Q. What is the definition of "treatment resistant depression?" Why do some people experience chronic depression after a lengthy trial of psychotropic medications?

In the BPD community, do you have an idea of the percentage of patients that fall into this category? How about the Bipolar community?

What are some of your strategies for treating these folks?

Do you feel that prescribers need more training in this area?


  A. Treatment resistant depression has a number or definitions. Most folks consider an individual treatment resistant if they have had three adequate trials (both length and dose) of three different classes of antidepressants. The word adequate is the sticking point since to some folks 20 mg of Prozac for six weeks is adequate, and for others its 80 mg for four weeks. I believe dosages of medication are important, so favor a definition that is more restrictive and insists on the top dosage of medication for at least four weeks without seeing much, if any, change.

The reasons for developing these treatment resistant or chronic depressions are many-fold. First, the disease may be getting worse. Just like diabetes worsens with time or heart disease worsens with time, so can depression. Another possibility is that the medications "poop out." We are really not sure why, but everyone seems to acknowledge it happens. Third, many patients are misdiagnosed with depression as the primary diagnosis, and may have another co-morbid illness that dictates treatment. For example, OCD accompanying depression virtually demands use of a SRI or SNRI to treat the illness. Other types of antidepressants are largely ineffectual.

Most borderlines are treated superficially with medications and hoarded into therapy for talk therapy. Borderlines are viewed as nontreatable, even though the literature strongly suggests otherwise. My best guess is that only 5-10% of borderlines get an adequate medication trial on even one drug.

Likewise, we like to treat mania in bipolars, but not depression. While poor decisions are made while manic, they overall tend to be markedly less life threatening than in depressed bipolars. I can only venture a guess on how many depressed bipolars are treated for depression, and would put it at around 50%. All too often they are told they are not really depressed (they are), but simply mourning because they "miss their highs."

I treat these folks aggressively with SRIs, SNRIs, and nefazodone. None seem to induce mania above placebo from the trials done to date, albeit tricyclics can induce rapid cycling in both groups at a rate six times higher than placebo. I tend to push the dosage of all these medications to fairly high levels. It is easy to back off if folks start to get hypomanic, and I am more comfortable with hypomania than suicidality which accompanies depression. We need to do lots of work here. No one really knows why some type of borderlines or bipolars do well on certain antidepressants but not others. Nor do we know which one to use in many cases. Why will Zoloft work in patient A who is exactly like patient B, but B either fails to respond or becomes hypomanic? We need more research.