Tool Predicts Difficult-to-Treat Depression, Even Before Drug Failure

Self-reported questionnaire data predicted difficult-to-treat depression, even in patients who weren’t considered treatment-resistant, observational data showed.

In a sample of 550 hospitalized patients — including those who had or had not failed multiple trials of antidepressant medications — higher scores on the Difficult-to-Treat Depression Questionnaire (DTDQ) correlated with Remission from Depression Questionnaire (RDQ) total discharge scores (r=0.28), reported Mark Zimmerman, MD, of South County Psychiatry in North Kingstown, Rhode Island.

Every RDQ subscale measure correlated with DTDQ scores, he explained at the American Psychiatric Association annual meeting. These included:

• Greater depressive symptoms (r=0.28)
• Greater non-depressive symptoms (r=0.38)
• Worse coping ability (r=0.20)
• Less positive mental health (r=0.19)
• More functional impairment (r=0.17)
• Poorer quality of life (r=0.19)

The DTDQ score was also correlated with the number of failed antidepressant trials (r=0.44, P<0.001). In addition, the association between the DTDQ and total RDQ scores remained significant even after adjusting for the number of failed medication trials (r=0.25), suggesting the questionnaire may capture factors beyond prior treatment failure.

RDQ and DTDQ measures also were correlated in a subset of 129 patients who had not yet failed two or more medication trials — that is, patients not yet classified as treatment-resistant.

The DTDQ tool was developed as nomenclature shifted toward using “difficult-to-treat” depression rather than “treatment-resistant” depression, Zimmerman explained. While the concept of difficult-to-treat depression was first introduced at a conference over 20 years ago, a consensus group recently highlighted the need for a clinical tool to measure it.

“I have never, in my 30-plus years of practice, said to a patient that they have treatment-resistant depression. I just intuitively viewed that as basically telling the person you’re never getting better,” Zimmerman said.

“I’ve had a couple of patients come to me and say that that’s what a clinician has told them, and they feel understandably hopeless, and then we deal with that. It’s less for me an issue of stigma, but more an issue of telling individuals, ‘I don’t know what to do, you’re not going to get better. The situation is grave and hopeless,'” he noted.

Difficult-to-treat depression is a different, but overlapping, construct with treatment-resistant depression, Zimmerman observed: it’s broader and includes clinical, longitudinal, social, and biological variables. “Most importantly, it shifts the paradigm of treatment,” he pointed out.

The treatment-resistant construct emphasizes a “treat-to-remission” model — continually changing treatments and medications with the sole goal of achieving remission. “That is not the paradigm for difficult-to-treat depression, where the focus is more on helping individuals improve their functioning. It’s much more of a disease-management model than a curative model,” Zimmerman noted.

A total of 550 patients with major depressive disorder from a partial hospital program completed the questionnaires. Most were female (70.4%) and white (72.1%), and the average age was 38.4.

The 39-item DTDQ examined a wide range of topics including severity and duration of depression, anxiety, and anger; childhood trauma or abuse; and whether patients felt they deserved to get better. Each item was graded on a 5-point scale from 0-4.

Zimmerman told MedPage Today that in clinical practice, he’d ideally like to see patients complete the questionnaire at their initial evaluation so clinicians can review and discuss it with them.

“They don’t need to score anything, they don’t need to come up with a total — even though we’ve published a cutoff — that’s not necessary. Just look at it, review it, and discuss it with patients,” he said.

While the DTDQ doesn’t offer guidance on antidepressant dosing, the tool can help clinicians think earlier about combining psychotherapeutic approaches with pharmacologic strategies, he noted. Zimmerman also advised a stronger, earlier focus on helping patients improve their quality of life, rather than just eliminating symptoms.

“Symptom improvement is more likely to follow functional improvement rather than precede it,” he stated.