Then another new-ish drug, Pfizer’s antipsychotic Zeldox (ziprasidone). Only the brand name was available. At this point I was uninsured and my drug bill topped $400 a month. I dipped into my savings and tried, with little success, to cut down my spending on necessities like food and books. For a while I was on an antipsychotic (ziprasidone), an anticonvulsant (lamotrigine), an antidepressant (sertraline) and a mood stabilizer (lithium) all at once. I relied on my multicoloured, fourteen-compartment dosette to keep it all straight.
For all the potentially lethal things I put in my body on a daily basis, it’s hilarious and not a little ironic that I remain alive. But it’s grimly comforting to know my madcap psychopharmacological hopscotch is not outside the norm. There’s been research supporting the use of various drug combos as adjunctive treatments for depression that doesn’t respond to conventional antidepressants right away, but it’s a crapshoot determining which you should try and in what order.
This is true even for masters of the neuropharmacological craft.
Richard Friedman, the Director of Psychopharmacology at Weill Cornell Medical College in New York, does this for a living.14 “Some [doctors] just clinically have a few they’re used to using and they’re comfortable with, and they try them, and you could say, ‘Why are you using strategy A instead of B or C?’ and the answer’s not going to be ‘Science.’” He’s tasked with figuring out what alchemical medication cocktail to use on people who don’t get better with the basic ones. (Andrew Solomon, the revered author of The Noonday Demon, told me he swears by Friedman’s pharmacological acumen.) Faced with a degree of treatment-resistant depression in a given patient, “I would give him something that, if they’ve had it in the past, worked if they’ve had prior episodes of depression. And, short of that, from a scientific point of view, you could take a coin out of your pocket and flip it.”
Has he gotten better at this guessing game?
“I would like to say the answer to that is yes. If you asked me to prove it, I couldn’t. So I’ll say yes, but. I don’t really know. Because this is not science. This is clinical gut feeling.”
As few as one in four people start to feel better on the first antidepressant they try, if they take it as directed and stick with it for the six-plus weeks it’ll take to kick in. That cumulative remission rate goes up to about 70 percent if you include people who go on to a second, third or fourth cocktail of drugs plus psychotherapy, with a smaller proportion of the remaining suckers getting better at each treatment step. The National Institute of Mental Health’s Sequenced Treatment Alternatives to Relieve Depression Study (call it STAR*D if you wanna impress your psychiatrist friends) ran 3,671 depressed Americans through a flowchart of treatments. People who didn’t respond to the first, second or third steps and continued on to Step 4 tended to be slightly poorer and older; they were more likely to be male, unemployed and uninsured. People whose depression had started before age eighteen and whose latest depressive episode has lasted for at least two years were also more likely to continue to Step 4.15 Feels like I’m on Step 8,000.
So much for getting well. Staying well is another matter entirely.
Of all those people whose despair lifted on the first, second, third or fourth treatment combo they tried, almost half will be plunged back into despair, back to baseline within a year. “And then you’re struggling to find out what is the next best treatment for them.” The University of Texas Southwestern’s Madhukar Trivedi is another master of his craft clearly distressed by the limitations of the field. “The more treatment steps you need to get better, the higher the relapse rate.”16
In other words, the earlier your depression starts, the longer it lasts and the longer you wait to start treatment, the longer it will take for treatment to work and the more treatment combinations you’ll need to try before something works. The longer your depression lasts and the more steps it takes for you to find something that works, the more likely it is you’ll relapse in a year and end up right back where you started. The longer and deeper and more frequent your depressive episodes, the more likely they are to keep coming back as your habit-loving brain starts to think this is normal.
The need for swift, effective action on depression makes it all the more important to catch it early and makes our lack of effective, accessible treatment all the more inexcusable.
Even using the most optimistic efficacy estimate we’re still left with about seven-million-odd North Americans enduring a chronic, debilitating illness and getting no lasting respite from any available treatment.
“There’s still going to be a huge gap of unmet medical need that is just awful,” says Steven Hyman, who heads the Harvard-MIT Broad Institute’s Stanley Center for Psychiatric Research.17 He’s spent years wrestling with treatment options for mood disorders, or lack thereof. “Even those who don’t kill themselves, their lives are very problematic. Because not only are they suffering but they are, I think we know by now, they’re highly impaired.”
(It’s at this point in the interview I find myself at pains not to bellow, “I knowwwww, right?”)
Given all that, is it any surprise that so few people suffering with depression take their drugs as directed? Even if they don’t mess with your bodily functions, popping them daily for years on end with so little to show for it is really, really discouraging. Adherence rates in the medium term (three months from initial prescription) are about 40 percent, on average. By comparison, almost three-quarters of people with hypertension and two-thirds of people with type 2 diabetes take their meds as instructed at least 80 percent of the time.18 This isn’t because people with severe depression just aren’t motivated enough to get better, although that’s doubtless part of the issue: when severely depressed, it’s impossible to get motivated enough to do much of anything. All too frequently, though, antidepressants’ side effects are so intolerable they outweigh the drugs’ (gradual, incremental) benefits. So people just stop taking them. The most common complaint is the havoc they wreak on your gastrointestinal tract, flooding it with neurotransmitters, increasing motility and making your gut all jumpy. That’s why doctors recommend against ingesting these drugs on an empty stomach: a little substrate can give those muscles something to play with so they’re not quite as cranky. Then you get anxiety, agitation, insomnia—also frequent antidepressant side effects, which is especially annoying because these tend to be either symptoms of depression or exacerbators of it.
But the one you’ll hear about the most is sexual dysfunction. Because who wants that? What further proof do you need that psychiatry is an enemy of joy? These drugs can lower your libido, make penis-owners impotent, delay orgasm or make it unreachable altogether. We’re not quite sure how this works; it may have something to do with receptors in your spinal cord.19 Antidepressants’ cock-block effect could be overblown, though: depression can do the same thing. (For this same reason, I’m personally skeptical of claims that antidepressants make you suicidal. It’s akin to blaming chemotherapy for metastatic tumours, or lozenges for a sore throat. Just ’cause a treatment is inadequately efficacious doesn’t mean it’s responsible for symptoms of the illness it’s supposed to treat. Antidepressants can, however, make you well enough to act on suicidal thoughts you lacked the energy and wherewithal to act on before, but which you were having anyway. Because life is a cruel trick.)
When every drug you take falls short of your desperate desire for remission, or when you simply get fed up with side-effect roulette, it’s easy to think it doesn’t matter whether you take the meds or not.
Wrong. Wrongety-wrong-wrong. I’ve had moments where I was convinced a drug was doing fuckall only for me to realize how much worse shit got when I was taken off it.
Just because something isn’t nearly good enough doesn’t make it entirely useless.
The ease with which antipsychiatry types use ignorance of how depression works and the limitations of existing treatments to bolster their arguments that the illness itself is a sham drives Madhuka
r Trivedi nuts. “I think that the efficacy challenges are real. We need to confess that. On the other hand, I can tell you that a lot of chronic medical diseases have the same efficacy challenges. We don’t question the existence of those diseases. We become humbled by the outcomes. The jump in logic is remarkable—that because the efficacy is modest maybe it’s not a real disease.”
He sees two fundamental problems: A lack of information—people don’t know what antidepressants can do, could do, probably won’t do. And a lack of seriousness accorded to the condition they’re supposed to ameliorate. “I still get asked questions about whether this is some kind of brain disorder.” (For the record and the umpteenth time, he says, it is.)
There’s evidence different kinds of treatment tend to work better when combined—drug plus psychotherapy is probably better than either in isolation; certain combinations of drugs may work differently on your brain; exercise can be a helpful adjunct to whatever else you’ve got going on (maybe something to do with those endorphins, or some other chemical reaction). But clinicians rarely coordinate them. “We should not rest on our laurels as soon as someone gets into remission. We need to think about what else needs to be done….When you add those treatments that work potentially through a different brain mechanism, you get higher rates of remission. Enough to be significant, absolutely.”
It’s hardly encouraging that the efficacy rates for antidepressants have actually dropped over the past half century. But this may have less to do with how good these drugs are and more to do with changes in how we’re measuring them: studies are getting better at differentiating between wishful thinking and statistically valid results. The under-representation of people of colour in clinical trials has resulted in meds that may not work as well in populations we know are already underserved. At the same time, changes to the way we define depression have included a whack of new people, which means drug trials suddenly contain more people with milder versions of the disorder, who we now know are way less likely to derive any real benefit from antidepressants. 20
We’re most aware of the people who aren’t helped by psychiatric meds, rather than people who are, which could be exacerbating our confusion over what actually works. “We see and hear the untreated, acutely psychotic shoeless man screaming in the street, or our loved ones who have not yet responded to their medications. By contrast, the mental illnesses of our colleagues or friends who have remitted with treatment are invisible,” says Benoit Mulsant, the clinician scientist with CAMH who specializes in “hard-to-treat” older populations.21 He also notes that part of antidepressants’ perceived inefficacy could be due to premature discontinuation: if you just go off your meds, or go off them prematurely, they aren’t going to make you better. This makes sense. But if the best meds you have are so awful for so many and require such a long-term commitment that people in the grips of illness don’t bother, then your meds kind of suck.
12
Good Noticing!
Combined with, and throughout, my variegated parade of drugs was cognitive behavioural therapy (CBT), which for me resembled more than anything an endless sadomasochistic Socratic logic exercise.
Pioneered by Aaron Beck in the 1960s,1 it uses thoughts as levers to tame and defuse overpowering emotions: you record your emotions, the thought underpinning them, and the evidence supporting and refuting that thought in the hopes of getting a more balanced view of yourself in the world. It’s supposed to make your brain more skeptical of its own bombardment of toxic convictions, carving out new, less harmful tracks of automatic thoughts and, hopefully, avoiding the vortex of inescapable despondent paralysis.
The evidence for CBT and a host of other psychotherapies in treating depression is pretty robust. Evidence-based psychotherapy has been found to enhance the effects of antidepressants2 and lessen the likelihood of relapse.3 Most people, when you ask them, prefer talk to pills. Most physicians either don’t ask or don’t care: stats indicate meds are used way more frequently, while psychotherapy use actually declined in the United States between 1996 and 2005.4 I struggled for a bajillion years to do the “thought records” that are at the centre of CBT efficaciously. Long after I basically memorized the patronizing Mind Over Mood book and the conceptual structure of its written exercises, I couldn’t make it work when I needed it most.5 All well and good to convince yourself of the fallacies of your convictions while you’re mostly okay; not super helpful if you can’t do it when shit gets real. Nonetheless, this method pulled me back from the ledge innumerable times. When I could make it work, it was great.
Mindfulness sounds flaky. The group classes are flakier. At my psychiatrist’s urging I shelled out $600 for a course—not cool: this exhortation on his part was unhappily timed with a stint during which I was uninsured. The classes consisted of a series of early-evening two-hour sessions where a pair of practitioners, one a registered naturopath and the other an MD, walked us in a group through various thought exercises. The idea is to become hyper-aware—mindful!—of thoughts and emotions preoccupying you and, rather than becoming subsumed in them, putting a bit of perspective-enhancing distance between you and whatever the overpowering thought happens to be. I found their encouraging monologues aggravatingly saccharine but listening to other people voice their psychic hang-ups was illuminating. Realizing the similarities and constants between people’s shit, as well as the striking differences, puts things in perspective in a helpful way. More importantly, despite my disdain, these methods actually kind of work.
I had to physically restrain myself every time one of the mindfulness course’s facilitators chirped “Good noticing!” But noticing is, seriously, a helpful thing to be able to do. The mere act of acknowledging a potent recurring automatic assumption does sometimes help me curb what would otherwise precipitate a spiral of awfulness. At the very least, it cues you to notice when this shit crops up again and again. Whoah, that’s a bad feeling. What’s that? Oh, it’s self-recrimination. I’m thinking I should die because I’ve ruined everything. That’s interesting. I had that same thought yesterday, too. Six hundred dollars was an exorbitant amount of cash to spend on this, but teaching yourself to become aware of your own feelings, disentangling feelings from thoughts and separating both from your self is actually worthwhile. I still try to create distance between my self and my thoughts, with varying degrees of success. Good noticing!
* * *
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TREATMENT METHOD MATTERS but its effectiveness depends on the person giving it to you. Despite knowing psychotherapy works and knowing which forms of psychotherapy work, most people don’t get psychotherapy that’s been proven to work in a way that’s proven to work. Canada’s psychotherapy landscape isn’t quite the free-for-all it was three decades ago, but it’s close.6 In many provinces I could hang up a “psychotherapist” sign on my apartment door and start charging $400 an hour to talk to people about their problems. Healing crystals: $50 extra. Most regulatory bodies will specify the kind of degree you need or the school where you can get it. Almost none will tell you what methods are legit and which are crap, much less check up on you.7 Credential confusion in psychotherapy presents yet another way to miss out on effective care. It’s hard to know what you’re looking for if you don’t have a background in the field. As a result, a lot of people get therapy that isn’t proven to work.
Even if the average therapy-seeking layperson knew what therapies have been proven to work for whatever ails them—and I’m willing to bet most don’t—“they don’t have a prayer of easily knowing whether a given therapist actually delivers,” says Michael Schoenbaum, a senior advisor on the epidemiology and economics of mental health care at the National Institute of Mental Health.8 One of his “formative experiences” in the field of mental health care happened at a meeting, watching the medical director of a major insurer bemoaning his inability to tell with any degree of certainty whether the therapists whose services he was reimbursing were actually any good at delivering therapy.
He
is clearly still incredulous that, even in a field characterized by subjectivity and uncertainty, we aren’t even acting on the information we have to make sure people are getting care (and organizations are paying for care) that actually works. We’d never accept a choose-your-own-adventure approach to dental abscesses but we’re totally cool with that norm for the world’s leading cause of disability.
Either way, it detracts somewhat from the relief of knowing your soul-destroying state of being is a disease outside your control if you’re then told to think your way out of it. I had a bitch of a time getting the hang of CBT, especially in those low moments when I needed a cognitive-emotional lifeline the most. And sometimes, in the depths of a snotty crying jag in your psychiatrist’s office, being told your thought patterns are “too outcome-focused” is not super helpful.
But I swear, I completed thought records and swallowed my meds religiously. Didn’t skip doses when they became ruinously expensive or hoard them when overdose possibilities tantalized. I held my breath and willed them to start working. I knew I was running out of drugs to try. And I knew that, once that happened, we might have to turn to more drastic measures.
13
Zapping, Shocking and Burning Your Brain into Submission
When one drug after another failed to deliver desired results, at my psychiatrist’s suggestion in the fall of 2018 we tried repetitive transcranial magnetic stimulation (rTMS)—a treatment still so experimental it wasn’t covered by Ontario’s public health system: my treatments, fifteen sessions’ worth, were paid for through donations.
Like just about everything else we use or want to use or are considering using to treat depression, TMS began as a tool for something else. It zapped magnetic waves at different bits of your brain to measure brain activity and track what happened when those neurons contracted.
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