It’s You, It’s Not Me: Treatment Resistant Depression and the Psychiatric Breakup

“Insanity is relative. It depends on who has who locked in what cage.”
—Ray Bradbury

The Break-Up

Justine¹ was in her mid-twenties, queer, a good dresser, and a little insecure about her pandemic weight-gain. She recently quit her security job. Justine’s security duties included kicking people out of the doorways and stairwells where they slept or got high. She didn’t like this part of her work—telling homeless people to go be homeless somewhere else.

Justine’s discomfort made her take a gentle approach. Her coworkers typically woke the sleepers and stood over them until they packed up and moved on. Justine crouched down and woke the vagrants in a gentle voice, and offered to call shelters to see if there was a bed. Justine sought naloxone² training in her own time in case she ever found someone overdosing. These were not requirements of the job.

Despite her goal to be kind and understanding, she got sworn at and threatened. She began to dread working, so she left and took an entry level position at a department store.

Justine and I first met two years earlier. I was a substance use counsellor and she wanted to quit drinking. She did stop drinking, but the issues that made alcohol appealing never entirely went away. She said that she had severe depression, anxiety, and PTSD. She also suspected she had ADHD and autism.

Justine texted to ask for an appointment. She wasn’t having a good time with life, and not just because of her recent career change.

We met in a coffee shop in a suburb of Vancouver, Canada. “How’s it going?” I asked.

“I met with my psychiatrist recently,” she said. “He’s not going to be able to keep working with me.”

“Oh?”

She smiled, but her eyes didn’t match. “He told me that I have treatment resistant depression.”

“What does that mean?” I said. I’d heard the term many times, but I didn’t know what it meant for Justine.

“It means that I’m fucked.”

“Fucked?” I echoed. “What was it like to hear this from the doctor?”

“Pretty debilitating.” Her smile vanished. “Two years of trying to get help.”

Justine explained that the doctor had tried her on three medications: two SSRIs and one SNRI³, all of which failed to make a satisfying dent in her depression. She felt worse now than when treatment began.

Not all psychiatrists are so quick to give up. They have a number of treatments in their medical bag, but this is the state of the mental health care system in Vancouver, which started buckling four years ago under the pressure of the pandemic. The demand is just too high. My clients referring to a psychiatrist in 2019 were typically told it would be a six month wait. By mid-2020 it was two years. Justine’s psychiatrist had done all he could and a lot of other people needed help. It was time for a breakup.

I was angry on Justine’s behalf, though I didn’t say so. It may seem unfair to get mad at the hard-working psychiatrists doing their best in an impossible situation. I would be more sympathetic if it wasn’t them who created this crisis. More on that shortly.

Justine’s diagnosis of treatment resistant depression poked at a question researchers have asked for more than fifty years: Why do many depressed people get better with medication while others don’t?

This question points us in the wrong direction. It has us look at the patient, has us trying to figure out what about them is different. It skips over a more urgent question: who is to blame when the treatment fails?

Justine accepted that the problem was her, or at least it was her depression. She didn’t know it, but her untreatable disorder was the symptom of an illness within psychiatry.

Diagnosing Dissonance

There’s a classic theoretical model that explains what happened with Justine, but it’s not the one we find most often in psychiatric literature. Psychiatry mostly investigates treatment resistance through the lens of biology: what is different about Justine from those who get better on antidepressants, and what else can we offer? That’s not the model we’re going to use.

To understand treatment resistance, we must look beyond the depressed person. We typically look at the patient’s physiology when we also need to look at the doctor’s psychology. Specifically, treatment resistance is best explained not as a medical issue but as a way for psychiatry to resolve cognitive dissonance.

Cognitive dissonance is a famous theory, used in therapy, marketing and by unhappy lovers explaining why they stay with the C- partner instead of searching for an A+. Cognitive dissonance is defined in many ways, but most simply, it is the discomfort you feel when reality and your beliefs about reality are having an argument. If you think you’re an honest person, you may find yourself a little uncomfortable explaining why you took a sick day from work when you were really taking a beach day. Either you must admit that you’re on honest person, weather pending, or you have to be flexible with social constructs like “sick” or “honest.”

April McGrath, of Mount Royal University in Calgary, outlined seven strategies for reducing cognitive dissonance. I’ll mention two. Say I’m on a diet and, when ordering my alfalfa sandwich, the server asks if I want fries. I say yes. How do I reconcile my diet to my fries? The most frequently studied way to resolve this is through attitude change: “How much do I want to be on this diet, anyways? Maybe this is a good weight.” Another way of resolving dissonance is to denial of responsibility: “If the server had said salad first, I would have ordered that, but I didn’t have time to think.”

We know much about the ways people resolve dissonance, but less about how they choose from their menu of options. But we have two clues that influence such a choice: 1) What problem are they trying to solve and 2) How much control do they have over the situation?

If I am convinced that I will get better by taking antidepressants but then don’t, this creates dissonance. If I continue to take the pills, I have to explain, at least to myself, why I do so. But the person prescribing them (or manufacturing them) has a different problem to solve: explaining why I should still trust them to guide me to wellness. The patient tends to change their attitude, towards themselves or their psychiatrist. Psychiatry protects itself by blaming the patient.

The Fix is Broken

An article about “Treatment resistant depression,” ought to define treatment resistant depression. This is hard to do; there is no universal understanding of the term. Hundreds of articles are devoted to defining it, observing that it is yet to be defined or saying we should really get on top of defining it. A condition that affects thirty percent of depressed people can’t be pinned down, meaning that it might only affect fifteen percent of depressed people, or fifty, depending on who you ask. When we speak of treatment resistant depression (TRD), we do so in broad parameters.

TRD is mostly understood as depression that doesn’t improve with medication or other medical procedures. Studies disagree on how many medications need to be tried before depression can be called treatment resistant, or what is a reasonable amount of time to try each medication or what is an acceptable improvement. Is a patient treatment resistant after trying one med or eight? For two months or six? Should they be a little better or in remission? And who gets to draw these lines?

We haven’t decided exactly what TRD is, yet there is massive clinical interest. As of May, 2024, a search of TRD on Google Scholar yields 96,300 hits. It showed up in the literature for the first time in 1974, when a small number of psychiatrists published some clinical observations of a “therapy resistant depression.” The therapy to which they referred was entirely pharmaceutical—it was always a failure to improve with medication.

“Treatment resistant” follows a core assumption: that depression is a result of biology, a disease that lives in your body like an invading virus or a failing kidney. This is called the medical model of mental disorder.

Psychiatry’s move to the medical model in the 70s and 80s sparked a debate, still going four decades later, as to how helpful this is for patients. It is undeniable that it has been helpful for the pharmaceutical industry, which continues to grow yearly, and as of 2022, the antidepressant market has reached $17.02 billion worldwide.

The eighties and nineties were a depression-treatment renaissance. The SSRI Prozac was brought to market in 1989, and a year later it was twenty-one percent of antidepressant prescriptions. Medications were improving, we were told, and the medical model seemed to be working. There was just one little problem: half the time, the pills, both the new and the old, didn’t do anything. That’s never how the research framed the problem, though. Instead, research said that a sizeable chunk of depressed people were treatment resistant.

TRD erupted in the research literature. There were a few dozen studies of TRD before 1980. There were hundreds by 1990. Still, it eluded clear definition and the DSM-III’s adoption of the medical model meant that it was almost always defined in terms of the patient’s response to medications. “Treatment” has a singular meaning—the kind of treatments you get filled at the pharmacy.

In 1997, psychiatrists M.E. Thase and A.J. Rush came up with the clearest system of TRD so far. Similar models have developed since then, but Thase’s and Rush’s is still in use. It’s a five-stage program that graduates the resistant patient from the most benign to more aggressive treatments: start with any antidepressant, then a different antidepressant, a tricyclic, an MAOI⁴, and finally, electroconvulsive therapy. Meds, other meds, tough meds, tougher meds, then shocks. The attempts to standardize medical treatments are so beautifully linear that we can almost forget that in 2024 we are still searching for the proof that depression is a disease.

A medical disorder becomes recognized when a breadth of accumulated evidence points to its existence. This is standard practice—an enterprising doctor can’t just invent a new disease. The APA decided to reverse this process—create the disorder, then find the evidence.

James Davies in his book Cracked: the Unhappy Truth About Psychiatry, along with hundreds of papers over forty years, documented how members of the APA created most disorders with little, and in many cases, no empirically reviewed studies. Mental health disorders were created by committee—if the committee agreed, a disease was real. It was science that skipped some steps.

The use of the disease model was enormously successful for psychiatry. Medicine took thousands of years to refine to the point where we could have confidence in—not always its results, but at least the methods by which if strives for results. Psychiatry got there by riding on medicine’s coattails. It needn’t go through its tedious task of constant refinement; it could just use the language of its older, more established sibling.

The medical model makes an assessment and a promise, that depression is biological and its treatment is chemical. The depression eggs are all in one pharmaceutical basket. Why is psychiatry so reluctant to embrace non-medical approaches to depression? The most obvious answer is that the pharmaceutical industry has a lot to gain from a medication-only approach, and they are allowed to market directly to physicians, who are, in turn, often rewarded with financial incentives and vacations. But this alone doesn’t explain it.

I’ve worked with many psychiatrists. I don’t know any who believe that environment and life factors play no role in depression. Most are kind, want to help and believe that prescriptions will improve patients’ lives. It’s too black and white to say that they’ve all been plugged into the pharmaceutical matrix.

It’s only when we go industry wide that we see patterns. The pattern is to treat depression as biological, to adhere to a medication regime even when that regime is not working, to omit non-medical treatments from the conversation and to describe the treatment’s failure as something to do with the patient.

It gets worse. A 2008 paper pulled together 74 studies for the twelve leading antidepressants. Just over half of the studies (38 of 74) showed a positive effect and half showed either no effect for antidepressants or that they performed worse than placebo. Yet, 37 out of the 38 positive studies were published in journals, versus only three of the negative ones, and the ones that were neutral were proclaimed as positive. The same authors updated this study in 2022 where they examined another thirty drug trials. They found that the omissions weren’t as extreme as in 2008, but still found that all the positive results (fifteen of thirty) were published compared to seven the fifteen that found negative or no effect were not published. This creates a distorted view: 75-94% of published studies makes it seem like the meds are effective and we never see most of the papers that say otherwise.

The accumulated weight or research indicates that antidepressants are helpful sixty percent of the time. This might sound impressive, until you realize that placebos alleviate depression fifty percent of the time. This doesn’t make antidepressants objectively useless, but it does give us cause to question why they are the first, and usually only, line of defense, especially with side effects ranging from jitteriness to lowered sex drive to increased risk of suicide. It’s not surprising that the pills won’t work for everyone. It’s harder to grasp why we rely on them.

There are patterns to how the medical and pharmaceutical fields respond to failure, and that pattern is to never admit failure. In the face of poor performance, psychiatry searches for the problem everywhere but in psychiatry.

Psychiatry’s foundation is built on a medical model that has never accumulated the kind of certainty it claims to have, that treats mental illness with drugs that often don’t work, ignores evidence that undermines its role in treatment, and locates the blame for ineffectiveness somewhere in the patient’s biology.

Denial of responsibility. Omitting contrary evidence. Limiting the conversation. This begins to sound a lot like cognitive dissonance.

Cures and Cares

The treatment resistant problem may not entirely be the fault of psychiatry, or even the drug companies. Chemical cures sell so well, in part, because we want them. We are a market ready and willing to throw our money at anything that promises to end our misery without massive personal change or social activism. And, if it sounds like science, if the person talking to me about my depression wears a white coat and can cite studies, then why doubt it? Psychiatry may be quick to hide its shortcomings, but we’re also willing to not dig for them.

There’s a cost to this agreement, though, and most of it is paid by people like Justine. When her psychiatrist says that she is treatment resistant, she is ready to accept this; the problem is her. Psychiatry gets to deny responsibility, meaning Justine has to accept it.

This leaves a conundrum: how do I help Justine?

Justine was unaware that she inherited a legacy of seventy years of marketing that successfully frames her perpetual low mood and sense of failure as a disease of biology, where a field of psychiatry struggles to retain its unstable ground as a scientific discipline, where the poor efficacy of her medications are downplayed and where her hopes for wellness are dependent on circumstances beyond her control. Depression’s history runs unseen in the background, like the coding for an app.

The only way I know how to help Justine is to invite her to explore this story she has inherited. One therapeutic discipline calls this “re-authoring,” meaning that the client is invited to reframe the story. Re-authoring is the well-adjusted stepchild of cognitive dissonance. Instead of creating tension for Justine to resolve, she is asked about details she may never have considered.

I asked her, “What kept you from giving up?”

She seemed to be mildly surprised at this question. She thought he’d made it clear that she had given up.

“Well,” I said, “all that you did to get help, I don’t imagine it was easy.”

“Nope.”

“And now you’re here, talking to me.”

“Yeah.”

“When it was hard and you had constant barriers and doors closed on your face, what kept you going?”

Her response was beautiful. I still tear up when I think of it.

“Because I have to believe that all this suffering counts for something.”

“What do you mean?” I’m sure I cocked my head, my reflexive response when someone evokes my curiosity.

“I mean, if I stop now, all that I’ve done will mean nothing.”

One of the most privileged aspects about a job like mine is I get to see surprises in every person. Justine was full of surprises. “So, it’s possible that all that you’ve been through can mean something.”

“I sure hope so.”

“What do you call that?”

“Call what?”

“What do you call the thing that keeps you believing that this will mean something?”

She was quiet for a moment. “I… guess I’d call it hope.”

She called it hope.

This question, “What kept you going?” is my favourite, because it makes clients acknowledge strengths, often ones they didn’t know they have. Clients frequently think they should tell me about the worst things that have ever happened to them. I am more interested in how they survived the worst things that ever happened to them. The focus on trauma revisits the idea that they are a victim. Stories of survival bring to light so much more.

I asked Justine how she had kept that hope alive. Her answers were too long to record here, but she spoke of her grandfather, who never gave up, and of her wish that her struggles can be an inspiration for others. She’d thought of her life as being ruled by depression; she re-wrote her story as someone who lived through depression by constantly pushing back on it.

I asked Justine what this conversation was like for her. She said that it left her in a different place. She hadn’t realized how much she’d been driven by hope.

Treatment resistant depression is a symptom of psychiatry that has pinned all its hope for credibility onto the medical model, but the medical model is itself a symptom of a greater problem, that there’s no place in our lives for suffering. We’ve come to see the mental health field as a take-out window of pills that will fix our pains the way a burger will fix our hunger. This makes it hard for the people in whom we trust with our wellness to offer some of the things we need to be well—emotional connection, empathy and a sense of control over our lives. It’s not that a psychiatrist can’t offer these things, it’s that it isn’t a necessary part of the interaction. Most psychiatrists I know would have stayed with Justine longer than hers did, but it was psychiatry that supplied her doctor with the reason for the breakup.

The psychiatrist failed because he tried to treat a disease when he just needed to take some time to see Justine. Her depression was treatment resistant but it wasn’t Justine resistant.

Sources:

Davies, James. Cracked: The Unhappy Truth About Psychiatry. (2013)

Greenberg, Gary. Manufacturing Depression: The Secret History of a Modern Disorder. (2010).

Hickie, Ian, Cuijpers, Pim, Scott, Elizabeth, Iorfino, Frank. Is it time to abandon the concept of treatment-resistant depression? (2024)

Mrazek, David A., Hornberger, John, Altar, C. Anthony, Degtiar, Irina, A Review of the Clinical, Economic, and Societal Burden of TreatmentResistant Depression: 1996–2013. (2014)

Pandarakalam, James Paul. Challenges of Treatment Resistant Depression. (2018)

Paykel, Eugene. Basic concepts of depression. (2008)

Rush, John, Thase, Michael. Strategies and Tactics in the Treatment of Chronic Depression. (1997)

Schroder, Hans, Patterson, Elissa, Hirshbein, Laura. Treatment-resistant depression reconsidered. (2022).

Souery, Daniel, Papakostas, George, Trivedi, Madhukar, Treatment-Resistant Depression (2006).

Turner, Erick, et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. (2008)

Turner, Erick, et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy:Updated Comparisons and Meta-analyses of Newer Versus Older Trials.(2022).

Voineskos, Daphne, Daskalakis, Zafiris, Blumberger, Daniel. Management of Treatment-Resistant Depression:Challenges and Strategies. (2020).