Treatment-resistant Depression: 5 Steps to Follow for Primary Care

April 19, 2018

Five tips for PCPs on managing treatment-resistant depression were offered at the ACP Internal Medicine Meeting 2018 today. Patient Care offers a summary.

Managing treatment-resistant depression is a perennial challenge. There are a dizzying array of options available, both pharmacologic and non-pharmacologic, and little guidance on what to choose next.

“We have many tools in our toolkit, but there is not a definitive evidence base,” says M. Philip Luber, MD, Hugo A. Auler Professor of Psychiatry at UT Health Science Center, San Antonio, Texas.

Expert guidance can be useful in devising strategies to help patients with depression achieve symptom relief and improved functioning.

Dr. Luber presented one reasonable, simple algorithmic approach to managing depression on Friday, April 20 at the ACP Internal Medicine Meeting 2018 in New Orleans, Louisiana.

Here’s how it works.

Define Your Terms. Before getting to Dr. Luber’s algorithm, it’s important to be clear on what is meant by treatment-resistant depression. The condition is generally defined as depression that has not sufficiently improved after two trials of antidepressant medication given at adequate doses for a sufficient time period.

The operative words here are “adequate” and “sufficient.”

“The common problem is that patients will come in and say, ‘I’ve been on…’ and then they give a list of 8 antidepressants, but we don’t really know that they’ve had an adequate trial of any of them,” Dr. Luber says. “Often, they haven’t been on a high enough dose for a sufficient length of time.”

Dr. Luber shared a couple of tips with Patient Care with regard to ensuring patients receive adequate and sufficient treatment.

First Things First. Check with a psychiatry colleague to get suggestions on challenging cases.

Second, get a copy of Prescriber's Guide: Stahl's Essential Psychopharmacology, Edition 6,¹ which includes comprehensive information on dosages, side effects, special populations, and more. “This is what a lot of us psychiatrists use in terms of choosing medications,” Dr. Luber says. “I would recommend every primary care doctor have a copy of that in their office or on their phone.”

Now, on to the algorithm.

1. Start with an SSRI. A reasonable approach to treating depression in a medical practice is to start with one of the commonly prescribed selective serotonin reuptake inhibitors (SSRIs), given for a sufficient length of time at adequate doses, as discussed above.

2. Switch to Another SSRI (or SNRI). If the response is inadequate, switch to another SSRI or to a serotonin–norepinephrine reuptake inhibitor (SNRI), again at adequate doses and for a sufficient length of time

3. Augment with psychosocial approaches. If response to that second-line approach is inadequate, it may be time for referral to behavioral health consultant or psychotherapist.

4. Augment with another medication. If response is still inadequate, adding treatment with bupropion or an atypical antipsychotic drug such as aripiprazole may be warranted. Dr. Luber cited a recent randomized clinical trial² showing that aripiprazole augmentation resulted in a significant, albeit modest, likelihood of improvement compared with bupropion augmentation, while both were superior to bupropion monotherapy.

5. Refer to a psychiatrist. If all else fails, it may be time to refer the patient to a psychiatrist for further steps.

Let best judgment be the guide. Depending on the primary care provider’s comfort with treating depression, they could refer to a psychiatrist at any step along the way, Dr. Luber notes.

Likewise, there’s no hard-and-fast rule that nonpharmacologic approaches need to be reserved for patients with depression that’s proven to be treatment resistant based on inadequate response to two adequate trials of therapy.

“The referral can be made at any time, because in my mind, the psychopharmacology and psychotherapeutic approaches are synergistic-one plus one equals three,” he says.