A Study of Medication With or Without Psychotherapy for Complicated Grief (HEAL)

• ClinicalTrials.gov Identifier: NCT01179568
• Recruitment Status: Completed
• First Posted: August 11, 2010
• Results First Posted: January 24, 2017
• Last Update Posted: January 24, 2017
• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH); American Foundation for Suicide Prevention
• Information provided by (Responsible Party): New York State Psychiatric Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Complicated Grief; Bereavement	Drug: Citalopram; Behavioral: Complicated Grief Treatment; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 395 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Optimizing Treatment for Complicated Grief (Healing Emotions After Loss:HEAL)
• Study Start Date: March 2010
• Actual Primary Completion Date: February 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: CGT with Citalopram; Targeted psychotherapy for complicated grief will be combined with SSRI medication.	Drug: Citalopram; 16 weeks of medication provided flexibly up to 40 mg/day. Medication will be administered in a double-blind fashion.; Other Name: Celexa; Behavioral: 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.; Other Name: CGT
Active Comparator: Citalopram; Citalopram is an Selective Serotonin Reuptake Inhibitor (SSRI) medication. It will be combined with grief-focused clinical management.	Drug: Citalopram; 16 weeks of medication provided flexibly up to 40 mg/day. Medication will be administered in a double-blind fashion.; Other Name: Celexa
Placebo Comparator: Placebo (Sugar pill); Inactive medication. It will be combined with grief-focused clinical management.	Other: Placebo; 16 weeks of daily inactive medication. It will be administered in a double-blind fashion.; Other Name: Sugar pill
Active Comparator: CGT with Placebo; The targeted psychotherapy for complicated grief will be combined with inactive medication.	Behavioral: 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.; Other Name: CGT; Other: Placebo; 16 weeks of daily inactive medication. It will be administered in a double-blind fashion.; Other Name: Sugar pill

Outcome Measures

Primary Outcome Measures :

1. Responder Status Based on Complicated Grief Clinical Global Impression-Improvement (CGI-I) Scale [ Time Frame: 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 :

1. Change From Baseline in Inventory of Complicated Grief (ICG) [ Time Frame: Baseline and week 12 ]
   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.
2. Change From Baseline in Inventory of Complicated Grief (ICG) [ Time Frame: 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.
3. Change From Baseline in Work and Social Adjustment Scale (WSAS) [ Time Frame: Baseline and week 12 ]
   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.
4. Change From Baseline in Work and Social Adjustment Scale (WSAS) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

VASDHS / University of California San Diego

San Diego, California, United States, 92161

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, New York

New York State Psychiatric Institute

New York, New York, United States, 10032

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

New York State Psychiatric Institute

National Institute of Mental Health (NIMH)

American Foundation for Suicide Prevention

Investigators

• Principal Investigator: Katherine Shear, MD; Columbia University

More Information

Additional Information:

Complicated Grief Program at Columbia University, New York 

Publications:

Simon NM, Thompson EH, Pollack MH, Shear MK. Complicated grief: a case series using escitalopram. Am J Psychiatry. 2007 Nov;164(11):1760-1. doi: 10.1176/appi.ajp.2007.07050800. No abstract available.

Shear K, Frank E, Houck PR, Reynolds CF 3rd. Treatment of complicated grief: a randomized controlled trial. JAMA. 2005 Jun 1;293(21):2601-8. doi: 10.1001/jama.293.21.2601.

Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Chronic Dis. 1967 Aug;20(8):637-48. doi: 10.1016/0021-9681(67)90041-0. No abstract available.

Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003 Sep 24;290(12):1624-32. doi: 10.1001/jama.290.12.1624.

Jacobs SC, Nelson JC, Zisook S. Treating depressions of bereavement with antidepressants. A pilot study. Psychiatr Clin North Am. 1987 Sep;10(3):501-10.

Shear MK. Clinical practice. Complicated grief. N Engl J Med. 2015 Jan 8;372(2):153-60. doi: 10.1056/NEJMcp1315618. No abstract available.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Na PJ, Adhikari S, Szuhany KL, Chen AZ, Suzuki RR, Malgaroli M, Robinaugh DJ, Bui E, Mauro C, Skritskaya NA, Lebowitz BD, Zisook S, Reynolds CF 3rd, Shear MK, Simon NM. Posttraumatic Distress Symptoms and Their Response to Treatment in Adults With Prolonged Grief Disorder. J Clin Psychiatry. 2021 Apr 20;82(3):20m13576. doi: 10.4088/JCP.20m13576.

Zisook S, Shear MK, Reynolds CF, Simon NM, Mauro C, Skritskaya NA, Lebowitz B, Wang Y, Tal I, Glorioso D, Wetherell JL, Iglewicz A, Robinaugh D, Qiu X. Treatment of Complicated Grief in Survivors of Suicide Loss: A HEAL Report. J Clin Psychiatry. 2018 Mar/Apr;79(2):17m11592. doi: 10.4088/JCP.17m11592.

Shear MK, Reynolds CF 3rd, Simon NM, Zisook S, Wang Y, Mauro C, Duan N, Lebowitz B, Skritskaya N. Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Jul 1;73(7):685-94. doi: 10.1001/jamapsychiatry.2016.0892.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01179568
• Other Study ID Numbers: 5971; R01MH060783 ( U.S. NIH Grant/Contract )
• First Posted: August 11, 2010
• Results First Posted: January 24, 2017
• Last Update Posted: January 24, 2017
• Last Verified: November 2016

Keywords provided by New York State Psychiatric Institute:

Grief; Bereavement; Psychotherapy; Medication; Treatment study

Additional relevant MeSH terms:

Citalopram; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs