A Study of Medication With or Without Psychotherapy for Complicated Grief

Phase 2

Completed

• Conditions: Bereavement; Complicated Grief
• Interventions: Drug: Citalopram; Other: Placebo; Behavioral: Complicated Grief Treatment

• Registration Number: NCT01179568
• Lead Sponsor: New York State Psychiatric Institute

Brief Summary

The major goal of this 4-site, double blind, placebo-controlled intervention trial is to assess the efficacy of medication (Citalopram) alone or with psychotherapy (Complicated Grief Therapy) to treat the symptoms of complicated grief.

Detailed Description

Complicated grief (CG) is a debilitating condition that is estimated to affect millions of people in the United States alone. We conducted the first randomized controlled study to address this condition (MH60783) and confirmed efficacy of a targeted psychotherapy, complicated grief treatment (CGT). Participants in our prior study continued stable antidepressant medication while receiving CGT or Interpersonal Psychotherapy (IPT). Individuals taking antidepressants had better outcome in both treatments, though CGT was superior to IPT when administered with (60% responders v. 40%) or without (42% v.19%) antidepressants. Studies of antidepressant medication alone have shown mixed results with SSRIs appearing to be promising. However, there has been no randomized controlled study of SSRIs for CG. Determining the efficacy of SSRI treatment for CG, when administered with and without CGT, is of great public health importance.

We assembled 4 groups of investigators with strong track records in bereavement research and extensive experience with intervention studies and multicenter projects, to conduct a study of citalopram (CIT) efficacy. We plan to enroll participants with a primary diagnosis of Complicated Grief and randomly assign them (n=480; 50 at Columbia) to receive treatment with CIT, Placebo (PBO), CIT + CGT or PBO + CGT over a period of approximately 16 weeks. We want to determine whether citalopram shows a better response than placebo, when administered either with or without CGT. We will also address the question of whether CIT performs as well when administered alone as it does when administered with CGT.

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-08-10
• Study First Posted: 2010-08-11
• Primary Completion: 2015-02
• Study Completion: 2015-07
• Results First Submitted: 2016-09-06
• Status Verified: 2016-11
• Results First Submitted QC: 2016-11-28
• Last Update Submitted: 2016-11-28
• Results First Posted: 2017-01-24
• Last Update Posted: 2017-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 395

Inclusion Criteria

• Diagnosed with Complicated Grief and this is the patient's most important (primary) problem
• Ability to give informed consent
• Fluent in English
• Willingness to have sessions audiotaped
• Willingness to undergo random assignment

Exclusion Criteria

• Diagnosis of one or more of the following disorders: Schizophrenia or other psychotic disorder, current (past 6 months) substance abuse, Bipolar Disorder, current manic episode, Dementia
• Pregnant or lactating women and women of childbearing potential not using medically accepted forms of contraception
• Acute, unstable or severe medical illness such as (but not limited to) stroke, epilepsy, or other neurodegenerative disorders, metastatic or active cancer, hepatic disease, or primary renal disease requiring dialysis
• Prior intolerance of citalopram
• Pending or active disability claim or lawsuit related to the death

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
CGT with Placebo	Placebo	The targeted psychotherapy for complicated grief will be combined with inactive medication.
CGT with Citalopram	Complicated Grief Treatment	Targeted psychotherapy for complicated grief will be combined with SSRI medication.
CGT with Placebo	Complicated Grief Treatment	The targeted psychotherapy for complicated grief will be combined with inactive medication.
CGT with Citalopram	Citalopram	Targeted psychotherapy for complicated grief will be combined with SSRI medication.
Placebo (Sugar pill)	Placebo	Inactive medication. It will be combined with grief-focused clinical management.
Citalopram	Citalopram	Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It will be combined with grief-focused clinical management.

Primary Outcome Measures

Name	Time	Method
Responder Status Based on Complicated Grief Clinical Global Impression-Improvement (CGI-I) Scale	Weeks 12 and 20	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Work and Social Adjustment Scale (WSAS)	Baseline and week 20	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.
Change From Baseline in Inventory of Complicated Grief (ICG)	Baseline and week 20	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.

Trial Locations

Locations (4)

VASDHS / University of California San Diego; 🇺🇸 San Diego, California, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

New York State Psychiatric Institute; 🇺🇸 New York, New York, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States