Treatment-resistant depression is a myth

Treatment-resistant depression is one of those clinical terms that has always been a bit unsettling to me.

Maybe I’m a pessimist, but when I hear this phrase, it reminds me that despite all the time, energy, and expense we have invested in understanding this all-too-common disease, we still have a long way to go. Perhaps more troubling, the phrase also suggests an air of resignation or abandonment: “We’ve tried everything, but you’re resistant to treatment, and there’s not much more we can do for you.”

But “everything” is a loaded term, and “treatment” takes many forms. The term “treatment-resistant depression” first appeared in the literature in 1974 and has been used widely in the literature. (Incidentally, despite appearing over 20 times in the APA’s 2010 revised treatment guidelines for major depression, it is never actually defined.) The phrase is often used to describe patients who have failed to respond to a certain number of antidepressant trials (typically two, each from a different class), each of a reasonable (6-12 week) duration, although many other definitions have emerged over the years.

Failure to respond to “adequate” trials of appropriate antidepressant medications does indeed suggest that a patient is resistant to those treatments, and the clinician should think of other ways to approach that patient’s condition. In today’s psychiatric practice, however, “treatment-resistant” is often a code word for simply adding another medication (like an atypical antipsychotic) or to consider somatic treatment options (such as electroconvulsive therapy, ECT, or transcranial magnetic stimulation, TMS).

Seen this way, it’s a fairly narrow view of “treatment.” The psychiatric literature—not to mention years and years of anecdotal data—suggests that a broad range of interventions can be helpful in the management of depression, such as exercise, dietary supplements, mindfulness meditation, acupuncture, light therapy, and literally dozens of different psychotherapeutic approaches. Call me obsessive, or pedantic, but to label someone’s depression as “treatment resistant” without an adequate trial of all of these approaches, seems premature at best, and fatalistic at worst.

What if we referred to someone’s weight problem as “diet-resistant obesity”? Sure, there are myriad “diets” out there, and some obese individuals have tried several and simply don’t lose weight. But perhaps these patients simply haven’t found the right one for their psychological/endocrine makeup and motivational level; there are also some genetic and biochemical causes of obesity that prevent weight loss regardless of diet. If we label someone as “diet-resistant” it means that we may overlook some diets that would work, or ignore other ways of managing this condition.

Back to depression. I recognize there’s not much of an evidence base for many of the potentially hundreds of different “cures” for depression in the popular and scientific literature. And it would take far too much time to try them all. Experienced clinicians will have seen plenty of examples of good antidepressant response to lithium, thyroid hormone, antipsychotics (such as Abilify), and somatic interventions like ECT. But they have also seen failures with the exact same agents.

Unfortunately, our “decision tree” for assigning patients to different treatments is more like a dartboard than an evidence-based flowchart. “Well, you’ve failed an SSRI and an SNRI, so let’s try an atypical,” goes the typical dialogue (not to mention the typical TV commercial or magazine ad), when we really should be trying to understand our patients at a deeper level in order to determine the ideal therapy for them.

Nevertheless, the “step therapy” requirements of insurance companies, as well as the large multicenter NIH-sponsored trials (like the STAR*D trial) which primarily focus on medications (yes, I am aware that STAR*D had a cognitive therapy component, although this has received little attention and was not widely chosen by study participants), continue to bias the clinician and patient in the direction of looking for the next pill or the next biological intervention, instead of thinking about patients as individuals with biological, genetic, psychological, and social determinants of their conditions.

Because in the long run, nobody is “treatment resistant,” they’re just resistant to what we’re currently offering them.

Steve Balt is a psychiatrist who blogs at Thought Broadcast.

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  • Rob Lindeman

    A pessimist? Clearly a psychiatrist who believes that everything must be tried before “treatment-resistance” is declared is anything but an pessimist. Dr. Bard neglected to mention leucotomy (lobotomy) which was widely employed in treatment-resistant depression. The mechanism of action of ECT is similar but obviously not as dramatic – it kills brain cells.

    Treatment-resistance is a misnomer. By definition, there can be no medical solution to a problem of living. With drugs and surgery we can change the way people feel, sometimes.

  • Steven Park. MD

    Depression is assumed to be a biochemical or neurologic problem of the brain. It’s also a given that people with depression will have sleep problems, which is thought to be due to the depression. What this also assumes is that you’re able to breathe properly at night when you’re able to sleep, which is absolutely not true. Everyone stops breathing to various degrees, but only the end extreme is called obstructive sleep apnea. Modern humans, due to our unique upper airway anatomy, are all susceptible to breathing pauses at night.

    You can stop breathing 20 to 30 times per hour and not officially have sleep apnea on a sleep study. Even if you had obstructive sleep apnea, 90% is estimated to be undiagnosed.

    Not being able to achieve quality deep sleep can wreak havoc on your brain function. Even worse, not getting enough oxygen to your brain can cause major biochemical changes and even structural damage.

    If someone has “treatment resistant” depression, it’s important to consider an underlying sleep-breathing problem. Medications or even ECT won’t help you recover if you’re not breathing properly at night. You can make an argument to screen for a sleep-breathing problem at the first sign of depression.

    I may sound like a hammer looking at depression as a nail, but if you accept the basic premise that everyone stops breathing at night to various degrees, and in light of the fact that most people with sleep-breathing problems are not diagnosed, it’s a simple condition that can be treated with gratifying results.

    If you’re still not convinced, why is it that the vast majority of people with depression can’t (or prefer not to) sleep on their backs? It’s due to smaller jaw anatomy, where the tongue takes up relatively too much space, and can obstruct breathing easier when supine, especially when in deep sleep. Parents of people with severe depression will snore heavily, and will have various degrees of cardiovascular disease (from untreated obstructive sleep apnea).

  • Roger V.

    My many-years-long “resistance” story includes GPs, a psychiatrist, a mental health counselor, and many presciptions for SSRIs, sleeping pills, and anti-anxiety medications. Then the story abruptly ended with a CPAP machine. Five years now and the sequel to the story is drug-free, depression-free, and anxiety-free with CPAP every night. The medical profession needs to listen to Dr. Park. Every patient presenting themselves to a medical professional with symptoms of depression or anxiety should be immediately screened for sleep-disordered breathing. This includes slim people like me!

  • BobBapaso

    Well, it looks like we still have a long way to go just to begin to define what depressive illness is. A person with depressive symptoms may suffer from:
    1. Biological (bipolar type) depressive illness
    2. Psychogenic depressive illness
    3. Depressive personality disorder
    4. Grief
    5. Normal sad feelings

    Only 1., and 2., should be expected to respond to antidepressant drugs, indicating similar brain changes, and antidepressant drugs are not the treatment of choice for 1..

  • Steve Steele

    I have been one of the ‘lab rats’ who have endured taking a variety of the evolution of anti-depressants for more than 10 years. A number of times from various specialists, I have been told about the need to keeping trying different meds until finding the one that works.
    Now in my senior years, I realize several of the most overlooked part of my diagnosis are: interactions with other Rx that I was taking, the long-term effects of some of the meds [for which there have not been longitudinal studies] & neglecting addressing stressors in my life contributing to my depression[e.g. pre-diabetic, skin carcinoma, high b.p. & more].

    The most important overlooked behavior [in my opinion] is that the realization one is in need of an anti-depressant contributes ‘in itself’ a reinforcement of the depression & creating additional source of anxiety.

    I have forwarded this article to a number of friends who have been told that they have a resistance to anti-depressants.
    Thank you for this articles insights.

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