Based on a conversation with psychiatrist Dr. Rebecca Allen
When most people think about treating depression, two things probably come to mind: therapy and antidepressant medication.
Those aren't the only options.
In a conversation with psychiatrist Dr. Rebecca Allen, we explored three treatments that approach depression in very different ways: transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and ketamine or esketamine.
Dr. Allen specializes in brain stimulation and interventional treatments for neuropsychiatric conditions and has been involved in research and clinical work involving TMS and other therapies.
What interested me most about our conversation wasn't simply that these treatments exist.
It was the larger question underneath them:
What problem are we actually trying to solve, and how do we decide which treatment makes sense for a particular person?
That question begins before treatment.
It begins with diagnosis.
Depression Isn't Just Having a Bad Day
We use the word depressed casually.
Someone has a difficult week, loses a job, goes through a breakup, or simply feels unhappy and says, "I'm depressed."
Clinical depression is different. Dr. Allen explained that a major depressive episode involves a cluster of symptoms—such as feeling depressed or hopeless and losing enjoyment in things—that occur most of the day, nearly every day, for at least two weeks.
The distinction isn't simply sadness. It is the severity, persistence, and combination of symptoms. She also challenged another common assumption: that someone who is depressed must necessarily be depressed because something happened. Sometimes there is an identifiable trigger. Sometimes there isn't.
The brain isn't merely the place where our thoughts happen. It is also a physical organ. We don't assume someone developed kidney disease or asthma because they failed to think correctly. Yet we often treat the brain differently.
That matters because if depression is viewed exclusively as a reaction to life circumstances, we may overlook treatments aimed directly at how the brain is functioning.
Before Choosing a Treatment, Diagnose the Problem
One of the most important points in our conversation came before we discussed any particular treatment. People increasingly arrive at doctors' offices having researched a treatment and already decided that they want it. That's backwards.
The first question isn't:
Which treatment do I want?
It's:
What is wrong?
Dr. Allen compared this to headaches. People sometimes use "migraine" to mean a severe headache. Medically, migraine is a particular type of headache. Different types of headaches have different treatment options.
The same principle applies to depression.
Diagnosis matters because the effectiveness, risks, and appropriateness of a treatment depend upon what is actually being treated.
Once the problem has been identified, the discussion changes from What is the treatment? to What are the available treatments, and what are their trade-offs?
That's where things become interesting.
TMS: Using Magnetism to Change Brain Activity
Transcranial magnetic stimulation sounds more intimidating than the procedure itself. "Transcranial" essentially means through the skull. TMS uses a coil placed against the head to generate rapidly changing magnetic fields. Those magnetic fields pass through the skull and affect electrical activity in neurons underneath the coil.
Why should magnetism affect brain cells? Neurons use electrical as well as chemical signaling. Antidepressant medications primarily attempt to influence chemical signaling. TMS provides another route: influencing the electrical behavior of neural circuits.
Depending upon how the magnetic pulses are delivered, activity in an area of the brain can generally be increased or decreased.
Dr. Allen described an important principle of neuroscience:
"Neurons that fire together, wire together."
The more certain neural pathways are activated together, the stronger their connections can become. It's similar to learning to play the piano. Repeatedly playing the same piece strengthens the neural networks involved in performing it. TMS attempts to influence those networks deliberately.
TMS Isn't a One-Time Treatment
The trade-off is time.
A typical TMS course for depression may involve treatment five days a week for approximately six weeks.
That's roughly 30 treatments.
The advantage is that the patient remains awake. There is no general anesthesia, and Dr. Allen described TMS as generally well tolerated.
She estimated that with commonly used TMS protocols, roughly six out of ten patients experience meaningful improvement, while approximately three out of ten experience remission of that depressive episode.
What if you want something with an even greater chance of working?
That's where ECT enters the discussion.
ECT: More Effective, but With Greater Trade-Offs
Electroconvulsive therapy carries considerable cultural baggage.Movies and television haven't exactly helped its reputation. Modern ECT is very different from the frightening images many people associate with the treatment.
The patient is placed under general anesthesia and given medication that prevents the body from moving significantly. A carefully controlled electrical current is applied to the brain to induce a brief therapeutic seizure.
Dr. Allen explained that the amount of electrical energy involved is much smaller than people often imagine—dramatically less than the energy used by a cardiac defibrillator.
ECT is still a substantially more involved procedure than TMS. That's where one of the most interesting treatment trade-offs appears. According to Dr. Allen, roughly eight out of ten patients receiving ECT can be expected to experience meaningful improvement, with about half of those reaching remission for that depressive episode.
Those are better odds than TMS.
So I asked the obvious question:
Why wouldn't everyone simply choose the treatment most likely to work?
Effectiveness is only one variable.
Every Treatment Has a Cost
ECT requires anesthesia.
A typical intensive course may involve approximately 12 to 15 treatments, often three times per week. Each treatment requires considerably more medical involvement than sitting in a chair for TMS.
There are side effects.
Some can result from anesthesia or the medications used during the procedure, including nausea and muscle aches. Other possible effects include jaw discomfort and temporary confusion.
The issue people worry about most is memory. There is some truth behind that concern. During an intensive ECT course, a person's ability to form new memories can temporarily become impaired. Dr. Allen explained that studies generally show the ability to learn and form new memories returning to baseline after treatment—and sometimes improving if the depression itself improves.
Some memories from the period preceding treatment can be lost, and not every lost memory necessarily returns.
That creates a very different calculation. For someone with relatively manageable depression, those trade-offs might not make sense. For someone whose depression has become debilitating, who isn't functioning, has failed other treatments, or is at serious risk of suicide, the calculation can look very different.
The question isn't whether ECT has disadvantages.
It's whether those disadvantages are acceptable relative to the problem being treated.
Ketamine: A Different Way of Influencing the Brain
The third treatment we discussed approaches the problem differently.
Ketamine isn't new. It has been used as an anesthetic since the 1960s and has also been used for pain management. Over time, researchers observed that ketamine appeared to have antidepressant effects. That observation eventually led to clinical research investigating whether the effect was real.
Ketamine can be administered in different ways, including intravenously. A related medication called esketamine is administered as a nasal spray and was FDA-approved for depression treatment in 2019. Despite sometimes being characterized online as merely a "horse tranquilizer," ketamine has long been used in human medicine as well.
The most interesting part of our conversation about ketamine wasn't the drug itself. It was the two questions:
Do we know that something works?
Do we know how it works?
We Don't Have to Understand Everything Before Knowing Something Works
We understand several things ketamine does within the brain, including effects on chemical signaling between neurons. According to Dr. Allen, we still don't know precisely which of those mechanisms is most important in producing its antidepressant effects.
That doesn't mean we know nothing. It doesn't mean the treatment doesn't work. This matters beyond ketamine. Medicine often develops evidence that a treatment produces a particular outcome before scientists completely understand every biological mechanism responsible for that outcome.
Those are different kinds of knowledge. You can have strong clinical evidence that something works while still having unanswered questions about precisely why it works.
Dr. Allen emphasized that ketamine and esketamine have progressed far beyond anecdotal observations. Their effects have been studied through clinical trials designed to distinguish actual treatment effects from correlations, coincidence, expectations, and other variables.
That brings us to another problem.
Correlation Isn't Causation
During our discussion of ketamine, Dr. Allen raised one of the most important principles in science. Two things occurring together doesn't mean one caused the other.
Her example was memorable. (You may have heard this one before.) Suppose a city with more priests also has more strip clubs. We could invent all sorts of explanations connecting the two, such as the strip clubs make people feel guilty, causing them to seek religion. Or perhaps religious environments somehow cause rebellion.
A third variable—population—explains both. Large cities have more people. Therefore they tend to have more priests and more strip clubs. The correlation is real. The causal story we invented isn't. (Caused by lack of information or as we didn't ask for example, what size the cities were.) That's why anecdotal evidence is useful for generating questions; weak for answering them.
Someone receiving ketamine and subsequently feeling better doesn't, by itself, prove ketamine caused the improvement.
Clinical trials attempt to remove alternative explanations by holding as many variables constant as possible and systematically changing the thing being investigated.
Dr. Allen's point applies well beyond medicine:
Our brains naturally create explanations from patterns. Science requires us to ask whether the explanation is actually supported by evidence.
TMS or Ketamine?
This leads to another question I asked Dr. Allen. Suppose someone is an appropriate candidate for either TMS or ketamine. Which should they choose?
The answer illustrates why medicine rarely reduces to "Treatment A is better than Treatment B."
Dr. Allen said that the kinds of patients considering TMS and ketamine or esketamine can be very similar. There isn't necessarily a symptom profile that clearly tells a doctor which of the two will be better for a particular individual.
Instead, the decision may involve factors such as durability, convenience, logistics, personal preference, and insurance coverage.
TMS requires a more intensive initial schedule—typically around 30 treatments—but people who respond may remain well without continuing regular treatments.
Esketamine can have an easier initial schedule. Dr. Allen described an intensive course of twice-weekly treatment for four weeks, followed by weekly treatments and eventually treatments every other week for maintenance.
Which is better?
That's the wrong question to aks.
A better question is:
Which trade-offs make the most sense for this particular person?
Treatment Doesn't Have to Be Either / Or
Perhaps the biggest mistake is assuming there must be one solution. Treat the medical problem or address what's happening in someone's life.
Medication or therapy.
TMS or therapy.
Instead of etither/or, Dr. Allen suggested thinking in terms of both/and. Different treatments can address different parts of the problem. Someone whose depression improves dramatically after years of illness may suddenly face another challenge: learning how to live without depression.
Therapy can still have an important role.
Medical problems contributing to depression may need treatment at the same time.
Different interventions aren't necessarily competitors. As Dr. Allen explained, addressing a problem through multiple modalities can often make more sense than forcing the decision into an either/or choice.
There are circumstances where treatments shouldn't be changed simultaneously, particularly when doing so would make it difficult to determine what is working or could affect treatment dosing. But the larger point remains: complex problems don't necessarily have single-variable solutions.
The Treatment Isn't the Starting Point
What I took away from my conversation with Dr. Allen wasn't that TMS is better than ketamine, that ECT should be used more often, or that antidepressants should be replaced by newer technologies.
There isn't one treatment for "depression" that makes sense for everyone.
TMS uses magnetic fields to influence electrical activity in neural circuits.
ECT deliberately induces a controlled seizure and has a higher response rate, but brings greater procedural and cognitive trade-offs.
Ketamine and esketamine influence brain chemistry through another pathway and introduce their own questions of treatment schedules and durability.
Psychotherapy approaches the problem from another direction.
The temptation is to ask:
Which one works best?
That's incomplete.
A better sequence of questions is:
- What is actually happening?
- Have we diagnosed the problem correctly?
- What treatments have evidence for that problem?
- What are the benefits, risks, and limitations of each?
- Which trade-offs make sense for this particular person?
- Could more than one approach be useful?
That way of thinking applies to far more than depression. We often become fascinated with solutions before we've adequately defined the problem. Sometimes the most innovative treatment isn't simply the newest technology.
→ It's choosing the right tool to solve the right problem.
About this article
This article is based on my recorded podcast conversation with psychiatrist Dr. Rebecca Allen about depression and interventional psychiatric treatments. Dr. Allen's work includes TMS, ECT, ketamine and esketamine, as well as clinical research involving novel therapies.
I have summarized and organized our conversation for readability. Unless specifically quoted, the wording and framing in this article are mine and should not be interpreted as a verbatim statement or independent written article by Dr. Allen.
Medical disclaimer: This article is for informational purposes only and is not medical advice, diagnosis, or a recommendation for any particular treatment. Treatment decisions should be made with an appropriately qualified healthcare professional.
About the Author / Host
Daniel Stih is an aerospace engineer, software engineer, indoor environmental consultant, and author of 12 books. Through engineering, investigations, and interdisciplinary research, he explores how people define problems, interpret evidence, and make conclusions when there's uncertainty. Learn more in Why I Think This Way.