Advances in Treating Depression
It may be somewhat surprising that there are many recent positive developments in the treatment of clinical depression. One development that has had an enormous impact are findings from large, federally funded studies like the "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) trial, which sought to elucidate the effectiveness of antidepressants.
"They found in the STAR*D that about a third of patients will respond and experience a full remission to the first drug, and about another one third will have a partial response, so from the start two thirds of people will get about 50% better or more," said Richard Alan Friedman, MD, the Director of the Psychopharmacology Clinic, Department of Psychiatry, at Weill Cornell Medical Center, NewYork-Presbyterian Hospital. "That still leaves a third of patients who don't respond, but if you keep treating them, you pick up an additional successful fraction with each new treatment. So those who don't respond to three or four antidepressant treatments probably are going to equal about 15% of the depressed sample. In my experience, and that of my colleagues, if you are very persistent and methodical over time and do not give up, you can get almost anybody better. In the past, many people who were called treatment-resistant just didn't get really good treatment." Dr. Friedman is also a Professor of Clinical Psychiatry at Weill Cornell Medical College.
David A. Kahn, MD, Clinical Professor and Vice Chair for Clinical Affairs, Department of Psychiatry, Columbia University Medical Center, NewYork-Presbyterian Hospital and the New York State Psychiatric Institute, agreed. "The rates in the STAR*D study of response when medications were combined were slightly greater than when medications were simply switched from one to another. So there is often a reason to combine antidepressants." Clinicians will look to combine medications if the patient with depression has tolerated the initial drug well, and a mix of different mechanisms of action is often preferable. Dr. Kahn offered an example: "Most commonly an SSRI [selective serotonin reuptake inhibitor] might be the first medication, but the second addition might be a combination with buproprion, or even a combination with such medications as lithium, thyroid hormone, or buspirone, none of which would be used as a solitary antidepressant agent, but all three of which can augment the response to antidepressants." Other options, like an SNRI (serotonin norepinephrine reuptake inhibitor), nefazodone, mirtazapine, the tricyclic antidepressants, MAO inhibitors, and others, all have their place and all can be extraordinarily valuable, although several require a great deal of expertise because of the significant burden of side effects. Promising pharmacologic clinical trials on new agents are, of course, ongoing.
Another recent development is a renewed appreciation for the role that psychotherapy and other nonpharmacologic treatments can play in treating depression. "The evidence for the value of psychotherapy was developed later than the scientific evidence supporting medication," Dr. Kahn said. The result is that psychotherapy has been underutilized by people with depression, despite there being excellent forms of psychotherapy—e.g., cognitive behavioral therapy and interpersonal therapy—that research has found are effective in treating these patients. Further, the evidence seems to suggest that the best treatment for depression incorporates both psychotherapy and pharmacologic treatment.
Electroconvulsive therapy is still the gold standard in nonpharmacologic somatic treatment, though other brain-stimulation treatments are now emerging. One is transcranial magnetic stimulation, recently approved by the FDA, which applies focused magnetic stimulation to certain areas of the brain of the patient, who is awake yet experiences no subjective sensations while receiving treatment. Response rates so far have rivaled those found with medication, but without serious side effects. Whether and how it can be combined with pharmacologic therapy, and whether it is successful in medication-refractory patients, are questions that are still subject to research.
Vagal nerve stimulation, also FDA-approved, is used for patients with medication-resistant depression. Small amounts of electricity are used to stimulate the vagus nerve with a surgically-implanted electrode. Although success rates for this modality are not high, some responses can be dramatic. Another form of somatic treatment, which is still experimental, is deep brain stimulation in which surgically implanted electrodes stimulate the ventral tegmental area, located deep at the base of the brain.
The promising nature of these developments underscores, however, that care for major depression is multifactorial, complicated, and specialized. It is vital that primary care providers—who by dint of sheer numbers treat many more cases of depression than the nation's psychiatrists—know when to refer their patients with major depression. Both Drs. Friedman and Kahn cited a few specific signs:
- If, at initial evaluation, the patient says they want to hurt or kill themselves or appears to be suicidal. (There are screening instruments for depression specifically designed for primary care providers, such as the PRIME-MD Patient Health Questionnaire, that the physician should not hesitate to use.)
- If the patient is psychotic, having delusions or hallucinations, or shows signs of a marked thought disorder.
- If the patient has a history of manic episodes or a diagnosis of bipolar disorder.
- If there is a history of complicated psychiatric problems like substance abuse disorder or a personality disorder.
- If the patient has a history of a failed treatment for depression.
Treatment for these patients is often quite complicated and requires the expertise of a psychiatrist's care.
Dr. Kahn summarized the attitude at NewYork-Presbyterian: "What excites me is making sure that patients who come here are not going for one treatment just because they walked in the door of a doctor who knows how to do one thing well, but that they instead meet an expert who is familiar with a wide range of clinical and research treatments so that we can design therapy using all that is available—sophisticated psychopharmacology, expertly delivered psychotherapy, the possibility of brain stimulation techniques—all of which rest on the foundation of an accurate diagnosis and gaining a full understanding of that person as a human being , knowing what he or she experiences in life, what their hopes and dreams are, what their family is like, what the context of their work is like—all the things that we need to know to try to make that individual feel better."
Treatment for depression has come a long way. Those interested in learning the state of the art on the care of the patient with depression should watch this webcast featuring Drs. Friedman and Kahn, leaders in psychiatry and examples of the expertise available at NewYork-Presbyterian Hospital.