Other study has reported that selective serotonin reuptake inhibitors may be associated with an increase in suicidal behavior particularly in young people (Barbui et al ., ).…”