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:
Story 1 (note that this person has only been on this combination for 3 days)
Day three of consistently taking my lamotrigine/wellbutrin xl combo. here’s what i’ve noticed so far:
– Reduced appetite/food noise. I have always had a problem in which I binge/restrict which has resulted in fluctuating weight my entire life. I’m not thinking about food as much and not craving it as much, which is awesome for me.
– Reduced chronic emptiness. For about a month I’ve been in a depressive episode in which i’ve had little to no interest in anything (hobbies, music artists, etc). I find that emptiness has more transformed to a general numbness, and more willingness to get back into things I enjoy doing.
Story 2
I started lamictal two weeks ago and recently bumped up from 25mg to 50mg and things are going so much better for me. Before this I was doom cycling and experiencing panic attacks. I couldn’t really deal with life at the moment. Even during a stressful move and an incoming baby … I feel like I’m handling everything instead of just worrying and freezing over it.
I also started with 150mg xl wellbutrin which i’ve been on in the past. Although the wellbutrin helps – alone it motivated me but I would just get irritable and angry instead of depressed. I feel like the lamictal really smooths out the rough parts of wellburtin.
Story 3
I have been using lamictal for depression and anxiety (combined with wellbutrin) since 2021. It has helped my life so much. I was able to confidently make decisions to create the life I want.
Story 4
Wellbutrin + Lamictal
I recently started taking my full dose of Lamictal after a month of slowly upping the dosage. It’s been about two weeks on the full dosage, and I feel a little weird. As if I had taken a low dose of Xanax. I feel very relaxed, but I can still function just fine. Plus my depression and anxiety almost non-existent at this point. The only negative seems to be some brain fog.
Lamotrigine + Seroquel
The second most common positive combination was lamotrigine + quetiapine (Seroquel), coming up in 4 of the 63 posts where people credited a second medication with actually helping.
Story 1
After months of being extremely suicidal on various drugs, things drastically changed on the day I dropped all the SSRIs (on my own), was put on Seroquel (100mg, then 200mg), and the day I initiated Lamotrigine – which has been the key player – on my own as well (titrated extremely carefully, no rash).
The medical landscape in my country is really awful, I had to navigate all this alone to save my life, and I’ve successfully done that – 1 month without any symptoms.
Story 2
I’ve been on Lamotrigine and Seroquel for 3 months and I couldn’t be happier. I can’t believe how life changing these medications have been for me. I have zero depressive episodes anymore, I’m not obsessively thinking about certain things, my whole demeanor is very chill. I no longer have PMDD.
Doses – lamotrigine 150mg morning, Seroquel 150mg night.
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.
– I’m on fluoxetine and lamotrigine which helped me get to a state of only moderate to mild depression.
– I do feel quite better on it, and taking it off label since August (100mg) for depression along with prozac, after going through dozens of other meds.
– I am now on Zoloft 150mg and lamictal 100mg, both of which have finally helped me to control my emotions greatly. I have felt happier than I ever have before and I just feel fantastic!
Lamotrigine + SNRI
There were also 3 posts about lamotrigine + Effexor (venlafaxine), which is an SNRI medication.
– Lamictal is amazing. I don’t know about the negative reviews but I believe every case is different. I started with 25 twice a day and now on 50 twice a day. Honestly, it has changed my life for the past two months. I feel confident emotionally stable and I don’t know how and I don’t know how but it reduced my anxiety. I do take effexor as, I believe the combination worked well for me. I managed to travel by myself to places that would heighten my anxiety, and I even took the subway which I absolutely despise.
Mixed post with some positives, but also some increased anxiety:
– Im on day 10, 200mg (lamotrigine) with venlafaxine 225mg, not bipolar, no mania/
Im deff feeling better but i still have anxiety, sometimes im nervous but then im good. Then I’m anxious.
Notes of a Neuropsychiatry Amateur 