DepressionPhase 1NCT00745017
Stress Generation and Recurrent Depression: The Role of Differential Treatment Response
A Phase 1 study testing Cognitive Behavioral Therapy, Interpersonal Therapy and Antidepressant medication in people with Depression and Major Depressive Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Depression affects over one million people in Canada, resulting in $14.4 billion per year in costs to Canadian society. In order to prevent this often lifelong disorder, it is critically important to identify risk factors for the recurrence of depression. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depression, Major Depressive Disorder
- What is being tested?
- Cognitive Behavioral Therapy, Interpersonal Therapy and Antidepressant medication
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2001to Jul 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Meet the criteria for DSM-IV diagnosis of non-psychotic, major depression based on the Structured Interview for DSM-IV, Axis I disorders
- Score > 16 the 17-item Hamilton Rating Scale for Depression
- Ages between 18 and 60
- Are medication-free (i.e., of antidepressants) for a minimum of two weeks prior to treatment are eligible for entry into treatment protocols
- Minimum eight grade education and fluency in reading English
- Ability to give informed consent and complete assessment instruments unassisted
Who cannot join
- a SCID-I diagnosis of:
- Bipolar Disorder (past or present),
- Schizoaffective Disorder,
- Schizophrenia,
- Substance Abuse Disorder (current or within the past 6 months),
- Borderline or Antisocial Personality Disorder,
Show all 9Show fewer
- Organic Brain Syndrome
- Electroconvulsive Therapy (ECT) within the past 6 months
- Concurrent active medical illness
Trial locations and contacts
1 site in 1 country.
About this study
Depression affects over one million people in Canada, resulting in $14.4 billion per year in costs to Canadian society. In order to prevent this often lifelong disorder, it is critically important to identify risk factors for the recurrence of depression. A crucial force in maintaining depression is the generation of stressful life events. That is, individuals who have a history of depression are likely to generate the very events that precipitate future depressive episodes (e.g., relationship break-up, fired from job, conflicts with the law) due to negative personality characteristics and disrupted social support networks resulting from previous episodes. This project is the first to test a model that examines the role of negative personality, low social support, and childhood abuse and neglect as risk factors for the generation of stressful life events that predict future depression. We will test this model in a group of patients meeting formal criteria for depression who will be treated and then followed up for 12 months or until depression recurrence. With this long-term design we will be in a unique position to understand how depression is maintained over time, thus suggesting important treatment strategies to prevent depression recurrence.
Read the detailed description
The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Programme (TDCRP) (Elkin et al., 1989; Sotsky et al., 1991) compared three forms of treatment for depression -- imipramine plus clinical management (IMI-CM), cognitive behaviour therapy alone (CBT), interpersonal therapy alone (IPT) -- against a placebo control plus clinical management (PLA-CM) condition. These three treatments were found equally effective in the treatment of the index episode of depression when compared to the placebo control (Elkin et al., 1989). The results from the TDCRP study also indicated that patient characteristics, irrespective of treatment modality, were predictive of treatment effects. Six patient dimensions -- social dysfunction, cognitive dysfunction, expectation for improvement, endogenous features, double depression and duration of current episode -- were all found to be significant predictors of outcome (Sotsky et al., 1991). Patient characteristics were also found to be associated with differential outcome depending on treatment modality. Elevated social dysfunction, for example, interfered with successful outcome in IPT, whereas cognitive dysfunction hindered successful outcome with CBT. Cognitive dysfunction also predicted poor treatment response in the IMI-CM condition. Cognitive vulnerability would be expected to mediate response to treatment in CBT, as the presumed mechanism of change is dysfunctional depressogenic cognitions (e.g., Beck et al., 1979; Whisman, 1993). The finding that cognitive vulnerability was also implicated in treatment response to a pharmacological intervention is without theoretical explanation or specific causal agency.
The purpose of the proposed research is to further examine the relationship between treatment outcome and patient characteristics associated depression. In particular, the relationship between treatment outcome and two personality/cognitive characteristics implicated as vulnerability factors for depression - self-criticism and dependency - will be explored.
The first aim of the proposed investigation is to examine the relationship between change in self-criticism and dependency and the relationship of this change to treatment response and reduction in severity of depression. Mode-specific outcome measures will be administered to outpatients with major depression randomly assigned and treated with CBT, IPT or PHT.
The second aim of this study is to examine the issue of whether successful targeting of either cognitive dysfunction in CBT or interpersonal functioning in IPT will result in a reduced risk for relapse and/or recurrence of a major depressive episode.
We believe that the dependent type, who centres their definition of self entirely around issues of affiliation with others, would be more likely to show changes related to such themes in a therapeutic intervention specifically designed to address interpersonal problems. In contrast, the self-critic who defines self primarily around issues related to achievement and engages in excessively harsh and unrealistic self-appraisal would respond best to an intervention that targeted these punitive cognitions.
HYPOTHESES/RESEARCH QUESTIONS
Prediction of Treatment Outcome (Objective 1):
Two sets of hypotheses are proposed. In all analyses the DEQ will be used to assess self-criticism and dependency. The first set of hypotheses involves mode specific treatment outcomes and the second set of hypotheses address differences in the mechanisms of change across the treatments.
The first set of hypotheses are: (a) all treatments will be equally effective in the treatment of the index episode, (b) baseline self-criticism and dependency scores will predict outcome in all treatments, with higher self-criticism and dependency scores related to poor outcome, (c) CBT will demonstrate greater specificity for targeting self-criticism than will either PHT or IPT, (d) IPT will demonstrate greater specificity for treating interpersonal functioning than will either PHT or CBT, (e) PHT will demonstrate greater specificity for treating endogenous symptoms than will either CBT or IPT.
The second set of hypotheses are: (a) change in self-criticism scores and dysfunctional cognitions will mediate a positive treatment response in CBT but not in IPT or PHT, (b) change in dependency scores and interpersonal deficits will mediate positive treatment response in IPT but not in CBT or PHT, (c) change in endogeneity will mediate positive treatment response in PHT but not in CBT or IPT.
Prediction of Relapse and Recurrence (Objective 2):
It is hypothesized that: (a) CBT and IPT will produce a lower rate of relapse and recurrence than PHT because of the greater reduction in stable dysfunctional cognitions related to either self-critical and/or interpersonal vulnerabilities; (b) in cases where interpersonal vulnerabilities are predominant, IPT will produce lower rates of relapse and recurrence than either CBT and PHT, in cases where self-critical vulnerabilities are predominant, CBT will produce lower rates of relapse and recurrence than either IPT or PHT.
- Conditions
- Depression, Major Depressive Disorder
- Being tested
- Cognitive Behavioral Therapy, Interpersonal Therapy, Antidepressant medication
- Keywords
- recurrent depression, major depressive disorder, interpersonal therapy, cognitive behavioral therapy, antidepressant therapies, outome predictors, personality dimensions
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral TherapyBehavioural
All patients randomized to this condition will receive 16 consecutive weeks of manualized cognitive-behaviour therapy provided by either M.S.W or Ph.D. psychotherapists trained and certified in CBT. Treatment will be conducted according to the manualized CBT treatment for depression outlined by Beck and colleagues (Beck et al., 1979), and consistent with the protocol administered in the NIMH study.
Interpersonal TherapyBehavioural
All patients randomized to this condition will receive 16 consecutive weeks of manualized interpersonal psychotherapy conducted by M.S.W., Ph.D., or M.Ed. psychotherapists trained and certified in IPT.
Antidepressant medicationDrug
Patients patients randomized to this condition will be treated for 16 weeks with different classes of anti-depressant medications, using standardized protocols. Patients will receive 16 weeks of treatment with either a SSRI (sertraline or paroxetine) or a SNRI (venlafaxine). The dose range is as follows: sertraline 50-200 mg/day, paroxetine 20-40 mg/day, venlafaxine 75-375 mg/day. Patients unable to continue with the prescribed medication due to side effects and/or lack of response will be prescribed an alternate medication during the first two weeks of the protocol.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Behavioral: Cognitive Behavioral Therapy |
| 2 | Experimental | Not described Receives: Behavioral: Interpersonal Therapy |
| 3 | Experimental | Not described Receives: Drug: Antidepressant medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Rating Scale for Depression
Measured: intermittent
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2008 (estimated)
- Study startJul 2001
- Primary completionJul 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Mental Health Foundation
- Investigators
- Kate L Harkness, PhD, Principal investigator, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00745017
- Sponsor's protocol ID
- 091/2003
- Status last verified
- Aug 2008
- First submitted
- 28 Aug 2008
- Last updated
- 1 Sep 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stress Generation and Recurrent Depression: The Role of Differential Treatment Response
- ClinicalTrials.gov ID
- NCT00745017
- Acronym / sponsor ID
- 091/2003
- Conditions
- Depression, Major Depressive Disorder
- Keywords
- recurrent depression, major depressive disorder, interpersonal therapy, cognitive behavioral therapy, antidepressant therapies, outome predictors, personality dimensions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Ontario Mental Health Foundation
- Study start
- Jul 2001
- Primary completion
- Jul 2006 (actual)
- First posted
- 1 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Depression affects over one million people in Canada, resulting in $14.4 billion per year in costs to Canadian society. In order to prevent this often lifelong disorder, it is critically important to identify risk factors for the recurrence of depression. A crucial force in maintaining depression is the generation of stressful life events. That is, individuals who have a history of depression are likely to generate the very events that precipitate future depressive episodes (e.g., relationship break-up, fired from job, conflicts with the law) due to negative personality characteristics and disrupted social support networks resulting from previous episodes. This project is the first to test a model that examines the role of negative personality, low social support, and childhood abuse and neglect as risk factors for the generation of stressful life events that predict future depression. We will test this model in a group of patients meeting formal criteria for depression who will be treated and then followed up for 12 months or until depression recurrence. With this long-term design we will be in a unique position to understand how depression is maintained over time, thus suggesting important treatment strategies to prevent depression recurrence.
Detailed description
The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Programme (TDCRP) (Elkin et al., 1989; Sotsky et al., 1991) compared three forms of treatment for depression -- imipramine plus clinical management (IMI-CM), cognitive behaviour therapy alone (CBT), interpersonal therapy alone (IPT) -- against a placebo control plus clinical management (PLA-CM) condition. These three treatments were found equally effective in the treatment of the index episode of depression when compared to the placebo control (Elkin et al., 1989). The results from the TDCRP study also indicated that patient characteristics, irrespective of treatment modality, were predictive of treatment effects. Six patient dimensions -- social dysfunction, cognitive dysfunction, expectation for improvement, endogenous features, double depression and duration of current episode -- were all found to be significant predictors of outcome (Sotsky et al., 1991). Patient characteristics were also found to be associated with differential outcome depending on treatment modality. Elevated social dysfunction, for example, interfered with successful outcome in IPT, whereas cognitive dysfunction hindered successful outcome with CBT. Cognitive dysfunction also predicted poor treatment response in the IMI-CM condition. Cognitive vulnerability would be expected to mediate response to treatment in CBT, as the presumed mechanism of change is dysfunctional depressogenic cognitions (e.g., Beck et al., 1979; Whisman, 1993). The finding that cognitive vulnerability was also implicated in treatment response to a pharmacological intervention is without theoretical explanation or specific causal agency.
The purpose of the proposed research is to further examine the relationship between treatment outcome and patient characteristics associated depression. In particular, the relationship between treatment outcome and two personality/cognitive characteristics implicated as vulnerability factors for depression - self-criticism and dependency - will be explored.
The first aim of the proposed investigation is to examine the relationship between change in self-criticism and dependency and the relationship of this change to treatment response and reduction in severity of depression. Mode-specific outcome measures will be administered to outpatients with major depression randomly assigned and treated with CBT, IPT or PHT.
The second aim of this study is to examine the issue of whether successful targeting of either cognitive dysfunction in CBT or interpersonal functioning in IPT will result in a reduced risk for relapse and/or recurrence of a major depressive episode.
We believe that the dependent type, who centres their definition of self entirely around issues of affiliation with others, would be more likely to show changes related to such themes in a therapeutic intervention specifically designed to address interpersonal problems. In contrast, the self-critic who defines self primarily around issues related to achievement and engages in excessively harsh and unrealistic self-appraisal would respond best to an intervention that targeted these punitive cognitions.
HYPOTHESES/RESEARCH QUESTIONS
Prediction of Treatment Outcome (Objective 1):
Two sets of hypotheses are proposed. In all analyses the DEQ will be used to assess self-criticism and dependency. The first set of hypotheses involves mode specific treatment outcomes and the second set of hypotheses address differences in the mechanisms of change across the treatments.
The first set of hypotheses are: (a) all treatments will be equally effective in the treatment of the index episode, (b) baseline self-criticism and dependency scores will predict outcome in all treatments, with higher self-criticism and dependency scores related to poor outcome, (c) CBT will demonstrate greater specificity for targeting self-criticism than will either PHT or IPT, (d) IPT will demonstrate greater specificity for treating interpersonal functioning than will either PHT or CBT, (e) PHT will demonstrate greater specificity for treating endogenous symptoms than will either CBT or IPT.
The second set of hypotheses are: (a) change in self-criticism scores and dysfunctional cognitions will mediate a positive treatment response in CBT but not in IPT or PHT, (b) change in dependency scores and interpersonal deficits will mediate positive treatment response in IPT but not in CBT or PHT, (c) change in endogeneity will mediate positive treatment response in PHT but not in CBT or IPT.
Prediction of Relapse and Recurrence (Objective 2):
It is hypothesized that: (a) CBT and IPT will produce a lower rate of relapse and recurrence than PHT because of the greater reduction in stable dysfunctional cognitions related to either self-critical and/or interpersonal vulnerabilities; (b) in cases where interpersonal vulnerabilities are predominant, IPT will produce lower rates of relapse and recurrence than either CBT and PHT, in cases where self-critical vulnerabilities are predominant, CBT will produce lower rates of relapse and recurrence than either IPT or PHT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Behavioral: Cognitive Behavioral Therapy |
| 2 | Experimental | Behavioral: Interpersonal Therapy |
| 3 | Experimental | Drug: Antidepressant medication |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Meet the criteria for DSM-IV diagnosis of non-psychotic, major depression based on the Structured Interview for DSM-IV, Axis I disorders
- Score > 16 the 17-item Hamilton Rating Scale for Depression
- Ages between 18 and 60
- Are medication-free (i.e., of antidepressants) for a minimum of two weeks prior to treatment are eligible for entry into treatment protocols
- Minimum eight grade education and fluency in reading English
Key exclusion criteria (9 listed)
- a SCID-I diagnosis of:
- Electroconvulsive Therapy (ECT) within the past 6 months
- Concurrent active medical illness
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral TherapyAll patients randomized to this condition will receive 16 consecutive weeks of manualized cognitive-behaviour therapy provided by either M.S.W or Ph.D. psychotherapists trained and certified in CBT. Treatment will be conducted according to the manualized CBT treatment for depression outlined by Beck and colleagues (Beck et al., 1979), and consistent with the protocol administered in the NIMH study. | Behavioural | 1 |
| Interpersonal TherapyAll patients randomized to this condition will receive 16 consecutive weeks of manualized interpersonal psychotherapy conducted by M.S.W., Ph.D., or M.Ed. psychotherapists trained and certified in IPT. | Behavioural | 2 |
| Antidepressant medicationPatients patients randomized to this condition will be treated for 16 weeks with different classes of anti-depressant medications, using standardized protocols. Patients will receive 16 weeks of treatment with either a SSRI (sertraline or paroxetine) or a SNRI (venlafaxine). The dose range is as follows: sertraline 50-200 mg/day, paroxetine 20-40 mg/day, venlafaxine 75-375 mg/day. Patients unable to continue with the prescribed medication due to side effects and/or lack of response will be prescribed an alternate medication during the first two weeks of the protocol. | Drug | 3 |
Primary outcome
Hamilton Rating Scale for Depression
Time frame: intermittent
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kate L Harkness, PhD principal investigator
Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cognitive Behavioral Therapy, Interpersonal Therapy and Antidepressant medication in people with Depression and Major Depressive Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Rating Scale for Depression (time frame: intermittent). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2008.