Reddit is a great source of information containing posts about depression treatments, supplements, diets, and nootropics. Since only specific psychotropic medications are prescribed for depression and anxiety and go through clinical trials with large enough sample sizes, for others we only have anecdotal stories from online users. I can’t perform a randomized controlled trial for green tea matcha’s possible antidepressant qualities without a lab and a grant, but we can use natural language processing to at least summarize some information based on user’s reviews of various supplements.
Below are top ngrams (unigrams, bigrams, and trigrams), based on the text from posts and comments from the depressionregimens subreddit. For this data sample only the top posts and top comments were selected. Posts or comments of word length less than three were removed. The data sample consisted of 1,458 documents (each document being a post of a comment). Data cleaning included removing html tags, expanding common contractions, removing newlines and tabs, removing urls, spelling correction (python’s SymSpell), lemmatization, lowercasing, and removing special characters and extra whitespaces. A list of names that included supplements, neurotransmitters, antidepressants, and other psychotropic medications, was created and excluded from spell check, in order to avoid changing these words (for example we don’t want to change ‘ssris’ to ‘saris’, which is what the SymSpell library was doing).
The ngrams were selected such that each ngram appears in less than 70% of the documents. Absolute and relative frequencies were calculated for each ngram. The top unigrams were as follows: get, depression, feel, go, try, thing, day, work, take, make, help, time, good, one, also.
Examples of posts/comments (original text, before data cleaning) with these top unigrams:
I am going to write this down somewhere.. and then take steps to figure out how to work them all away…I do all of these.. The social media/phone time one is the hardest for me. Maybe I’ll invest in one of those timer boxes I can throw it into. Then I’ll have no choice but to be productive and hopefully more creative. My depression always gets so bad around shark week. So hard to sleep and stay asleep. So for a few days out of the month I really don’t have a choice on that one. But it can easily spiral out of control if I’m not putting in constant effort. I am very tired but also wired feeling right now.
Being diagnosed with terminal cancer you will probably die. There are a lot alternatives to treat depression, regular cardio, different therapy methods, drugs and non-drugs treatments (rTMS, ECT etc.), and if you try everything and nothing work, you can survive until a new treatment arrives. Anyway, I read a lot people refusing antidepressant because “side effects”, so I think depression isn’t so bad for them, Because think about this: a guy/girl with terminal cancer will take any treatment on market if he/she can pay, ignoring side effects because she/he want live.
Thanks for sharing – having a particular difficult day today, it’s nice to hear a success story. I’ve researched this in my area, seems quite expensive, hence I’ve not been able to try it, though I’ve wanted to. Has it been that way for you?
Also, I’ve been told several times that those dependent on benzodiazepine medications do not respond as well (or at all) to IV ketamine, so those must be discontinued before infusions. During the 25 years of so many medicines, did you take benzodiazepines at all?
> But I’m stable. I actually know what happiness feels like. And most importantly, I’m alive.
Amazing to read! Thanks again for a real success story. I wish you the very best of continued health and happiness!
The top bigrams were as follows: side effect, every day, make feel, feel well, mental health, long term, year ago, depression anxiety, treatment resistant, treat depression. Below are some post/comment examples with the top bigrams:
Ketamine crushed rumination that I had been trapped in my whole life. Repeating intrusive negative thoughts of the past. Wiping out the massive, crippling fog of depression was wonderful but that side effect of stopping those negative thoughts was life altering. Glad we found it, even if I am approaching 50 years old.
I broke the sleep/ work depression routine by walking at first. Hour long walks at a quick pace, fast enough that it was challenging. Did that for a month or so. I actually managed to lose 5 pounds that first month so there was a nice bonus. It got me thinking my diet needed improving so I cut out fast food as much as I could and starting making lean meals for myself as much as I could. After another month, that “swollen” feeling you describe started to lessen. So two months in, down 12 pounds, I joined a gym but never touched free weight. Just cardio. It was more intense than walking and took a bit to adjust to the new pace. I left a sweaty mess every day. Did that for about 6 months. I was in decent shape. Down about 30 pounds overall. My brain felt clearer and I had more energy. It’s important to isolate the depression, give it less ammunition to use against you. **One way to do that is to not let it use your body against you.**
After trying over 15 different medications and several rounds of Ketamine IV infusions for my severe treatment-resistant depression, I was about to give up. On everything. I saw a couple posts on this group about how some people have had success with Trintellix, so in a last ditch effort in desperation, I talked to my doctor and started it about a month ago. Within a week my life had changed. The existential dread had lifted. I became interested in things again. For the first time since I can remember I wasn’t exhausted in the middle of the day. I had energy. I smiled. I felt some joy. And it has continued and it’s only been getting better. I think what really happened was that it gave me the jumpstart I needed to start a small exercise regimen and care about eating right, which made me feel even better. It did make me extremely nauseous for the first week but it helped to take it with food and then the side effect went away. Thank you to those who shared their experience and I hope maybe this helps someone as well. There is hope, just keep swimming.
The top trigrams were as follows: treatment resistant depression, major depressive disorder, sexual side effect, make feel good, make feel well, mental health issue, get new psychiatrist, severe treatment resistant, stay bed day, time every day. Below are some post/comment examples with the top trigrams:
Speaking from personal experience, the only type of medication that improved my symptoms were the MAOIs.
These are more old school, and more dangerous. But many have said they are a life saver for treatment resistant depression.
Contrary to conventional antidepressants, they don’t just boost serotonin/dopamine/norepinephrine – they also boost a range of neurochemicals such as trace amines like b-phenylethylamine, which themselves promote the release of neurotransmitters.
MAOIs are so powerful that you have to watch your diet and abstain from a whole range of other drugs.
The sexual side effects, tiredness, agitation and added anxiety all pushed me away from SSRIs. I did like being numb though. Except in the genital area… that created a huge depression in itself. Been off for months now.
Wait, you’ve told your psychiatrist about this, and they didn’t do anything? If so, you need to get a new psychiatrist.
I don’t want to make a diagnosis but have you considered the possibility that you might have bipolar depression? SSRIs can cause hypomania and are considered dangerous for patients with BP. That’s why I said a new doctor is in order. Thankfully, there are antidepressants that don’t cause this reaction, as well as mood stabilizers to prevent the crash you talked about.
Lastly, it sounds like you’re also dealing with a lot of stuff from your past. Are you seeing a therapist right now? They can help you work through those memories and deal with the intense emotions you get in a way that makes your life better and not worse.
We can even obtain some four grams: severe treatment resistant depression, job really well respected, amazing job really well, previous alcoholism push man, girl ever meet amazing.
Post/comment examples below. I really enjoyed reading the first story as I have not heard previously about diphenidine and it was interesting to find out about this substance and the user’s experience.
I meant to post about this sooner and regret not doing so, but hopefully it’s helpful to some and doesn’t break any rules I’m not aware of. I know this subreddit has a focus on safe and researched substances and realise that this is an entirely anecdotal report concerning a not very well-researched substance, but I hope it’s not a problem and think it’s valuable information for someone suffering from severe treatment-resistant depression.
Back in 2015, my husband (23 years old, weight 62 kg) had been feeling severely depressed with suicidal ideation for several weeks. It got to the point where I felt I had to either call in the mental-health people (whom I knew from previous experience to be quite inept) or take a drastic pharmacological measure.
I had read about the rapid and long-lasting antidepressant responses to NMDA-receptor antagonists like ketamine before, and acquired samples of two of ones that are orally active (diphenidine, as well as methoxphenidine, also known as MXP).
NMDA-receptor antagonists appear to produce their antidepressant effects by causing an increase in levels of brain-derived neurotrophic factor (BDNF) that can last for days or weeks following a single dose, whereas the most commonly used antidepressants produce a similar increase in BDNF only after weeks of continuous administration, while also causing many side effects.
Neither of us had ever used any kind of dissociative before, just classical psychedelics, stimulants and marijuana (while visiting a country where that’s legal), so, given his fragile psychological state, I wanted to start with a very careful small dose.
Looking at people’s comments on diphenidine and methoxphenidine online, I couldn’t find anything related to attempts at therapeutic use, nor a clear consensus on a preference for either one. I ended up looking up dosage information for diphenidine, and read that 50 mg was considered a threshold dose.
I first gave him 10 mg of diphenidine in a capsule the first time to be safe; as expected, that had no noticeable effects.
2 hours later I gave him another 20 mg, which still led to no noticeable effects, except possibly a very mild numbing of the senses.
Another 2 hours later I gave him another 30 mg. About 15-20 minutes after this, he reported that he was maybe starting to feel slight derealisation effects.
Until this point he had been playing Skyrim to try to take his mind off his bad feelings; he really wasn’t expecting this to work at all, but he trusted my knowledge of drugs and figured it couldn’t hurt to at least try it.
When the effects started to set in, I told him I’d read that some people like to lie in bed while on drugs like this, and he did so.
His mood didn’t seem much changed, but after lying in bed for a bit, he started talking to me about some of the things that had been bothering him. He sounded sad while talking about these things, but I tried to steer the conversation toward solutions that we could decide on that would make life more satisfying for him.
After chatting for a bit, he seemed to be getting somewhat amused by the effects of the drug; he said things he touched felt very different, and everything felt strange, but not in a bad way.
As we talked some more about his issues, his mood slowly lifted (I think this was around the peak of the experience, which lasted a good portion of the day), and suddenly he got a little smile on his face and said that he was starting to feel… happy. Of course this made me really happy.
He started saying how things felt “solid”, “thick”, “real” and “tangible”, in contrast not only to the way things normally felt but also to the way things had been feeling to him particularly during his weeks of feeling depressed. He related this more solid experience of physical objects to an improved outlook on life.
Interestingly, despite diphenidine being a dissociative drug, it appears to have triggered a reversal of symptoms of dissociation/derealisation that accompanied his depression prior to the treatment.
He said he kind of felt similar to being very drunk, I assume in relation to physical coordination.
He also reported feeling significant time dilation, “in a good way”. (He contrasted this with the time dilation he feels on classical psychedelics, which he tends to find uncomfortable or scary, as though a moment will last forever.)
He then seemed to get a big urge to get up and do lots of tidying and cleaning around our apartment, and he started doing so; I helped. We folded clothes, organised the living room, cleaned the kitchen, stuff like that.
He said that he felt like everything was being put in its place again, both physically and mentally; that his mind was tidy again.
Around this point, he seemed to have this constant feeling of awe at how content he was feeling with life. This wasn’t some kind of unnatural euphoria, just a very strong feeling of contentness, which had obviously been missing from his life for a long time.
Several times, he seemed to have tears in his eyes in awe of how at peace he felt with the world.
Seeing someone emerge from such a deep depression in a matter of hours was really beautiful.
Several times, he hugged me and told me how grateful he was to me for finding this drug for him.
I imagine the talking was therapeutic (which could also have happened without the drug, but was, I imagine, stimulated by it), but mainly I’m certain the drug caused a biochemical change in his brain that has reversed, at least for a time, the natural process that makes him prone to feeling depressed all the time.
The dissociative effects did not fully diminish until he slept; he had no trouble sleeping.
Two days later I asked him how he was feeling, and he smiled and said he was feeling just fine.
More than two weeks later, his depression still had not returned.
This was a massive change. It seems diphenidine can be a powerful medicine. 🙂
He later took it again, this time at 60 mg in one go (about 1 mg/kg), and he felt that this reinforced the antidepressant effects, and that repeating this every few weeks would probably keep him happy in the long term, and the interval we settled on was one dose every 12 days (taken right after waking up to avoid impacting sleep the next night).
In the 5 years that followed, he continued to benefit enormously from diphenidine, and he continues to take it every 12 days. Although after a while there was some tolerance and it no longer led to complete resolution of symptoms, he continues to find it well worth it. The dosage has slowly had to be raised from 60 mg 5 years ago to around 125 mg currently (by about 16% per year) to maintain a similar level of acute effects. We’ve also discovered that adding 200-250 mg of black pepper (which contains piperine, a bioavailability enhancer) in the same capsule makes it a lot more potent.
I wonder how many people commit suicide every year who could have been saved by something like this… granted not a lot of research has been done on using NMDA-receptor antagonists for this indication and there may be unknown risks, but when someone has severe depression that cannot be managed effectively with approved medication or is even ready to commit suicide, I think there’s a very strong case to be made that something like diphenidine should be tried, at least as a last resort.
Of course it’s important to be careful not to use substances like this too frequently, since they have been known to lead to addiction with very frequent use (although, having tried it myself, I personally don’t see how the effects of this particular one could be considered enjoyable by most people). But for my husband, there has been no addiction or any other ill effect over 5 years of regular use.
He is now also taking the MAOI tranylcypromine (Parnate); based on the limited research that has been done, and our experience, there is no interaction between it and diphenidine, although there probably would be with various other dissociatives.
Another example with four gram:
We’ve all been there brother. I lost the best girl I’ve ever met, an amazing job at a really well respected business and a lot of good friends through my previous alcoholism. You just have to push through it man. Even making the tiniest changes in your life will snowball into a world of difference, life always finds a way of working itself out.
Notes of a Neuropsychiatry Amateur 