Ignite Creation Date:
2024-05-05 @ 5:12 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00400088
Status:
TERMINATED
Last Update Posted:
2021-01-29
First Post:
2006-11-15
Brief Title:
Lithium Versus Paroxetine in Patients With Major Depression Who Have a Family History of Bipolar Disorder or Suicide
Sponsor:
Nova Scotia Health Authority
Organization:
Nova Scotia Health Authority
Study Overview
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
Status:
TERMINATED
Status Verified Date:
2021-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Recruitment difficulties
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 ie 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
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
Detailed Description:
Introduction Bipolar disorder is an illness that consists of distinct episodes or poles of both major depression and mania bipolar I or major depression and hypomania bipolar II Both poles of the illness may be fully present simultaneously in what is referred to as a Mixed episode The poles of Major depression Mania and Mixed mood are currently defined by descriptive criteria in the psychiatric diagnostic manual DSMIV
Estimates of the prevalence of Bipolar disorder are as high as 6 of the population1 It is a severe and potentially lethal illness which has a different course and treatment profile to unipolar depression commonly known simply as major depression In 50-60 of cases however the initial presentation of bipolar disorder is one of major depression and several episodes of depression may occur before declaration of bipolarity by virtue of a manic or hypomanic episode pre-bipolar depression23 The mainstay of treatment for unipolar major depression is antidepressants In contrast antidepressant monotherapy is contraindicated in Bipolar I depression and must be used very cautiously in Bipolar II illness 4 with much concern for an unacceptable cost benefit ratio because of the risk of antidepressant induction of mania and rapid cycling increase in frequency of episodes as a consequence of antidepressants 5 Hence treatment of the early depressive episodes of bipolar illness requires recognition of depression specific to bipolar disorder and appropriate choice of medication
Unfortunately efforts to clearly distinguish bipolar from unipolar depression cross-sectionally have been mostly disappointing Most evidence supports the value of family history6 and there is variable predictive value for specific phenomenological and course descriptors such as hypersomnia psychomotor retardation early-onset and psychotic sub types78
The dilemma then is two-fold
1 Identifying patients suffering from major depression who are at high risk of bipolar disorder
2 Choosing appropriate pharmacological treatment
In choosing pharmacological treatment for a high risk group there is the possibility of causing harm with antidepressants if the true diagnosis is bipolar disorder and of not treating the depression adequately if using mood stabilizers in what is truly a unipolar illness This dilemma applies to a large subgroup of those presenting with depression A recent study in a primary care setting suggested that as many as 21 of patients currently treated with antidepressants for a presumed depressive disorder may in fact have a bipolar diathesis thus representing a large group that may be improperly treated9
The concerns with the use of antidepressants in known bipolar depression have focused on antidepressant - induction of mania and rapid cycling but these do not always present themselves immediately However there may be other subtle and immediate antidepressant treatment effects that make the diagnostic distinction possible and more pressing510Indeed it has been postulated that undetected bipolar depression may explain the apparent poor treatment response and increase in suicidality with the use of antidepressants in the adolescent population where one might expect an increased prevalence of depression as first episode of bipolar disorder by virtue of earlier age of onset compared to unipolar illness11
Objectives
The objective of this proposal is to investigate response to acute lithium treatment in subjects who meet the diagnostic criteria for major depression but are potentially at risk for bipolar disorder by virtue of family history of bipolarity or completed suicide
Primary Hypothesis
Subjects with depression considered at risk for bipolar disorder will show a significant clinical response to lithium
Secondary Hypothesis
1 Subjects with depression considered at risk for bipolar disorder will show a significant clinical response to paroxetine
2 Treatment emergent mixed symptoms in particular agitation will occur only in the antidepressant treated group
Study Design
This is a 6 week double-blind randomized controlled pilot trial of lithium versus paroxetine in subjects with major depression who have either a family history of bipolar disorder or completed suicide 20 subjects men or women above the age of 18 will be recruited at this centre
Patients will be randomized to receive either lithium or paroxetine at their first study visit and the dose of drug will be adjusted to find the right one for each patient Patients will be assessed on a weekly basis thereafterData from this pilot study will help in the development of a larger adequately powered study to compare lithium and paroxetine in the treatment of depression in this high risk group
Patients excluded from the study would include subjects not able to give informed consentpregnant or breast-feeding womena current diagnosis of panic disorder post traumatic stress disorder or psychosisa history of mania or hypomaniaactive substance abuse or dependence in the last 6 months a current depressive episode less than 4 weeks or greater than 12 months in duration a current or prior adequate trial of lithium or paroxetineconcurrent use of other antidepressants or augmenting agents for the treatment of depressionor a clinically significant medical illness in particular renal impairment
Estimates of the prevalence of Bipolar disorder are as high as 6 of the population1 It is a severe and potentially lethal illness which has a different course and treatment profile to unipolar depression commonly known simply as major depression In 50-60 of cases however the initial presentation of bipolar disorder is one of major depression and several episodes of depression may occur before declaration of bipolarity by virtue of a manic or hypomanic episode pre-bipolar depression23 The mainstay of treatment for unipolar major depression is antidepressants In contrast antidepressant monotherapy is contraindicated in Bipolar I depression and must be used very cautiously in Bipolar II illness 4 with much concern for an unacceptable cost benefit ratio because of the risk of antidepressant induction of mania and rapid cycling increase in frequency of episodes as a consequence of antidepressants 5 Hence treatment of the early depressive episodes of bipolar illness requires recognition of depression specific to bipolar disorder and appropriate choice of medication
Unfortunately efforts to clearly distinguish bipolar from unipolar depression cross-sectionally have been mostly disappointing Most evidence supports the value of family history6 and there is variable predictive value for specific phenomenological and course descriptors such as hypersomnia psychomotor retardation early-onset and psychotic sub types78
The dilemma then is two-fold
1 Identifying patients suffering from major depression who are at high risk of bipolar disorder
2 Choosing appropriate pharmacological treatment
In choosing pharmacological treatment for a high risk group there is the possibility of causing harm with antidepressants if the true diagnosis is bipolar disorder and of not treating the depression adequately if using mood stabilizers in what is truly a unipolar illness This dilemma applies to a large subgroup of those presenting with depression A recent study in a primary care setting suggested that as many as 21 of patients currently treated with antidepressants for a presumed depressive disorder may in fact have a bipolar diathesis thus representing a large group that may be improperly treated9
The concerns with the use of antidepressants in known bipolar depression have focused on antidepressant - induction of mania and rapid cycling but these do not always present themselves immediately However there may be other subtle and immediate antidepressant treatment effects that make the diagnostic distinction possible and more pressing510Indeed it has been postulated that undetected bipolar depression may explain the apparent poor treatment response and increase in suicidality with the use of antidepressants in the adolescent population where one might expect an increased prevalence of depression as first episode of bipolar disorder by virtue of earlier age of onset compared to unipolar illness11
Objectives
The objective of this proposal is to investigate response to acute lithium treatment in subjects who meet the diagnostic criteria for major depression but are potentially at risk for bipolar disorder by virtue of family history of bipolarity or completed suicide
Primary Hypothesis
Subjects with depression considered at risk for bipolar disorder will show a significant clinical response to lithium
Secondary Hypothesis
1 Subjects with depression considered at risk for bipolar disorder will show a significant clinical response to paroxetine
2 Treatment emergent mixed symptoms in particular agitation will occur only in the antidepressant treated group
Study Design
This is a 6 week double-blind randomized controlled pilot trial of lithium versus paroxetine in subjects with major depression who have either a family history of bipolar disorder or completed suicide 20 subjects men or women above the age of 18 will be recruited at this centre
Patients will be randomized to receive either lithium or paroxetine at their first study visit and the dose of drug will be adjusted to find the right one for each patient Patients will be assessed on a weekly basis thereafterData from this pilot study will help in the development of a larger adequately powered study to compare lithium and paroxetine in the treatment of depression in this high risk group
Patients excluded from the study would include subjects not able to give informed consentpregnant or breast-feeding womena current diagnosis of panic disorder post traumatic stress disorder or psychosisa history of mania or hypomaniaactive substance abuse or dependence in the last 6 months a current depressive episode less than 4 weeks or greater than 12 months in duration a current or prior adequate trial of lithium or paroxetineconcurrent use of other antidepressants or augmenting agents for the treatment of depressionor a clinically significant medical illness in particular renal impairment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CDHA-RS2006-076 | None | None | None |