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

NCT00400088 | Terminated Phase 3

• 2 other identifiers: CDHA012CDHA-RS/2006-076
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Depression; Bipolar Disorder; Manic Depressive Illness; Randomized Trial; Antidepressant Treatment; Lithium Treatment

Outcome Measures

Primary Outcomes (3)

• Response will be defined as 50% reduction in MADRS score.

  weekly

• Remission will be defined as MADRS ≤ 12.

  weekly

• The MADRS will be done at week 0,1,2,3,4,5,6.

  weekly

Secondary Outcomes (6)

• The Hamilton Depression Rating Scale (HAM -D)-17 item scale, at weeks 0 and 6.

  weeks 0 and 6

• Hamilton Anxiety Rating Scale (HAM-A),at weeks 0 and 6.

  weeks 0 and 6

• The Young Mania Rating Scale (YMRS), at weeks 0,1,2,3,4,5,6.

  weekly

• The Bipolar Depression Rating Scale (BDRS) (42),at weeks 0,1,2,3,4,5,6.

  weekly

• 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.

  weekly

Study Arms (2)

lithium group

EXPERIMENTAL

Start at 600 mg po hs. Dose titrated up to a serum level of between 0.6 and 1.1 mmol/l.

Drug: lithium

paroxetine group

ACTIVE COMPARATOR

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

Interventions

paroxetine DRUG

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.

Also known as: paxil

paroxetine group

lithium DRUG

start at 600mg po hs with dose to be flexibly titrated to a serum level of between 0.6 and 1.1 mmol/l.

Also known as: lithane, lithium carbonate

lithium group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nova Scotia Health Authority: lead

Study Sites (1)

Capital District Health Authority - Dept. of Psychiatry

Halifax, Nova Scotia, B3H 2E2, Canada

Location

Related Publications (11)

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  PMID: 10646613 BACKGROUND

• Roy-Byrne P, Post RM, Uhde TW, Porcu T, Davis D. The longitudinal course of recurrent affective illness: life chart data from research patients at the NIMH. Acta Psychiatr Scand Suppl. 1985;317:1-34. doi: 10.1111/j.1600-0447.1985.tb10510.x.

  PMID: 3861072 BACKGROUND

• Yatham LN, Kennedy SH, O'Donovan C, Parikh S, MacQueen G, McIntyre R, Sharma V, Silverstone P, Alda M, Baruch P, Beaulieu S, Daigneault A, Milev R, Young LT, Ravindran A, Schaffer A, Connolly M, Gorman CP; Canadian Network for Mood and Anxiety Treatments. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disord. 2005;7 Suppl 3:5-69. doi: 10.1111/j.1399-5618.2005.00219.x.

  PMID: 15952957 BACKGROUND

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  PMID: 14702267 BACKGROUND

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• Berk M, Dodd S. Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression? Med Hypotheses. 2005;65(1):39-43. doi: 10.1016/j.mehy.2005.02.010.

  PMID: 15893115 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Bipolar Disorder

Interventions

Paroxetine; Lithium; Lithium Carbonate

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Claire O'Donovan M O'Donovan, MB FRCPC

  Capital District Health Authority and Dalhousie University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Claire O'Donovan

Study Record Dates

• First Submitted: November 15, 2006
• First Posted: November 16, 2006
• Study Start: June 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: January 29, 2021

Record last verified: 2021-01

Locations

CA (1)