Lithium Versus Paroxetine in Major Depression

Sponsor

Nova Scotia Health Authority (Other)

Overall Status

Completed

CT.gov ID

NCT01416220

Collaborator

(none)

Enrollment

Location

Arms

17.1

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being done to look at how well people respond to two different drug treatments for depression. Clinically, people can respond differently to different treatments for reasons which are not always clear. Some research shows that people with a family history of bipolar disorder or completed suicide may react differently to standard medications used to treat depression than those without a family history. The investigators need to know if these drugs are effective to use in patients with depression who have a family history of bipolar disorder or completed suicide.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Lithium Drug: Paroxetine	Phase 4

Detailed Description

Lithium is a mood stabilizing drug that has been used to treat people with both bipolar disorder and depression for the last 50 years. It is available to the public by prescription in Canada and has been used by millions of people world wide. Paroxetine is an antidepressant drug that has been used to treat people with depression for the past 10 years. It is also available to the public by prescription in Canada and has been used by millions world wide.

Subjects who join the study, will be given one of the study drugs, either lithium or paroxetine.

Subjects will be randomized "like the flip of a coin" to receive either lithium or paroxetine.

The study drug will be taken once a day by mouth and the daily dose adjusted to find the right dose for the subject. The study drug will be taken for a 6-week period and subjects will be assessed by the research team on a weekly basis.

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-label, Trial of Lithium Versus Paroxetine in Subjects With Major Depression Who Have a Family History of Bipolar Disorder or Completed Suicide

Study Start Date :

Sep 1, 2011

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lithium Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or paroxetine. Lithium carbonate will be commenced at 600mgs hs, with increase to 900mgs at day 7. Dose will be flexibly titrated to give a serum level between 0.5 and 1.1mmol/l. At visit 4, the dose of lithium may be adjusted (within the range of 0.6 and 1.1 mmol/l).	Drug: Lithium Study drug will be packaged and supplied in an open-label fashion. There will be a washout period of all active psychotropic medication. Psychotropics will be withdrawn over 5 half-lives with the exception of drugs known to cause withdrawal symptoms (primarily antidepressants), which will be tapered over 10 days. Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or paroxetine. Lithium carbonate will be commenced at 600mgs hs, with increase to 900mgs at day 7. Dose will be flexibly titrated to give a serum level between 0.5 and 1.1mmol/l. At visit 4, the dose of lithium may be adjusted (within the range of 0.6 and 1.1 mmol/l. Other Names: lithium carbonate
Active Comparator: Paroxetine Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or Paroxetine.Paroxetine will be commenced at 10mgs and increased to 20mgs on day 7.At visit 4, the dose of paroxetine may be increased to 40mgs, if there is no response (less than 20% reduction in MADRS score) as per current Canadian guidelines.	Drug: Paroxetine Study drug will be packaged and supplied in an open-label fashion. There will be a washout period of all active psychotropic medication. Psychotropics will be withdrawn over 5 half-lives with the exception of drugs known to cause withdrawal symptoms (primarily antidepressants), which will be tapered over 10 days. Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or paroxetine. Paroxetine will be commenced at 10mgs and increased to 20mgs on day 7. At visit 4, the dose of paroxetine may be increased to 40mgs, if there is no response (less than 20% reduction in MADRS score) as per current Canadian guidelines. Other Names: paxil

Arm

Intervention/Treatment

Experimental: Lithium

Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or paroxetine. Lithium carbonate will be commenced at 600mgs hs, with increase to 900mgs at day 7. Dose will be flexibly titrated to give a serum level between 0.5 and 1.1mmol/l. At visit 4, the dose of lithium may be adjusted (within the range of 0.6 and 1.1 mmol/l).

Drug: Lithium

Study drug will be packaged and supplied in an open-label fashion. There will be a washout period of all active psychotropic medication. Psychotropics will be withdrawn over 5 half-lives with the exception of drugs known to cause withdrawal symptoms (primarily antidepressants), which will be tapered over 10 days. Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or paroxetine. Lithium carbonate will be commenced at 600mgs hs, with increase to 900mgs at day 7. Dose will be flexibly titrated to give a serum level between 0.5 and 1.1mmol/l. At visit 4, the dose of lithium may be adjusted (within the range of 0.6 and 1.1 mmol/l.

Other Names:

lithium carbonate

Active Comparator: Paroxetine

Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or Paroxetine.Paroxetine will be commenced at 10mgs and increased to 20mgs on day 7.At visit 4, the dose of paroxetine may be increased to 40mgs, if there is no response (less than 20% reduction in MADRS score) as per current Canadian guidelines.

Drug: Paroxetine

Study drug will be packaged and supplied in an open-label fashion. There will be a washout period of all active psychotropic medication. Psychotropics will be withdrawn over 5 half-lives with the exception of drugs known to cause withdrawal symptoms (primarily antidepressants), which will be tapered over 10 days. Following the enrollment period, subjects will enter a six-week randomized treatment period with either lithium or paroxetine. Paroxetine will be commenced at 10mgs and increased to 20mgs on day 7. At visit 4, the dose of paroxetine may be increased to 40mgs, if there is no response (less than 20% reduction in MADRS score) as per current Canadian guidelines.

Other Names:

paxil

Outcome Measures

Primary Outcome Measures

Montgomery Asberg Depression Rating Scale (MADRS) [Assessed after 6 weeks of treatment]
The primary outcome measure will be reduction in the score on the Montgomery Asberg Depression Rating Scale (MADRS), which has become the standard outcome tool in clinical trials for assessing symptoms of depression. Response will be defined as 50% reduction in MADRS Remission will be defined as MADRS ≤ 12.

Secondary Outcome Measures

The Young Mania Rating Scale (YMRS) [Assessed after 6 weeks of treatment]
This is a standard outcome tool used to assess mania.
The Clinical Global Impression (CGI) [Assessed after 6 weeks of treatment]
The Clinical Global Impression (CGI)is a scale used to measure overall symptom severity, treatment response, and treatment efficacy in patients with mood disorders.
The Columbia Suicide Classification Scale [Assessed over 6 weeks of treatment.]
The Columbia Suicide Classification Scale, used in the FDA analysis of pediatric antidepressants, has become a standard tool used in clinical depression trials and will be used to monitor changes in suicide risk or self-harm weekly.
Barnes Akathisia Rating Scale (BARS) [Assessed over 6 weeks of treatment]
Barnes Akathisia Rating Scale (BARS): The BARS is a very brief clinical assessment for the presences of akathisia. Akathisia secondary to antidepressants has been associated with increased suicidality. The inclusion of the BARS will serve to delineate akathisia from psychomotor agitation as part of treatment -emergent mixed symptoms.
Treatment -emergent symptom checklist and questionnaire [Assessed over 6 weeks of treatment]
This checklist and questionnaire will be used to capture a potential range of treatment emergent mixed symptoms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

men or women
age of 18 years or older
meet criteria for major depressive episode, and have a family history of bipolar disorder or completed suicide

Exclusion Criteria:

subjects not able to give informed consent
pregnant or breast-feeding women
current panic disorder, post traumatic stress disorder or psychosis
subjects with a history of mania or hypomania
subjects with active substance abuse or dependence in the last 6 months
current depressive episode less than 4 weeks or greater than 12 months in duration
adequate trial of lithium or paroxetine (lithium level ≥ 0.6mmols/l; paroxetine 20mgs ≥ 5 weeks) for this episode of depression
concurrent use of other antidepressants or augmenting agents for the treatment of depression
clinically significant medical illness, in particular renal impairment