TLDR: Expect the process to take a long time and to cycle through many drugs. Avoid MAOIs with Vyvanse (with few exceptions), try to vary your drug class instead of taking multiples of very similar drugs until you start to find something that works, then focus on finding one within the class that is most effective and has the least side effects that are most tolerable. A little bit of reading goes a long way toward understanding what you are taking before you start taking it. Drugs.com is a good place to start unless you like scientific literature. Seek out therapy during this process because it’s discouraging. Check out dialectical behavioral therapy.

The long-winded, ranty version:

Don’t expect a miracle with the SSRIs or anything similar. They feel pretty hand-wavy compared to most meds due to the nature of psychological symptom monitoring and how life can interfere with this. It is no exaggeration to say this is a game of guess and check. This process takes forever and sucks.

You may be offered a pharmacogenetics test to help guide this process. Get it if you want it and if it won’t cost you a bunch, but quite frankly, the diagnostic use of these tests is fairly immature and doesn’t seem particularly useful at the current time. I suspect it will improve in the future, but it’s a waste of money currently IMO and I’m someone who thinks pharmacogenetics are cool.

There are a lot of SSRIs, SNRIs and SSBULLSHITS out there. I suggest that while playing the guess and check game, you try to spread the focus around to drugs that are dissimilar. Different classes, ones that act on mechanisms that aRe relatively different rather than ones that are similar. Providers like to go down the cu king list and be like “sertealine, venlafaxine, fluoxitine, Trintellix, escitalopram, mirteazapine, blah blah blah” and they are all relatively similar.

Try an SSRI, try bupropion XR, try a mood stabilizer like lamotrigine (if you do this one, you need to titrate up slowly as it can cause severe allergic reactions if you jump in quickly), then try a low dose of lithium (<=400mg). This is in no particular order. If you are willing, try a tricyclic antidepressant (old-school, normally not used anymore because they make you drowsy. Low doses of amitriptyline are fucking great for sleep granted that you never ever ever miss a dose and you ignore the first week on and first week off).

There are MAO inhibitors too, but this is one I would suggest avoiding and you will likely see suggestions for that everywhere. Aside from everyone needing a little Mao in their lives, MAO inhibitors tend to require some dietary restrictions and lead to heart and blood pressure problems when combined with amphetamines (Adderall, Vyvanse). It is possible the combination could work with the addition of a blood pressure medication, but I’d try it as a last resort. Too many things to worry about, too many life changes, additional medications and higher risk.

I’m diagnosed with ADHD, MDD, and experience seasonal affect. These have been persistent for over 20 years. The only medication that has ever helped with symptoms of either is amphetamines and I prefer lisdexamfetamine (Vyvanse) because it has all the benefits of Adderall with none of the side effects. The only downside is if your supply gets cut off suddenly, and I find that I have 2 weeks of withdrawal symptoms with the majority taking place from days 2 to 4 after my last dose. There’s a 3-5 day period where I have side effects while getting back on it with the majority of side effects (increased resting heart rate in particular) take place over day 1 and 2 of being back on my dose. For reference, I use 50-70 mg, the only difference being how long the effects last.

I’ve tried just about every SSRI, SNRI, and similar. The only one that I can remember not trying is vilazodone. I’ve taken mood stabilizers, bupropion, tricyclics, weed, and booze. None of these helped with depression. I tried high doses of vitamin D despite this being the biggest fucking cop-out a provider can give for any type of persistent depression. If you encounter this pointedly ask them if they really think a change in vitamin D is going to have a significant effect on your depression. A small one, some relief for seasonal affect, I can give them those, but if they refuse to try something else until you go with a high dose of vitamin D, they aren’t serious about your treatment. I know there is scientific evidence for it, but I’ve always found that the providers who lean into this early aren’t team players and should be dropped for a different provider quickly.

I haven’t tried lithium or MAOIs at this time and am currently considering just coping with being depressed constantly again while not taking drugs that do nothing for me. I’ll let my therapist be the voice of reason.

My work is in pharmaceutical R&D, but not specifically with antidepressants. The field I’m in is small enough that I prefer not to associate it with my account, but my background gives me enough confidence to inform myself on these and similar drugs through the literature. Some of what I deal with is drug interactions and delivery, so this is close enough to home.

I find that despite working with these drugs daily, most medical providers do not look into this with much depth, so it’s pretty easy to get ahead of their specific knowledge on drugs just by reading a little. One example is the interaction between amphetamines and some antidepressants that you mentioned. This isn’t meant to disparage medical workers, there’s just a shit-ton of drugs out there and they need to cover a wide field of knowledge.

My journey may not be very inspiring, perhaps because it’s not over, but you should understand that searching for an effective antidepressant is a roll of the dice and can take a lot of time and frustration unless you get lucky and find one that works for you quickly. It can take years and you may not find any relief this season, so be patient and seek additional relief such as therapy. I know cognitive behavior therapy is in vogue, but have you heard of dialectical behavioral therapy? It includes some of the CBT strategies, but it’s similar to dialectical philosophy, which us Marxists drool over…give it a try and good luck!