Lithium and Standard Therapy in Resistant Depression

Depression Clinical Trial

— LAST  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00927550
• Other study ID #: LAST_RD_FARM77Z3BL-5.1_132009
• Status: Recruiting
• Phase: Phase 4
• First received: June 24, 2009
• Last updated: September 15, 2009
• Start date: June 2009
• Est. completion date: December 2012

Study information

• Verified date: September 2009
• Source: Universita di Verona
• Contact: corrado barbui, MD
• Phone: +39 0458126418
• Email: corrado.barbui[@]univr.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

Intervention

Drug:
• lithium
Patients allocated to lithium will be administered an oral starting dose ranging between 150 and 300 milligrams. Suggested final oral dose will have to achieve plasma levels of 0.4 to 1.0 mmol/L. Clinicians will be free of increasing or decreasing the dose according to clinical status and circumstances. Dose changes will be recorded. Following randomization, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Patients allocated to the lithium arm will receive usual pharmacological and non-pharmacological treatment as clinically indicated. Any other pharmacological treatment will be allowed.
• usual care
Patients allocated to the control arm will receive usual pharmacological and non-pharmacological treatment as clinically indicated. Patients allocated to the control arm will not be allowed to receive lithium. Any other pharmacological treatment will be allowed.

Locations

Country	Name	City	State
Italy	University of Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Universita di Verona

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Suicide completion and acts of deliberate self harm (DSH) will constitute the composite primary outcome		One year	Yes
Secondary	All-cause mortality		One year	Yes
Secondary	Suicide mortality		One year	Yes
Secondary	Deliberate self-harm or attempted suicide		One year	Yes
Secondary	Change in severity of depressive symptoms from baseline		One year	Yes
Secondary	Adverse reactions during the study		One year	Yes