Antidepressants of Little Benefit for Complicated Grief

Megan Brooks

June 08, 2016

For complicated grief (CG), adding an antidepressant does not significantly enhance the efficacy of targeted complicated grief treatment (CGT) psychotherapy, but it is helpful for patients with co-occurring depressive symptoms, new research shows.

"Complicated grief treatment is the treatment of choice for complicated grief, and the addition of citalopram [multiple brands] optimizes the treatment of co-occurring depressive symptoms," the investigators, led by M Katherine Shear, MD, Columbia University College of Physicians and Surgeons, in New York City, write.

The investigators also note that "CG is often confused with depression and treatment may be focused on medication. Unlike depression, it is unclear whether there is any benefit from antidepressant medication for CG symptoms."

"Clinicians should know how to recognize CG and differentiate it from depression," Dr Shear told Medscape Medical News.

The study was published online June 8 in JAMA Psychiatry.

Distinct Disorder

About 7% of bereaved individuals develop CG, which is characterized by persistent, maladaptive thoughts, dysfunctional behaviors, and poorly regulated emotions that interfere with the ability to adapt to loss. Co-occurring depressive symptoms are common, but CG can be "clearly differentiated" from major depression both in its primary symptoms and with respect to response to treatment, the researchers note.

The new study looked at whether an antidepressant would enhance CGT psychotherapy and whether it would be effective on its own for CG.

"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," the investigators write.

The study included 395 bereaved adults (308 women) who scored 30 or greater on the Inventory of Complicated Grief. To confirm the presence and primacy of CG, independent evaluators completed the Structured Clinical Interview for DSM-IV Axis I, a supplemental interview for CG.

Two thirds of the patients met criteria for current major depression, and more than half reported a wish die since the loss. The median time since the loss was 2.3 years. Patients were stratified with respect to major depression and were randomly divided into four groups: those receiving citalopram 40 mg, those receiving placebo, those receiving 16 sessions of CGT plus citalopram, or those receiving CGT plus placebo. Standard assessments were made monthly for 20 weeks. Response was reflected by a rating of either "much improved" or "very much improved."

In confirmation of the efficacy of CGT, far more patients responded to CGT than to placebo (82.5% vs 54.8%; relative risk [RR], 1.51; 95% confidence interval [CI], 1.16 - 1.95; P = .002; number needed to treat [NNT] = 3.6).

Contrary to expectations, adding citalopram to CGT did not significantly improve CG outcomes (CGT with citalopram vs CGT with placebo: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88 - 1.17; P = .84; NNT = 84). However, co-occurring depressive symptoms decreased significantly more when citalopram was added to CGT (P = .04).

Rates of suicidal ideation diminished to a substantially greater extent in those who received CGT compared with those who did not.

Landmark Study

"This is a very important study," Rita Rosner, PhD, Catholic University of Eichstätt-Ingolstadt, Germany, who has studied treatment for complicated grief but was not involved in the study, told Medscape Medical News.

She noted that CG is not a verified diagnosis in the DSM-5 but that it will be, under the name, "prolonged grief disorder," in the upcoming ICD-11. "The evidence for this disorder is compelling, and it is often overlooked," Dr Rosner said.

Currently, there are "very few pharmacological studies out there, and they usually have flawed designs. And there are no comparison studies between pharmacotherapy and psychotherapy. So this study is a landmark: it is well designed, has a large enough sample, and has clear results," Dr Rosner added.

The study also shows that "complicated grief (or prolonged grief disorder) differs from major depression. If complicated grief would be some form of depression, antidepressant medication should help. But as it does not, you can assume it is different," Dr Rosner noted.

Echoing Dr Rosner, Elizabeth Hembree, PhD, associate professor of psychology in the Department of Psychiatry at the University of Pennsylvania, Philadelphia, who has used CGT in her work, said this is an "important study" on an "unrecognized and often underdiagnosed problem. This is one of several studies now that have demonstrated the efficacy of focused treatment for complicated grief, and that is extremely important."

Although the diagnostic criteria for CG have not yet been formally codified in the DSM, "articles like this let practitioners and clinicians know that you still can reliably identify this syndrome with a self-report screening questionnaire and clinical interview," Dr Hembree told Medscape Medical News.

She noted that a prior study by Dr Shear and colleagues showed that CGT outperformed interpersonal psychotherapy (IPT).

"IPT is a very good treatment for depression, and the fact that CGT was demonstrated in that study to be more effective than IPT for complicated grief is further evidence I think of the specificity of the treatment for complicated grief. I have used it myself and have been impressed with it," Dr Hembree said.

The CGT psychotherapy manual is available online.

The study was funded by grants from the National Institutes of Health and the American Foundation for Suicide Prevention. Dr Shear received grant funding from the US Department of Defense, Congressionally Directed Medical Research Programs, and has a contract with Guilford Press to write a book on grief.

JAMA Psychiatry. Published online June 8, 2016. Full text

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