Disclaimer: I am not a doctor, and this is not medical advice. Do not take any medication without appropriate medical supervision.
One of the most fascinating articles I’ve ever read is “New Frontiers of Sobriety” by Hamilton Morris of VICE. Morris describes several medications which have an effect roughly opposite to various recreational drugs: rimonabant, a cannabinoid receptor blocker that also works against the action of the body’s endogenous cannabinoids; risperidone, an atypical antipsychotic that counteracts many of the effects of LSD; and naltrexone, an opioid antagonist used to manage opioid dependence by blocking the action of drugs like heroin and fentanyl — as well as natural endorphins.
Morris then takes large doses of these compounds in isolation, finding each to be a broadly uncomfortable experience. Rimonabant is a potent appetite suppressant with unpleasant physical and psychiatric side effects, risperidone is heavily sedating, and naltrexone produces sensations he describes as “Wow, am I on edge!” None of them sound even remotely enjoyable to use whether medically indicated or not.
Lamotrigine: the anti-ketamine
One anti-high that Morris did not explore is the closest thing to an “anti-ketamine”: lamotrigine (Lamictal), an anticonvulsant and mood stabilizer used to treat epilepsy and bipolar disorder, along with experimental uses for schizophrenia, depression, and borderline personality disorder. The dissociative anesthetic ketamine, often used as a recreational drug, induces pronounced symptoms of depersonalization and derealization (emotional blunting, feelings that one has “no self”, and a sense that the world is “unreal”). Like most dissociatives, such as PCP and DXM, ketamine acts as an antagonist at the NMDA receptor, and stimulates release of the neurotransmitter glutamate. Conversely, lamotrigine functions as an inhibitor of glutamate release, and has been found to lessen the effects of ketamine, including depersonalization and derealization.
Lamotrigine in combination with SSRIs is also one of the very few approaches that has shown some efficacy in treating chronic depersonalization, the syndrome of unremitting depersonalization and derealization symptoms that can last for decades. Depersonalization disorder is highly distressing to sufferers and associated with a wide array of negative mental health and social outcomes. It’s also something I struggled with for most of my life.
My life with depersonalization
There was no point where I didn’t feel somehow removed from the world around me — this disconcerting sensation was present from my earliest memories. As a child I just didn’t really see the point of practically anything I was doing, or that anyone else was doing; it held no real emotional resonance or meaning for me. Whatever interests I chose to pursue felt more like an obligatory way of filling time, not something that had any value or importance in its own right. I always felt the lack of spontaneity characteristic of depersonalization disorder, and whenever I chose to say anything, it felt rehearsed and acted out as if I had to engage my every word and action manually. Most of the time I would choose to say nothing at all. My feelings seemed to be kept at a distance, happening as something separate from an interior “me” who didn’t truly experience these emotions and seemingly couldn’t be touched by them. I was painfully conscious of all of these things.
Most sufferers of chronic depersonalization experience its onset at adolescence, while others have faced these symptoms for as long as they can remember. I was unlucky enough to experience both. The onset of puberty brought with it a deeper and even more malignant spectrum of depersonalization symptoms, and I can pinpoint when it happened. I was 13, and it was fall of 2002, about halfway through the first semester of sophomore year. One day, as if overnight, I simply stopped feeling anything. If there were any emotions present in me, they were now so far removed that I could no longer see them at all. When I would try to cry, it felt like trying to force a physical function more than any natural expression of emotion; when I would try to feel angry, it seemed so hollow and utterly perfunctory. The world itself seemed to have faded away in some sense, like a video game level that I was moving around in while not actually being part of it. The profound numbness lasted for more than a year, and in this state, I couldn’t gather any motivation to do what was expected of me. I ignored my homework and filled in random answers on tests; getting in trouble with my parents and faculty simply meant nothing to me. I dropped out right before junior year.
When everything changed
The utter emotional deadness faded somewhat over my teenage years, and I found various ways to distract myself from the feeling that everything was just very wrong. Music could bring me a brief uplift, and it was one of the only things that helped to keep me alive through this time. I started training myself to disrupt my ruminating thoughts by immediately shifting my attention to something else. I started a YouTube channel and forced myself to create new videos every day or two, as a way of running and keeping ahead of the emptiness always threatening to envelop me. I was afraid that if I ever stopped, it would consume my entire life again. Developing a feminine presentation in my videos was one of the first things I ever decided to do for its own sake, simply because I wanted to — something that had evaded me for all of my life. Still, any real emotion felt out of my reach, and I continued to feel separated from the world as if by some elastic skin that I could never pierce. I wanted so badly just to touch the real world and finally feel alive, whatever that would feel like.
After a lengthy period of consideration and living as a woman, in 2012 I concluded that I needed to start HRT. I realized I wouldn’t be comfortable at all with my body continuing to masculinize throughout my life, and I was also curious about how HRT might affect my mood. There was very little information available on its emotional effects aside from isolated references to feeling like one’s brain is “running on the right fuel”, so I had no reason to expect that within a week or two after starting hormones, those lifelong symptoms of depersonalization and derealization would dissolve completely. I had no idea HRT could do that — I didn’t even think it was possible for me to feel anything other than that constant dislocation from myself and the world. This was a revelation more significant to me than anything else in my life before or since. The skin could be pierced, there was a real world out there full of depth and richness and life, and I could be part of it — as real a person as everyone else, at last. I wasn’t hollow after all, and neither was the world; everything became so fleshed out with meaning. For the first time, there was a point to life: not just filling time running out the clock, but discovering there were things that really mattered to me, things worth working towards and the true satisfaction that came with it. I’ve accomplished more since transitioning than I did in my entire life before, and I’ve never been happier. My life matters now.
The right fuel
Since experiencing this completely unexpected shift in my consciousness, I’ve been deeply interested in what the physical basis for this change could be. While research on HRT in trans people consistently indicates that it can relieve depressive and anxious symptoms, very little information is available on the biological basis of depersonalization symptoms, let alone the specifics of how depersonalization disorder can affect trans people. Medical transition, particularly HRT, is associated with a reduction in depersonalization and derealization — but how? Intriguingly, estrogen itself modulates NMDA receptors, and some of its effects can be blocked by NMDA antagonists (implicated in the effects of dissociative drugs). Estrogen has also shown some success in treating the negative symptoms of schizophrenia, which have a degree of phenomenological overlap with experiences of depersonalization. There are many pieces that seem relevant here, but as of yet very little to fit them together into a more complete model of how the action of estrogen can treat depersonalization (and even less to explain how testosterone treatment is equally successful at reducing depersonalization in trans men).
In short, these phenomena fascinate me, and there is an urgent need for more research into these areas given the severe impact of this syndrome on those trying to bear this living death. Depersonalization wrecked my life, draining it of all the promise it supposedly held. It stole my soul without the courtesy of killing me. If there is anything that can help us fight back against this condition, that matters.
And that’s why I decided to try lamotrigine.
Don’t try this at home
I’ve already been on an SSRI, Lexapro, for the past year, which has been spectacularly successful in insulating me both from my depression and from the stresses that come with living in the United States right now. But unlike the compounds tried by Morris, lamotrigine is not a medication that can be taken once with immediate effect. The dosage must be titrated up over a period of weeks, with close monitoring of any side effects, which can be potentially fatal. It carries a black box warning about Stevens-Johnson syndrome, a life-threatening skin reaction that you should not Google unless you have a strong stomach. There’s also a long list of possible drug interactions. Lamotrigine is absolutely not something you should take without medical supervision, and I only tried this after consulting with a practicing psychiatrist.
That said, I was able to take it without experiencing serious side effects, and my experience with lamotrigine turned out to be a very interesting exploration of the many dimensions of depersonalization that had haunted my life for decades. I wanted to understand depersonalization better, both as a general phenomenon and as something that affected me so deeply, and lamotrigine did give me that.
During the first couple days, my thoughts feel almost “tingly”, a bit like rolling a Koosh ball around in your hands. It’s not unpleasant or distracting. I’m feeling like I’ve got myself together pretty well, and I face a six-hour car ride to St. Augustine with two bored kids without any issue. Having a picnic and visiting the Castillo de San Marcos fort is a pleasant experience even in 39-degree “bomb cyclone” weather, and we stop to pick up citrus and souvenirs on the way back.
When I do feel a bit prickly, it’s still hard to hold on to bad feelings for long, and it’s easy to get it under control. This is a good thing. I cook dinner for everyone effortlessly, without any fogginess, disorganization or disorientation. It’s like I don’t even have to think very hard about it. Throughout the first week, I’m just in a good mood. I notice that shades of blue seem to be slightly more vivid, not in terms of visual perception, but as if they have more substance to them.
The real test
After nine days, I stopped my hormones entirely.
This is broadly a very bad idea — the last time I was unable to access HRT, I experienced a notable return of prominent depersonalization symptoms within days. That was hellish: my mind wouldn’t stop narrating everything to itself at all time, everything I did felt robotic, and the world just flattened out:
Heather takes me out to the food court and I can’t stop quoting movies at her. What the hell is going on? The entirety of my sensory input is like flat noise, everything amped up to the maximum power spectrum value, becoming a constant static in the foreground of my brain. None of it feels like it should — the people around us, the books at the store, the taste of my coffee, all of it is like the partially eclipsed sun, beating down on my face, blinding, utterly devoid of heat.
None of this got any better until I had my hormones again. HRT turns depersonalization on and off like a switch for me, and if lamotrigine with an SSRI can do anything for that, this is how I’ll find out.
Certain songs begin to get stuck in my head for the first couple of days, as if playing in the back of my mind even as I’m speaking or doing anything else. “Donatella” by Lady Gaga, “Gimmie Love” by Carly Rae Jepsen, “Funplex” by the B-52s — even “Someone Ate the Baby” by Shel Silverstein, which I hadn’t even read since I was a kid. But this doesn’t disruptively force itself into the forefront of my consciousness, and it’s definitely not as bad as it would usually be off hormones. I listen to other music when I feel the need to tune it out, and I make a point to step out more often and get as much sunlight as I can.
I’m being a bit more patient than usual with bad-faith trolls on Twitter. There’s an energetic feeling — I’m engaged and having plenty of conversations, and enjoying it. In the afternoon, I look over at the door we keep propped open with a shoe so our cats can come in and out freely, and it keeps looking like it’s opening even as it’s staying in place, kind of like the song from ascending the staircase in Super Mario 64. But it passes quickly. Three days into being off hormones, I’m still having no prominent depersonalization symptoms. My moods are entirely fine, even if something feels a bit “off” in a way I can’t put my finger on. There’s no sense of feeling robotic or running my entire life on manual — I’m still just as spontaneous as ever, and having normal emotional reactions without having to think about it. Normally I’d be an utter mess by this time, but so far it doesn’t feel anything like the other times when I’ve been off HRT.
After four days off HRT, Heather and I go to our local Scottish Highland Games, a yearly event that we always look forward to. If anything would set off my depersonalization and derealization, this would be it: a huge and loud space full of thousands of strangers, on a cold, gray, blustery day. As a kid, this was the kind of place where I would typically find myself dissociating — dragged along by my family, I would tune out the entire time until it was over, or my senses would become so overstimulated that I couldn’t bear it.
I’m still experiencing songs getting stuck in my head, but it seems to be at its worst in the morning before my brain has fully woken up. This faded almost immediately as soon as we got to the Highland Games — it tends to go away if something else can keep me sufficiently occupied. We wander through the rock-tossing events, the booths for each of the clans, the food stands and petting zoo, and… I’m having fun. Not stuck in my head, not feeling removed from everything around me — I’m actually happy! There was so much to do there and so many shops to explore, and it was all just really cool. Even when paying close attention to any possible dissociative symptoms, they’re not there at all. Somehow, everything is normal.
By the end of the night, I’ve had a very large pitcher of ale, and I run down to the front of the stage to dance frenetically with the crowd to Albannach’s bagpipe and didgeridoo music. I had such a great time, only stopping when I was finally out of breath. Getting drunk was a bit of a mistake, and I have a terrible headache later that night — I really can’t handle my alcohol, and it’s not my substance of choice. But after drinking lots of water and a good night’s sleep, I feel fine.
For the past few days, I feel like I’ve been mixing up or dropping words a lot when talking, but I’m not sure if this is something different or if it’s just because I’m talking very fast. I’m also having strange dreams that take on an unpleasant tone: visceral dreams, of weird things happening to my body, of entire expansive worlds so much bigger and more vivid than my usual dreams. Every other night, I seem to wake up in some kind of anxiety for no apparent reason, and I often have to step outside to collect myself before going back to sleep.
Some part of me still feels like something is different, something is missing. Maybe I’ll be able to tell when I start HRT again. But on the whole, I feel so normal that I want to see how long I can keep this up — I’d like to try for at least a week off hormones, and it doesn’t seem like it’ll even be difficult. We watch “You Get Me” on Netflix, and the teenage romance is painfully inane, but the visual aesthetic is oddly appealing to me. It seems dreamlike, but not in the bad way that makes you feel distanced from the world — it’s inviting and pleasant. The expansive environments, the bright colors, is it unreal? Hyperreal?
The thin shell
After 11 days off hormones, the world feels a bit less immediate and less intense, but not in a way that’s actively troubling to me. I start to feel cognitively slowed or disrupted, like a kind of brain fog. I forget to do simple things like take my wallet to the store or put the garage door back down when going inside. I struggle to remember all the items to get at the grocery, about 20 in total, although I only forget one. Normally this would be a clear and orderly list in my head that’s immediately available as a whole without thinking about it. Now it feels like I have to make a conscious effort to recall the next thing, and several times I pass by items that I only later remember to get. This is distracting and I don’t like it — it’s not an effect I’d be comfortable putting up with for a longer length of time. I start to think that I want to get back on my hormones as soon as possible.
In sufferers of depersonalization, symptoms can become more prominent in the form of sudden attacks — and it gets worse the more you keep thinking about it. Later that night, I step outside to get some air, and the thought enters my mind that the trees, cars, and houses on our street could just be particularly elaborate Lego pieces. The clouds in the night sky could easily pass for a simple rendering in Blender. Isn’t at least half of what we see practically a hallucination that’s filled in by our brain without us even noticing? If all these things were just renderings, it seems like it would be easy to take advantage of that.
I can almost envision everything on our street coming apart piece by piece like an exploded technical diagram. The asphalt, the curb, the patches of grass, all of them could just lift into the air and drift apart, nothing but thin surfaces, almost like abstractions or mere representations. If I were to take a shovel and start digging a hole in the road, it would just be an indentation in that surface, pushing it to extend a bit in one direction or another — but underneath it, nothing. The houses along the street are just outgrowths of the surface, a sort of puckering in it, like a ball on a rubber sheet to demonstrate how gravity is the curvature of spacetime.
I tell Penny about this — she’s a computer animator, and says she experiences something similar when watching movies, seeing all the CGI effects as just flat and artificial creations overlaid on a background. The difference is that I’m seeing this when I look at the real world. It’s an incredibly uneasy thought, but I can’t shake it. I start to realize what’s been missing in my world for the past week. It feels like there could be an infinite chasm behind the surface of everything — the idea of objects having solidity and depth is unconvincing, and it just doesn’t register for me. There’s a sense of standing at some cliffside, with the entire world nothing but a thin and fragile shell between me and the endless void. Perceiving the world felt like walking on ice that could crack at any moment.
This isn’t something I want to continue to experience, and I go back on my hormones immediately. The strange sensations subside within a couple days.
Potential use cases for lamotrigine
There’s a tendency among many cis people to view transitioning as regrettable, a kind of last resort meant to stave off something worse, potentially acceptable only if there are no other options, and even then something to be avoided if possible. When I’ve discussed these experiences with trans people, they’ve often correctly raised the concern that treatment with lamotrigine might be seen in this light and construed as some kind of viable substitute for transitioning. As someone who has experienced the difference: This is not a substitute for transitioning.
When on hormones, my depersonalization and derealization stay at around a 0 or 1 out of 10, almost always unnoticeable and typically only worsening in times of stress or in unfamiliar environments. Without hormones, my symptoms are a bleak and deafening 9 or 10 that swallows up anything that matters in this world. On lamotrigine without hormones, this held steady at around a 3 or 4. Some of the more prominent symptoms were kept in check most of the time, but it was still disconcerting and very far from optimal, with intermittent attacks where it would become suddenly worse. For me, this is not remotely an equal to estrogen.
Furthermore, even as lamotrigine held off a large part of my depersonalization, it was not a substitute for the beneficial effects of estrogen on anxiety and mood overall. I began to feel “on edge” and my sleep was repeatedly disrupted by panic attacks of no clear origin. Finally, it’s certainly not a substitute for HRT in treating gender dysphoria itself: my skin felt rougher, I had outbreaks of pimples, and my body odor took on a scent that some trans women have artfully termed “boy stink”. Absolutely none of this is something I would be willing to put up with in the long term.
There are also plenty of possible cases where lamotrigine could be used for trans people and would not conflict with or invalidate affirming treatment at all:
- Trans people who don’t want to take HRT but still seek relief from their depersonalization symptoms
- Trans people who continue to experience prominent symptoms of depersonalization while on HRT
- Trans people who have to go off their hormones in order to conceive or bank sperm
- Trans people who can’t take HRT or have had to discontinue their HRT for medical reasons
- Trans people who are required to discontinue HRT for several weeks prior to gender-affirming surgeries
- Trans people who lack access to prescribers who will provide HRT
- Trans people who live in jurisdictions where being trans is unsafe or illegal and affirming care is unavailable
As for me, I feel confident in saying that if this treatment had been available to me in the many years before I discovered my gender and chose to transition, I could have been spared a great deal of the suffering that deeply traumatized me and still defines my life. If there is a viable treatment that can help to ameliorate this unique pain that many of us are all too familiar with, that’s another arrow in our quiver. And I think we deserve to have as many as possible. ■
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