Depression
Conditions
Brief summary
This study will determine whether the addition of Cognitive Therapy (CT) to antidepressant medication (ADM) enhances treatment for depression. This study will also test whether the addition of CT to ADM will prevent recurrences of depression after therapy is over.
Detailed description
It is commonly believed that the combination of ADM and psychotherapy is more effective in treating depression than either treatment alone. Data indicate that CT enhances the initial effects of ADM, but little research has been conducted to determine whether prior exposure to CT prevents the onset of new depressive episodes. This study will determine the effectiveness of adding CT to ADM for the treatment of depression. Participants are randomly assigned to receive either ADM alone or ADM plus CT for up to 18 months. Remitted patients are continued on medication for up to 36 months from the point of initial randomization until they meet criteria for recovery. At recovery, patients receiving combined treatment discontinue cognitive therapy; all recovered patients are randomized a second time to either maintenance medication or medication withdrawal. Patients are then monitored over 36 months to ascertain risk for recurrence of depressive symptoms.
Interventions
BEHAVIORALCognitive Therapy
CT sessions occur weekly during acute treatment and monthly during continuation. Acute treatment may last up to 18 months. Remitted patients are continued on medication for up to 36 months from initial randomization until they meet criteria for recovery. At recovery, patients receiving combined treatment discontinue CT.
DRUGMedications
Antidepressant medication is distributed as clinically indicated with augmentation and ancillary medications as needed. Acute treatment may last up to 18 months. Remitted patients are continued on medication for up to 36 months from the point of initial randomization until they meet criteria for recovery. All recovered patients are randomized a second time to either maintenance medication or medication withdrawal. Patients are then monitored over 36 months to ascertain risk for recurrence of depressive symptoms.
Sponsors
National Institute of Mental Health (NIMH)
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recurrent or chronic major depressive disorder
Exclusion criteria
* Current diagnosis of psychotic affective disorder * History of nonaffective psychotic disorder * Substance dependence last three months requiring detox * Schizotypal, antisocial, or borderline personality disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Remission According to the Longitudinal Interval Follow-up Evaluation (LIFE) and the Hamilton Rating Scale for Depression (HRSD) | Through month 18 of treatment | Remission defined as four consecutive weeks of LIFE Problem Symptom Rating (PSR) values of 2 or less and HRSD scores of 8 or less for four consecutive weeks (with partial remission defined as LIFE PSR values of 3 or less and HRSD scores of 12 or less after month 12 only) |
| Number of Participants in Recovery According to the LIFE and HRSD | Through 36 months of treatment | Six consecutive months following remission without relapse (two weeks of elevated LIFE PSR scores of 4 or more and HRSD scores of 14 and above) |
| Number of Participants in Recurrence According to the LIFE and HRSD | Measured up to Month 36 from recovery | Recurrence defined as two consecutive weeks of elevated LIFE PSR scores of 5 or above and HRSD scores of 16 or above (three weeks during period of medication withdrawal) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | Throughout study, up to 54 months | Number Serious Adverse Events (SAEs) as reported to the Institutional Review Boards and Data Safety Monitoring Board throughout the duration of the study |
Countries
United States
Participant flow
Recruitment details
Recruitment into the study started in October 2002 and the last of the 452 patients randomized completed up to three years of treatment and a subsequent three your maintenance/follow-up in July 2012
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Therapy Plus Antidepressant Medications Participants will receive antidepressant medication plus cognitive therapy
Cognitive Therapy (CT): CT sessions occur weekly during acute treatment and monthly during continuation. Acute treatment may last up to 18 months. Remitted patients are continued on medication for up to 36 months from initial randomization until they meet criteria for recovery. At recovery, patients receiving combined treatment discontinue CT.
Antidepressant medications: Antidepressant medication is distributed as clinically indicated with augmentation and ancillary medications as needed. Acute treatment may last up to 18 months. Remitted patients are continued on medication for up to 36 months from the point of initial randomization until they meet criteria for recovery. All recovered patients are randomized a second time to either maintenance medication or medication withdrawal. Patients are then monitored over 36 months to ascertain risk for recurrence of depressive symptoms. | 227 |
| Antidepressant Medications Alone Participants will receive maintenance of antidepressant medication alone
Antidepressant medications: Antidepressant medication is distributed as clinically indicated with augmentation and ancillary medications as needed. Acute treatment may last up to 18 months. Remitted patients are continued on medication for up to 36 months from the point of initial randomization until they meet criteria for recovery. All recovered patients are randomized a second time to either maintenance medication or medication withdrawal. Patients are then monitored over 36 months to ascertain risk for recurrence of depressive symptoms. | 225 |
| Total | 452 |
Baseline characteristics
| Characteristic | Cognitive Therapy Plus Antidepressant Medications | Antidepressant Medications Alone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 214 Participants | 214 Participants | 428 Participants |
| Age, Continuous | 43.3 years STANDARD_DEVIATION 12.9 | 43.0 years STANDARD_DEVIATION 13.4 | 43.2 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 10 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 210 Participants | 215 Participants | 425 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of participants who met criteria for Major Depressive Disorder via SCID-MDD | 227 participants | 225 participants | 452 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 27 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 194 Participants | 193 Participants | 387 Participants |
| Region of Enrollment United States | 227 participants | 225 participants | 452 participants |
| Sex: Female, Male Female | 130 Participants | 136 Participants | 266 Participants |
| Sex: Female, Male Male | 97 Participants | 89 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 227 | 0 / 225 |
| serious Total, serious adverse events | 59 / 227 | 82 / 225 |
Outcome results
Primary
Number of Participants in Recovery According to the LIFE and HRSD
Six consecutive months following remission without relapse (two weeks of elevated LIFE PSR scores of 4 or more and HRSD scores of 14 and above)
Time frame: Through 36 months of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cognitive Therapy Plus Antidepressant Medications | Number of Participants in Recovery According to the LIFE and HRSD | 165 number participants that reach recovery |
| Antidepressant Medications Alone | Number of Participants in Recovery According to the LIFE and HRSD | 140 number participants that reach recovery |
p-value: <0.01Subdistribution hazard model
Primary
Number of Participants in Recurrence According to the LIFE and HRSD
Recurrence defined as two consecutive weeks of elevated LIFE PSR scores of 5 or above and HRSD scores of 16 or above (three weeks during period of medication withdrawal)
Time frame: Measured up to Month 36 from recovery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cognitive Therapy Plus Antidepressant Medications | Number of Participants in Recurrence According to the LIFE and HRSD | 78 Participants |
| Antidepressant Medications Alone | Number of Participants in Recurrence According to the LIFE and HRSD | 85 Participants |
| Prioir Meds Maintained | Number of Participants in Recurrence According to the LIFE and HRSD | 79 Participants |
| Prior Meds Withdrawn | Number of Participants in Recurrence According to the LIFE and HRSD | 103 Participants |
Primary
Number of Participants in Remission According to the Longitudinal Interval Follow-up Evaluation (LIFE) and the Hamilton Rating Scale for Depression (HRSD)
Remission defined as four consecutive weeks of LIFE Problem Symptom Rating (PSR) values of 2 or less and HRSD scores of 8 or less for four consecutive weeks (with partial remission defined as LIFE PSR values of 3 or less and HRSD scores of 12 or less after month 12 only)
Time frame: Through month 18 of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cognitive Therapy Plus Antidepressant Medications | Number of Participants in Remission According to the Longitudinal Interval Follow-up Evaluation (LIFE) and the Hamilton Rating Scale for Depression (HRSD) | 187 number participants that reach remission |
| Antidepressant Medications Alone | Number of Participants in Remission According to the Longitudinal Interval Follow-up Evaluation (LIFE) and the Hamilton Rating Scale for Depression (HRSD) | 170 number participants that reach remission |
p-value: =0.038Subdistribution hazard model
Other Pre-specified
Serious Adverse Events
Number Serious Adverse Events (SAEs) as reported to the Institutional Review Boards and Data Safety Monitoring Board throughout the duration of the study
Time frame: Throughout study, up to 54 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cognitive Therapy Plus Antidepressant Medications | Serious Adverse Events | 59 number of SAE's |
| Antidepressant Medications Alone | Serious Adverse Events | 82 number of SAE's |