Depression
Conditions
Keywords
Cognitive therapy, Antidepressants, Psychotherapy
Brief summary
This study determined the effectiveness of continuation phase cognitive therapy versus antidepressant medication in preventing relapse of depression in people with recurrent depression.
Detailed description
Cognitive therapy (CT) is a short-term talking therapy that focuses on changing negative thinking patterns and helping patients develop coping skills to deal with their experiences. Evidence suggests that CT is effective in treating a number of psychiatric conditions, including anxiety and anger. This study will determine the effectiveness of cognitive therapy versus antidepressant medication or placebo in preventing relapse of depression in people with recurrent depression. This study lasted approximately 36 months and comprised three phases. For the first 12 weeks, all participants received between 16 and 20 CT sessions. Participants were then randomly assigned to receive additional CT sessions, antidepressants, or placebo for an additional 8 months. Upon completing treatment, participants entered follow-up study visits once every 4 months for the next 24 months. Clinician-rated scales and questionnaires were used to assess depressive symptoms of participants at study start and at the end of each study phase.
Interventions
BEHAVIORALContinuation phase cognitive therapy
Continuation phase cognitive therapy included 10 sessions over 8 months.
DRUGContinuation phase fluoxetine
The dosage of fluoxetine was increased to 40 mg over 8 months.
OTHERContinuation phase pill placebo
The dosage of pill placebo was increased to 40 mg over 8 months.
BEHAVIORALAcute phase cognitive therapy
For the first 12 weeks, all participants received between 16 and 20 cognitive therapy sessions.
Sponsors
National Institute of Mental Health (NIMH)
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Recurrent unipolar major depressive disorder * Have experienced at least two episodes of major depression * Have experienced at least one period of recovery during a depressive episode or have a history of dysthymia (a mood disorder characterized by depression) prior to the onset of current or past depressive episodes * Willing and able to comply with all study requirements * Able to speak and read English
Exclusion criteria
* Active alcohol or other substance dependence within 6 months prior to study entry * Currently at risk for suicide * Mood disorders due to a medical condition or substance abuse * Bipolar, schizoaffective, obsessive compulsive, or eating disorders * Schizophrenia * Unable to stop mood-altering medications * Current use of medication or diagnosis of a medical disorder that may cause depression (e.g., diabetes, head injury, stroke, cancer, multiple sclerosis) * Previous failure to experience a reduction in depressive symptoms after 8 weeks of cognitive therapy with a certified therapist * Previous failure to experience a reduction in depressive symptoms after 6 weeks of 40 mg of Prozac * Pregnancy or plan to become pregnant in the next 11-12 months * Unable to attend clinic twice weekly during business hours * Unable to complete questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Relapse or MDD | Measured at month 8 | Longitudinal Interval Follow-up Evaluation - Psychiatric Status Rating (LIFE-PSR) of 5 or more (on a scale from 1 to 6 measuring major depressive disorder) for 2 consecutive weeks according to evaluator blinded to randomized assignment LIFE-PSR Scale: 1. = No residual symptoms, no current evidence of the disorder. 2. = Mild symptoms 3. = Considerably less psychopathology than full criteria with no more than moderate impairment 4. = Does not meet full criteria but has major symptoms of impairment 5. = Meets criteria without extreme impairment in functioning 6. = Meets criteria with extreme impairment in functioning The relapse rate was estimated using Kaplan-Meier estimates (Kaplan, Meier J Am Stat, 1958, pp.457-481) |
| Depressive Relapse/Recurrence or MDD | Measured at month 20 | Longitudinal Interval Follow-up Evaluation - Psychiatric Status Rating (LIFE-PSR) of 5 or more (on a scale from 1 to 6 measuring MDD) for 2 consecutive weeks according to evaluator blinded to randomized assignment LIFE-PSR Scale: 1. = No residual symptoms, no current evidence of the disorder. 2. = Mild symptoms 3. = Considerably less psychopathology than full criteria with no more than moderate impairment 4. = Does not meet full criteria but has major symptoms of impairment 5. = Meets criteria without extreme impairment in functioning 6. = Meets criteria with extreme impairment in functioning Relapse/recurrence rate was estimated using Kaplan-Meier estimates (Kaplan, Meier J Am Stat, 1958, pp.457-481) |
Countries
United States
Participant flow
Recruitment details
Adult outpatients diagnosed with recurrent major depressive disorder (MDD) using the Structured Clinical Interview for Diagnostic and Statistical Manual-IV were recruited from January 2000-July 2008. The first diagnostic evaluation was completed in March 2000.
Pre-assignment details
Eligible patients (n=523) entered 12-14 weeks of acute phase cognitive therapy. Responders (no MDD & Hamilton Rating Scale for Depression \[HRSD\] ≤12) were divided by lower & higher risk based on the final 7 HRSD scores. Only consenting, higher risk patients (N=241) were randomized into the 3 arms below. See Jarrett &Thase (2010) for design details.
Participants by arm
| Arm | Count |
|---|---|
| Continuation Phase Fluoxetine Participants received acute phase cognitive therapy and continuation phase pill placebo
Acute phase cognitive therapy : For the first 12 weeks, all participants received between 16 and 20 cognitive therapy sessions.
Continuation phase pill placebo : The dosage of pill placebo was increased to 40 mg over 8 months. | 86 |
| Continuation Phase Cognitive Therapy Participants received acute phase and continuation phase cognitive therapy
Acute phase cognitive therapy : For the first 12 weeks, all participants received between 16 and 20 cognitive therapy sessions.
Continuation phase cognitive therapy : Continuation phase cognitive therapy included 10 sessions over 8 months. | 86 |
| Continuation Phase Pill Placebo Participants received acute phase cognitive therapy and continuation phase fluoxetine
Acute phase cognitive therapy : For the first 12 weeks, all participants received between 16 and 20 cognitive therapy sessions.
Continuation phase fluoxetine : The dosage of fluoxetine was increased to 40 mg over 8 months. | 69 |
| Total | 241 |
Baseline characteristics
| Characteristic | Continuation Phase Cognitive Therapy | Continuation Phase Pill Placebo | Continuation Phase Fluoxetine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 86 Participants | 69 Participants | 86 Participants | 241 Participants |
| Age, Continuous | 43.1 years STANDARD_DEVIATION 11.5 | 43.6 years STANDARD_DEVIATION 12.3 | 41.6 years STANDARD_DEVIATION 11.8 | 42.7 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment United States | 86 participants | 69 participants | 86 participants | 241 participants |
| Sex: Female, Male Female | 63 Participants | 42 Participants | 57 Participants | 162 Participants |
| Sex: Female, Male Male | 23 Participants | 27 Participants | 29 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 86 | 0 / 86 | 0 / 69 |
| serious Total, serious adverse events | 0 / 86 | 0 / 86 | 0 / 69 |
Outcome results
Primary
Depressive Relapse or MDD
Longitudinal Interval Follow-up Evaluation - Psychiatric Status Rating (LIFE-PSR) of 5 or more (on a scale from 1 to 6 measuring major depressive disorder) for 2 consecutive weeks according to evaluator blinded to randomized assignment LIFE-PSR Scale: 1. = No residual symptoms, no current evidence of the disorder. 2. = Mild symptoms 3. = Considerably less psychopathology than full criteria with no more than moderate impairment 4. = Does not meet full criteria but has major symptoms of impairment 5. = Meets criteria without extreme impairment in functioning 6. = Meets criteria with extreme impairment in functioning The relapse rate was estimated using Kaplan-Meier estimates (Kaplan, Meier J Am Stat, 1958, pp.457-481)
Time frame: Measured at month 8
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuation Phase Fluoxetine | Depressive Relapse or MDD | 18 % patients who relapsed |
| Continuation Phase Cognitive Therapy | Depressive Relapse or MDD | 18.3 % patients who relapsed |
| Continuation Phase Pill Placebo | Depressive Relapse or MDD | 32.7 % patients who relapsed |
Comparison: The sample size was based on a predicted 30% difference in relapse/recurrence rates between C-CT and fluoxetine (ie,30% vs 60%) across both the experimental phase and the first 12 months of follow-up. With these assumptions, 180 randomized patients (60 per cell) were required to detect a statistically significant difference using a log-rank test with 1-sided α = 0.05 and 80% power.p-value: 0.4295% CI: [0.5, 2.34]Log Rank
p-value: 0.0295% CI: [0.23, 1.01]Log Rank
p-value: 0.0395% CI: [0.26, 1.06]Log Rank
p-value: 0.0195% CI: [0.27, 0.93]Log Rank
Primary
Depressive Relapse/Recurrence or MDD
Longitudinal Interval Follow-up Evaluation - Psychiatric Status Rating (LIFE-PSR) of 5 or more (on a scale from 1 to 6 measuring MDD) for 2 consecutive weeks according to evaluator blinded to randomized assignment LIFE-PSR Scale: 1. = No residual symptoms, no current evidence of the disorder. 2. = Mild symptoms 3. = Considerably less psychopathology than full criteria with no more than moderate impairment 4. = Does not meet full criteria but has major symptoms of impairment 5. = Meets criteria without extreme impairment in functioning 6. = Meets criteria with extreme impairment in functioning Relapse/recurrence rate was estimated using Kaplan-Meier estimates (Kaplan, Meier J Am Stat, 1958, pp.457-481)
Time frame: Measured at month 20
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuation Phase Fluoxetine | Depressive Relapse/Recurrence or MDD | 35.1 % patients who relapsed/recurred |
| Continuation Phase Cognitive Therapy | Depressive Relapse/Recurrence or MDD | 35.0 % patients who relapsed/recurred |
| Continuation Phase Pill Placebo | Depressive Relapse/Recurrence or MDD | 42.7 % patients who relapsed/recurred |
p-value: 0.4895% CI: [0.55, 1.76]Log Rank
p-value: 0.1495% CI: [0.39, 1.31]Log Rank
p-value: 0.1395% CI: [0.4, 1.29]Log Rank
p-value: 0.195% CI: [0.43, 1.2]Log Rank
Primary
Depressive Relapse/Recurrence or MDD
Longitudinal Interval Follow-up Evaluation - Psychiatric Status Rating (LIFE-PSR) of 5 or more (on a scale from 1 to 6 measuring MDD) for 2 consecutive weeks according to evaluator blinded to randomized assignment LIFE-PSR Scale: 1. = No residual symptoms, no current evidence of the disorder. 2. = Mild symptoms 3. = Considerably less psychopathology than full criteria with no more than moderate impairment 4. = Does not meet full criteria but has major symptoms of impairment 5. = Meets criteria without extreme impairment in functioning 6. = Meets criteria with extreme impairment in functioning Relapse/recurrence rate was estimated using Kaplan-Meier estimates (Kaplan, Meier J Am Stat, 1958, pp.457-481).
Time frame: Measured at month 32
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Continuation Phase Fluoxetine | Depressive Relapse/Recurrence or MDD | 41.1 % patients who relapsed/recurred |
| Continuation Phase Cognitive Therapy | Depressive Relapse/Recurrence or MDD | 45.2 % patients who relapsed/recurred |
| Continuation Phase Pill Placebo | Depressive Relapse/Recurrence or MDD | 56.3 % patients who relapsed/recurred |
p-value: 0.495% CI: [0.63, 1.84]Log Rank
p-value: 0.6195% CI: [0.37, 1.13]Log Rank
p-value: 0.0995% CI: [0.41, 1.19]Log Rank
p-value: 0.0595% CI: [0.42, 1.08]Log Rank