Efficacy of Antidepressants in Chronic Back Pain

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00964886
• Collaborator: University of California, San Diego (Other)
• Enrollment: 142
• Location: 1
• Arms: 4
• Duration (Months): 71
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This 12 week placebo controlled clinical trial tests the individual and combined effects of an antidepressant medication and cognitive behavioral therapy for chronic back pain.

Condition or Disease	Intervention/Treatment	Phase
Back Pain	Behavioral: cognitive behavioral therapy; Drug: desipramine hydrochloride; Behavioral: cognitive behavioral therapy; Drug: benztropine mesylate 0.125 mg daily; Drug: desipramine hydrochloride	Phase 2

Detailed Description

This is a 4 arm 12 week randomized clinical trial comparing the efficacy of 1) low concentration desipramine (< 60 ng/ml); 2) cognitive behavioral therapy; 3) low concentration desipramine + cognitive behavioral therapy; and 4) placebo medication (benzotropine mesylate).

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Antidepressants in Chronic Back Pain
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 desipramine hydrochloride	Drug: desipramine hydrochloride; desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml; Other Names: Anafranil
Experimental: Arm 2 cognitive behavioral therapy	Behavioral: cognitive behavioral therapy; cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life
Experimental: Arm 3 desipramine hydrochloride and cognitive behavioral therapy	Drug: desipramine hydrochloride; desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml; Other Names: Anafranil ; Behavioral: cognitive behavioral therapy; cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life
Placebo Comparator: Arm 4 anticholinergic medication; active placebo	Drug: benztropine mesylate 0.125 mg daily; benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride; Other Names: Cogentin

Outcome Measures

Primary Outcome Measures

1. Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity [12 weeks after baseline (or last observation carried forward)]

   The DDS is self-report measure of "current" pain intensity of chronic back pain. Participants rate pain on a 20 point scale as being greater or less intense relative to 12 adjectival descriptor words which serve as anchors (eg, greater or less than "faint," "moderate," "strong"). Scores range from 0 to 20 with higher scores indicating higher pain intensity. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline or last observation carried forward, after co-varying for baseline (pre-treatment) values.

Secondary Outcome Measures

1. Roland and Morris Disability Questionnaire [12 weeks after baseline (or last observation carried forward)]

   This questionnaire measures disability in everyday function due to back pain. It is a 24-item checklist asking patients to endorse whether or not back pain limits activities they normally do (eg, "I stay at home most of the time because of my back"). Scores range from 0 to 24, with higher scores indicating greater disability in everyday function due to back pain. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline, after co-varying for baseline (pre-treatment) values.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Chronic back pain (daily pain for > 6 months)

Exclusion Criteria:

• Major medical conditions which might contraindicate antidepressant treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA San Diego Healthcare System, San Diego, CA	San Diego	California	United States	92161

Sponsors and Collaborators

• VA Office of Research and Development
• University of California, San Diego

Investigators

• Principal Investigator: Joseph H Atkinson, MD, VA San Diego Healthcare System, San Diego, CA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00964886
• Other Study ID Numbers: NURA-019-09S
• First Posted: Aug 25, 2009
• Last Update Posted: Nov 29, 2016
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by VA Office of Research and Development: chronic pain; back pain; antidepressants
• Additional relevant MeSH terms: Back Pain; Benztropine; Desipramine; Clomipramine

Study Results

Participant Flow

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	desipramine hydrochloride desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml	cognitive behavioral therapy cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life	desipramine hydrochloride and cognitive behavioral therapy desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life	anticholinergic medication; active placebo benztropine mesylate 0.125 mg daily: benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride
Period Title: Overall Study
STARTED	38	34	37	33
COMPLETED	27	27	21	24
NOT COMPLETED	11	7	16	9

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4	Total
Arm/Group Description	desipramine hydrochloride desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml	cognitive behavioral therapy cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life	desipramine hydrochloride and cognitive behavioral therapy desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life	anticholinergic medication; active placebo benztropine mesylate 0.125 mg daily: benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride	Total of all reporting groups
Overall Participants	37	33	37	32	139
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (11.7)	57.8 (9.2)	51.5 (13.7)	57.9 (10.9)	55.8 (11.7)
Gender (Count of Participants)
Female	5 13.5%	4 12.1%	3 8.1%	3 9.4%	15 10.8%
Male	32 86.5%	29 87.9%	34 91.9%	28 87.5%	123 88.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 16.2%	10 30.3%	5 13.5%	4 12.5%	25 18%
Not Hispanic or Latino	29 78.4%	22 66.7%	28 75.7%	24 75%	103 74.1%
Unknown or Not Reported	2 5.4%	1 3%	4 10.8%	4 12.5%	11 7.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 6.1%	1 2.7%	0 0%	3 2.2%
Asian	1 2.7%	1 3%	2 5.4%	1 3.1%	5 3.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 2.7%	1 3.1%	2 1.4%
Black or African American	6 16.2%	6 18.2%	4 10.8%	5 15.6%	21 15.1%
White	25 67.6%	18 54.5%	21 56.8%	20 62.5%	84 60.4%
More than one race	4 10.8%	2 6.1%	7 18.9%	3 9.4%	16 11.5%
Unknown or Not Reported	1 2.7%	3 9.1%	1 2.7%	2 6.3%	7 5%
Region of Enrollment (participants) [Number]
United States	37 100%	33 100%	37 100%	32 100%	139 100%
Pain Intensity and Back Pain Disability (units on a scale) [Mean (Standard Deviation) ]
Pain Intensity (Descriptor Differential Scale)	9.9 (4.9)	11.9 (4.3)	11.9 (5.1)	12.1 (4.6)	11.4 (4.0)
Back Pain Disability (Roland and Morris)	8.7 (5.4)	13.0 (4.3)	11.7 (5.4)	12.6 (3.8)	11.8 (4.9)

Outcome Measures

1. Primary Outcome

Title	Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity
Description	The DDS is self-report measure of "current" pain intensity of chronic back pain. Participants rate pain on a 20 point scale as being greater or less intense relative to 12 adjectival descriptor words which serve as anchors (eg, greater or less than "faint," "moderate," "strong"). Scores range from 0 to 20 with higher scores indicating higher pain intensity. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline or last observation carried forward, after co-varying for baseline (pre-treatment) values.
Time Frame	12 weeks after baseline (or last observation carried forward)

Outcome Measure Data

Analysis Population Description

We conducted an intent-to-treat analysis of all randomized participants assigned to desipramine or to active drug placebo (benztropine) comparing mean DDS pain intensity at Week 12 (or the last observation carried forward) adjusted for mean baseline score.

Arm/Group Title	Arm 1 + Arm 3	Arm 2 + Arm 4
Arm/Group Description	Factor desipramine hydrochloride desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml	Factor anticholinergic medication; active placebo benztropine mesylate 0.125 mg daily: benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride
Measure Participants	75	67
Mean (Standard Error) [units on a scale]	8.3 (0.5)	8.1 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 + Arm 3, Arm 2 + Arm 4
	Comments	In an intent-to-treat analysis of all randomized participants assigned to experimental drug (desipramine) or active placebo (benztropine) an analysis of variance compared mean Descriptor Differential Scale scores at 12 weeks (or last observation carried forward) adjusted fro mean baseline score ( = ).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Roland and Morris Disability Questionnaire
Description	This questionnaire measures disability in everyday function due to back pain. It is a 24-item checklist asking patients to endorse whether or not back pain limits activities they normally do (eg, "I stay at home most of the time because of my back"). Scores range from 0 to 24, with higher scores indicating greater disability in everyday function due to back pain. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline, after co-varying for baseline (pre-treatment) values.
Time Frame	12 weeks after baseline (or last observation carried forward)

Outcome Measure Data

Analysis Population Description

All participants assigned at baseline to receive desipramine hydrochloride or benztropine mesylate (drug effect). This is an 'as randomized' Intent-to-Treat analysis. Values are mean scores at Week 12 (or last observation carried forward). Means are adjusted for baseline Roland and Morris scores

Arm/Group Title	Arm 1 + Arm 3	Arm 2 + Arm 4
Arm/Group Description	Factor all participants assigned at baseline to receive desipramine hydrochloride	Factor all participants assigned at baseline to receive benztropine mesylate (active placebo)
Measure Participants	75	67
Mean (Standard Error) [Units on a scale.]	8.7 (0.5)	8.9 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 + Arm 3, Arm 2 + Arm 4
	Comments	In the intent-to-treat sample of all randomized participants assigned to experimental drug (desipramine) or active placebo (benztropine) an analysis of variance (ANOVA) compared mean Roland and Morris scores at 12 weeks adjusted for mean baseline scores.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	ANCOVA
	Comments	Means are adjusted for baseline Roland and Morris scores.

3. Primary Outcome

Title	Intent-toTreat Analysis of Descriptor Differential Scale (DDS) of Pain Intensity
Description	The DDS is self-report measure of "current" pain intensity of chronic back pain. Participants rate pain on a 20 point scale as being greater or less intense relative to 12 adjectival descriptor words which serve as anchors (eg, greater or less than "faint," "moderate," "strong"). Scores range from 0 to 20 with higher scores indicating higher pain intensity. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline or last observation carried forward, after co-varying for baseline (pre-treatment) values.
Time Frame	12 weeks after baseline (or last observation carried forward)

Outcome Measure Data

Analysis Population Description

We conducted an intent-to-treat analysis of all randomized participants assigned to cognitive behavioral therapy to or no behavior therapy comparing mean DDS pain intensity at Week 12 (or the last observation carried forward) adjusted for mean baseline score.

Arm/Group Title	Arm 2 + Arm 3	Arm 1 + Arm 4
Arm/Group Description	Factor cognitive behavioral therapy cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life	Factor no cognitive behavioral therapy
Measure Participants	71	71
Mean (Standard Error) [units on a scale]	8.0 (0.6)	8.4 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 + Arm 3, Arm 2 + Arm 4
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Roland and Morris Disability Questionnaire
Description	This questionnaire measures disability in everyday function due to back pain. It is a 24-item checklist asking patients to endorse whether or not back pain limits activities they normally do (eg, "I stay at home most of the time because of my back"). Scores range from 0 to 24, with higher scores indicating greater disability in everyday function due to back pain. The analysis evaluated the 'as randomized' sample at 12 weeks after baseline, after co-varying for baseline (pre-treatment) values.
Time Frame	12 weeks after baseline (or last observation carried forward)

Outcome Measure Data

Analysis Population Description

All participants assigned at baseline to receive cognitive behavioral therapy or to no cognitive behavioral therapy (behavioral effect). This is an 'as randomized' Intent-to-Treat analysis. Values are mean scores at Week 12 (or last observation carried forward). Means are adjusted for baseline Roland and Morris scores

Arm/Group Title	Arm 2 + Arm 3	Arm 1 + Arm 4
Arm/Group Description	Factor all participants assigned at baseline to receive cognitive behavioral therapy	Factor all participants assigned at baseline not to receive cognitive behavioral therapy
Measure Participants	71	71
Mean (Standard Error) [Units on a scale.]	8.7 (0.5)	8.9 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 + Arm 3, Arm 2 + Arm 4
	Comments	This analysis compares outcomes for participants assigned at baseline to receive cognitive behavioral therapy or not to receive cognitive behavioral therapy (behavioral effect)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Report of side effects experienced within the past 3 days by participants completing the Week 12 visit.
Adverse Event Reporting Description	Non-serious adverse advents were monitored for 70 participants.
Arm/Group Title	Arm 1		Arm 2		Arm 3		Arm 4
Arm/Group Description	desipramine hydrochloride desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml		cognitive behavioral therapy cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life		desipramine hydrochloride and cognitive behavioral therapy desipramine hydrochloride: desipramine hydrochloride, with dose targeted to achieve a serum concentration of 5-60ng/ml cognitive behavioral therapy: cognitive behavioral therapy, a type of psychotherapy oriented towards restoring function and reducing impact of pain on everyday life		anticholinergic medication; active placebo benztropine mesylate 0.125 mg daily: benztropine mesylate is a placebo, some of whose side effects mimic those of experimental intervention, desipramine hydrochloride
All Cause Mortality
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)		0/34 (0%)		1/37 (2.7%)		0/33 (0%)
Cardiac disorders
fall	0/38 (0%)	0	0/34 (0%)	0	1/37 (2.7%)	1	0/33 (0%)	0
Renal and urinary disorders
urosepsis	1/38 (2.6%)	1	0/34 (0%)	0	0/37 (0%)	0	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/17 (70.6%)		8/20 (40%)		7/16 (43.8%)		6/17 (35.3%)
Endocrine disorders
gynecomastia	0/17 (0%)	0	1/20 (5%)	1	0/16 (0%)	0	0/17 (0%)	0
weight gain	0/17 (0%)	0	1/20 (5%)	1	0/16 (0%)	0	0/17 (0%)	0
Eye disorders
accomodation disturbance	2/17 (11.8%)	2	0/20 (0%)	0	2/16 (12.5%)	2	1/17 (5.9%)	1
Gastrointestinal disorders
dry mouth	5/17 (29.4%)	5	3/20 (15%)	3	4/16 (25%)	4	1/17 (5.9%)	1
constipation	4/17 (23.5%)	4	1/20 (5%)	1	1/16 (6.3%)	1	1/17 (5.9%)	1
General disorders
diaphoresis	1/17 (5.9%)	1	1/20 (5%)	1	0/16 (0%)	0	0/17 (0%)	0
nausea	0/17 (0%)	0	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1
photosensitivity	1/17 (5.9%)	1	0/20 (0%)	0	0/16 (0%)	0	0/17 (0%)	0
Nervous system disorders
decreased libido	1/17 (5.9%)	1	0/20 (0%)	0	0/16 (0%)	0	3/17 (17.6%)	3
increased dreaming	1/17 (5.9%)	1	2/20 (10%)	2	0/16 (0%)	0	1/17 (5.9%)	1
sedation	0/17 (0%)	0	1/20 (5%)	1	2/16 (12.5%)	2	0/17 (0%)	0
increased sleep duration	0/17 (0%)	0	2/20 (10%)	2	1/16 (6.3%)	1	0/17 (0%)	0
asthenia	0/17 (0%)	0	1/20 (5%)	1	0/16 (0%)	0	1/17 (5.9%)	1
muscle rigidity	1/17 (5.9%)	1	1/20 (5%)	1	0/16 (0%)	0	0/17 (0%)	0
hyperkinesis	0/17 (0%)	0	1/20 (5%)	1	0/16 (0%)	0	1/17 (5.9%)	1
dystonia	0/17 (0%)	0	1/20 (5%)	1	0/16 (0%)	0	0/17 (0%)	0
dysarthria	0/17 (0%)	0	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1
ataxia	0/17 (0%)	0	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1
insomnia	1/17 (5.9%)	1	0/20 (0%)	0	0/16 (0%)	0	0/17 (0%)	0
paresthesia	0/17 (0%)	0	1/20 (5%)	1	0/16 (0%)	0	0/17 (0%)	0
Psychiatric disorders
depression	0/17 (0%)	0	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1
Renal and urinary disorders
difficulty urinating	4/17 (23.5%)	4	1/20 (5%)	1	1/16 (6.3%)	1	1/17 (5.9%)	1
erectile dysfunction	3/17 (17.6%)	3	0/20 (0%)	0	0/16 (0%)	0	3/17 (17.6%)	3
ejaculatory dysfunction	2/17 (11.8%)	2	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1
orgasm dysfunction	2/17 (11.8%)	2	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1
polyuria	0/17 (0%)	0	0/20 (0%)	0	0/16 (0%)	0	1/17 (5.9%)	1

Limitations/Caveats

Failure to attain recruitment goals and attrition resulted in lack of power to detect an effect. A strong active placebo control condition (benztropine) and frequent follow up visits may have led to improvement in all groups over time.

More Information

Certain Agreements

All Principal Investigators ARE 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.