Weighing risks and benefits of drug treatment for major depression

June 12, 2019

Science Daily/American Geriatrics Society

For some people, medication is an effective part of treatment for depression. However, when considering whether to prescribe antidepressant medication for older adults, healthcare providers must weigh the safety risks these medications pose against the often modest benefits they can provide compared to other options.

Depression is a common and serious problem for older adults. Some 15 to 20 percent of people aged 65 and older who live independently deal with symptoms of major depressive disorder. For residents of nursing homes, the rates of depression may be as high as 50 percent.

For some people, medication is an effective part of treatment for depression. However, when considering whether to prescribe antidepressant medication for older adults, healthcare providers must weigh the safety risks these medications pose against the often modest benefits they can provide compared to other options.

For example, tools like the American Geriatrics Society (AGS) Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults recommended that healthcare providers avoid prescribing certain antidepressant medications to older adults who have a history of falls or fractures. These include selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). That's because these medications may actually increase the risk of falls and fractures.

Understanding these and other risks associated with "potentially inappropriate medications" is key to building better care for us all as we age. That's why a team of researchers recently reviewed and analyzed studies to learn more specifically about the harmful effects of antidepressants for treating major depressive disorder in adults 65 years of age or older. Their study was published in the Journal of the American Geriatrics Society.

The systematic review was performed at the University of Connecticut Evidence-based Practice Center (EPC). The researchers reviewed studies that examined how many older adults experienced a harmful event during the study.

The researchers looked at patients 65 years of age or older who are prescribed serotonin and norepinephrine reuptake inhibitors (SNRIs) to treat the acute phase of major depressive disorder (the earliest stage of the condition, when the goal is to address the symptoms associated with an episode of depression). They found that taking SNRIs led to a greater number of harmful events compared to people who took a placebo (a harmless sugar pill that has no effect on health and is prescribed to some study participants to help with comparing their results to results from people who were treated with actual medication). Older adults who took SSRIs experienced about the same number of harmful events as did people who took a placebo.

The researchers said that taking either SSRIs or SNRIs led to a greater number of people leaving the study due to harmful events of the drugs compared to placebos. They also noted that the drug duloxetine, an SSRI, increased the risk of falls.

"Some of the antidepressants have not been studied in older patients with major depression, and studies don't often describe specific side effects. Future research in this field is critical to better inform how the safety profiles of different antidepressants compare in older adults," said study co-author Diana M. Sobieraj, Pharm.D., FCCP, BCPS, Assistant Professor, University of Connecticut School of Pharmacy.

https://www.sciencedaily.com/releases/2019/06/190612141302.htm

Brain activity can predict success of depression treatment

April 11, 2018

Science Daily/McLean Hospital

Researchers believe they have uncovered a method that could be useful in predicting a depressed patient's treatment prognosis, prior to starting treatment.

McLean Hospital and Harvard Medical School researchers believe they have uncovered a method that could be useful in predicting a depressed patient's treatment prognosis, prior to starting treatment.

In the paper "Pretreatment Rostral Anterior Cingulate Cortex Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial," currently available online and scheduled to appear in the June 2018 edition of JAMA Psychiatry, the investigative team details its work in identifying whether certain markers in the brain could allow clinicians to identify patients with a high or low likelihood of responding to certain treatments for depression.

The study was jointly first-authored by Diego A. Pizzagalli, PhD, and Christian A. Webb, PhD. "Our work shows that we could predict a patient's response to an antidepressant by looking at the activation level of the rostral anterior cingulate cortex (ACC) region of the brain by using a non-invasive monitoring system to test brain activity called an electroencephalogram -- also known as an EEG," said Diego A. Pizzagalli, director of the McLean Imaging Center as well as the hospital's Center For Depression, Anxiety and Stress Research and Laboratory for Translational and Affective Neuroscience. Webb, assistant professor at Harvard Medical School and director of the Treatment and Etiology of Depression in Youth Laboratory, noted that this is the first study to "demonstrate the 'incremental predictive validity' of this neural marker, that is, the fact that activity in this brain region predicts the likelihood of treatment response above and beyond the contribution of a range of low-cost and easily administered clinical and demographic characteristics previously shown to predict treatment outcome."

For this study, the team built upon Pizzagalli's previous work showing that EEG recordings of rostral ACC activity could predict the eventual response. "In that prior study, we saw that the higher the activity before the start of the treatment, the better the clinical response months later," noted Pizzagalli, who is also a professor of psychiatry at Harvard Medical School.

For the new study, more than 300 patients were tested at four sites in the United States -- using sertraline for the treatment group. "We showed that the rostral ACC marker predicted clinical response eight weeks later, even when statistically controlling for demographics and clinical variables previously linked to treatment response," said Pizzagalli. "For those with the marker of good response, a clinician could tell patients that they have a high chance of benefitting from the intervention, and they should stay engaged in treatment," he explained. Conversely, he said, for patients with the marker of low response, "clinicians could decide to start with more aggressive treatment at the outset, such as a combination of pharmacology and psychotherapy, and importantly, monitor these patients more closely."

Soon, Webb, Pizzagalli, and their colleagues plan to deploy these approaches on patients at McLean Hospital to determine whether they can lead to treatment-specific predictions. "Our vision is to determine if an optimal combination of markers -- including brain-based but also clinical and demographic characteristics -- might allow us to predict response to drug A but not drug B or psychotherapy, for example," Webb explained.

Also, if an ACC marker predicts better response, researchers might develop cognitive training that specifically targets this region, which could increase brain activation to accelerate or boost response to more traditional intervention. Pizzagalli and his team hope to engage in further research into this concept by testing patients with major depressive disorder.

https://www.sciencedaily.com/releases/2018/04/180411111103.htm