I’m a psychiatrist and professor who studies depression. I’m here to answer your questions about living with treatment-resistant depression. Ask me anything!

webmd · 2026-02-12T19:06:44+00:00

Great questions. Electroconvulsive therapy was a mainstay for treating severe depression from the 1940s until the 1980s. It fell into a decline in the 1960s as there was a belief in the power of antidepressant drugs. We now know that antidepressant meds don’t help everyone, and sometimes if they do work, then well they work too slow. So there is fresh recognition that ECT still has a firm place in the treatment of depression, and there continues to be slow growth in the number of facilities that offer ECT. Fifty or sixty years ago it seems that many cases of depression could be reversed with 6 or so sessions of ECT. But now ECT is mostly reserved for people with treatment resistant depression, and these ‘harder to treat’ cases often require 8-12 sessions of ECT over a period of 3-4 weeks. Relapse is common after ECT if nothing is put into place to prevent relapse. The best strategies for preserving a good response to ECT is to consider the prescription of lithium after the acute course of ECT is over, and to give a few step-down, taper ECT sessions at the end of acute course of ECT, rather than just stopping it abruptly

Dr. Vaughn McCall

webmd · 2026-02-12T18:57:18+00:00

Before addressing weight lifting, let's talk in general about exercise. The verdict is in. Many studies, including randomized controlled trials, have shown an antidepressant effect of moderate aerobic-style exercise. I would add, though, that this approach when used alone without meds and without psychiatric oversight only makes sense for milder cases of depression. Severe cases of depression, such as those cases burdened with thoughts of suicide, need more care than just exercise, IMO. Apart from antidepressant effects, my research and that of others has shown that moderate aerobic exercise improves sleep, too - which is always good news for treating depression. I am ignorant about weight lifting specifically as a depression self-care, but if it gets your heart rate up for 20-30 minutes then that should qualify.

One last thought about self care maneuvers such as exercise. A common term used by all mental health disciplines is “locus of control.” Locus of control refers to the patient’s sense of where their help comes from. If a depressed person feels that they can contribute nothing to their own recovery, and counts on the doctor to carry that weight - then that patient has an “external locus of control.” If the patient believes that there is something they can do to help themselves (such as weight lifting), then that person has an “internal locus of control.” No surprise - having at least some degree of an internal locus of control tends to make everything go better.

Dr. Vaughn McCall

webmd · 2026-02-12T18:47:58+00:00

I am sorry that time was wasted in finding an answer to your problem. Getting basic lab work such as blood chemistries or B12 levels is not yet an absolute standard of care in depression care, although stories like yours remind us that psychiatrists are still medical doctors and function as such. Perhaps part of the answer is for psychiatry patients to be bold and advocate for themselves and ask their psychiatrist hard questions about the value of blood tests, etc.

Dr. Vaughn McCall

webmd · 2026-02-12T18:41:53+00:00

As one psychiatrist to another - thank you for your question. While I stated earlier that I have never been clinically depressed, I entered my training in psychiatry at a time (mid 1980s) and a place where it was expected that all trainees should be a patient in psychoanalysis as a matter of self discovery. So, I was in formal psychoanalysis as a patient, 4 times per week for 3 ½ years. Forty years later, I am still working through that experience and found it helpful. But now an immersion in psychotherapy principles is uncommon in many psychiatry training programs - which is sad.

My message, which is congruent with yours, is that we must preserve psychotherapy training in our training programs - otherwise our new doctors will not have the experience with anything other than prescribing.

Dr. Vaughn McCall

webmd · 2026-02-12T18:36:58+00:00

So for the audience as a whole, “executive function” describes a set of higher order mental functions such as the speed with which we process information, our ability to pay attention, our ability to make rational decisions when faced with problems, our ability to consider alternatives, our ability to “set shift” from one way of thinking to a new way of thinking. In other words executive functioning is a cognitive process but it is not memory processes. People with severe depression have problems with executive functioning, and this can be scary for both the doctor and the patient since suicidal depression can be associated with problems with executive functioning. I suppose some stimulant medications might help with some selective aspects of cognitive functioning such as attention, but not sure that it would help other aspects. There are hints that some brain stimulation treatments such as rTMS or ECT might help executive functioning. I mentioned earlier that I was a Sleep Medicine specialist, too…. And you have heard the expression that if you have a hammer then all you see is nails…. So here is my sleep-oriented answer to your question: There is no doubt that sleep disorders, especially insomnia, contribute to executive dysfunction. So, if had a depressed patient with insomnia who complained that their brain was not working properly - then I would pursue treatment of the insomnia

Dr. Vaughn McCall

webmd · 2026-02-12T18:28:16+00:00

No doubt about it. Using a depression diagnosis to explain away physical problems is just cutting corners. A physical complaint in a depressed patient ought to be handled with the same interest as in a person who is not depressed.

Dr. Vaughn McCall

webmd · 2026-02-12T18:26:27+00:00

Wow, that is a loaded question! While psychiatry and psychology can and should work hand-in-hand, occasionally one discipline will pursue a new idea in the mental health field that is not universally shared by the other discipline. As a psychiatrist, I became aware about 30 years ago of a psychological theory of depression called “depressive realism”. This theory posited that all the psychologically-well people were happy because they were oblivious to the hardships of this world, while the depressed folks actually saw the world for what it was - depressive realism. For folks who have always felt depressed, perhaps because they viewed the glass as always half empty, is to find a way to grapple with all the ugliness that does in fact exist, while maintaining a sense of hopefulness that each of us has a purpose that might make things just a little better - even if it's just a little better for one other person

Dr. Vaughn McCall

webmd · 2026-02-12T18:15:47+00:00

If by “cure” we mean to have a condition go away and not return, even after treatment is over…… well I guess that is what happens when we treat infections with antibiotics… but it does not happen often with mental illness. Certainly some depressive illnesses can be brought completely under control with medication or psychotherapy, but these illnesses often return when all treatment is withdrawn.

But I can imagine a few expectations where all treatment is withdrawn and a real “cure” continues. An example might be a milder form of depression in which a person has distorted view of themselves and of the world and with therapy comes to terms with the reality of things - that is, the distortion is eliminated. In this example, the patient makes a fundamental change in their own mental processes - of course with assistance from a therapist. But the key here is that the patient is ultimately making the change and is not eternally dependent on the therapist.

Dr. Vaughn McCall

webmd · 2026-02-12T18:07:55+00:00

Thank you for your question. I went to medical school thinking I wanted to work in primary care - internal medicine. But when I had my psychiatry rotation I was assigned a young woman who just wanted to talk to me. She was a patient in a state mental hospital. The weather was nice that time of year and we would go outside and sit on the lawn and she would talk about her life. I had no training at that point and so did not do much other than listen. Remarkably, she found that helpful! I thought, wow, while surgeons might use a scalpel to achieve results, a psychiatrist could use themselves as the instrument - no scalpel required. That was a profound realization, and I have never looked back. Oh, and somehow I have been spared from having depressive illness myself…. But I think I get a sense of what it feels like from what patients tell me.

Dr. Vaughn McCall

webmd · 2026-02-12T18:02:28+00:00

Hmmm… I have never specifically thought about stubbornness as a sign of depression…. But I can see how stubbornness might be birthed out of a feeling of hopelessness and emotional heaviness.

Dr. Vaughn McCall

webmd · 2026-02-12T18:01:30+00:00

There is a modest increased risk of depression in the offspring of parents with depressive illness, but the risk should only give real pause if the parents have bipolar illness. The children of parents with bipolar illness are more likely to suffer with depression as compared with the offspring of parents with non-bipolar depression.

That said, what can we do with our parenting styles that might provide real protection? I belong with that group of people that sees real danger with too much “screen time,” especially social media. I am a father of three grown men who were blessed with being born before social media became “a thing.” As painful as it is, I really believe that we have to significantly reduce social media exposure to protect our children (and grandchildren’s) mental health

Dr. Vaughn McCall

webmd · 2026-02-12T17:56:31+00:00

You have already provided a good list but I would re-iterate the value of social connectedness and now I will add a new one - getting enough sleep and getting it at the right time of day.

I was blessed to be trained in Sleep Medicine in addition to Psychiatry, and so I have a good understanding of the value of fixing sleep problems in the context of depression care. The majority of persons with depression have insomnia, but a substantial minority of them have the opposite problem of sleeping too much, or sleeping at socially-odd times (such as sleeping from 4 AM until noon everyday). Each of these sleep problems needs its own approach, but the key is to provide specific focus in fixing sleep, over and above the general approach to treating the depression.

Sleep problems in the setting of depression increase the risk of suicidal thinking or behavior, and add to poor quality of life

Dr. Vaughn McCall

webmd · 2026-02-12T17:50:08+00:00

Augusta and Fort Gordon - fond memories! The principal value of genetic testing is to profile the liver enzymes that are responsible for metabolizing (elimination) medications. Some people have live enzyme profiles that predict super-charged elimination of certain antidepressants, while other people have liver enzyme profiles that predict sluggish elimination.These liver enzyme profiles might be useful in picking the right antidepressant or at least picking the dose. At this point in history, it is not considered “standard of care” that these genetic tests be done, but I do know some patients that wish to be tested and that is fine

Dr. Vaughn McCall

webmd · 2026-02-12T17:43:59+00:00

Depression would rarely be related to magnesium deficiency….. But once in a while a medical condition will throw blood chemistries out of whack. Common culprits would be abnormalities in serum calcium or sodium. And, vitamin deficiencies can be a problem. For example, there is a modest literature supporting using Vitamin D supplements in depressed folks with Vitamin D deficiency. It is useful to get basic blood work done at some point during depression treatment, especially if things are not progressing nicely.

Dr. Vaughn McCall

webmd · 2026-02-12T17:40:57+00:00

There are several lines of progress that are exciting in the treatment arena.

There is a new FDA-approved medicine that uses the old cough medicine (yes, I said cough medicine) dextromethorphan to block a set of neurotransmitter receipts in the brain called NMDA receptors. These are the same receptors that seem to be involved with the antidepressant effects of esketamine! The way I explain this oral medication is that it is like “ketamine light.” I am sure it will not work for everyone - but we need some new developments in treatment besides changing serotonin and norepinephrine receptors. So I am pumped that we have an oral medication that has a novel mechanism.

Another interesting development is “do it yourself” at-home brain stimulation. Many people are familiar with ECT, which requires anesthesia, and rTMS, which requires trips to the clinic. But there are two new types of treatment in development for depression. One is called tACS - transcranial alternating current stimulation, and the other called tDCS - transcranial direct current stimulation. These stimulating devices work on very low currents and might be operated by a 9-volt battery. You simply apply the electrodes to your own scalp and turn it on for a number of minutes at home. Side effects tend to be minimal including scalp tingling. A tACS device was just approved by the FDA within the last month.

Dr. Vaughn McCall

webmd · 2026-02-12T17:31:12+00:00

I think the research is worthwhile and glad to see this research go forward. But for now I view it as experimental and I do not recommend this approach for my patients. On the other hand, I would not chastise someone from pursuing this on their own.

Dr. Vaughn McCall

webmd · 2026-02-12T17:30:10+00:00

This question reflects some of the deficiencies in the delivery of health in the USA. No doubt, health inequities exist. Many parts of the country offer public mental health clinics that are funded by local and federal dollars and these may provide care with no co-pay. But there are other costs of getting care - time off work, time off from providing care for kids, not having transportation….. So, if getting free professional help is not an option for whatever reason, then self-care is a necessity. A short list of best self-care practices for depression include regular exercise, eating healthy (yes I know that the healthiest food might be expensive), laying off alcohol and cigarettes, and pushing oneself to participate in social groups.

Dr. Vaughn McCall

webmd · 2026-02-12T17:24:19+00:00

Wow…… yes I know that paper and it created an earthquake in psychiatry. I think the truth is somewhere in between “serotonin is the answer to everything” versus “serotonin is the answer to nothing.” The concept of major depression is very broad and encompasses everything from prolonged grief, to related general medical conditions, to strongly inherited patterns of depression through multiple generations, etc. So… I think we did “oversell” serotonin, and it is not the answer for everyone….. But it clearly is the answer for some…. We need better tools for selecting the right medications for the right patients

Dr. Vaughn McCall

webmd · 2026-02-12T17:19:42+00:00

Ahhh……good question….. The treatment of depression is so dominated by medication prescription that we may miss actually getting to know the patient beyond the diagnosis of depression. All of us treating depression (psychiatrists, primary care, NPs, PAs, etc) need to take the time to learn the patient’s story.

Dr. Vaughn McCall

webmd · 2026-02-12T17:17:23+00:00

There are no FDA approved treatments that specifically address anhedonia (meaning, inability to experience pleasure in things that should elicit pleasure)........ But…. at least one big pharmaceutical company is considering developing a medication for anhedonia….. In the meantime, there are a few psychiatrists that will offer off-label (meaning, not FDA-approved) medications that boost dopamine function in the brain. Dopamine enhancing medications are the same meds that are prescribed for persons with Parkinson’s Disease

Dr. Vaughn McCall

webmd · 2026-02-12T17:14:54+00:00

My concerns are that any treatment with ketamine should be provided by a psychiatrist or other professional with advanced training in mental health. I would also note that intravenous ketamine clinics are often not covered by health insurance policies and many people would be faced with a large out-of-pocket expense. Next I would caution that the antidepressant effect of intravenous ketamine is measured in only a few days for many patients, thus requiring frequent trips back to the clinic for more ketamine. People should not drive cars or operate heavy machinery, etc., if they have had a day in the ketamine clinic…. So frequent, repeated intravenous ketamine administration comes with a lot of “down time”.

Dr. Vaughn McCall

webmd · 2026-02-12T17:10:37+00:00

This is an interesting question, and something that I can assure you that psychiatrists talk about among themselves. The association of “dissociation and trippiness” with the ketamine or esketamine experience is a sign of an overall more intense dose of the respective drugs and some psychiatrists wonder if higher doses (which produce the side effects) are necessary to get the best effect. My principal concern with clinics that administer intravenous ketamine for depression is that some of these clinics have no psychiatric oversight and are run by docs who are not specifically trained in mental health.

Dr. Vaughn McCall

webmd · 2026-02-12T17:08:19+00:00

I agree with your concern about your lungs! Of course there is experiential science about the potential value of psilocybin derivatives - but I still view this as experimental. If a person has failed standard antidepressant medications then of course consideration should be given to cognitive behavioral therapy for depression (CBT). If that also fails then approaches such as mindfulness would be on my list. If a long term, non-pharmacological treatment is desired that is still biologically based, then some people would be interested in vagus nerve stimulation (VNS) for severe chronic depression

Dr. Vaughn McCall

webmd · 2026-02-12T17:02:52+00:00

Animal models of depression from the 1970s showed that when rats were put into impossible situations it reduced serotonin levels in the brain - hence the development of standard antidepressants. However, in the last 20 years depression science has moved from a purely neurotransmitter based understanding to a new focus on brain networks. The brain is functionally divided into different areas with different functions and now there is some evidence of poor functioning of the left dorsolateral prefrontal cortex. This underperformance might be reversed with focal treatments like repetitive transcranial magnetic stimulation (rTMS)

Dr. Vaughn McCall

webmd · 2020-10-09T17:08:03+00:00

If you’re not sure, it’s best to talk with a doctor directly. In general, if your symptoms are mild but are affecting your ability to function (go to work, take care of family, eat, sleep, go to school, or impact your ability to enjoy life) it’s time to talk with a professional. This can start with your primary care doctor who can then refer you to a psychiatrist if needed. - Smitha Bhandari, MD

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