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Original Investigation |

Optimizing Treatment of Complicated Grief A Randomized Clinical Trial

M. Katherine Shear, MD1,2; Charles F. Reynolds III, MD3; Naomi M. Simon, MD, MSc4,5; Sidney Zisook, MD6,7,8; Yuanjia Wang, PhD9; Christine Mauro, PhD9; Naihua Duan, PhD10; Barry Lebowitz, PhD6; Natalia Skritskaya, PhD1
[+] Author Affiliations
1Columbia School of Social Work, Columbia University College of Physicians and Surgeons, New York, New York
2Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York
3Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
4Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston
5Harvard Medical School, Boston, Massachusetts
6Department of Psychiatry, University of California, San Diego
7Veterans Affairs San Diego Healthcare System, La Jolla, California
8Veterans Medical and Research Foundation, La Jolla, California
9Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York
10Division of Biostatistics, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York
JAMA Psychiatry. 2016;73(7):685-694. doi:10.1001/jamapsychiatry.2016.0892.
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Importance  To our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief.

Objective  To confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT.

Design, Setting, and Participants  Included in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co-occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting.

Interventions  All participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions.

Main Outcomes and Measures  Complicated grief–anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of “much improved” or “very much improved.”

Results  Of the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants’ response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88-1.17; P = .84; NNT, 84). However, depressive symptoms decreased significantly more when CIT was added to treatment (CGT with CIT vs CGT with PLA: model-based adjusted mean [standard error] difference, −2.06 [1.00]; 95% CI, −4.02 to −0.11; P = .04). By contrast, adding CGT improved CIT outcome (CIT vs CGT with CIT: 69.3% vs 83.7%; RR, 1.21; 95% CI, 1.00-1.46; P = .05; NNT, 6.9). Last, participant response to CIT was not significantly different from PLA at week 12 (45.9% vs 37.9%; RR, 1.21; 95% CI, 0.82-1.81; P = .35; NNT, 12.4) or at week 20 (69.3% vs 54.8%; RR, 1.26; 95% CI, 0.95-1.68; P = .11; NNT, 6.9). Rates of suicidal ideation diminished to a substantially greater extent among participants receiving CGT than among those who did not.

Conclusions and Relevance  Complicated grief treatment is the treatment of choice for CG, and the addition of CIT optimizes the treatment of co-occurring depressive symptoms.

Trial Registration  clinicaltrials.gov Identifier: NCT01179568

Figures in this Article


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Figure 1.
CONSORT Flowchart

CGT indicates complicated grief treatment; CIT, citalopram; PLA, placebo.

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Figure 2.
Inventory of Complicated Grief Scores

A, Scores on the Inventory of Complicated Grief (ICG) show improvement in participants randomized to complicated grief treatment (CGT) but no specific benefit of citalopram (CIT) relative to placebo (PLA). B, Depression self-ratings on the Quick Inventory of Depressive Symptoms (QIDS) show improvement when CIT is co-administered with CGT but little improvement in the absence of CGT. The ICG total score range is 0 to 76; the QIDS total score range is 0 to 27. IPW indicates inverse probability weighting.

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