Real Experiences with Lamotrigine Combination Therapy

My experience with lamotrigine has been only positive. I have been on it for over two years, and it is the only psych med that actually worked for me. I continue to take a low dose of 50mg for depression, without any other psychiatric medications. Recently, I also discovered that I have chronic malabsorption, which causes chronic iron deficiency anemia alongside low B12 and low vitamin D. I ended up getting an iron infusion that raised my ferritin from 29 ug/l to over 60 ug/l, and my family doctor told me to keep taking an iron supplement every other day, plus B12 and vitamin D a few times a week.

Since lamotrigine is primarily a mood stabilizer for bipolar disorder, using it for unipolar depression is an off-label route. While taking it alone has worked well for me, many people end up needing a second psychiatric medication.

I analyzed 541 Reddit posts where people reported that lamotrigine helped their unipolar depression. Out of those, 141 mentioned taking a co-medication. However, 78 of those posts only mentioned the second drug in a negative or unclear light – either it was started recently with no verdict yet, it was unclear, or it explicitly made things worse. That leaves 63 posts where the person explicitly credited at least one co-medication with helping them.

Lamotrigine + Wellbutrin
The single most common pairing mentioned was lamotrigine + bupropion (Wellbutrin), showing up in 9 of those combination-therapy stories. I am not posting the full stories here as some of them are quite long, but here are the main relevant points from those stories:

Lamotrigine + SSRI
After quetiapine, the next most common positive pairings were lamotrigine + fluoxetine (Prozac) with 3 posts, and lamotrigine + sertraline (Zoloft) with another 3 posts. Both of these are SSRIs.

Rumination and the life I “should” have had

I have been thinking lately about how the brain creates continuous narratives about our past and future, stories about what should have happened and what is supposed to happen next. These narratives set expectations, but in depression, this tendency often turns into rumination. The APA Monitor describes rumination as part of a self-reinforcing cycle where negative thinking deepens a low mood, which in turn fuels more negative thinking (https://www.apa.org/monitor/nov05/cycle).

A depressed brain can easily fixate on how life “should” have gone, how it did not, and why the current outcomes now seem bad. Instead of moving toward problem-solving, the mind circles the same themes over and over. What interests me even more, though, is not just the repetition of these thoughts, but the underlying assumption behind them.

The content of those thoughts does not always make logical sense. Since I do not believe in higher powers or destinies, I don’t believe any human is born to be anything specific; people just happen to be born. The idea that my life “should” have followed a particular path isn’t grounded in any law of physics or biology. It is simply the brain constructing a narrative and then treating that narrative as if it were objective truth.

Psychologists also point out that rumination is less about the negative content and more about a repetitive style of thinking. It is the act of recycling thoughts without moving toward action. It feels like analysis, but it isn’t actually solving anything.

https://www.psychologytoday.com/ca/blog/triggered/201912/when-depression-meets-ocd-understanding-rumination

I have definitely been prone to forming these rigid narratives about how things “should” be for me. Until my early twenties, I carried a constant narrative that I was an “upcoming writer,” even though I only really wrote in a diary, some LiveJournal posts, and a few short stories. While I wasn’t depressed at the time, my brain was already getting stuck in specific stories. During much of my undergrad, for instance, I told myself that finance courses were boring and “not for me.” I convinced myself I wasn’t like the students destined for corporate jobs; my passion was writing, and I just needed to get my degree over with so I could finally focus on it.

After undergrad, when I had to get a job to pay rent and still hadn’t started a book, my narrative simply shifted. I decided I would be a professor because 9-to-5 jobs weren’t for me. I told myself I was smarter than that and was going to do something more impactful, like research, even though I had always been an average student. Consequently, when I couldn’t complete my PhD because I didn’t actually have any thesis ideas, I started to feel like I was disappearing.

I have written before about having autoimmune encephalitis in my mid-twenties, which definitely contributed to my depression. However, I also think a lack of cognitive behavioral therapy skills and the persistence of these rigid narratives played a role in that feeling of disappearing.

The CBT advice for dealing with this is often quite simple: interrupt the loop. The American Psychiatric Association suggests deliberately breaking the cycle through physical activity or by breaking problems into small, actionable steps. The goal is to turn abstract thinking into concrete movement (https://www.psychiatry.org/news-room/apa-blogs/rumination-a-cycle-of-negative-thinking).

I’ve noticed that these narratives create a direct conflict in my brain. One part of me insists that I failed because I didn’t become a professor, writer, economist, or doctor. I just have a regular 9-to-5 job. But at the same time, I realize I don’t actually want to work long hours or deal with high-level work stress. I enjoy hiking or cross-country skiing during my lunch breaks. I like swimming in an outdoor pool at noon on a weekday. I actually prefer lower responsibility and more free time.

There is a clear tension here: one part of my brain insists I should have been something extraordinary, while another part actually prefers a calm and ordinary life. Perhaps the skill isn’t to eliminate these narratives entirely, but to simply notice that they are stories, not laws of nature.