Treatment-Resistant Depression
Rakesh Jain, MD, MPH:
Question:
“Is it ever appropriate for me to tell my treatment refractory patients: ‘There’s nothing more that can be done to help you’?”
Let me respond by telling a recent, personal story. My sister-in-law was diagnosed with lung cancer two years ago and despite initial success in treatment, the cancer came back aggressively. She was taken care of by one of the finest oncology teams anywhere in the United States. Multiple treatments were tried—alas, no success. Her health deteriorated remarkably, and her quality of life fell sharply.
We were asked by the doctors to consider stopping treatment and offered hospice care. They told us that, realistically speaking, my sister-in-law’s chances of survival beyond four weeks were less than 1%. We were told her condition was treatment-refractory, and they had no more to offer.
By this time, my sister-in-law was in a coma, and the family turned to me (as the only physician in the family) and asked for my opinion. I told them that, honestly, there was no realistic hope of recovery. They did decide to stop treatment, turned to hospice care, and six days later my sister-in-law died peacefully. This happened about six months ago.
I am at peace in my heart that I gave the right advice. The situation was hopeless and further treatment was simply cruel and unproductive. Now, I share this very personal story with all of you to say that there are circumstances in clinical medicine where making a reasoned judgment to withhold any further treatment is prudent and humane.
However, in the treatment of depression, this is not—emphatically not—the way to go. I want to be very clear on this point. I wish to state as clearly as I can: In the treatment of depression, even in the refractory patients, there is never a time to recommend withholding treatment or from not attempting further treatment trials.
You have the right to question my stance. You may be asking yourself, “Is he just being a wild-eyed optimist or is his thinking based on good science?” This is a fair question. Let me present some evidence that supports my position of never giving up on any patient afflicted with depression, no mater how refractory it seems at this point.
First of all, let’s examine evidence from one of our premier studies in depression—the famed STAR*D study.1,2 If you recall, more and more patients kept achieving remission as patients moved from one step to another. Certainly, the rates kept going lower with each step, but note, never did a step lead to zero increase in gain. Each step produced incremental benefit, no matter how small it was. This is evidence that therapeutic nihilism has no place in the treatment of depression.
We now have FDA options approved specifically for treatment refractory depression and for suboptimally treated depression.3-5 Thyroid augmentation is continuing to show promise.6 The number of options is increasing rapidly. We clinicians have more tools at our disposal today than we have ever had.
Let’s not forget that well-controlled studies of psychotherapy in depression reveal the power of these interventions.7 Happily, it’s one more option to help our patients with treatment-resistant depression. Even less reason to practice therapeutic negativity.
What about the multiple somatic treatments available to us? Electroconvulsive therapy is still one of the “great friends” for treatment refractory patents, and I feel more patients should be offered this as a treatment option when they run into treatment resistance (both unipolar and bipolar depression).8 The advent of vagus nerve stimulation9 and transcranial magnetic stimulation10 for difficult-to-treat depression are welcome additions to our armamentarium. Deep brain stimulation11,12 is showing promising results in this population as well. Even psychosurgery for extraordinarily refractory patients shows promise.13
This Q&A is not to discuss a step-by-step approach to treating refractory patients afflicted with depression, but rather to vigorously defend the position that it’s never appropriate to give up hope. Giving up hope is not appropriate for the patient or the clinician who takes care of them. This is not a “pie in the sky” kind of approach. It’s scientifically, ethically, and realistically an accurate position for all to take. There is always hope for even the most treatment-refractory depressed patient out there. I believe this personally, and I believe science backs up this position.
What do you think? I cordially invite your thoughts!
—Rakesh Jain, MD, MPH
References
Warden D, Rush AJ, Trivedi MH, et al. The STAR*D Project results: a comprehensive review of findings. Curr Psychiatry Rep. 2007;9(6):449-459.
Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007;164(2):201-204.
Bobo WV, Shelton RC. Efficacy, safety and tolerability of Symbyax for acute-phase management of treatment-resistant depression. Expert Rev Neurother. 2010;10(5):651-670.
Berman RM, Fava M, Thase ME, et al. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009;14(4):197-206.
Bauer M, Pretorius HW, Constant EL, et al. Extended-release quetiapine as adjunct to an antidepressant in patients with major depressive disorder: results of a randomized, placebo-controlled, double-blind study. J Clin Psychiatry. 2009;70(4):540-549.
Kelly TF, Lieberman DZ. Long term augmentation with T3 in refractory major depression. J Affect Disord. 2009;115(1-2):230-233.
Matsunaga M, Okamoto Y, Suzuki S, et al. Psychosocial functioning in patients with Treatment-Resistant Depression after group cognitive behavioral therapy. BMC Psychiatry. 2010;10:22.
Medda P, Perugi G, Zanello S, et al. Comparative response to electroconvulsive therapy in medication-resistant bipolar I patients with depression and mixed state. J ECT. 2010;26(2):82-86.
Ansari S, Chaudhri K, Al Moutaery KA. Vagus nerve stimulation: indications and limitations. Acta Neurochir Suppl. 2007;97(pt 2):281-286.
Krisanaprakornkit T, Paholpak S, Tassaniyom K, Pimpanit V. Transcranial magnetic stimulation for treatment resistant depression: six case reports and review. J Med Assoc Thai. 2010;93(5):580-586.
Mohr P. Deep brain stimulation in psychiatry. Neuro Endocrinol Lett. 2008;29(suppl 1):123-132.
Pereira EA, Green AL, Nandi D, Aziz TZ. Deep brain stimulation: indications and evidence. Expert Rev Med Devices. 2007;4(5):591-603.
Steele JD, Christmas D, Eljamel MS, Matthews K. Anterior cingulotomy for major depression: clinical outcome and relationship to lesion characteristics. Biol Psychiatry. 2008;63(7):670-677.
