Hello I Want to Die Please Fix Me

by Anna Mehler Paperny

  Seriously, no matter how useless your drugs are (or seem) I highly recommend talking to your doctor before you go rogue and stop taking them. Your synaptic clefts will thank me.

  PART II

  TREATMENT ATTEMPTS

  11

  A Pill-Popping Parade

  Turns out I have a great metabolism for toxins. So says my psychiatrist—the second one I saw in hospital, the deep-voiced runner and motorcyclist who agreed to take me on as an outpatient and has seen me regularly, dealing with my freak-outs, meltdowns and cynicism, for the past seven years—when he ups the dosage of my latest drug for the umpteenth time. This freakish toxin tolerance does not apply to food or to booze, unfortunately. But fill me with neurotransmitter-altering substances notorious for wreaking havoc on gastrointestinal tracts and sundry endocrine mechanics, and they zip unnoticed through my bloodstream.

  I am a reluctant pill-popper. I started out militantly opposed to pharmacologic treatment. I’d heard and believed all the horror stories: that these drugs wouldn’t work but would have devastating side effects; that they’d turn me into a different person; that they’d leave me neither happy nor miserable but merely an unfeeling automaton lost in a neutralizing fog. That they’d backfire and just make me want to kill myself even more.

  My psychiatrist had little sympathy for these fears. How could I claim to want to get better—as I had, vehemently, to get him and my parents and everyone else off my back and to get out of psych-ward custody and back to work—if I was unwilling to try even the most basic meds?

  So, okay, fine, I swallowed my objections and a tiny daily pill in the hopes of being set free of the locked ward.

  With the benefit of hindsight, I would like to note that my acquiescence was influenced by substantial pressure: I wanted to leave the hospital; leaving hospital required a doctor’s approval. I wanted to go back to work; my workplace wanted a doctor’s approval. My doctor wanted me on meds. Of course I went on meds. Years later I think this was the right move but I maybe made it for not the best reasons.

  So I launched myself onto the psychopharmacological merry-go-round.

  I started on a tiny dose of a little white pill called Cipralex (the brand name for escitalopram). It’s one of the newer drugs in a group known as selective serotonin reuptake inhibitors (SSRIs—brace yourself for a whack of acronyms) and their great trick is supposed to be keeping more serotonin bouncing around your synaptic clefts. Like most of the drugs I took, Cipralex has been accused of being a “me-too” antidepressant,1 where a tiny molecular alteration to an existing compound used for the same purpose does little to make it more efficacious but, once approved, allows drug companies to establish or preserve a lucrative patent while competing in the same therapeutic space.2

  For a long time serotonin was believed to be The Answer—the key to depression, mood regulation and happiness. It’s basically a chemical messenger your body produces that carries signals from one neuron to another, from your brain to your gut to your blood. Selective serotonin reuptake inhibitors are supposed to selectively keep the serotonin bouncing about in the gaps between neurons, the synaptic clefts, stopping it from being reabsorbed (that’s the reuptake) back into the neuron. Instead, the serotonin just keeps making you happy as it bounces around for extended periods of time in those clefts. In theory, anyway.

  Then it was thought The Answer was serotonin along with a couple of other neurotransmitters: dopamine and norepinephrine. They, too, are chemical messengers, bouncing around your synaptic clefts between neurons before being sucked in, reconstituted and shot back out again.

  But the truth is, these popular explanations of antidepressant mechanisms are wrong. In theory, depression negates happiness; antidepressants alleviate depression symptoms; antidepressants increase concentration of serotonin, dopamine and their chemical cousins; ergo serotonin and dopamine create happiness. Wrong. I spent years picturing the synaptic cleft as pinball machine, reuptake inhibitors as “ball lock” mechanisms allowing a player with my cruddy emotional reflexes to keep more balls active, more happy lights flashing, more digital points accumulating.

  Doesn’t work that way. Neurotransmitters are not discrete silvery balls but molecular combinations of a series of smaller balls that keep getting broken down and put back together once they get yanked back into the neuron. And as I was to learn, increasing concentrations of one or all of those neurotransmitters does not guarantee happiness or even the alleviation of despair.

  So our decades-old assumptions about, first, what those neurotransmitters do for us and, second, what drugs do to those neurotransmitters, are primitive at best. Large amounts of the bodily chemicals that psychiatric drugs target exist outside of the brain—they proliferate in your stomach, intestines, platelets. Turns out, we have only the vaguest idea how they work on a biochemical level, and no clue how that biochemical reaction changes your mood.

  The depth of that uncertainty is destabilizing in the extreme when you’re depending on those drugs to keep you going. So I can understand the allure of simple, wrong explanations. In the face of so much weird stuff going on in your brain, you fill in the gaps in comprehension however you can.

  The first time I swallowed a single small elliptical white Cipralex pill, standing beside my curtained-off hospital bed, I was petrified, convinced it would brainwash me, rob me of personality. I sent a panicky idiotic text to a friend: “I’ll love you even if this thing totally wrecks my brain forever, okay?”

  I waited. It didn’t. Apart from a little bit of jitters and a little bit of drowsiness, both of which soon dissipated, I experienced zero side effects from that first drug. This pattern repeated, more or less, with every drug I was prescribed: no seizures, no massive weight gain or loss, no loss of libido, no loss of self, no loss of emotional range, no worsening of suicidal thoughts, which I was learning to call by their more official-sounding name of suicidal ideation. Chronic lassitude and fatigue were, for me, more a familiar symptom of depression than a side effect of any new medication. Ditto sporadic insomnia, which for me seemed more a function of tightly wound anxiety than pharmacological intervention. Sure, there was wonkiness: some drugs made me trembly, some made me antsy, one made me sweaty; one made me dizzy if I rose from a chair too quickly right after increasing a dose; one blurred my vision (we rapidly decreased that dose); one made me sneeze endlessly; some made me nauseous, especially on an empty stomach, especially with espresso on an empty stomach, which makes for less than pleasant morning commutes. But that’s par for the course when you bombard a GI tract with digestion-muscle-moving meds and nothing to digest.

  Not all of those dodged bullets were as great as they sound: intensifying social withdrawal—a typical symptom of depression—meant I was going for weeks without interacting with anyone outside of work and psychiatric appointments and maybe family phone calls. I was certainly not banging anyone. Preserving one’s sex drive is hardly a blessing when you’re simultaneously suicidal and sexually frustrated.

  And any advantage conferred by my lack of side effects was erased by my lack of any effects, period. I felt like I was popping sugar pills. My psychiatrist contended that the lack of improvement was at least partly in my head: that I’d have been far worse off—and may have killed myself for real—without that parade of meds. And he could be right. (His counterfactual’s impossible to disprove, anyway.) There were certainly periods when things got better, or plateaued, and periods when they got worse, and it’s possible my meds played a role in those shifts. It’s also possible they didn’t. But I wanted to feel better: not happiness or even an escape from despair but simply a consistent, propulsive sense of purpose. I need to keep getting up and out of bed and into the office in the morning.

  Over the next seven years we experimented with fourteen different drugs in dozens of different combinations. As I write this we’re considering others. We haven’t yet found a combination that works.

  We tried the circular lilac pills of bupropion, the generic
version of Wellbutrin, which targets dopamine and norepinephrine. It was not until much later I learned Wellbutrin has become a common drug of misuse:3 It produces a powerful high comparable to amphetamines and crack cocaine if you crush and then snort or inject it. Doing so can also produce gross, potentially fatal abscesses or blood clots or masses of dead tissue. Don’t chance it. (That said, I have a couple dozen pills left lying around, if anyone wants to hit me up.)

  We tried lithium, white and pale pink capsules. Popping lithium freaked me out at first—it’s the one they give people with bipolar disorder, to balance the swing between manic highs and depressive lows, the one Claire Danes’ bipolar character Carrie Mathison takes in Homeland to keep herself together. It’s an effective mood stabilizer but long-term use can kick you in the kidneys if you aren’t careful.4 A friend in family medicine told me he had a patient whose bipolarity was so debilitating she’d been on high doses of lithium since early childhood. It regulated her mood but messed with her insides over time. The trade-off was worth it, my friend said, for the three decades of liveable existence. Suicidal ideation at least negates fear of terminal illness, which is a plus.

  But more than kidney failure, what scared me was that being prescribed lithium proved I was even crazier than I thought.

  “Are you sure I’m not bipolar?” I asked my psychiatrist for the zillionth time. “Are you sure?”

  “You wish.”

  I just don’t get the exuberant-invincible-impulsive-boundlessly energetic episodes characteristic of mania. That didn’t stop me from periodically suspecting I’d experienced a manic or hypomanic episode. My psychiatrist raised his eyebrows at my descriptions of such brief, bizarre bouts of irrational motivation or well-being.

  “Yeah, no, that’s not mania. That’s called feeling normal.” The fleeting sense of being energized by, engaged in, hopeful about what I was doing felt so foreign I was sure it was symptomatic of another mental disorder.

  Lithium’s been used as a psychiatric medication for millennia. The mineral was isolated and defined in the mid-nineteenth century but its use goes as far back as the great Greek physician Galen, who got manic patients to bathe in and drink alkaline, likely lithium-containing, water.5 But we don’t really know what it does for people who aren’t manic-depressive. We don’t really know, on a molecular level, what lithium does, period.6 But it is supposed to curb suicidal ideation, which in my case was a fairly urgent necessity.

  We tried Cymbalta, olive green and navy blue, to inhibit my reuptake of serotonin and norepinephrine. By this time I’d become a reluctant expert at dry-swallowing handfuls of pills, throwing them to the back of my throat and swallow-shuddering, swinging my head side to side like a floppy-eared wet dog to encourage downward peristalsis.

  We tried olanzapine, aka Zyprexa, an antipsychotic. It’s a terrible thing to be told to take if you live in fear of losing your grip on reality. This fear dissipated with repetition, as I kept taking pills designed for different kinds of disorders than what I thought I was going through: studies have found various mood stabilizers, antipsychotics, anticonvulsants, anti-anxiety meds and other fun things can help alleviate treatment-resistant depression, especially when combined with a more conventional antidepressant.7 And our ignorance of these drugs’ biomechanisms is about equal, so why not?

  That was when we tried Parnate, an old-school MAOI, a monoamine oxidase inhibitor, that seemed to be working until I tried to kill myself with it. Parnate, aka tranylcypromine, targets a different step in the same neurochemical pathway: it impedes the breakdown of all those neurotransmitters once they’re sucked back into the neuron,8 so instead of being taken apart and rebuilt in the neuron they just get shot back into the synapse to bounce around again like those happy-making pinballs.

  I asked a med-school friend if he’d ever prescribed an MAOI.

  “Of course not. I’m not a dinosaur.”

  MAOIs were popular in the 1950s and ’60s. They worked well, by the flawed measures we have. But no one’s prescribed them much since. There’s so little demand for these drugs that the Quebec GlaxoSmithKline facility producing my Parnate put it on back order at one point, making it unobtainable for weeks and sending me into a minor panic, calling every pharmacist in the city seeking drugs. It led to surreal scenes that made filling a prescription resemble the world’s most boring iteration of The Wire:

  Man in white coat slides white bag across counter.

  “Do you want to count that?”

  Open the crinkling white paper, rip staple and reach inside to roll the cylindrical bottle of softly rattling pills out onto palm.

  “Looks right. Thank you.” Pause. “So…I can come back in three weeks for a refill?”

  “Well, insurance usually prefers refilling at least two-thirds into dose, but that’s four weeks’ worth, so, yeah, I guess….”

  “I mean, will you have enough? Will you run out again?”

  “Oh. Right. Yeah, should be fine. And…” —glances around—“I know who’ll have it. I’ll hook you up.”

  All this for a plastic container of crimson pills that’d be way easier to get if they had any street value whatsoever. The lack of demand isn’t because MAOIs are less chemically efficacious than the various reuptake inhibitors that replaced them.9 MAOIs are deemed too dangerous if you overdose, and possess so many unpleasant side effects, even if taken as directed, that patients just stop taking them. For me, this was the trembling- and vertigo-inducing drug. More troublesome were the nonsensical new dietary restrictions: MAOIs impede your body’s ability to break down tyramine, found in a long list of foods from cheese to draught beer (but not bottled; don’t ask me why) to miso and other fermented soy products to cured or smoked or pickled meats.

  I cheated, of course. Usually because I forgot. And because cheese. And because on the rare occasion I’d meet friends at a pub, ordering bottled beer while everyone else sipped pints felt weird. Most of the time this illicit ingestion made no difference. But sporadically it gave me hours-long killer headaches, pain pulsating from somewhere beneath the front of my skull before eventually dissipating. Each time I vowed never again to eat whatever had so upset my wonky benighted internal chemistry—a pledge that lasted a day, maybe.

  Doses went up when shit got rough or after I’d passed some invisible tolerance boundary and I took them as directed and prayed they worked with the same fervent hope you’d place in an amulet of dried goat testicles, if you could read peer-reviewed papers about the testicle-amulet’s efficacy online and pose goat-testicle questions to the person who’d prescribed them to you.

  But seriously: I believe in medicine and in scientific method; I gradually got better at sorting bullshit claims of causation from more believable ones; I got better at asking more informed nosy questions about effects and efficacy during my psychiatric appointments. But at the end of the day, health care relationships are predicated on trust—brain-health relationships overwhelmingly so. In part because all the things prescribed to me, all there was available to prescribe, did pretty much the same thing, on a biochemical level, as far as we know. And in part because the symptoms they were supposed to alleviate are so tough to measure, especially because depression’s proclivity for seeing everything through shit-coloured glasses also applies to one’s own prognosis. People with especially bad depression tend to be the last ones to realize they’re getting better, but knowing that hardly helps. I had to believe each pharmacological adjustment would be the thing that tipped some imperceptible scale and took the draining effort out of the simplest tasks, leaving me energy left over for the projects meant to give life purpose.

  My friend Omar called Parnate my hipster drug—“Really old-school; you’ve probably never heard of it.” For a while my psychiatrist seemed to think it was working, till that aforementioned spectacular fuckup on my part eliminated it as an option.

  We tried buspirone (Buspar), an anti-anxiety med.10 And Zoloft, or sertraline, which targets serotonin (it was America’s most-
prescribed psychiatric drug in 2016).11 We tried Lamictal (lamotrigine), an anticonvulsant with the delicious potential for eating flesh—a very rare, lurid, potentially lethal allergic reaction. Toxic epidermal necrolysis does pretty much exactly what its name suggests.12 Watch out for painful red-purple rashes spreading from torso to face and limbs; for inflamed sores in your eyes, mouth, genitals. Skin and mucous membranes blister and peel away. If left untreated the disease can wreak deadly havoc on your internal organs. But to my dismay, no flesh-eating disease materialized; no skin sloughed off to reveal the oozing dermis I’d been promised. Perhaps not so coincidentally, I clawed lesions into my skin even more compulsively in the months following that disappointment, as though compensating for my lack of dermal necrosis.

  My psychiatrist thought maybe trying a stimulant would ameliorate my paralytic enervation. So we tried the generic version of Adderall. Given Adderall’s reputed popularity as a drug of misuse among overachieving students intent on pulling all-nighters, I assumed I’d pop a cerulean-blue, Dijon-yellow two-tone capsule and morph into a wicked-focused shark with a laser attached to my head. Not so much. I felt normal. Was able to work, which was great, but no better or more focused than before. No lasers. No searing propulsive purposeful energy. This was a letdown.

  We tried Trintellix, one of the newest and not-yet-well-understood antidepressants out there,13 but the pink egg-shaped pills did not seem to help any.