A living guideline for depression treatment

ACP recommends choosing between a second-generation antidepressant or cognitive behavioral therapy for adults in the acute phase of moderate to severe major depressive disorder.

Depression is a worsening health issue. A recent Gallup poll found that 29% of U.S. adults reported being diagnosed with depression at some point in their lives, an increase of nearly 10 percentage points since 2015.Major depressive disorder (MDD) has major impacts on individuals and society, and therefore has been one of the core topics for an ACP guideline.

ACP's most recent recommendations, designed to help outpatient clinicians make treatment decisions in adult patients in the acute phase of MDD, were published as a living clinical guideline in January by Annals of Internal Medicine. “We are planning to maintain this topic as a living guideline with quarterly literature surveillance and periodic updating of the recommendations,” said Amir Qaseem, MD, PhD, MHA, FACP, the College's Chief Science Officer and lead author of the guideline.

An informed treatment decision for depression should be personalized and based on a discussion of the patients specific symptoms such as insomnia as well as potential treatment benefits harms and
An informed treatment decision for depression should be personalized and based on a discussion of the patient's specific symptoms, such as insomnia, as well as potential treatment benefits, harms, and costs, according to ACP's guideline. Image by Brian Jackson

Making an accurate diagnosis of MDD and determining its severity is critical to providing timely treatment and monitoring the patient, he noted. The guideline discusses nonpharmacological and pharmacological treatments (as monotherapy or in combination) for both initial treatment and in patients who do not respond to initial treatment.

The guideline was difficult to develop because of the nature of MDD, said J. Thomas Cross Jr., MD, MPH, FACP, a member of ACP's Clinical Guidelines Committee and coauthor of the guideline. “There currently is no blood test or truly objective measure that we can use to make the diagnosis of depression and then follow with treatment,” he said. “That is what makes diagnosis and treatment of depression so difficult in many cases.”

Based on the committee's review of the evidence, there was only one strong recommendation for treatment for patients with moderate to severe MDD, and it's not definitive. “Our recommendation is to choose between monotherapy with a second-generation antidepressant or cognitive behavioral therapy (CBT). Period,” Dr. Cross said. “We unfortunately just don't have the evidence for which is best, and it comes down to generally a couple of factors.”

Those factors include what the patient can afford. “Therapy is generally expensive or not readily available in many communities versus medications, which commonly are generic and inexpensive,” said Dr. Cross. If the patient decides to proceed with medication, then side effects are another crucial factor to consider, he added.

The guideline authors, as well as psychiatry experts, offered more details on ACP's recommendations and other clinical considerations in the diagnosis and treatment of patients with depression.

Screening and diagnosis

It's important not to miss a diagnosis of MDD in a patient who might harm themselves or who is so ill that they cannot take care of themselves or others, noted Dr. Cross. “These scenarios are very difficult, especially in the elderly who live alone or in a single parent who cannot provide for their minor children because of their disease,” he said.

The DSM-5 defines MDD as the presence of a depressed mood or a loss of interest or pleasure in normally enjoyable activities that occurs along with at least four additional diagnostic criteria or symptoms for at least two weeks and that causes clinically significant distress or impairment in the patient's social life, occupation, or other key areas of functioning.

On average, 13 million ambulatory care visits per year have a primary diagnosis of MDD, according to the guideline. But most of the time, depression won't be the patient's chief symptom, said Heidi Combs, MD, vice chair of education for the department of psychiatry and behavioral science at University of Washington Medicine in Seattle.

“The majority are not complaining about depression; there's a somatic manifestation of their depression. One way to improve detection is for internists to keep that fact in the forefront of their mind and have depression on their differential,” she said. “When someone comes in with medically unexplained symptoms, there are many etiologies for that, including depression.”

Having sleep disturbances, low energy, fatigue, or pain, for example, often leads patients to believe there's a physical explanation, not necessarily a psychiatric one, she noted. That can be a teachable moment. “The first step is to teach the patient about what depression can look like … because if the patient doesn't accept the diagnosis, why would they engage in treatment?” Dr. Combs said.

Current diagnostic methods have their issues, Dr. Cross acknowledged. Most practices use a version of the Patient Health Questionnaire-2 (PHQ-2) screen, commonly embedded in a long series of questions, often asked by a medical assistant, that also assesses smoking status, exercise habits, alcohol use, family history changes, and medication lists, he said.

“In the middle of all of this they'll ask, ‘In the last two weeks have you felt down, depressed, or had little interest in doing your normal activities?’” Dr. Cross said. “You can see how it can easily get lost, and commonly it is very rushed, and patients don't really have time to think about it. So the screen is only as good as the person doing the screen.”

If the screen is positive, it's up to the physician to follow up, typically with the PHQ-9 or similar evaluation, said Dr. Cross, who is also president and CEO of A-Cross Medicine Reviews in Colorado Springs, Colo. “Then, based on that, you'll make the determination about whether depression is present or not.”

The PHQ-9 has the additional benefit of monitoring for changes in symptoms over time, Dr. Combs noted. “People can repeat this and see actually how they're evolving in their treatment, if their symptoms are getting better or not,” she said.

Screening tools have clear cutoffs for diagnosing mild, moderate, and severe MDD, although a clinician can also assess impacts on the patient's function to determine severity, Dr. Combs noted. “Some people meet all the diagnostic criteria for depression, but it really isn't impairing their function much,” she said. “And then there are other people who seem to barely [meet] the diagnostic criteria; however, it is severely impacting them.”

Of course, the limited time internal medicine physicians have for each visit can make clinching the diagnosis challenging, Dr. Cross noted. “Unfortunately, deep down there is going to be some bias about opening this disease up for discussion, because you know if the patient says ‘yes' to the screen, your 15-minute hypertension visit is now going to be a 45-minute visit as you sort this out,” he said.

As difficult as it may be, there are certain high-yield times in which physicians should ask the screening questions themselves, Dr. Cross noted. For instance, data show that depression is common after hospitalization for chronic diseases, particularly coronary disease and heart failure, he said.

“Generally, we should make it a point, after a patient is hospitalized, to ask these screening questions ourselves and plan on spending some time discussing this,” Dr. Cross said. “Saying all that, I know in the real world this can be difficult to navigate, because most of us don't have the luxury of time in our schedules. But the reality is we have patients with depression who are not being diagnosed.”

Making treatment decisions

After making the diagnosis and helping the patient understand it, it's time to make a shared decision about treatment.

As stated, for patients in the acute phase of moderate to severe MDD, ACP strongly recommends monotherapy with either CBT or a second-generation antidepressant as initial treatment (moderate-certainty evidence). The guideline also suggests combination therapy with both treatments in these patients as an option (low-certainty evidence).

The informed treatment decision “should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences,” the guideline said.

When discussing symptoms with patients, have a conversation about what affects them most and what they would most like to see change, said Stephanie Schmitz, MD, a clinical assistant professor of medicine and psychiatry at the NYU Grossman School of Medicine in New York City. “Then I can really direct my treatment to whatever that symptom might be,” she said.

Social history is also important to consider when weighing treatment options, Dr. Schmitz said. “Do they have a full-time job? Are they working two jobs? Are they responsible for childcare during the day?” she said. “Is it feasible for them to do some sort of therapy where they can take 30 minutes or an hour and talk to someone? Are they even interested in taking medications?”

For patients in the acute phase of mild MDD, ACP suggests monotherapy with CBT as initial treatment. While CBT is quite beneficial for many patients, it is often costly, Dr. Cross noted.

“The costs are not just the therapy itself, but the patient has other costs to consider, including taking off from work and/or arranging childcare—especially, for instance, if you are having weekly CBT,” he said. Weekly CBT is typical, and a course of therapy usually lasts for 10 to 20 sessions, Dr. Combs added.

The COVID-19 pandemic has led to new options for medical care, including telemedicine for CBT, which is effective and can cost much less, said Dr. Cross, who has transitioned to a telemedicine-only practice. “Within the organization I work for, patients have direct access to telemedicine mental health providers that they can schedule on their own, and commonly someone is available that day or the next day or two. … Anecdotally, it appears to be as effective as in-person therapy and more convenient for the patient,” he said.

If CBT resources are unavailable or scarce, Dr. Cross said he commonly discusses the available medications, taking the time to sort out which side effects the patient is most concerned about (e.g., weight gain, insomnia/somnolence, and diarrhea) before making a shared decision about medications based on that information.

If initial treatment with an adequate dose of a second-generation antidepressant does not work in a patient with moderate to severe MDD, ACP suggests either switching to or augmenting with CBT or switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (low-certainty evidence for both conditional recommendations).

It may take less time for the patient to see progress on medications than you might think, Dr. Schmitz noted. “What we're often taught in medical schools is that you're not going to see anything for six to eight weeks, which is false,” she said. “In somebody who I'm titrating up to a good, moderate dose of an antidepressant, I should be noticing some kind of effect in two weeks, and if I'm not noticing anything by six, I'm probably going to switch [most likely to a different class].”

For a new MDD diagnosis without previous treatment, most patients will require about four to nine months of treatment, with many ending up closer to the nine-month duration, Dr. Cross said. Patients who have had one episode of MDD have more than a 60% chance of having a second, said Dr. Combs, adding that since this proportion increases with each episode, those who have had multiple episodes should be on lifelong treatment, especially if they have had psychosis.

“If someone's just having a first episode, if it's been mild to moderate, I'll usually say, ‘I want you to be on treatment for six months,’ and then tapering treatment and see how the person does,” she said. “More than half of individuals will at some point have another episode, but there's a group of people that won't, and you don't want to commit individuals to a life of treatment that they don't need.”

For physicians, part of treating MDD is letting patients know that if they ever feel in trouble or concerned for themselves or someone else, they must know how to call for immediate help, Dr. Cross emphasized. “They need to be aware of the national hotline number 988 and, in an emergency, that 911 can be accessed,” he said. “The biggest issue I see for physicians is the lack of resources available for our patients during times of suicide. Unfortunately, for many of us, if a patient is thought to be at risk to themselves or others, our only recourse is the emergency room.”

Follow-up of depression treatment is not simply saying, “Hey, how are you doing?” Dr. Cross said. “It requires a deliberate approach to determine if the patient is improving and then, if not, how do we modify therapy to help them improve,” he said.

Teaching the patient about how to recognize symptoms can be helpful for monitoring progress, Dr. Combs said. “They keep an eye on those things, along with you as their clinician,” she said. “If this is someone who's had an episode before, knowing when they come in for their annual exam or however often you see them, making sure you're keeping an eye out for the depression to recur.”

In a patient concerned about physical symptoms, it can be helpful to focus on those both when talking about the diagnosis and as a marker of progress, said Dr. Combs, who has referred to MDD as stress, fatigue, and pain in patients who don't identify with the label of depression.

“I had a patient I had diagnosed with depression, but that wasn't a construct that made sense to her, so I talked about it in the way that she spoke about it. Every time when I would see her, she would talk to me about her back pain and low energy,” she said. “When I saw her last, when her depression was remitted, I asked about her back pain, and she said, ‘I don't have back pain. Why are you asking me that?’”

Finally, remember that there is a bidirectional relationship with mental health issues like depression and anxiety and chronic medical conditions, Dr. Combs said. In patients with chronic medical conditions and MDD, it not only will take longer to treat their depression, but it will be harder to manage their medical conditions as well, she said.

Fortunately, treating MDD can improve both problems. “There's really beautiful data in looking at HbA1c management and depression, and if you treat depression, their HbA1cs get better,” Dr. Combs said.