A Study of Medication With or Without Psychotherapy for Complicated Grief

Study Overview
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Brief Summary
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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
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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.

Official Title
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Optimizing Treatment for Complicated Grief (Healing Emotions After Loss:HEAL)

Conditions
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Bereavement, Complicated Grief

Intervention / Treatment
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* Drug: Citalopram
* Behavioral: Complicated Grief Treatment
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Status Based on Complicated Grief Clinical Global Impression-Improvement (CGI-I) Scale | 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. | Weeks 12 and 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Inventory of Complicated Grief (ICG) | 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. | Baseline and week 12 | 
| Change From Baseline in Inventory of Complicated Grief (ICG) | 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. | Baseline and week 20 | 
| Change From Baseline in Work and Social Adjustment Scale (WSAS) | 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. | Baseline and week 12 | 
| Change From Baseline in Work and Social Adjustment Scale (WSAS) | 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. | Baseline and week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Grief, Bereavement, Psychotherapy, Medication, Treatment study