Improving Outcomes for Today’s Patients

Psychiatrists today rely on a combination of pharmacologic agents and psychotherapy to treat patients with depression or bipolar disorder. Stanford scientists are actively exploring which strategies, based on existing drugs and psychotherapeutic techniques, are most successful. At the same time, they are developing new approaches to boost the effectiveness of these therapies.

One team is investigated whether a specific form of psychotherapy in combination with medication is more effective than aggressive pharmacologic treatment in patients with chronic depression. In this study, they were able to demonstrate that variation for a gene that controls efflux of medication from brain predicted efficacy and side effects.  Another team led by Rachel Manber, PhD, professor of psychiatry and behavioral sciences, is studying optimal psychosocial treatments for reducing insomnia in major depression and exploring whether these treatments can alleviate depression as well. Rebecca Bernert is exploring treatments to prevent the development of suicidal behavior.

Stanford scientists are also assessing whether other genetic variations can predict which of today’s antidepressants will work best on specific patients. Over time, it may be possible to develop a series of genetic markers to help doctors identify the most promising treatment for each patient.

Bipolar disorder often requires a combination of mood stabilizers and antidepressants to bring relief to patients. However, some commonly used medications are associated with insulin resistance and diabetes. In collaboration with a national research network, one Stanford team is combining novel brain imaging and endocrinology techniques to explore risk factors for the development of these complications and to reduce the risk of side effects.

Creating New Therapies

Although most people with mood disorders eventually respond to treatment, many must try several therapies before they find one (or a combination) that works. And some therapies are associated with considerable side effects. To usher in a new era of mood disorder care— more effective, faster acting, better tolerated—Stanford is taking the lead in developing groundbreaking treatment approaches.

One of the most severe forms of depression, delusional depression, has a high mortality rate due to physical causes or suicide. People with the disorder often receive electroconvulsive therapy, one of the most effective treatments available. Researchers at Stanford are working to reduce and in some cases eliminate the memory loss that can be a side effect of this treatment. Following up on a number of studies that reveal elevated cortisol as an indicator of delusional depression, Stanford research has led to the use of a fast-acting alternative medication that blocks a specific cortisol receptor in the brain.

Other Stanford teams are investigating which areas or circuits of the brain are potentially overactive in depression to develop new treatments that provide electrical stimulation to targeted areas of the brain through the scalp. Since some key areas associated with mood disorders lie deep within the brain, Stanford specialists are exploring deep brain stimulation— implanting electrodes into specific regions, such as the subgenual cortex, guided by imaging—as part of a national multicenter project.  Karl Deisseroth's team developed optogenetics to turn on or turn off brain circuits in lower animals.

Stanford is also pursuing alternative strategies to stimulate deep brain regions. One approach focuses stimulation on these regions using 3-D telemetry and magnetic or radiosurgical stimulatory techniques. Other Stanford researchers are exploring acupuncture— a safer alternative for pregnant women with depression—mindfulness techniques, and dialectic behavioral therapy.