Scott Aaronson, M.D., Treatment-Resistant Depression

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expert_profile_aaronson_finalDr. Aaronson directs the clinical research programs at Sheppard Pratt Health System, based in Baltimore, Md. Below he discusses his practice and some of the recent news surrounding treatment-resistant depression - including new treatments and how various medication classes and psychotherapy can be helpful.

What is treatment-resistant depression?
There isn't a single standard definition. Generally speaking it's a depression that has failed to respond to an adequate dose of at least two distinct approved psychiatric medications taken for at least four to six weeks. However, I wouldn't consider a patient to be significantly treatment resistant until he or she has failed to see results with at least three to four different medications. It's important to remember that some 35% of patients do not respond to initial treatment - so if you haven't experienced good results with one medication, this does not necessarily mean you are treatment resistant.

Who typically has treatment resistant depression?
Almost everyone has a chance of becoming treatment resistant. I usually see patients who have been through several doctors and medications. They get referred to me because their doctors have run out of options. The first thing I do is to check whether I agree with the diagnosis. Often patients who have a depression that does not respond to treatment may have a co-existing condition such as substance abuse, an anxiety disorder or a personality disorder that severely limits their ability to respond. Sometimes I may think they have a bipolar disorder or a psychotic disorder that has not been addressed. Next, I want to make sure the patient has had adequate trials of medication with regard to dosage and duration. Misdiagnosis and under-treatment need to be ruled out before making a diagnosis of treatment-resistant depression.

What therapies are available for treatment-resistant depression?
The number of choices is growing. I can for example move a patient to a different class of medication, or combine medications. Many new medications are being researched, including those approved for other psychiatric conditions. For example, some antipsychotics (for schizophrenia) are being tested in combination with antidepressants. There are also studies on newer classes of medicines that affect different systems and different neurotransmitters in the brain. There are other alternatives as well, which I discuss below.

What are the success rates?
About 70% of the patients I see respond to a medication, but it may be a partial response and sometimes not as much as I would like. So it is important to combine medication with other therapies, such as talk therapy. Talk therapies help patients change their perceptions of themselves and the world around them. This is a real, practical step and is important to consider.

What is the good news out there?
One very interesting piece of news, in my opinion, was the results of what's called the STAR*D trial, funded by the National Institutes of Mental Health (NIMH). This was the most comprehensive U.S. study of antidepressant use for depression. The study was meant to identify best treatment strategies when the current therapy has provided insufficient response. One alarming message is that the incidence of treatment-resistant depression may be much higher than we have estimated, perhaps even as high as 40% of the population of patients with depression. One interesting thing about this study was that it looked at whether treatments could completely end the symptoms of depression. The goal with most studies is to see whether there is a significant decrease in symptoms, but often this means there is some residual depression. The conclusion of the study, and the good news, was that even when initial treatment fails, as many as one in three patients may achieve remission - and ending or near-ending of their symptoms - by continuing on with treatment and augmenting or switching medications.

Other new and potentially promising therapies include vagal nerve stimulation. In this therapy a small device is implanted to send electrical impulses to stimulate the vagus nerve for 30 seconds every five minutes throughout the day. I often see a 25% improvement in symptoms. For some patients, a 25 percent improvement might be considered marginal, or even a failure. But my take is that for severely ill patients, a 25% improvement can mean the difference between being disabled and at least partially functioning. For some of my patients it has meant enjoying a hobby again or being able to return to part or full time employment.

Repetitive Transcranial Magnetic Stimulation. This is another novel treatment in which magnetic energy is applied to the brain. I see this as potentially promising, and possibly something to consider as a precursor or alternative to electroconvulsive therapy. It may require daily treatment for four to six weeks. This mode of treatment is currently being reviewed by the FDA.

One therapy that isn't new, but may be under used, is electroconvulsive therapy - ECT. Advances in the use of ECT have improved patients' tolerance of the procedure as well as reduced some of the adverse reactions. ECT patients are anesthetized; an electrical current is passed through the brain, inducing a very short seizure which passes through the brain but not the body. Treatment is often effective. There are concerns. Risks include prolonged seizure, memory loss and the risks associated with general anesthesia.

What can family members do to help someone with treatment-resistant depression?
It is very important to be supportive. As difficult as it is to support a loved one with depression it is more difficult if they have a depression not responding to treatment over several months. Family members need to be open to discussing their feelings which may at times mean getting their own support from friends or family or getting their own therapy. Depression can be hard on everybody, so everybody needs to take care.

If someone in your family is not getting better after several months, you may want to seek consultations from additional experts. It is helpful to see what courses of treatment a specialist may come up with. If there is a local medical school in your area you can call for referral recommendations or you can ask your own psychiatrist. If you're not located in a big city, you can contact an academically affiliated institution.

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