Lithium Versus Paroxetine in Patients With Major Depression Who Have a Family History of Bipolar Disorder or Suicide

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00400088
Recruitment Status : Terminated (Recruitment difficulties)
First Posted : November 16, 2006
Last Update Posted : February 27, 2013
Information provided by (Responsible Party):
Julie Garnham, Nova Scotia Health Authority

Brief Summary:

This study is being done to look at how well people respond to two very different drug treatments for depression. Clinically, people with depression can respond differently to drug treatments for reasons which are not always clear. Some of our own recent research suggests that people with depression who have a family history of bipolar disorder or completed suicide, may react differently to standard antidepressant medications than those without such a family history. Our data shows that family history of completed suicide, as well as the known predictor of family history of bipolar disorder, may help identify a pre-bipolar high risk group i.e. they currently have depression but at some future date will declare a bipolar illness (manic-depression) by virtue of development of a manic episode also. Our research suggests that treatment- emergent symptoms in response to a trial of antidepressant, such as agitation may be strong predictors of future bipolarity and inherently dangerous particularly as they are not ascribed to the antidepressant treatment. Finally, it is possible that this subgroup of those with depressive illness may respond better and more safely to lithium, a mood stabiliser used in known bipolar depression.

The objective of this proposal is to investigate response to acute lithium treatment in subjects who meet the diagnostic criteria for major depression, but who are potentially at risk for bipolar disorder, by virtue of family history of bipolarity or completed suicide.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: paroxetine Drug: lithium Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Double-dummy, Controlled Trial of Lithium Versus Paroxetine in Subjects With Major Depression Who Have a Family History of Bipolar Disorder or Completed Suicide - a Pilot Study
Study Start Date : June 2007
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

Arm Intervention/treatment
Experimental: lithium group
Start at 600 mg po hs. Dose titrated up to a serum level of between 0.6 and 1.1 mmol/l.
Drug: lithium
start at 600mg po hs with dose to be flexibly titrated to a serum level of between 0.6 and 1.1 mmol/l.
Other Names:
  • lithane
  • lithium carbonate

Active Comparator: paroxetine group
Start dose at 20 mg po od. If no clinical improvement(<20% reduction in MADRS score) by week 4 dose to be increased to 40 mg po od.
Drug: paroxetine
Start at 20 mg po od. Increase dose to 40 mg po od at week 4 if there is less than 20 % reduction in MADRS scores.
Other Name: paxil

Primary Outcome Measures :
  1. Response will be defined as 50% reduction in MADRS score. [ Time Frame: weekly ]
  2. Remission will be defined as MADRS ≤ 12. [ Time Frame: weekly ]
  3. The MADRS will be done at week 0,1,2,3,4,5,6. [ Time Frame: weekly ]

Secondary Outcome Measures :
  1. The Hamilton Depression Rating Scale (HAM -D)-17 item scale, at weeks 0 and 6. [ Time Frame: weeks 0 and 6 ]
  2. Hamilton Anxiety Rating Scale (HAM-A),at weeks 0 and 6. [ Time Frame: weeks 0 and 6 ]
  3. The Young Mania Rating Scale (YMRS), at weeks 0,1,2,3,4,5,6. [ Time Frame: weekly ]
  4. The Bipolar Depression Rating Scale (BDRS) (42),at weeks 0,1,2,3,4,5,6. [ Time Frame: weekly ]
  5. Checklist of DSM IV symptoms of mania/ hypomania, with additional questions assessing the presence of mood lability, abnormally high energy, abnormally high libido, and rage. Done at weeks 0,1,2,3,4,5,6. [ Time Frame: weekly ]
  6. The Beck Suicide Scale (BSS), at weeks 0, 1, 2,3,4,5, 6. [ Time Frame: weekly ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Not currently participating in a drug or medical device clinical trial
  • Male or female over the age of 18
  • DSM - IV Diagnosis of major depression
  • Positive family history of bipolar disorder or completed suicide

Exclusion Criteria:

  • Not able to give informed consent
  • Pregnant or breast-feeding
  • Current additional psychiatric diagnoses including Panic Disorder, Post -Traumatic Stress Disorder (PTSD) or Psychosis
  • History of mania or hypomania
  • Active substance abuse or dependence in the last 6 months
  • Current depressive episode less than 4 weeks or greater than 12 months in duration
  • Current or prior adequate trial of lithium or paroxetine
  • Current use of other medications such as antidepressants for the treatment of depression
  • Clinically significant medical illness, in particular kidney problems

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00400088

Canada, Nova Scotia
Capital District Health Authority - Dept. of Psychiatry
Halifax, Nova Scotia, Canada, B3H 2E2
Sponsors and Collaborators
Nova Scotia Health Authority
Principal Investigator: Claire O'Donovan M O'Donovan, MB FRCPC Capital District Health Authority and Dalhousie University


Responsible Party: Julie Garnham, Dr. Claire O'Donovan, Nova Scotia Health Authority Identifier: NCT00400088     History of Changes
Other Study ID Numbers: CDHA012
First Posted: November 16, 2006    Key Record Dates
Last Update Posted: February 27, 2013
Last Verified: February 2013

Keywords provided by Julie Garnham, Nova Scotia Health Authority:
Major Depressive Disorder
Bipolar Disorder
Manic Depressive Illness
Randomized Trial
Antidepressant Treatment
Lithium Treatment

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Major
Bipolar Disorder
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Self-Injurious Behavior
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents, Second-Generation
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors