Clinical trial NCT00927550: Lithium and Standard Therapy in Resistant Depression
Official title: Randomized Evaluation of the Effectiveness of Lithium in Subjects With Treatment-Resistant Depression and Suicide Risk. An Independent, Pragmatic, Multicentre, Parallel-Group, Superiority Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Depression
Keywords: resistant depression
lithium
RCT
lithium therapy
standard therapy
Lead sponsor: Universita di Verona
Sponsor class: OTHER
First posted: 2009-06-25
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The principal clinical question is whether lithium is effective in reducing the risk of suicidal behaviour in subjects with treatment-resistant depression and suicide risk. Additionally aims of the study are: (a) to assess whether lithium is effective in improving depressive symptomatology in subjects with treatment-resistant depression and suicide risk; (b) to assess the tolerability profile of lithium.

Detailed description: Inclusion criteria:

1. Diagnosis of major depression (clinical diagnosis, guided by DSM-IV criteria).
2. History of attempted suicide or deliberate self-harm in the previous 12 months.
3. Inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode.
4. Uncertainty about which treatment arm would be best for the participant.
5. Age 18 or above.
6. Agreement between investigator and patient to enter the study.

Exclusion criteria:

1. In addition to major depression, a primary diagnosis of any concurrent Axis I disorder (according to DSM-IV criteria) will constitute an exclusion criterion; by contrast, any concurrent Axis II disorder (according to DSM-IV criteria) will not constitute an exclusion criterion.
2. Previous exposure to lithium was associated with lack of efficacy or unwanted adverse reactions.
3. Clinical conditions contraindicate the experimental treatment arm (for example thyroid or kidney disease or abnormalities).
4. Pregnant/lactating women.
5. Women of childbearing potential not practicing a reliable method of contraception.

PRIMARY OUTCOME DEFINITION

Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome. The term "suicide" is defined as an act with a fatal outcome, deliberately initiated and performed by the person with the knowledge or expectation of its fatal outcome.

DSH is defined as intentional self-poisoning or self-injury, irrespective of motivation. Self-poisoning includes the intentional self-ingestion of more than the prescribed amount of any drug, whether or not there is evidence that the act was intended to result in death. This also includes poisoning with non-ingestible substances and gas, overdoses of "recreational drugs" and severe alcohol intoxication where clinical staff consider such cases to be an act of intentional self-harm (rather than recreational binge drinking). Self-injury is defined as any injury that has been intentionally self-inflicted, including self-cutting. The intention to end life may be absent or present to a variable degree. Other terms used to describe this phenomenon are "attempted suicide" and "parasuicide". Some acts of DSH are characterised by high suicidal intent, meticulous planning (including precautions against being found out), and severe lethality of the method used. Other acts of DSH are characterised by no or low intention of suicide, lack of planning and concealing of the act, and low lethality of the method used.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of major depression (clinical diagnosis, guided by DSM-IV criteria).
* History of attempted suicide or deliberate self-harm in the previous 12 months.
* Inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode.
* Uncertainty about which treatment arm would be best for participant.
* Age 18 or above.
* Agreement between investigator and patient to enter the study.

Exclusion Criteria:

* In addition to major depression, a primary diagnosis of any concurrent Axis I disorder (according to DSM-IV criteria) will constitute an exclusion criterion; by contrast, any concurrent Axis II disorder (according to DSM-IV criteria) will not constitute an exclusion criterion.
* Previous exposure to lithium was associated with lack of efficacy or unwanted adverse reactions.
* Clinical conditions contraindicate the experimental treatment arm (for example thyroid or kidney disease or abnormalities).
* Pregnant/lactating women.
* Women of childbearing potential not practicing a reliable method of contraception.

Primary outcomes:
measure: Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome
timeFrame: One year
Secondary outcomes:
measure: All-cause mortality
timeFrame: One year
measure: Suicide mortality
timeFrame: One year
measure: Deliberate self-harm or attempted suicide
timeFrame: One year
measure: Change in severity of depressive symptoms from baseline
timeFrame: One year
measure: Adverse reactions during the study
timeFrame: One year
Other outcomes:
Locations:
city: Verona
country: Italy
facility: University of Verona
Study officials:
affiliation: Universita di Verona
name: Michele Tansella, MD, Professor of psychiatry
role: STUDY_CHAIR
References:
citation: Girlanda F, Cipriani A, Agrimi E, Appino MG, Barichello A, Beneduce R, Bighelli I, Bisoffi G, Bisogno A, Bortolaso P, Boso M, Calandra C, Cascone L, Castellazzi M, Corbascio C, Parise VF, Gardellin F, Gennaro D, Hanife B, Lintas C, Lorusso M, Luca A, Luca M, Luchetta C, Lucii C, Maio F, Marsilio A, Mattei C, Moretti D, Nose M, Occhionero G, Papanti D, Pecile D, Percudani M, Prestia D, Purgato M, Restaino F, Romeo S, Sciarma T, Strizzolo S, Tamborini S, Todarello O, Tozzi F, Ziero S, Zotos S, Barbui C. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial. BMC Res Notes. 2014 Oct 17;7:731. doi: 10.1186/1756-0500-7-731.
citation: Cipriani A, Girlanda F, Agrimi E, Barichello A, Beneduce R, Bighelli I, Bisoffi G, Bisogno A, Bortolaso P, Boso M, Calandra C, Cascone L, Corbascio C, Parise VF, Gardellin F, Gennaro D, Hanife B, Lintas C, Lorusso M, Luchetta C, Lucii C, Cernuto F, Tozzi F, Marsilio A, Maio F, Mattei C, Moretti D, Appino MG, Nose M, Occhionero G, Papanti D, Pecile D, Purgato M, Prestia D, Restaino F, Sciarma T, Ruberto A, Strizzolo S, Tamborini S, Todarello O, Ziero S, Zotos S, Barbui C. 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. BMC Psychiatry. 2013 Aug 13;13:212. doi: 10.1186/1471-244X-13-212.