Treatments for Depression: Drug Versus Psychotherapy

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00043550
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 156
• Location: 1
• Arms: 3
• Duration (Months): 91
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This 4-8 month study, with a 2-year follow up period, will compare sertraline (Zoloft®), venlafaxine (Effexor®), supportive-expressive psychotherapy, and placebo to determine which is more effective in treating major depression.

Condition or Disease	Intervention/Treatment	Phase
Depression	Behavioral: Supportive Expressive Therapy; Drug: Sertraline; Drug: Pill Placebo; Drug: Venlafaxine	Phase 3

Detailed Description

MDD is one of the most prevalent psychiatric disorders. Different forms of psychotherapy for depression have been found effective. This study compares a form of dynamic psychotherapy called supportive-expressive psychotherapy to medication and to placebo.

Participants are evaluated on 2 occasions, 1 week apart, before they are randomly assigned to receive either supportive-expressive psychotherapy, sertraline (Zoloft) (followed by venlafaxine [Effexor] if patients do not respond to sertraline), or placebo. The active phase of treatment lasts 4 months. The frequency of patients' visits depends on the assigned treatment.

Patients who are randomized to receive medication or placebo are initially seen on a weekly basis, then less often, depending on the rate of symptomatic improvement. Patients who are randomized to psychotherapy are seen twice a week for the first 4 weeks, then once a week for the remaining 12 weeks. Outcome is monitored at week 2,4,6,7,8, 12, 15 and 16. At the end of the first 16 weeks of treatment, patients are thoroughly evaluated. Those who have responded to treatment are assigned to a continuation phase and are seen once a month for another 16 weeks. At the end of the 16-week continuation phase, patients are again evaluated and all treatments are stopped. Follow-up continues every 3 months for up to 2 years to ensure that the patients' depression remains under control.

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Dynamic Therapy Versus Selective Serotonin Reuptake Inhibitor for Depression
• Study Start Date: Nov 1, 2001
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Sertraline/Venlafaxine Participants receive sertraline for the first 8 weeks. Participants will receive venlafaxine if they do not respond to sertraline by week 8	Drug: Sertraline; Participants will receive sertraline.; Other Names: Zoloft ; Drug: Venlafaxine; Participants will receive venlafaxine.; Other Names: Effexor
Active Comparator: 2 Supportive Expressive Therapy Participants will receive supportive-expressive psychotherapy.	Behavioral: Supportive Expressive Therapy; The aim of supportive-expressive psychotherapy is to help patients understand the causes of relationship conflicts in the context of a supportive relationship.
Placebo Comparator: 3 Pill Placebo Participants receive placebo.	Drug: Pill Placebo; Participants will receive a pill placebo.

Outcome Measures

Primary Outcome Measures

1. Hamilton Rating Scale for Depression-17 Item [symptoms assessed during past 7 days, measure taken at baseline, week 8 and week 16]

   Hamilton Rating Scale for Depression (HRSD) (Hamilton, 1960). We used the 17-item version of the 27-item HRSD, a measure of depression severity. The Structured Interview Guide was used to conduct the interviews (SIGH-D; Williams, 1988). The reliability and validity of the HRSD are well documented (Rabkin & Klein, 1987). Interjudge reliability as assessed by interclass correlations was .92 in our sample. Total 17-item scores could range from 17-48 with higher scores indicating greater distress.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Major Depressive Disorder diagnosis

Exclusion criteria:

• Psychotic or bipolar disorder diagnosis

• Substance dependence in the last 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Jacques Barber, PhD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00043550
• Other Study ID Numbers: R01MH061410; R01MH061410; DSIR 83-ATAS
• First Posted: Aug 12, 2002
• Last Update Posted: Jun 2, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by University of Pennsylvania: Major Depressive Disorder
• Additional relevant MeSH terms: Depression; Depressive Disorder; Sertraline; Venlafaxine Hydrochloride

Study Results

Participant Flow

Recruitment Details	374 individuals, ages 18 to 70 years, were recruited through advertisements on public transportation, free news publications, area physicians, and outpatient clinics during the period of 2001-2006.
Pre-assignment Detail	Individuals not meeting MDD diagnostic criteria11 using the Structured Clinical Interviews for DSM-IV12 or scoring less than 14 on the 17-item Hamilton Rating Scale for Depression (HRSD)13,14 at two evaluations one week apart were excluded (n=88).

Arm/Group Title	1 Sertraline	2 Supportive-expressive Psychotherapy	3 Pill Placebo
Arm/Group Description	Participants receive sertraline. Sertraline : Participants will receive sertraline.	Participants will receive supportive-expressive psychotherapy. Supportive Expressive Therapy : The aim of supportive-expressive psychotherapy is to help patients understand the causes of relationship conflicts in the context of a supportive relationship.	Participants receive placebo. Pill Placebo : Participants will receive a pill placebo.
Period Title: Overall Study
STARTED	55	51	50
Week 8 Completed	35	40	35
COMPLETED	33	39	30
NOT COMPLETED	22	12	20

Baseline Characteristics

Arm/Group Title	1 Sertraline	2 Supportive-expressive Psychotherapy	3 Pill Placebo	Total
Arm/Group Description	Participants receive sertraline. Sertraline : Participants will receive sertraline.	Participants will receive supportive-expressive psychotherapy. Supportive Expressive Therapy : The aim of supportive-expressive psychotherapy is to help patients understand the causes of relationship conflicts in the context of a supportive relationship.	Participants receive placebo. Pill Placebo : Participants will receive a pill placebo.	Total of all reporting groups
Overall Participants	55	51	50	156
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	55 100%	51 100%	50 100%	156 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.0 (12.5)	36.2 (12.2)	38.3 (12.0)	37.5 (12.2)
Sex: Female, Male (Count of Participants)
Female	30 54.5%	31 60.8%	31 62%	92 59%
Male	25 45.5%	20 39.2%	19 38%	64 41%
Region of Enrollment (participants) [Number]
United States	55 100%	51 100%	50 100%	156 100%

Outcome Measures

1. Primary Outcome

Title	Hamilton Rating Scale for Depression-17 Item
Description	Hamilton Rating Scale for Depression (HRSD) (Hamilton, 1960). We used the 17-item version of the 27-item HRSD, a measure of depression severity. The Structured Interview Guide was used to conduct the interviews (SIGH-D; Williams, 1988). The reliability and validity of the HRSD are well documented (Rabkin & Klein, 1987). Interjudge reliability as assessed by interclass correlations was .92 in our sample. Total 17-item scores could range from 17-48 with higher scores indicating greater distress.
Time Frame	symptoms assessed during past 7 days, measure taken at baseline, week 8 and week 16

Outcome Measure Data

Analysis Population Description

Numbers vary from consented due to dropout prior to start of study. 156 patients consented and randomized. 11 patients did not complete at least one post-randomization measure and were therefore not included in these analyses.

Arm/Group Title	1 Sertraline	2 Supportive-expressive Psychotherapy	3 Pill Placebo
Arm/Group Description	Participants receive sertraline. Sertraline : Participants will receive sertraline.	Participants will receive supportive-expressive psychotherapy. Supportive Expressive Therapy : The aim of supportive-expressive psychotherapy is to help patients understand the causes of relationship conflicts in the context of a supportive relationship.	Participants receive placebo. Pill Placebo : Participants will receive a pill placebo.
Measure Participants	51	46	48
Initial HRSD-17	19.0 (3.4)	19.9 (3.9)	19.4 (3.7)
Mid-treatment HRSD-17	13.9 (7.2)	12.5 (6.9)	12.7 (6.8)
LOCF HRSD-17	14.2 (7.6)	14.5 (8.3)	14.3 (7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1 Sertraline, 2 Supportive-expressive Psychotherapy, 3 Pill Placebo
	Comments	Comparison of conditions
	Type of Statistical Test	Superiority
	Comments	The proposed sample size had at least 80% power to detect effect sizes of 0.36 between the two active treatment conditions and placebo during the active phase. These power calculations were based on a priori values of within-subject correlation of 0.50, 10% attrition, and 6 assessment points.
Statistical Test of Hypothesis	p-Value	.95
	Comments	Overall significant effect for treatment, as well as the two moderating effects, used a Bonferroni-corrected alpha level of 0.0167 (0.05/3).
	Method	HLM
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1 Sertraline, 2 Supportive-expressive Psychotherapy, 3 Pill Placebo
	Comments	effects of conditions over time
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	HLM
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	1 Sertraline, 3 Pill Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	.03
	Confidence Interval	(2-Sided) 95%; -.35 to .41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	2 Supportive-expressive Psychotherapy, 3 Pill Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	.06
	Confidence Interval	(2-Sided) 95%; -.33 to .45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	1 Sertraline		2 Supportive-expressive Psychotherapy		3 Pill Placebo
Arm/Group Description	Participants receive sertraline. Sertraline : Participants will receive sertraline.		Participants will receive supportive-expressive psychotherapy. Supportive Expressive Therapy : The aim of supportive-expressive psychotherapy is to help patients understand the causes of relationship conflicts in the context of a supportive relationship.		Participants receive placebo. Pill Placebo : Participants will receive a pill placebo.
All Cause Mortality
	1 Sertraline		2 Supportive-expressive Psychotherapy		3 Pill Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	1 Sertraline		2 Supportive-expressive Psychotherapy		3 Pill Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/51 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	1 Sertraline		2 Supportive-expressive Psychotherapy		3 Pill Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		1/51 (2%)		0/50 (0%)
Psychiatric disorders
passive suicide attempt	0/55 (0%)	0	1/51 (2%)	1	0/50 (0%)	0

Limitations/Caveats

Two limitations are the relatively high level of attrition and small sample size for specific combinations within our moderation analysis.

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.