Depression can be effectively treated with psychotherapy and medication. But it takes time to find the correct medication and dose. Still, for about one million patients with depression, even several trials of medication don’t seem to be enough, and their symptoms linger.
These individuals may have treatment-resistant depression (TRD) or refractory depression. While there’s some debate over the precise definition, treatment-resistant depression is typically thought of as failing to achieve remission after two treatments or two antidepressants, according to George Papakostas, M.D., director of Treatment-Resistant Depression Studies in the Department of Psychiatry at Massachusetts General Hospital.
Why Some People Have Treatment-Resistant Depression
People develop treatment-resistant depression for many reasons. Some struggle with severe depression, which is difficult to treat. Medical illness and comorbid psychological disorders — such as drug or alcohol abuse or eating disorders — also complicate treatment response, according to Dr. Papakostas and Yvette Sheline, M.D., professor of psychiatry and the director for the Center for Depression Stress & Neuroimaging at the Washington University in St. Louis. Severe stress also can impact improvement, Dr. Sheline said.
A variety of genetic, neuroimaging and electrophysiological studies have investigated the underlying causes of treatment-resistant depression. And researchers know one thing for sure: Refractory depression is not the result of one brain region or neurotransmitter system.
Preliminary research suggests that individuals with depression may have abnormalities in the frontal and temporal regions in the brain and dysfunction in serotonin modulation. Also, the subgenual cingulate (Cg25), which is located under the cortex along the midline of the brain, may play a role. Cg25 is activated when an individual experiences sadness. It also connects to other regions involved in mood, motivation and sleep. When antidepressants are effective, this area is less active. Some researchers have hypothesized that in refractory depression, Cg25 doesn’t turn off. In general, according to Papakostas, there isn’t enough evidence to show a consistent or unifying theory.
Other individuals may not have refractory depression after all. For instance, according to Sheline, a thyroid problem may mimic depression. Individuals may have bipolar disorder — though there’s recent evidence that bipolar disorder may be overdiagnosed in patients who appear to have treatment-resistant depression — or a long-term low-grade depression called dysthymia. If a treatment isn’t working, it’s critical that your physician re-evaluate your diagnosis.
Treatment Options for Treatment-Resistant Depression
According to Sheline, there’s disagreement about the number of medication trials a person needs to try before moving onto more invasive interventions. While physicians determine this on an individual basis, it’s important for patients to have an adequate dose of medication for an adequate amount of time, Sheline said. “Each antidepressant has different therapeutic dose ranges, and these also vary according to individual factors, such as age,” she said. An adequate duration of treatment is usually six weeks. If there’s partial improvement, doctors may recommend patients stay on the medication for six to 12 weeks, Papakostas said.
This is why it’s especially important to take medication as prescribed. Many patients stop taking their medication after a week if they don’t get better, Sheline said. But this isn’t enough time to see improvement. Skipping or forgetting a dose can decrease a medication’s efficacy and make it look like it’s not the right medication for you. Also critical is practicing healthy habits, such as engaging in physical activities and getting enough sleep, and managing stress. Exercise boosts mood, while stress and lack of sleep exacerbate depression.