CPT3: Prevention of Recurrence in Depression With Drugs and CT

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00057577
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 452
• Locations: 3
• Arms: 2
• Duration (Months): 137
• Patients Per Site: 150.7
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression	Behavioral: Cognitive Therapy; Drug: Medications	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 452 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Prevention of Recurrence in Depression With Drugs and CT
• Study Start Date: Oct 1, 2002
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cognitive therapy plus medications Participants will receive antidepressant medication plus cognitive therapy	Behavioral: Cognitive 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.; Other Names: CT ; Drug: 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.; Other Names: ADM
Experimental: Medications alone Participants will receive maintenance of antidepressant medication alone	Drug: 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.; Other Names: ADM

Outcome Measures

Primary Outcome Measures

1. 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)

2. 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)

3. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush Medical Center - Treatment Research Unit	Chicago	Illinois	United States	60612
2	Depression Research Unit, University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
3	Vanderbilt Adult Outpatient Psychiatry	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• Vanderbilt University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Steven D. Hollon, PhD, Vanderbilt University
• Principal Investigator: Robert J. DeRubeis, PhD, University of Pennsylvania
• Principal Investigator: Jan A. Fawcett, MD, Rush Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Steven Hollon, Professor of Psychology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00057577
• Other Study ID Numbers: R01MH060713; R01MH060713
• First Posted: Apr 8, 2003
• Last Update Posted: May 30, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Recurrence; Depression; Depressive Disorder

Study Results

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

Arm/Group Title	Cognitive Therapy Plus Antidepressant Medications	Antidepressant Medications Alone
Arm/Group Description	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 19 months. Remitted patients are continued on medication for up to 42 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 19 months. Remitted patients are continued on medication for up to 42 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.	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 19 months. Remitted patients are continued on medication for up to 42 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.
Period Title: Overall Study
STARTED	227	225
COMPLETED	227	225
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cognitive Therapy Plus Antidepressant Medications	Antidepressant Medications Alone	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	227	225	452
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.3 (12.9)	43.0 (13.4)	43.2 (13.1)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	214 94.3%	214 95.1%	428 94.7%
>=65 years	13 5.7%	11 4.9%	24 5.3%
Sex: Female, Male (Count of Participants)
Female	130 57.3%	136 60.4%	266 58.8%
Male	97 42.7%	89 39.6%	186 41.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 1.8%	1 0.4%	5 1.1%
Asian	6 2.6%	4 1.8%	10 2.2%
Native Hawaiian or Other Pacific Islander	1 0.4%	0 0%	1 0.2%
Black or African American	21 9.3%	27 12%	48 10.6%
White	194 85.5%	193 85.8%	387 85.6%
More than one race	1 0.4%	0 0%	1 0.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 7.5%	10 4.4%	27 6%
Not Hispanic or Latino	210 92.5%	215 95.6%	425 94%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	227 100%	225 100%	452 100%
Number of participants who met criteria for Major Depressive Disorder via SCID-MDD (participants) [Number]
Number [participants]	227 100%	225 100%	452 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Remission According to the Longitudinal Interval Follow-up Evaluation (LIFE) and the Hamilton Rating Scale for Depression (HRSD)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive Therapy Plus Antidepressant Medications	Antidepressant Medications Alone
Arm/Group Description	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.	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.
Measure Participants	227	225
Number [number participants that reach remission]	187 82.4%	170 75.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive Therapy Plus Antidepressant Medications, Antidepressant Medications Alone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=.038
	Comments
	Method	Subdistribution hazard model
	Comments

2. Primary Outcome

Title	Number of Participants in Recovery According to the LIFE and HRSD
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive Therapy Plus Antidepressant Medications	Antidepressant Medications Only
Arm/Group Description	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.	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.
Measure Participants	227	225
Number [number participants that reach recovery]	165 72.7%	140 62.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive Therapy Plus Antidepressant Medications, Antidepressant Medications Alone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Subdistribution hazard model
	Comments

3. Primary Outcome

Title	Number of Participants in Recurrence According to the LIFE and HRSD
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prior CBT + Meds Maintained	Prior CBT + Meds Withdrawn	Prioir Meds Maintained	Prior Meds Withdrawn
Arm/Group Description	Patients who recovered on combined treatment (CBT + Meds) were phased out of cognitive therapy and maintained on medications	Patients who recovered on combined treatment (CBT + Meds) were phased out of cognitive therapy and withdrawn from medications	Patients who recovered on medication treatment were maintained on medications	Patients who recovered on medication treatment were withdrawn from medications
Measure Participants	124	103	111	114
Count of Participants [Participants]	78 34.4%	85 37.8%	79 17.5%	103 NaN

4. Other Pre-specified Outcome

Title	Serious Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive Therapy Plus Antidepressant Medications	Antidepressant Medications Only
Arm/Group Description	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.	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.
Measure Participants	227	225
Number [number of SAE's]	59	82

Adverse Events

Time Frame	Acute treatment up to 18 months and continuation treatment up to 36 months following randomization with subsequent 36 month maintenance phase following recovery
Arm/Group Title	Cognitive Therapy Plus Antidepressant Medications		Antidepressant Medications Alone
Arm/Group Description	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.		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.
All Cause Mortality
	Cognitive Therapy Plus Antidepressant Medications		Antidepressant Medications Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cognitive Therapy Plus Antidepressant Medications		Antidepressant Medications Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/227 (26%)		82/225 (36.4%)
General disorders
Death (any cause)	3/227 (1.3%)	3	1/225 (0.4%)	1
Medical Hospitalizations	30/227 (13.2%)	46	37/225 (16.4%)	61
Motor Vehicle Accidents (MVA)	1/227 (0.4%)	1	3/225 (1.3%)	3
Other	2/227 (0.9%)	2	0/225 (0%)	0
Pregnancy, puerperium and perinatal conditions
Pregnancy	4/227 (1.8%)	5	5/225 (2.2%)	6
Psychiatric disorders
Suicide Attempt	4/227 (1.8%)	5	8/225 (3.6%)	9
Psychiatric Hospitalizations	15/227 (6.6%)	19	28/225 (12.4%)	36
Other (Not Including Serious) Adverse Events
	Cognitive Therapy Plus Antidepressant Medications		Antidepressant Medications Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/227 (0%)		0/225 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.