Depression's impact on health is often profound and far-reaching. It can have an effect on quality of life that's equivalent to that of coronary artery disease, said Richard L. Kravitz, MD, FACP, professor and co-vice chair of research in the department of medicine at University of California, Davis. “When combined with other comorbidities, [it] makes things even worse,” he said.
To provide clinicians with guidance on treatment of depression, ACP has released a new clinical practice guideline that underscores the severe burden of depression and outlines viable treatment options for patients.
“We are increasingly learning that many people with chronic medical conditions are also depressed and that untreated depression can interfere with the management of their other medical problems,” said Michael J. Barry, MD, MACP, medical director of the John D. Stoeckle Center for Primary Care Innovation at Massachusetts General Hospital, professor of medicine at Harvard Medical School, and an author of the guideline.
For example, Dr. Kravitz noted that diabetic patients with depression have more diabetic complications, have more adverse long-term outcomes, and do not engage as actively in self-care. The prevalence of depression in diabetes and other long-term medical conditions is higher than in the general population, he said.
The single recommendation in the new guideline, published in the March 1, 2016, Annals of Internal Medicine, is that clinicians should select either cognitive behavioral therapy (CBT) or a second-generation antidepressant (SGA) to treat patients with major depressive disorder, given that both therapies have been found similarly effective in randomized controlled trials. The guideline committee emphasizes that clinicians should discuss the treatment effects, adverse effect profiles, cost accessibility, and preferences with the patient before prescribing CBT or SGA therapy.
In an editorial published with the guideline, John W. Williams Jr., MD, MHSc, FACP, professor of medicine and psychiatry at Duke University School of Medicine in Durham, N.C., and co-author Gary Maslow, MD, MPH, said that the opportunities to improve the health of people with depression are tangible. Even though implementing high-quality depression care is not easy, it is “possible and rewarding. ... Generalist physicians should seize the day and act to implement these guidelines,” they wrote.
Seizing the day
Although the ACP guideline does not specifically make recommendations about depression screening, implementation of the guideline begins with a clinician recognizing the symptoms of major depressive disorder in their patients, said Drs. Kravitz and Barry. Symptoms can range from mild to moderate to severe and can include depressed mood or loss of pleasure or interest, significant changes in weight or appetite, insomnia or hypersomnia, psychomotor agitation or retardation nearly every day, fatigue or loss of energy, feelings of worthlessness or excessive or inappropriate guilt, indecisiveness or decreased ability to concentrate, and recurrent thoughts of death or suicide.
Although depression screening is used in some primary care settings, it is not yet widespread, according to Dr. Kravitz. “There are a fair number of clinics that say they do screening but probably don't screen the majority of their patients, and there are some clinics that don't screen at all.”
One reason for the lack of widespread adoption is that screening was not recommended routinely until the most recent guideline from the U.S. Preventive Services Task Force (USPSTF), which appeared in the Jan. 26, 2016, Journal of the American Medical Association, Dr. Kravitz said. The USPSTF found “convincing evidence that screening improves the accurate identification of adult patients with depression in primary care settings” and said that programs that combine depression screening with adequate support systems in place improve clinical outcomes in adults. However, Dr. Kravitz noted that screening requires a high level of organization, such as having reminders in the medical record, distributing the screening tool to patients, collecting the screening tool, and then having a system in place to respond.
In their editorial accompanying the ACP guideline, Drs. Williams and Maslow noted that quick screening tools like the Patient Health Questionnaire can be administered verbally to adults and that practices with electronic health records can use clinical reminders to prompt staff to distribute screening questionnaires or verbally administer questions along with assessment of vital signs. Dr. Barry said that his practice routinely uses a 2-question screener to check for the presence of depressed mood and anhedonia. If a patient screens positive, then more in-depth screening is used to confirm the diagnosis, he said.
Most patients who receive treatment for depression obtain that treatment in primary care settings, according to the evidence report prepared for the ACP guideline. The SGA agents often prescribed are selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, as well as other such as bupropion, mirtazapine, and trazodone. A previous ACP systematic review on SGAs, published in the Nov. 18, 2008, Annals of Internal Medicine, found similar safety and efficacy among the different SGAs.
The review of randomized, controlled trials for the new guideline found moderate-quality evidence that CBT and SGAs are similarly effective treatments for major depressive disorder and that they have similar discontinuation rates. CBT is defined as a psychological intervention that adds a behavioral component (such as homework or an activity schedule) to cognitive therapy and may include targeting thought processes to help with awareness and acceptance. It has no more and possibly fewer adverse effects than SGAs, according to the guideline, and lower rates of relapse have been reported with CBT. According to the systematic review, 2 trials with medium risk of bias reported lower relapse rates for patients treated with CBT (range, 2% to 39%) than for those on SGAs (range, 11% to 59%).
The guideline committee concluded that CBT is “a reasonable approach for initial treatment and should be strongly considered as an alternative treatment to SGAs where available.”
“These guidelines and most guidelines say that CBT alone and SGA alone are equally effective. A treatment decision comes down to patient preference and accessibility in terms of treatment,” said Raymond W. Lam, MD, professor and head of the mood and anxiety disorders program in the department of psychiatry at the University of British Columbia in Vancouver.
He continued, “More and more, medicine is a shared collaborative enterprise these days because patients have smartphones and are looking up the treatment options they have while you are talking to them. It is important to go over the pros and cons of the treatments that are available. Some people will prefer medication and some will prefer psychotherapy.”
Dr. Williams said that shared decision making with the patient includes discussing not only the options but also the patient's values and preferences. Some patients don't want to take another medicine or any medication. Others may like the idea of psychotherapy but cannot deal with the loss of income that may be necessary if time off from work is needed to see a therapist.
“Shared decision making means talking with patients and finding out what matters to them and helping them incorporate that into their choice about what treatment plan they will do,” he said.
Translating this recommendation into the real-world practice of a busy internist's office can be a significant challenge, Dr. Kravitz said. “One problem for in-the-trenches community practitioners is that there is a severe limitation in the availability of CBT practitioners,” he noted. Even when there is a therapist available, a patient's health insurance plan may restrict the number of visits, and plans can have mental health carveouts that restrict coverage.
Dr. Williams agreed. “It's very easy for internists to send an electronic prescription for an antidepressant, but connecting the patient to a good therapist and having confidence that they are getting treatment is a harder thing for an internist. Our connections [to therapists] are just not as good.”
Some patients will express no treatment preference and will ask the physician to decide. “From my perspective, if the depression is milder and the impairment is not as great, I would definitely say the patient should start with CBT. If a patient's depression is more on the moderate side with more moderate impairment of functioning, I would say let's start with medication, and I would also refer the patient to CBT when they have an opportunity to see a therapist,” Dr. Lam said.
Patients with severe depression, however, should be treated differently and should be promptly referred to a specialist or psychiatrist. A referral should also be made when patients have complex psychological conditions or comorbidities, he said. Many studies have concluded that CBT is beneficial across the range of depression severity, but “most clinicians would tend to disagree with that and would say that psychotherapy alone for severe depression would be difficult to do. The recommendation for severe depression is always going to be, even though our evidence is not that great for it, to keep using psychotherapy and medication,” he said.
Adherence with therapy
Dr. Kravitz said that helping a patient with depression requires persistence and an understanding that initial treatment may not work.
Discontinuation rates are similar for CBT and SGAs in the first 8 to 14 weeks of therapy, according to the ACP guideline. For example, SGAs are associated with more side effects, such as sexual dysfunction, constipation, diarrhea, dizziness, headache, insomnia, nausea, and somnolence, and discontinuation due to adverse events is nonstatistically significantly increased with SGAs, according to the guideline. The rates of discontinuation due to adverse events were numerically higher for patients on SGAs but did not reach statistical significance. There are very few trials, 3 in all, that actually have even looked at these issues.
CBT has discontinuation drawbacks, too the guideline stated. Showing up for 10 or more appointments can be challenging for many patients, who may opt out of therapy before they establish an ongoing relationship with the therapist.
“The lesson of many of the stepped-care and collaborative care trials is that you have to work at this,” Dr. Kravitz said. “The STAR*D study tells us that less than half of patients will respond to the first treatment and that you often have to try another therapy.”
The STAR*D study, published in the Nov. 1, 2006, American Journal of Psychiatry, examined medical treatment of depression and also found that some patients may require several treatment strategies. The study emphasized the importance of physician follow-up and monitoring to help patients avoid relapse.
Physicians should follow up with patients within the first 1 to 3 weeks of starting medical therapy, the period when a patient is most likely to not respond or to have a side effect that causes them to stop their medication, Dr. Kravitz said. Patients also need to understand that their side effects can often be managed by changing the dose or the time of administration or by switching medications, he said. He noted that side effects are reversible and many go away after the first few weeks of therapy.
Patients who do not respond to standard treatment after, for example, trying more than 2 SGAs should be referred to a psychiatrist for a second opinion about other treatment options, Dr. Lam said. The systematic review found that about 40% of patients do not respond to SGAs, and approximately 70% do not achieve remission and will need to try another therapy.
According to Dr. Barry, the guideline committee did not find evidence that combining both SGA therapy with CBT was more effective than either alone. “However, it may make common sense that an internist would reasonably decide to start a patient who is severely depressed on an antidepressant and also refer that patient to a mental health professional for CBT or further evaluation,” he said.
The guideline committee considered available evidence from a very limited number of trials that compared SGA therapy with complementary and alternative options, such as yoga, acupuncture, exercise, and St. John's wort. Most evidence from the handful of trials was rated low quality or insufficient to make a comparison about discontinuation rates, adverse events, response, or remission.
Although low-quality evidence found that St. John's wort may be as effective as SGAs and may be better tolerated, there is no current standard in place related to the contents and potency of the medication in the United States because it is unregulated by the Food and Drug Administration. St. John's wort can have adverse side effects such as gastrointestinal symptoms, dizziness or confusion, and fatigue or sedation, the guideline stated. It is also associated with important drug-drug interactions and can reduce the bioavailability or efficacy of some drugs, including oral contraceptives and immunosuppressants.
Dr. Williams said that the ACP guideline “is not a soup-to-nuts guideline for how to care for depression, but it is useful guidance for helping internists add value when interacting with patients around this issue. We have the potential to do good, to help people recover from depression. Not only will they feel better and function better, but they will probably be better able to take care of themselves, function, and interact with people around them. There are many good downstream benefits.”