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

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 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. METHODS: We carried 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 were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

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.

BACKGROUND: Data 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/DESIGN: We 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. DISCUSSION: The 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 REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Clinical picture of obsessive-compulsive disorder with poor insight: a regression model.

DSM-IV included a type of obsessive-compulsive disorder (OCD) with poor insight in the official classification. The present study was performed using a continuous measure of the level of insight to analyze the association between this variable and characteristics of the disorder. Seventy-four consecutive OCD outpatients (DSM-IV criteria) were assessed using: a semistructured interview for sociodemographic and clinical features, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive Scale (NIMH-OCS), the Hamilton Depression and Anxiety Rating Scales (HDRS, HARS), and the Overvalued Ideas Scale (OVIS) as a continuous measure of the level of insight. Stepwise multiple regression analysis revealed that demographic and clinical factors were related to the OVIS score. The following four factors were found to be significantly related to the OVIS score: the Y-BOCS score for compulsions, OCD chronic course, and family history of OCD were positively related, while obsessive-compulsive personality disorder was negatively related. These results suggest that poor insight identifies a group of OCD patients with distinct clinical characteristics.

Antipsychotic augmentation for treatment resistant obsessive-compulsive disorder: what if antipsychotic is discontinued?

The aim of the present study was to retrospectively review the charts of obsessive-compulsive disorder (OCD) patients who responded to the addition of an antipsychotic to the seroronin reuptake inhibitor (SRI), and who subsequently discontinued the antipsychotic, in order to evaluate whether antipsychotic discontinuation resulted in a relapse of the disorder. Charts of patients with a principal diagnosis of OCD (DSM-IV) treated with pharmacotherapy were reviewed in order to select patients who: (i) did not respond to a trial with a first-line drug (clomipramine or a selective SRI); (ii) received an antipsychotic at low doses (haloperidol, pimozide, risperidone or olanzapine) in order to potentiate the SRI; (iii) responded to this augmentation strategy; and (iv) discontinued the antipsychotic drug for any reason while continuing the SRI at the same dose. Relapse was defined as a worsening of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score >/= 35% with respect to last evaluation before antipsychotic discontinuation or, for patients with a Y-BOCS < 16 at the end of the combination period, as a Y-BOCS total score >/= 16 at any time after antipsychotic discontinuation. According to our definition of relapse, 15 patients out of 18 (83.3%) relapsed after antipsychotic discontinuation, with a mean worsening of symptoms of 6.6 +/- 1.7 points in the Y-BOCS total score. Thirteen patients out of the 15 who relapsed did so by week 8 after discontinuation. Two subjects relapsed at the end of the 1-year study. Although retrospective, our study provides initial evidence that antipsychotic augmentation has to be maintained for patients who respond to this strategy, because the vast majority of subjects who discontinue the antipsychotic relapse within 2 months.