Trial Outcomes & Findings for A Study of Medication With or Without Psychotherapy for Complicated Grief (NCT NCT01179568)

NCT ID: NCT01179568

Last Updated: 2017-01-24

Results Overview

Brief rating scale frequently used in clinical trials. For this study, version modified for complicated grief was be used. Response is defined as a score of 1(very much improved) or 2 (much improved) on the scale. The rating was done by an Independent Evaluator.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

395 participants

Primary outcome timeframe

Weeks 12 and 20

Results posted on

2017-01-24

Participant Flow

Bereaved individuals age 18-95 were recruited between March 2010 and September 2014 using professional and public outreach, print, broadcast and internet media. Referrals were made by health care professionals, bereavement counselors and patients or family members.

Participant milestones

Participant milestones
Measure
Citalopram
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (Sugar Pill)
Inactive medication. It is combined with grief-focused clinical management. Placebo: 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
CGT With Citalopram
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment: Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
CGT With Placebo
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment: Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Overall Study
STARTED
101
99
99
96
Overall Study
Completed Week 12 Assessment
69
69
76
75
Overall Study
COMPLETED
73
61
76
76
Overall Study
NOT COMPLETED
28
38
23
20

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Medication With or Without Psychotherapy for Complicated Grief

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Citalopram
n=101 Participants
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (Sugar Pill)
n=99 Participants
Inactive medication. It is combined with grief-focused clinical management. Placebo: 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
CGT With Citalopram
n=99 Participants
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment: Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
CGT With Placebo
n=96 Participants
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment: Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Total
n=395 Participants
Total of all reporting groups
Age, Continuous
52.4 years
STANDARD_DEVIATION 13.1 • n=5 Participants
53.9 years
STANDARD_DEVIATION 13.8 • n=7 Participants
52.1 years
STANDARD_DEVIATION 15.3 • n=5 Participants
53.5 years
STANDARD_DEVIATION 16.0 • n=4 Participants
53.0 years
STANDARD_DEVIATION 14.5 • n=21 Participants
Gender
Female
82 Participants
n=5 Participants
69 Participants
n=7 Participants
78 Participants
n=5 Participants
79 Participants
n=4 Participants
308 Participants
n=21 Participants
Gender
Male
19 Participants
n=5 Participants
30 Participants
n=7 Participants
21 Participants
n=5 Participants
17 Participants
n=4 Participants
87 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
10 Participants
n=5 Participants
7 Participants
n=7 Participants
8 Participants
n=5 Participants
20 Participants
n=4 Participants
45 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
91 Participants
n=5 Participants
92 Participants
n=7 Participants
91 Participants
n=5 Participants
76 Participants
n=4 Participants
350 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race/Ethnicity, Customized
While
85 participants
n=5 Participants
80 participants
n=7 Participants
81 participants
n=5 Participants
79 participants
n=4 Participants
325 participants
n=21 Participants
Race/Ethnicity, Customized
Black
10 participants
n=5 Participants
8 participants
n=7 Participants
11 participants
n=5 Participants
10 participants
n=4 Participants
39 participants
n=21 Participants
Race/Ethnicity, Customized
Others
6 participants
n=5 Participants
11 participants
n=7 Participants
7 participants
n=5 Participants
7 participants
n=4 Participants
31 participants
n=21 Participants

PRIMARY outcome

Timeframe: Weeks 12 and 20

Population: Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting .

Brief rating scale frequently used in clinical trials. For this study, version modified for complicated grief was be used. Response is defined as a score of 1(very much improved) or 2 (much improved) on the scale. The rating was done by an Independent Evaluator.

Outcome measures

Outcome measures
Measure
Citalopram (CIT)
n=101 Participants
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (PLA; Sugar Pill)
n=99 Participants
Inactive medication. It is combined with grief-focused clinical management. Placebo (PLA): 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
Complicated Grief Treatment With Citalopram (CGT With CIT)
n=99 Participants
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Complicated Grief Treatment With Placebo (CGT With PLA)
n=96 Participants
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Responder Status Based on Complicated Grief Clinical Global Impression-Improvement (CGI-I) Scale
46 percentage of responders
38 percentage of responders
84 percentage of responders
83 percentage of responders

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Prespecified secondary analyses of self-report ratings of CG symptoms (ICG) compared changes in scores using a weighted linear regression with inverse probability weighting to adjust for missing assessments.

The 19-item self-report instrument assesses symptoms of complicated grief. Responses on individual items are added up to a total score, which can range from 0 to 76 with higher scores indicating more intense symptoms. This scale has been utilized previously in treatment studies of CG. Additional times points include weeks 4, 8, 12, 16, 20 and 40. For the pre-specified analyses we compared change in the ICG total score from baseline (calculated as baseline score minus week 12 score) for CIT vs PLA at week 12 (aim 1), based on the intention-to-treat principle including all randomized participants.

Outcome measures

Outcome measures
Measure
Citalopram (CIT)
n=101 Participants
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (PLA; Sugar Pill)
n=99 Participants
Inactive medication. It is combined with grief-focused clinical management. Placebo (PLA): 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
Complicated Grief Treatment With Citalopram (CGT With CIT)
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Complicated Grief Treatment With Placebo (CGT With PLA)
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Change From Baseline in Inventory of Complicated Grief (ICG)
18 score change from baseline to wk12
Standard Deviation 11
16 score change from baseline to wk12
Standard Deviation 12

SECONDARY outcome

Timeframe: Baseline and week 20

Population: Prespecified secondary analyses of self-report ratings of CG symptoms (ICG) compared changes in scores using a weighted linear regression with inverse probability weighting to adjust for missing assessments.

The 19-item self-report instrument assesses symptoms of complicated grief. Responses on individual items are added up to a total score, which can range from 0 to 76 with higher scores indicating more intense symptoms. This scale has been utilized previously in treatment studies of CG. Additional times points include weeks 4, 8, 12, 16, 20 and 40. For the pre-specified analyses we compared change in the ICG total score from baseline (calculated as baseline score minus week 20 score) for CIT with CGT vs PLA with CGT (aim 2), and for CIT with CGT vs CIT (aim 3) based on the intention-to-treat principle including all randomized participants.

Outcome measures

Outcome measures
Measure
Citalopram (CIT)
n=101 Participants
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (PLA; Sugar Pill)
n=99 Participants
Inactive medication. It is combined with grief-focused clinical management. Placebo (PLA): 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
Complicated Grief Treatment With Citalopram (CGT With CIT)
n=96 Participants
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Complicated Grief Treatment With Placebo (CGT With PLA)
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Change From Baseline in Inventory of Complicated Grief (ICG)
20 score change from baseline to wk20
Standard Deviation 12
25 score change from baseline to wk20
Standard Deviation 14
26 score change from baseline to wk20
Standard Deviation 12

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Prespecified secondary analyses of self-report ratings of grief-related functional impairment (WSAS) compared changes in scores using a weighted linear regression with inverse probability weighting to adjust for missing assessments.

The WSAS is a modification of a scale introduced by Hafner and Marks (1976), consisting of 0-8 point ratings of the extent to which symptoms interfere with five areas of daily functioning: work, home management, private leisure, social leisure, and family relationships. It is a well-validated, widely used self-report measure. Additional time points include weeks 4, 8, 12, 16, and 40. A total score calculated as a sum of all items (possible range 0-40) was used in the analyses with higher scores indicating more impairment. For the pre-specified analyses we compared change in the WSAS total score from baseline (calculated as baseline score minus week 12 score) for CIT vs PLA at week 12 (aim 1), based on the intention-to-treat principle including all randomized participants.

Outcome measures

Outcome measures
Measure
Citalopram (CIT)
n=101 Participants
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (PLA; Sugar Pill)
n=99 Participants
Inactive medication. It is combined with grief-focused clinical management. Placebo (PLA): 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
Complicated Grief Treatment With Citalopram (CGT With CIT)
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Complicated Grief Treatment With Placebo (CGT With PLA)
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Change From Baseline in Work and Social Adjustment Scale (WSAS)
10 score change from baseline to wk12
Standard Deviation 11
8 score change from baseline to wk12
Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline and week 20

Population: Prespecified secondary analyses of self-report ratings of grief-related functional impairment (WSAS) compared changes in scores using a weighted linear regression with inverse probability weighting to adjust for missing assessments.

The WSAS is a modification of a scale introduced by Hafner and Marks (1976), consisting of 0-8 point ratings of the extent to which symptoms interfere with five areas of daily functioning: work, home management, private leisure, social leisure, and family relationships. It is a well-validated, widely used self-report measure. Additional time points include weeks 4, 8, 12, 16, and 40. A total score calculated as a sum of all items (possible range 0-40) was used in the analyses with higher scores indicating more impairment. For the pre-specified analyses we compared change in the WSAS total score from baseline (calculated as baseline score minus week 20 score) for CIT with CGT vs PLA with CGT (aim 2), and for CIT with CGT vs CIT (aim 3) based on the intention-to-treat principle including all randomized participants.

Outcome measures

Outcome measures
Measure
Citalopram (CIT)
n=101 Participants
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (PLA; Sugar Pill)
n=99 Participants
Inactive medication. It is combined with grief-focused clinical management. Placebo (PLA): 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
Complicated Grief Treatment With Citalopram (CGT With CIT)
n=96 Participants
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Complicated Grief Treatment With Placebo (CGT With PLA)
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Change From Baseline in Work and Social Adjustment Scale (WSAS)
10 score change from baseline to wk20
Standard Deviation 12
14 score change from baseline to wk20
Standard Deviation 10
16 score change from baseline to wk20
Standard Deviation 11

Adverse Events

Citalopram

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo (Sugar Pill)

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

CGT With Citalopram

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

CGT With Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Citalopram
n=101 participants at risk
Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It is combined with grief-focused clinical management. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
Placebo (Sugar Pill)
n=99 participants at risk
Inactive medication. It is combined with grief-focused clinical management. Placebo: 16 weeks of daily inactive medication. It is administered in a double-blind fashion.
CGT With Citalopram
n=99 participants at risk
The targeted psychotherapy for complicated grief combined with SSRI medication. Complicated Grief Treatment: Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Citalopram: 16 weeks of medication provided flexibly up to 40 mg/day. Medication is administered in a double-blind fashion.
CGT With Placebo
n=96 participants at risk
The targeted psychotherapy for complicated grief combined with inactive medication. Complicated Grief Treatment: Complicated Grief Treatment (CGT) is a targeted psychotherapy for complicated grief. The treatment integrates principles, strategies and techniques from interpersonal psychotherapy, trauma-focused cognitive behavioral treatment and motivational interviewing. Treatment includes 16 sessions provided within 20 weeks. Placebo: 16 weeks of daily inactive medication. Medication is administered in a double-blind fashion.
Injury, poisoning and procedural complications
death by suicide
0.00%
0/101 • 5 years
We observed no serious adverse medication effects. CGT therapists monitored participant response to emotionally activating procedures; no serious untoward responses were documented.
0.00%
0/99 • 5 years
We observed no serious adverse medication effects. CGT therapists monitored participant response to emotionally activating procedures; no serious untoward responses were documented.
1.0%
1/99 • Number of events 1 • 5 years
We observed no serious adverse medication effects. CGT therapists monitored participant response to emotionally activating procedures; no serious untoward responses were documented.
0.00%
0/96 • 5 years
We observed no serious adverse medication effects. CGT therapists monitored participant response to emotionally activating procedures; no serious untoward responses were documented.

Other adverse events

Adverse event data not reported

Additional Information

M. Katherine Shear, MD

Columbia School of Social Work

Phone: 212-851-2176

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place