Lithium Versus Paroxetine in Major Depression

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Lithium; Drug: Paroxetine

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2E2
      • Queen Elizabeth II Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale (MADRS)	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.	Assessed after 6 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Young Mania Rating Scale (YMRS)	This is a standard outcome tool used to assess mania.	Assessed after 6 weeks of treatment
The Clinical Global Impression (CGI)	The Clinical Global Impression (CGI)is a scale used to measure overall symptom severity, treatment response, and treatment efficacy in patients with mood disorders.	Assessed after 6 weeks of treatment
The Columbia Suicide Classification Scale	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.	Assessed over 6 weeks of treatment.
Barnes Akathisia Rating Scale (BARS)	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.	Assessed over 6 weeks of treatment
Treatment -emergent symptom checklist and questionnaire	This checklist and questionnaire will be used to capture a potential range of treatment emergent mixed symptoms.	Assessed over 6 weeks of treatment

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority
• Investigators: Principal Investigator: Claire O'Donovan, MD, FRCPC, Queen Elizabeth II Health Sciences Centre, CDHA

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: August 11, 2011
• First Submitted That Met QC Criteria: August 11, 2011
• First Posted (Estimate): August 12, 2011

Study Record Updates

• Last Update Posted (Actual): July 16, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: depression; bipolar disorder; manic depressive illness
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Antimanic Agents; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine; Lithium Carbonate
• Other Study ID Numbers: MoodDig-001