Lithium and Standard Therapy in Resistant Depression

NCT ID: NCT00927550

Last Updated: 2009-09-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2012-12-31

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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lithium plus usual care

Group Type: EXPERIMENTAL

lithium

Intervention Type: DRUG

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 without lithium therapy

Group Type: ACTIVE_COMPARATOR

usual care

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Carbolithium

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universita di Verona

OTHER

Sponsor Role: lead

Responsible Party

University of Verona

Principal Investigators

Michele Tansella, MD, Professor of psychiatry

Role: STUDY_CHAIR

Universita di Verona

Locations

University of Verona

Verona, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

corrado barbui, MD

Role: CONTACT

corrado.barbui@univr.it

+39 0458126418

Facility Contacts

Corrado Barbui, MD

Role: primary

corrado.barbui@univr.it

References

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.

Reference Type: DERIVED

PMID: 25326163 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23941474 (View on PubMed)

Other Identifiers

LAST_RD_FARM77Z3BL-5.1_132009

Identifier Type: -

Identifier Source: org_study_id