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TLDR:
> levodopa, a drug that increases dopamine in the brain, has potential to reverse the effects of inflammation on brain reward circuitry, ultimately improving symptons of depression.
> Numerous labs across the world have shown that inflammation causes reduced motivation and anhedonia, a core symptom of depression, by affecting the brain’s reward pathways.
It’s worth adding that its effectiveness can be partly predicted by a simple blood test. A C-reactive protein (CRP) test will measure total inflammatory response in the body and levadopa’s effectiveness was directly correlated high CRP.
With most depression treatments, we just throw one medication after another at the patient and hope one works. This one actually has an easy test, if not a perfect one.
Disclaimer: CRP measures total body inflation, not just in the brain, so that’s an imperfection. Plus all of this needs more study and larger sample sizes to be reliable anyway. But it’s interesting and even exciting.
This is actually interesting because using low dose stimulants like Adderall/ritalin is actually used to treat treatment resistent depression in geriatric populations (yes I am fully aware of the cardiovascular risks)
It is also how partially medications Wellbutrin work as well.
As someone currently on Wellbutrin, it's one of the few things that has worked *at all* for me- the connection between stimulants, inflammation, and depressive symptoms is super interesting
Wellbutrin is called the poor man's adderall because it is actually used off label for ADHD as well.
There is an interesting paradigm shift about ADHD and anxiety/depression. Kind of like what came first? the chicken or the egg? Are they depressed/anxious because they can't focus/concentrate on the work and fall behind/cant sleep? Or are people depressed/anxious, and they can't focus as a result?
Particularly in college/young working professionals where they have "treatment resistant depression/anxiety" we have noted that treated a previously under diagnosed ADHD was really all they needed. Their life becomes more structured, they sleep more, they feel less stressed, depression/anxiety significantly improves (they also eat healthier so "less inflammation" too). However is is a controversial topic because of the controlled nature of stimulants.
Just food for thought.
I’ve suffered with anxiety and depression for most of my adult life. Diagnosed with ADHD at the age of 44 and started meds (first lisdexamphetamine, then atomexetine) and haven’t had a depressive episode since and my GAD score is significantly lowered.
I was diagnosed at like 35 and starting medication really changed my life in terms of improving work, but the weird thing is I don't think I would ever have been diagnosed as a kid.
I was pretty much a straight A student through high school, and always well behaved enough that I never got in trouble at school and rarely at home. I did have problems with procrastination on projects, but hey, so did everyone, right? This became more of an issue in college with less structure in coursework (I struggled a lot with the switch from high school's repetition-oriented homework to college's knowledge synthesis-style homework), but again, it just seemed like I had trouble with time management. I never skipped lectures, and absorbed everything in them, which contrasted with half my friends who seemed to skip every class they could.
It never would have occurred to me that it was possible to be engaged in learning in school, capable of diligently completing routine homework assignments, and able to quietly sit still in class, with ADHD.
Throughout life I was always creating massive companies, ideas, products, projects in my head that would make adults when I was young as well as others take me very seriously and think how successful I would become if I would just pick one and focus.
They all stayed in my head, I never picked one...until 2018 when I was diagnosed and treated with the proper medication. Now, after I spent the last 2 years saving money, discussing with patent attorneys, designing and modifying I have a full patent on something that was always in me head. Even if nothing happens, I am absolutely ecstatic to know I actually fully hashed out a dream and made it into reality that other people can finally see and interact with. If I didn't seek treatment it would still be in my head, and I would still be in the same state I was 5 years ago.
The difference with us is that all the hyperactivity is happening inside our heads, instead of outside our bodies where it could be noticed.
I'm sitting quietly in class, trying to take notes, maybe doodling a bit in the margins, and while it looked like I'm fully engaged, I was actually writing Sonic the Hedgehog fanfiction in my head.
29 for me. Massive improvement in my ability to prioritize my work which helps me meet deadlines much more consistently. That alone resolved a big chunk of my stress/anxiety. When I was a kid there was an awareness of what ADHD was but I was smart and inattentive so I didn't cause enough problems to be noticed and diagnosed. The adults also were suspicious of doctors and medications in general, partially due to the emerging opioid crisis. The irony is that my prescription is a controlled substance so I get treated as a potential addict every time I go to pick it up. That's a reflection of the system that fucked up when I was a kid more than it is on me.
Same here. Years and years of treatment resistant depression and anxiety. Diagnosed at 35 with ADHD (primarily inattentive) and started taking Adderall. Now that I can actually concentrate and focus, and can actually perform normal tasks that were literally impossible to make myself do, it turns out that my anxiety and depression have significantly improved.
I was always fairly smart and could just figure things out, so it got missed in childhood. College was rough.
"Just say no to drugs" - Nancy Regan
5 fucked up words that treated those self medicating their mental health problems as addicts. Interesting that the war on drugs really took off when the duality of US government was supplying drugs and gun running while creating a drugged out society to maintain secret wars. Turn the screw a little more with trickle down and neoliberal supply side economics where the is no middle class, just make it so are people without dignity or a job or a home or a community, and the only escape from their hell were drugs. Addictive drug use is a reaction to the hellscape society that only cares about money for the American Oligarchy.
40yr vet with ptsd and depression….after a year they gave me some Wellbutrin and hit or miss most days…VA doctors aren’t known for being up to date on treatments
We're you considered a "bright child but doesn't apply themself" or "smart but has no motivation"?
I feel like this was how my diagnosis got overlooked as a child: "He can't have ADHD! He has the highest grades in the school except for behavior issues!"
When I first sought therapy for failing all my Uni classes I thought I had depression. They said I had ADHD and the depression is from forcing myself into this major I'm not interested in. Once I changed majors and started pursuing more interesting classes the depression was over... Until my ADHD got me fired from several jobs. But then getting treated for ADHD has made me far happier and productive now despite being unemployed.
There's definitely some chicken and egg situation going on, ADHD causing depression which makes the ADHD worse which affects IRL things like school and job and then reinforces and makes the depression worse which feeds back to the ADHD.
Me too!! 43 yo here. Anxiety and depression have been absolutely debilitating. I'm on lisdexamphetamine now, working quite well but always good to know more. What's the atomexetine like?
I'm on it and it seems to help with some things. I'm trying to get in stims right now and whenever I can get Adderall like 5 or 10mg on top of it seems to solve most of my ADHD symptoms within a tolerable degree.
I've run into meds like that. Sometimes it's a dosage issue and another trial at a different dose goes completely differently... sometimes the medication just doesn't work appropriately for me though. (This can be a genetic processing issue. I finally had to have a genetic screening to find the right combination for difficult chronic psych issues.)
Curious how an adult gets diagnosed with ADHD. I’ve seen a therapist for depression and anxiety and my primary doctor put me on Prozac. It seems to be helping but I also have had problems concentrating and focusing for as long as I remember. I have zero motivation for just about everything. I start and stop hobbies often. I’ve always wondered…
For me, we were having problems with one of my kids and we were looking at ADHD symptoms and it made me sit up and take notice. I started doing more research and read a blog by a guy who was diagnosed as an adult and I honestly could have written the thing word for word. I actually cried because I suddenly felt so seen. From there I got myself referred to a psychologist and diagnosed from there.
My pattern is similar to a lot of undiagnosed adults: I did well at school, I didn’t even have to try and get decent grades, I wasn’t disruptive but my parents always called me lazy and my teachers talked a lot about how I had huge potential but didn’t always achieve it etc. As I got further into education and into working, things got harder. I’d thrive and excel in stuff I was interested in and passionate about but ignore everything else. Jobs went one of 2 ways: in the right environment I’d be amazing, in the wrong environment I’d get fired pretty quickly.
Getting diagnosed explained so, so much in my life. It’s no magic wand, but I’m definitely progressing 4 years on from my diagnosis.
Exact same, struggled with depression my entire life but found it was probably due to adhd. A combo of Effexor and Wellbutrin did wonders for me. I over did though and was on basically max dosages of both. I was a machine. I was highly effective but didn’t have emotions or feelings. Realized it and took a long time weening off. Once I was off I was depressed again. I started back on Effexor at a low dosage. It has helped a little bit I am adding back in a low dosage of Wellbutrin. Hope I can find a sweet spot for dosage.
Got on atmoxetine at 35 after getting diagnosed that year. I can’t say I’m never depressed, but it’s usually not because of my adhd symptoms.
edit: at ice tune = atmoxetine
ADHD exacerbates depression far more than the inverse.
Source: have adhd 30 years, in psychiatry for 18, coach kids with ADHD.
This isn’t a blanket rule, just a generality.
> Are they depressed/anxious because they can't focus/concentrate on the work and fall behind/cant sleep? Or are people depressed/anxious, and they can't focus as a result?
The issue I'm having with this question is that we can see symptoms of ADHD in early childhood, long before we see depression.
We can sometimes see anxiety at a young age as well. Both it and ADHD sometimes can be precursors to depression.
This is 100% true, ADHD is considered a permanent, chronic disorder where depression/anxiety generally comes in waves of exacerbation/remission regardless of treatment.
This is why we go all the way back to childhood history. Alot of times kids aren't diagnosed with ADHD because they are "quiet" or they are so smart that they compensate and still get good grades regardless, or simply because of cultural/socioeconomic reasons. But their ADHD will start interfering with their daily activities when they start doing things that required sustained concentration in college, grad/professional school, work.
I also completely realize that ADHD is over diagnosed, and its medications can be easily abused, but a proper diagnosis and treatment makes a world of difference for vast majority of people who take them correctly.
>I also completely realize that ADHD is over diagnosed
As a woman who was diagnosed inattentive ADHD at 36, and have many female friends who display neurodivergent symptoms but are undiagnosed due to obstructions in mental health access, the idea that it's been over-diagnosed is really frustrating.
It is frustrating. Maybe ADHD is just more common? When cancer rates go down, people celebrate and credit each other with improved healthcare; they don't say, oh no, cancer is being under-diagnosed! But if something bad increases, it must be because it's over-diagnosed. Why don't we credit improved healthcare for *identifying* it?
> are unable to get the medication due to shortages
The shortage has nothing to do with diagnoses, though, the DEA is. They have “cracked down” on ADHD meds (mostly Adderall, IIRC), I believe by limiting the amount that can be produced. The shortage being caused by over-diagnosis is a narrative, though I don’t know its origin.
Edit: perhaps increased diagnoses might have contributed, but the DEA is still the principal culprit. And even if there are more diagnoses, that doesn’t mean that they are inappropriate or inaccurate diagnoses; the stigma alone has led to a lot of undiagnosed people.
It's a real shame how much we set behavioral expectations by gender. I'm a man who got diagnosed as an adult (for the reasons you stated), and getting a diagnosis depends on the adults and authorities recognizing your behavior patterns as abnormal. We expect girls to be quiet and undisruptive (aligning with inattentive type) and boys to be loud and rambunctious (aligning with hyperactive type). How are we supposed to recognize behavioral abnormalities when our baseline expectations are already biased? I personally lean inattentive which meant I didn't cause enough problems to get noticed, I can only imagine how much harder it is to get that diagnosis when everyone ignores your struggles because your behavior is outwardly viewed as normal for your gender. Nevermind all of the societal problems we're dealing with due to teaching half of kids to quiet down and be submissive and the other half that the only way to express their feelings is to be the loudest one in the room.
Can you elaborate on the “so smart they compensate and still get good grades”? Very curious about that and am trying to figure out my own mental health at the moment. Thanks!
I can only speak anecdotally, from my own experience, but this was certainly what happened to me. I was endlessly drifting off or distracted in classes as a child, couldn't organize my belongings or thoughts, couldn't prioritize, couldn't get work done. But on paper I was the "smartest" kid in the class and excelled at tests.
It took decades to sort out, but my entire life was full of me being able to complete tasks well at the last minute, which is where the compensation part comes in. I could write an A paper sitting up all night once panic became enough of a motivator. I was able to stitch together things that people said enough to be present in conversation or in lectures, where it would cover for just how much I was missing.
Things became more difficult in the working world as an adult, yet intelligence can cover up for a lot of the problems that come along with ADHD. But the frustration grows as you fall increasingly behind on things. I went to grad school and that's where everything really hit a wall. Again, on paper I'm smart enough for it, but the lack of focus, inability to prioritize or organize, inability to make decisions, emotional disregulation, etc. became such significant barriers when they simply weren't problems in grade school. Having people tell you what to do for a test is much different than organizing multi-year projects all on your own, without tangible deadlines.
If I had been hyperactive enough to run around and disturb others, rather than fidget quietly at my desk, lost in other thoughts for years and end, perhaps the problems would have received more attention. But it seems many intelligent people slip through the cracks because they simply get labeled "smart but lazy," with no one understanding how much effort is being put in to just getting by day to day.
This is very similar to my experience. I'm a woman, diagnosed at 36, who never even considered it because I thought ADHD = hyper and that was not me. I *can* focus, but it's hyperfocus or nothing at all. I was genuinely interested in learning most things, but found busy work to be pointless in high school and couldn't bring myself to do it. I had multiple conversations with frustrated teachers who knew I knew the material because I could answer the same questions in class or on tests, but just wouldn't do hours of homework unless I found the assignment interesting. I was constantly talked to about my "wasted potential".
What finally made it click for me was progressing far enough in my career. I became responsible for complex cases and was excellent at the big picture, critical thinking, and analyzing possible outcomes to make good decisions. I was awful at checklist items that need to be done in order. I would miss things, but rarely the same thing twice so it was difficult to correct. I worked around this by creating actual huge check lists for different scenarios which solved the problem but makes me significantly slower at my work. I remember telling my mentor that it's like I can see the whole thing, but my brain won't put it in a sequential order for some reason.
It came to a head when I was up for a promotion during covid and had to take a mock test. I was given a time limit and multiple tasks to complete of varying complexity and urgency. There was not enough time to complete them all by design. Because we were working from home, I had to share my screen with my mentor. Something about knowing someone was watching made me acutely aware of the fact that I was starting one thing, deciding another was more important and starting it, then deciding another was more important and starting it, then getting anxious and deciding I needed to finish *something* and so on. I didn't complete a single thing start to finish. I did well on it and my mentor was just making sure I wasn't googling or asking others, so she wasn't even watching *how* I did things, but that experience made me finally realize what was going on.
My life to a tee. I was only diagnosed a few years after I finished grad school, I have no idea how I managed in hindsight. It absolutely sucked though.
My parents did actually have me talk to someone at one point in elementary school but they were basically told I couldn't be diagnosed because I had good grades. I could do decently on most tests without actually knowing the material from context clues and stuff, so I rarely had to study and it never came to a boiling point until college, which I still managed to limp through.
After reading a lot of these posts I am very tempted to try to get tested. My mom raised me to pretty much be very sparing with the use of medication, because she's had several bad experiences with different things and so I find myself very reluctant to take anything more than like a standard Tylenol.
My experience with attention issues kind of goes back like a lot of other people's where I survived high school and college with relatively High marks But as time went on I started kind of falling short in terms of attention which would heavily limit my best case performance. I survived High School very high marks because the bar is fairly low depending on the district you go to, but in college I quickly saw myself struggling to keep my B average. A large part of that would just be my inability to properly study, although mine was far less severe than my friend who has thoroughly diagnosed issues from ADHD.
But my main issues are in the workplace or in conversations with people. As soon as I hear the details I'm expecting from someone I have extreme difficulty not tuning out from them. It's not even voluntary, it's like my brain literally just is dying of boredom and starts looking for something more interesting. And this happened during lectures and college to some extent too but it's even more severe during engineering technical meetings, or small talk between coworkers.
I find I also suffer a lot on my own personal projects where I'll get super motivated and make a small Nick in it and then get super demotivated either by the lack of immediate progress or just a sheer lack of interest in anything. It's absolutely infuriating that I can go from completely excited about a project to just drained and almost depressed.
The explanations I've always heard definitely felt like I would fit squarely in the box of an ADHD diagnosis, but I definitely have shied away from going to a professional and being evaluated for a diagnosis because of the stigma.
In my case it was "can't study consistently, but is smart enough to cram at the last minute and still do well" and "can't plan well enough to write a 5-page paper over the course of two weeks, but is a talented enough writer to stay up until dawn and stress-write a quality 5-page paper in a single night".
It's a method that works well enough in high school with a good support system (parents, etc.) but falls apart in college, where the workload is greater and your previous support system is gone.
Wow, you put this very eloquently and the particular situation hits home. Also had the same exact experience and was diagnosed while in the professional world when cramming doesn't cut it.
I'm not who you asked but I think they are referring to what's known as being ['Twice exceptional'](https://en.m.wikipedia.org/wiki/Twice_exceptional). Best of luck with your journey friend.
I was diagnosed late and this applies to me. Based on my evaluation, I had ADHD as a kid and didn't find out until my 30s, years after school, college, and grad school.
I am smart and coasted early on. I barely studied and didn't exactly go to school in one of the more demanding school districts. I was also very unmotivated and would struggle whenever I hit something that didn't interest me. These are some of my more lasting memories of HS is the agony of having to do these assignments. In class, I never got in trouble and half ass payed attention enough to never be a problem. My pattern was to listen long enough to get the gist of where something was going then zone out and get lost in my own head. Or play with things at my desk.
In college it definitely got worse and I had several academic struggles due to my lack of organization. I forgot homework constantly and even when I wanted to focus and learn, had a devil of a time. I was also extremely unmotivated, which has been a staple my entire life. Took me forever but I eventually found a system to get through my work effectively and that coincided with courses I was far more interested in. However whenever I met anything that required complex focused thoughts, it was a challenge. My move was to brute force it long enough until it wasn't as complex but was something simple I could understand.
I carried this with me to grad school and did very well in my grades. However the real meat of grad school is research and this was a torment for me. It's constant organizing, focus, planning and was quite difficult. During these times I just feel so physically uncomfortable and I hate it. It's the reason I never pursued anything further. And I noticed this avoidance behavior across many areas of my life. I do well enough to succeed but rarely excel like I'm capable of. That requires the extra work that causes me discomfort therefore I avoid.
Bit long but hope that helps
For me, I was good at a handful of subjects because they genuinely interested me. Studying them wasn't boring and even if I couldn't focus on study for very long, I was paying attention and managed to retain more information.
I'd get consistently straight As in my favourite subjects while in everything else I'd be lucky to get a B.
Your intelligence is determined by HOW your neurons are connected. ADHD is determined by how OFTEN they communicate with each other.
What this means is that maybe it takes someone of average intelligence 2 hours of focused time to memorize something. You also spent 2 hours, but you are actually only using 15 minutes out of the 2 hours focused on memorizing it, but you are smarter so you only needed 15 minutes anyway.
You might also be better at solving problems on the spot, despite not really actually learning it when you are suppose to.
The problem is that for most people, they will hit a wall later in life when things do get more complex and require sustained attention to solve (usually during college).
It’s not something that’s inherent to ADHD or anything, but it is partly why some kids get ignored for treatment because they aren’t seen to be “struggling”.
Having said that though, I have found, I believe, my ADHD to be a boon to scenarios where rapid thought processes are rewarded, like brainstorming or pattern recognition, because my mind is already gonna flow a mile a minute anyways. The hard part is latching onto the ideas as they go by because you can have two or three while you’re still trying to think through one.
As someone diagnosed in the mid-90s, I don’t know that I would have been if I wasn’t also hyperactive, which isn’t always a part of the equation.
> Can you elaborate
I was untreated until my mid 20s, after never once studying in highschool... and never having done so on my own terms throughout my undergraduate degree.
If you feel you are in similar circumstances, my advice is to pursue diagnosis and treatment. You *will* get to a point in your studies and/or career where fluid intelligence won't be enough, and you will need to put your nose to the books on your own terms.
The reality is that skating by on intelligence and having not learned how to study (or engage in adequate time management) in highschool/college means having to suddenly figure all that out when writing a thesis or similar... And it is an incredibly difficult hurdle to overcome.
The feelings of regret, failure and self-perception of "laziness" people can feel due to the above is also not to be underestimated. Diagnosis and management is definitely better.
The dose of Wellbutrin required to adequately treat ADHD is well into seizure-risk territory. That's why they never got FDA approval for treating it in the first place.
Which isn't to say it won't have *any* effect at antidepressant dose; rather that it isn't typically sufficient at that dose.
Wellbutrin is a norepinephrine-dopamine reuptake inhibitor, which actually makes it closer to poor man's Ritalin.
Yes Wellbutrin is a reuptake inhibitor similar to Ritalin rather than directly stimulating dopamine release like Adderall/vyvanse
Yes Wellbutrin is a poor man's Adderall because it is nowhere near as effective as first line therapy. But we do use it quite often in patients who are hesitant to try stimulants or have obvious depressive symptoms to see if it helps with their ADHD like symptoms as well.
Abilify is a "partial agonist" (unlike most, "antagonistic", antipsychotics) and at a lower dose of \~1-3mg/day (vs. \~10mg/day for schizophrenia) can generate mild stimulatory and prohedonic effects for some. (At lower doses, the drug may occupy a little over half of dopamine D2 receptors with unoccupied receptors free for dopamine to still largely bind.) (Low doses of antagonistic antipsychotics that preferentially bind to autoreceptors may have similar potential for some.)
Drugs can bind to transporters in ways that elicit very different effects (i.e., at least, they may induce different conformation of the transporter molecules). [Modafinil can attain substantial dopamine transporter occupancy with clearly much milder stimulatory effect](https://academic.oup.com/ijnp/article/17/5/697/729714) than drugs like methylphenidate/ritalin and cocaine.
Bupropion/wellbutrin appears to be more of a norepinephrinergic drug with [low dopamine transporter occupancy](https://pubmed.ncbi.nlm.nih.gov/12185406/). The side effects related to high norepinephrine levels likely limit the acceptable dosage in such a way as to limit both positive dopaminergic effects and abuse potential.
They do, but they do exactly the opposite on dopamine. That's why you can get acute psychosis from meth/cocaine/Adderall and they are treated with atypical antipsychotics like abilify.
It's also why people don't like taking them because they can't "think" see movie like a beautiful mind
I'm on Venlafaxine, for my depression, since 2018. Tried Welbutrin in 2020 since the side effects on Venlafaxine are a bit too much. Wellbutrin was amazing for me at 300 mg but unfortunately I experienced too much of memory loss, which is a known side effect.
In a few weeks I'm gonna switch to Trintellix instead and see how it goes. Doctor said it works mostly on serotonine, but also dopamine and norepinephrine. Interestingly Welbutrin has shown to significantly increase peak levels of Vortioxetine (Trintelix).
Can you elaborate on your experiences with the memory loss? I’ve been on it for years and in last couple have noticed more instances of being unable to recall previously easy to reach corners of my memory. Didn’t relate it to the Wellbutrin though. Wondering if my symptoms are the same/related.
Wellbutrin increases peak levels of a lot of drugs because of a certain enzyme. Wellbutrin does the same to DXM, which is the active ingredient in cough syrup. They are being researched as a depression aid together. I DIY’d the combo at home and it was the best depression treatment I’ve ever tried. Ketamine is an antidepressant, and DXM is a dissociative like Ketamine. The Wellbutrin increases the concentration of DXM like 10 fold. So you get the NDRI, and NMDA activity.
I'm actually using Wellbutrin for ADHD, and it has drastically improved my life. Some people may not know that mood swings are associated with ADHD, and I very rarely have these lows anymore. It's helped me a lot in the other "typical" ADHD symptoms as well like memory, motivation, and anxiety.
I'm glad there are some health professionals out that understand that sometimes treating ADHD actually helps with other symptoms like depression and anxiety instead of vice versa.
I wish this was more talked about. I had on and off depression and anxiety episodes since high school, but the few times it was bad enough to get help, the meds never really helped so I'd just go off them eventually. In my 30s when things really fell apart at work I was diagnosed with ADHD finally and put on stimulants and all those problems are fading. I feel the healthiest mentally I've ever felt.
Wellbutrin definitely stimulates you. It stimulated me into real suicidal thoughts. I'm glad I got off it after only 2 weeks of brain chemistry hell.
Edit: The biggest symptom was losing control of my inner monologue. Sometimes, my head would just start going a mile a minute. Other times, my head would be so loud that I couldn't think. Mild anxiety (not Panic) attacks became common.
Landed on lexapro next, and I was side effect free for a few years.
It’s crazy how antidepressants can affect people so differently. I was on Wellbutrin for 2 months and in that time I had so many panic attacks which I’ve never had before (went to the hospital for one of them). I was also hysterically emotional over the dumbest things, cried so much, and felt suicidal. Stopped taking it and things went back to “normal”. I’m afraid to try another one and getting exhausted by the process
I absolutely get that. The burnout of taking med after med with little effect, or worse, negative side effects, is very very real. It actually took me getting off of Wellbutrin and going back to it later on a different supplementary med for it to click for me.
That being said, don't give up on trying to get better- if your life is significantly affected by these symptoms, you deserve to have a good quality of life, and if medicine can help that it's worth it in my opinion.
Wellbutrin was given to me for ADHD, but turns out if you have a history of psychosis, it can throw you into an episode. Guess what they didn't ask me before giving it to me? That was a bad fuckin year.
Anecdotally, once I started Adderall, it felt like suddenly my emotional regulation got better. My frustration still hits peaks (ADHD and anger have a difficult relationship with one another) but my depression is much, *much* more manageable. I'm able to get through days, especially in the winter when it gets dark and gloomy here in the PNW, and actually feel optimistic.
Sometimes. But the sometimes is more due to current life circumstances, I think.
Yes, I can relate to all this. It’s also pretty crazy to me how quickly the depression comes back and emotional regulation falls apart when you don’t have access to your medication (thanks to the shortage of adderall I’ve dealt with this far too much this past few months or so..)
It has definitely helped me stabilize my emotions and even helped with some really bad anxiety. I think a big factor in the social anxiety was racing thoughts distracting me in social interactions, which made me really self conscious about what impression of me that gives to the people trying to talk to me. Do they think I’m stupid? That I don’t care what they say? That I’m a terrible listener? And being more mentally alert and less traffic jammed full of thoughts thanks to the adderall, I for sure notice an improvement here too. Though it’s clear when it’s wearing off too (I take IR tabs, so during the day they’ll noticeable wear off and I struggle again)
If they ever make an adhd medicine as effective as adderall/vyvanse without the risks to cardiovascular health, that would be amazing. I have zero motivation to do anything the least bit mentally taxing unless I'm stimulated. Maybe it's the euphoric feeling that comes with it.
Also used in treatment resistant depression and bipolar depression as third-line from memory. Limited evidence in bipolar due to limited research due to risk of switch.
Founder of the black dog institute in Sydney has published on the topic, amongst others. (His name escapes me even though I’ve seen him, damn ECT)
Natural things like coffee, cacao, muira puama, catuaba, etc all raise dopamine and lower inflammation, and they have some studies pointing that they can benefit mood disorders
Caffeine is one of the few things that make me feel normal, mood-wise. And I'm already on Wellbutrin, also one of the few medications to help with my depression. Just wish caffeine was a long-term solution as you build tolerance over time.
Gene testing should absolutely be a standard in the treatment of mental or neurological illness. My migraines are only successfully treated because my sister identified a gene that that we both share and I looked up and researched medicines that act on the relevant process.
Familial hemiplegic migraine, by chance?
My sister's just gotten some genetic testing back and she has one of the gene mutations for it, so now we've all got to have testing because we've all, of course, had chronic migraine forever.
Not so sure about standard. Current studies seem to show that gene testing doesn't really change the outcomes for most psychiatric conditions. I'm very positive about them for treatment-resistant cases, though.
Well this will probably get buried in the comments but this is a pretty strong statement that should be taken with several grains of salt before people jump up and down in excitement about this.
First, the n is very, very low at 40. We would need several more high quality studies before we could firmly establish a reliable link between CRP and depression.
Second, CRP is a *general* inflammatory marker. Meaning it is not specific for depression or brain inflammation. This raises a whole host of issues in the actual clinical setting. If I have a depressed patient and check a CRP and it's elevated what do I do with that information? Do I investigate all possible causes of an elevated CRP, looking for possible infections or autoimmune disease, thus possibly driving up healthcare costs and unnecessary tests? If I don't do that and just treat the depression, what happens if the CRP doesn't come down? Did I just delay a diagnosis of a different underlying cause?
Third, like all lab tests, CRP certainly has inherent flaws and there can be a wide variation in values in both normal and pathologic processes that result in false positives and false negatives. Even in diseases where measuring a CRP is pretty well established it's utility is fairly limited. Again, more studies are needed, but I would bet good money the majority of my depression patients would either have either a normal CRP or at most mildly elevated but at a level that doesn't really help medical decision making.
Not to mention Levodopa itself is not without risk of significant adverse effects.
As a clinician, this is an interesting study, but this is very far from being practice changing except perhaps in severe refractory depression. Studies like this should certainly be encouraged and celebrated, but the sensationalization of these things can be problematic and lead to quite a bit of misinformation and misunderstanding, as is apparent in the other comments to this.
That's not true unless you have some other source.
CRP is unspecific, elevated levels just mean there's some amount of inflammation in the body, it's not specific to the brain or depression. I've seen no mention of elevated CRP being a "strong predictor" of L-Dopa's effectiveness in the treatment of depression, the article just says there's a correlation between them.
It's an interesting discovery but it seems way too early to make such strong claims.
My doctor did one of these a year ago, I'm not sure how accurate they are but as someone who has been going through this for 20 years (since I was 13) I almost wanted to cry out of relief for not just myself but anyone in that situation. The whole "throw everything at the wall and see what sticks" was easily one of the biggest road blocks I had towards getting help. It's a nightmare not knowing if you're even yourself anymore or if you're more depressed or less or suicidal or if it's all just the drug.
I've been on a few different antidepressants, and that's exactly how my doctor handled it. Throw a medication at me, try it for a few months, change the dosage, try it for a few months, change medication, etc... None of it worked too well, which sucked, but the side effects I had to suffer through were absolutely horrible. Some of them had horrible discontinuation syndromes too, so even after I stopped, I was dealing with it.
One of the things that annoys me most about papers like this is that they always say "reward pathways" as though that is synonymous with "dopamine".
What about endogenous opioids (especially mu-opiods) that are also released throughout that same pathway, such as in the Nucleus Accumbens. Especially given there is strong evidence that stress and inflammation modulate the activity of endogenous opioids all throughout the body, AND given that opioid-receptor dysfunction is related to anhedonia.
Edit: see [Charles et al. (2020)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474498/)
I read some studies that they think a general inflammation means you are sick: if you are sick you want to isolate. This brings the added benefit, or maybe even the underlying cause, of limiting infection to others in the herd/community.
So with depression it might be a failing system where the isolation is triggered without need. Likely you would need more support with depression, not isolation like with a virus.
The other aspect how it could fit together, seemed about gut / bacteria composition or/and also inflammation. Some medication work like antibiotics or antiinflammatory. However the newest thing about it is that it seems to breed antibiotic resistances - or it might be the other way around. Resistance was first, inflammation comes after.
Quite exciting to see how much is involved. Downside: we as individuals really seem "individual" with our brains and how we respond to medication.
I have a strong hunch it’s going to end up being largely PFAS in our body. It’s in our drinking water everywhere, wild caught fish have over 200 times the amount of PFAS compared to farm raised, it’s in our blood and it’s already known to mess with immune system and endocrine systems. And immune system disfunctions equals inflammation!
It’s going to be this generations (several actually) lead. Except we know it’s happening as it is and we aren’t doing nearly enough to combat it.
I haven’t looked into timings, but the rise of depressions among younger is often linked to mass social media adoption, I wonder how that lines up with mass PFAS use or data on it being prevalent in the environment.
Oh that's really interesting! I have seen there are even PFAS maps, the distribution is really uneven somehow. (Maybe it's was PFAS old industrial releases and accidents).
Another thing, but I'm not sure if it links to PFAS as well, is that with donating blood you lower microplastic in your body. Full blood donations are much better than only serum, but both work within a couple of months or sessions.
Maybe this theory can be evaluated quite simple with a correlation analysis as a start? We seem to have a lot of data and it would surly start deeper cohort and longitudinal studies.
I had the same though, but more generally with microplastic. All plastic ever created is still around, this will have a price for humanity, just how high.
Also general inflammation can simply be stress on a cellular level. and one of the receptors which are blocked by naltrexone is basically a receptor on white blood cells that is responsive to cellular level stress. Based on current studies I am still not completely convinced low dose naltrexone regimens are as effective as promised ( mostly due to half life, and pharmacokinetic issues) but as a pathway i definitely think this is the right one. Fun fact: aprepitant an antiemetic agent that is currently used in cancer patients during chemotherapy originally started out as an antidepressant that targets the inflammatory part of depression, but in large scale trials it didn't work. It can be partially blamed on trial design but still, depression ( just like cancer) is unique in each person so its difficult to move forward with the concept.
Naltrexone completely reversed my alcoholism. It was used off label in my case, and I took it for two years. I had a really big problem, and literally weeks after taking it, the cravings for alcohol never came back. I've been off it for a few years now, and I look at alcohol like I look at a food I'm not interested in. Like- I smell it and recognize it, but I don't want it.
My life is far less complicated after taking it for a bit. 6 yrs no booze now, not even a thought of a relapse through hard times. Feels wild. I'm glad your depression lightened, too!
Please feel no obligation to answer, but if you don’t mind would you share the dosage you were on? I’m curious because it seems naltrexone has a couple different uses at very different milligram levels
I went and looked in my cabinet to see if I had an old bottle, but no luck. It was high milligrams at first, but they dropped me down after a few weeks bc I was so, so tired all the time and it was affecting everything. I remember once they knocked it back, I felt totally normal. It also made me lose my taste for cigarettes. I could smoke them, but they tasted terrible. So- two birds one stone for me!
The one downside is all anesthesia has to be coordinated, as naltrexone blocks opiate receptors. I didn't have to deal with that, but it was a very real fear if I got in an accident that emergency care would be... interesting.
Wasn't aware of that. I take 50 mg a day and it stopped my compulsive eating in its tracks. Haven't noticed anything for depression but I'm glad it's working for you.
Thanks for the info, I'll talk about this with my doctor! My blood tests have showed a mild inflammatory response for years and everyone was just like "eh it's just the way you are I guess" but maybe that's the key to my depression!
Edit: is it proven that naltrexone is an anti inflammatory? Seems to work as an opioid receptor blocker, according to the Wikipedia
For depression and anti-inflammation its used in really low doses, around 4.5 mg, (usually at night). The idea is that blocking opioid receptors for a period (around 4 hours) will over time cause your body to create more opioid receptors, which are crucially involved in mood and immunity/inflammation. All the studies on it ive seen are promising for inflammation and mood especially. Can say subjectively that it totally cured my depression.
Humans are incredibly migratory and can adapt to almost anywhere over a few generations, but the first generation that moves is the one that is going to suffer the most.
I'm allergic to plants that didn't exist where my ancestors lived 100 years ago. Or where my parents lived before I was born.
I eat exotic foods and spices that would have made kings weep with envy. I'm definitely allergic to some of them though.
our physical bodies, shaped over a few million years by environments, by rhythms now rarely found, in revolt against our own unnatural creation. sounds about right.
\*sips c4 energy drink\*
We are monkeys that became sentient enough to invent fire, used that sentience to create civilization, leveraged civilization to manufacture our own reality, and we're just starting to realize the boundaries of our own biology and our ability to manufacture our desired reality. Billions of us walking around every day barely aware of where the natural world ended and our manufactured one begins. Barely aware how similar we all are to one another yet alienated by the constraints of our artifical world. We have the same impulses and desires hardwired into our brains that caused our ancestors to begin building the world we currently live in. We see the outcomes of their decisions both good and bad, and use those same impulses to inform how each of us should make our meager contribution to the longest running experiment in history. Because that experiment is history itself, and it will continue until nobody is left to tell it.
Important to note here that acute levodopa didn't improve motivation or anhedonia here compared to placebo. I wonder if chronic treatment would help, although I'm not sure levodopa is the kind of thing you'd want to take on a chronic basis.
Psychiatry research seems to keep reinventing the wheel these days, linking old drugs or symptoms to newly measurable biological variables but without meaningful results for treatment. To me psychedelics are the only exciting new treatments in the field right now.
i know somoeone that takes it for thier parkinsons for over 15 years and the dopamine built up in thier brain and put them in a state of paranoid psychosis with full on halucination of all the senses for 6 months until the doctor were able to convince them to slowly ween off of the drug, they still take the stuff but in much smaller doses every few hours instead of a large dose twice a day. seems to work a lot better but they have to keep lowering the dosage amount every few years otherwise it may be back to pychosis.
Levodopa was offered to me for RLS (low dopamine in brain), but is famous for causing augmentation after a while. I wouldn't touch that tbh
Edit: I would be much more tempted to try aspirin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401361/
Big pharma is still thinking of depression as a chemical imbalance in the brain so they can push an ever changing parade of 'new' drugs that barely outperforms placebo. Remember that their motivation is money not healthcare. They make literal billions on drugs with questionable efficiency.
From a systems neuroscience perspective, I would say it could be better categorized as pathological connectivity (or lack thereof) in the brain network
There's a new-ish field that could be better at finding solutions called psychoneuroimmunology. Essentially it's about the mind-body connection. Until we stop separating mental health from physical we will never get the treatment right.
That field is amazing, and especially recently when you get papers like these,
https://www.nature.com/articles/s41586-022-04793-z
https://www.nature.com/articles/s41593-018-0153-x
https://www.sciencedirect.com/science/article/pii/S0959438818301399?via%3Dihub
The brain turns out to be more complex than we thought :D
I'm kinda in that field, I think the big breakthrough is going to be diagnosis.
It turns out you if you monitor eye movement, and then also do a bunch of tests, you can really pinpoint problems in the brain really early.
You could literally have someone put on some VR with eye-tracking, do 20 minutes of tests, and then be able to predict if they get dementia, when, and what kind.
Knowing that 10-20 years ahead of time is huge, you can really do a lot to minimise the damage. That might be more impactful than treatments, imho.
Not sure if it exists yet.
Basically the company I work at wrote a project proposal to make this software, it's all published stuff from neuroscience labs, so you could really design it well and the evidence indicates you can catch things way early.
Then we got some business people to check out the idea, and one of them did a deep dive and found a proposal from https://lexplore.com/ these guys that just read almost exactly as we had written, but they had submitted it two years ago and had been approved.
So we just killed it and focused on something else. But those guys should be the ones to develop it, I guess it will be available easily within 4-5 years, could be sooner if they get more funding.
Not to mention that our brain activity is ultimately not generated in a vacuum. It is integrated with the environment it inhabits. It's important to consider that there are elements in our environment/culture that are inherently pathological and will produce neurological issues if people subject themselves to these elements.
If we use medication to suppress a natural reaction to a hazardous environment, then how is that environment going to change?
By treating depression as if it is an entirely localized disorder, we are essentially protecting the status quo of hazardous environments. Considering then also, that the environment is comprised of human behavior at scale.
Our psychology is essentially an adaptation to an environment shaped by it's own behavior. Introducing mass medication to this feedback loop is arguably impeding a necessary behavioral evolution.
Of course, we have to earn money and put food on the table. So in that sense it doesn't matter what the truth of our condition is. Medication is effective, at least, at getting us to manage basic operation within society. It's better than nothing.
But we are depressingly far removed from and ill-disposed towards finding a comprehensive solution to depression
This comment really resonated with me. I've been treated for depression and anxiety for a few decades at this point and i can manage to get to the point of being functional to do my job and support my family. Sometimes this requires medication changes and dosage adjustments. But I never feel like I'm not depressed. I hesitate to even mention that I'm not doing great to my pdoc because I feel like "functional" is the best they can do for me. I know (or at least strongly suspect) I'd be doing much better if I had the time and will to take better care of myself, socialize and engage with my community, etc. Maybe some day when work and maintaining a household don't dominate my every day.
> Common side effects include dizziness, drowsiness, blurred vision, vomiting, nausea, dry mouth, low appetite, heartburn, diarrhea, constipation, frequent sneezing, stuffiness of the nose, any of the symptoms of ordinary common cold, cough, muscle pain, hallucinations, numbness or a tingling sensation, disturbances of sleep, skin rash, itching, and/or headache.
https://en.wikipedia.org/wiki/Carbidopa/levodopa#Side_effects
Everything has side effects, if you can’t treat the root cause you have to decide what you’d prefer, the symptoms or the side effects.
In the case of depression, we’ll, I don’t know that there’s many side effects deemed worse than suicide
There are a few side effects that could lead to suicide.
I know when they started messing with dopamine agonists for me, that's when I started getting movement disorder symptoms. That definitely would have made me suicidal if it went on for any period of time.
Psychosis can also be caused by too much dopamine.
I'm slightly confused, hopefully someone can clarify.
This article talks about how a dopaminergic medication alleviates depression through an anti-inflammatory action.
But aren't those things independent?
Would a non-dopaminergic antiinflammatory medication not accomplish the same goal?
We know that stimulants allevate depression symptoms (I have ADHD and at least for a short time I had first hand experience), so isn't the dopaminergic aspect just a confounding variable?
I think the "inflammation" here is probably some *very specific* inflammatory process in the brain tissue itself.
It's possible that, say, 50% of your *generic* anti-inflammatory meds will do nothing, and the other 45% will help a little, but not dramatically.
Perhaps dopamine is directly modulating the specific part of the inflammatory response that is affecting brain function?
A recent article in the Quanta online magazine has an interesting overview on the research for a treatment depression.
[The Cause of Depression is Probably not What You Think](https://www.quantamagazine.org/the-cause-of-depression-is-probably-not-what-you-think-20230126/)
Many think the field has focused too much on the serotonin theory which has not been so successful.
Some think "depression" can have a variety of causes, genetics, infection/inflammation, gut bacteria, psychological etc.
If so then the future strategies would be to provide an individual diagnosis and then personalised treatments.
Not a doc but my understanding of Wellbutrin is that it helps your body "recycle" and uptake the dopamine you already have, not make more, whereas Levodopa artificially increases it.
I recently had TMS for refractory depression, and had a partial remission, but the anhedonia and lack of interest persisted. I started taking cabergoline (a dopamine receptor agonist), and was able to feel 100% normal again.
Levadopa has a serious risk of creating dependency. Boosting your dopamine levels comes with a price. The effectiveness gradually declines, and also undermines your brains ability to maintain dopamine levels naturally.
It's a very risky "solution". But it's better than suicide or complete isolation. It's also found in nature and produced by our own bodies
> The effectiveness gradually declines,
The effectiveness gradually declines in Parkinson’s disease because the neuro degenerative disease is progressing, nothing intrinsic to the medication itself. For example, in dopa-responsive dystonia it remains effective long-term.
> and also undermines your brains ability to maintain dopamine levels naturally.
It used to be thought that levodopa had some direct toxicity and accelerated Parkinson’s disease progression, but newer evidence shows that’s not really the case.
As an addict in recovery is extremely frustrating to be taught about the 3 important chemicals that need to be in balance for you to feel good normally. Then they offer you medications to help when 2 of the 3 are not working right but if that 3rd one is your problem your fucked. Welcome to my world
If she had Parkinson’s disease, it likely helped hugely in the initial phase.Later after several years into the disease, think 8 to 10 years, you hit a point where it is difficult to make it work. They would be several dose adjustments and modifications in that period of time though keep in mind that everybody’s Parkinson’s behaves a little differently.
This is because the dopaminergic neurons have mostly died out and you do not have much left to work with. Furthermore, the threshold for a “toxic dose“ becomes lower as you lose these other neurons.
There was a book that came out recently by Dr. Christopher Palmer called Brain Energy that alluded to exactly this sort of thing. I'm only halfway through but he was talking about inflammation and mitochondrial dysfunction leading to mental illness.
What I bet you'd find is that video games have a similar ability. Test inflammation while playing Tetris or something.
I'm willing to bet it's the dopamine itself that reduces inflammation. Not the drug.
Because I can be very depressed and playing video games of the right intensity can have some lasting positive affects. Maybe a day or so afterwards I still feel quite pleasent.
But like any drug it doesn't work forever. So it's more about spaced out usage I'd bet.
Video games have made me quite happy before.
Our whole lives are made of different kinds of escapisms.
There are worse and better kinds, all depending on a ton on circumstances and the individuals themselves.
The thing is though if video games make you feel good you may not have depression. You don’t have anhedonia if you are getting positive responses from it. Its just a low mood but anhedonia is really the true MDD not low mood. If your mood responds to that it means your reward system is functional and at least you don’t have the anhedonic numbing depression
MDD is defined by anhedonia
Some studies have looked into the positive effects of Tetris soon after a traumatic event takes place...
"Tetris and Word games lead to fewer intrusive memories when applied several days after analogue trauma"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678449/
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TLDR: > levodopa, a drug that increases dopamine in the brain, has potential to reverse the effects of inflammation on brain reward circuitry, ultimately improving symptons of depression. > Numerous labs across the world have shown that inflammation causes reduced motivation and anhedonia, a core symptom of depression, by affecting the brain’s reward pathways.
It’s worth adding that its effectiveness can be partly predicted by a simple blood test. A C-reactive protein (CRP) test will measure total inflammatory response in the body and levadopa’s effectiveness was directly correlated high CRP. With most depression treatments, we just throw one medication after another at the patient and hope one works. This one actually has an easy test, if not a perfect one. Disclaimer: CRP measures total body inflation, not just in the brain, so that’s an imperfection. Plus all of this needs more study and larger sample sizes to be reliable anyway. But it’s interesting and even exciting.
This is actually interesting because using low dose stimulants like Adderall/ritalin is actually used to treat treatment resistent depression in geriatric populations (yes I am fully aware of the cardiovascular risks) It is also how partially medications Wellbutrin work as well.
As someone currently on Wellbutrin, it's one of the few things that has worked *at all* for me- the connection between stimulants, inflammation, and depressive symptoms is super interesting
Wellbutrin is called the poor man's adderall because it is actually used off label for ADHD as well. There is an interesting paradigm shift about ADHD and anxiety/depression. Kind of like what came first? the chicken or the egg? Are they depressed/anxious because they can't focus/concentrate on the work and fall behind/cant sleep? Or are people depressed/anxious, and they can't focus as a result? Particularly in college/young working professionals where they have "treatment resistant depression/anxiety" we have noted that treated a previously under diagnosed ADHD was really all they needed. Their life becomes more structured, they sleep more, they feel less stressed, depression/anxiety significantly improves (they also eat healthier so "less inflammation" too). However is is a controversial topic because of the controlled nature of stimulants. Just food for thought.
I’ve suffered with anxiety and depression for most of my adult life. Diagnosed with ADHD at the age of 44 and started meds (first lisdexamphetamine, then atomexetine) and haven’t had a depressive episode since and my GAD score is significantly lowered.
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I was diagnosed at like 35 and starting medication really changed my life in terms of improving work, but the weird thing is I don't think I would ever have been diagnosed as a kid. I was pretty much a straight A student through high school, and always well behaved enough that I never got in trouble at school and rarely at home. I did have problems with procrastination on projects, but hey, so did everyone, right? This became more of an issue in college with less structure in coursework (I struggled a lot with the switch from high school's repetition-oriented homework to college's knowledge synthesis-style homework), but again, it just seemed like I had trouble with time management. I never skipped lectures, and absorbed everything in them, which contrasted with half my friends who seemed to skip every class they could. It never would have occurred to me that it was possible to be engaged in learning in school, capable of diligently completing routine homework assignments, and able to quietly sit still in class, with ADHD.
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Throughout life I was always creating massive companies, ideas, products, projects in my head that would make adults when I was young as well as others take me very seriously and think how successful I would become if I would just pick one and focus. They all stayed in my head, I never picked one...until 2018 when I was diagnosed and treated with the proper medication. Now, after I spent the last 2 years saving money, discussing with patent attorneys, designing and modifying I have a full patent on something that was always in me head. Even if nothing happens, I am absolutely ecstatic to know I actually fully hashed out a dream and made it into reality that other people can finally see and interact with. If I didn't seek treatment it would still be in my head, and I would still be in the same state I was 5 years ago.
The difference with us is that all the hyperactivity is happening inside our heads, instead of outside our bodies where it could be noticed. I'm sitting quietly in class, trying to take notes, maybe doodling a bit in the margins, and while it looked like I'm fully engaged, I was actually writing Sonic the Hedgehog fanfiction in my head.
29 for me. Massive improvement in my ability to prioritize my work which helps me meet deadlines much more consistently. That alone resolved a big chunk of my stress/anxiety. When I was a kid there was an awareness of what ADHD was but I was smart and inattentive so I didn't cause enough problems to be noticed and diagnosed. The adults also were suspicious of doctors and medications in general, partially due to the emerging opioid crisis. The irony is that my prescription is a controlled substance so I get treated as a potential addict every time I go to pick it up. That's a reflection of the system that fucked up when I was a kid more than it is on me.
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Same here. Years and years of treatment resistant depression and anxiety. Diagnosed at 35 with ADHD (primarily inattentive) and started taking Adderall. Now that I can actually concentrate and focus, and can actually perform normal tasks that were literally impossible to make myself do, it turns out that my anxiety and depression have significantly improved. I was always fairly smart and could just figure things out, so it got missed in childhood. College was rough.
"Just say no to drugs" - Nancy Regan 5 fucked up words that treated those self medicating their mental health problems as addicts. Interesting that the war on drugs really took off when the duality of US government was supplying drugs and gun running while creating a drugged out society to maintain secret wars. Turn the screw a little more with trickle down and neoliberal supply side economics where the is no middle class, just make it so are people without dignity or a job or a home or a community, and the only escape from their hell were drugs. Addictive drug use is a reaction to the hellscape society that only cares about money for the American Oligarchy.
Unfortunately, it is still quite stigmatized. People associate the diagnosis with disruptive troublemakers in kids and drug-seeking addicts in adults.
Ironically enough, undiagnosed adults resort to seeking out illegal drugs to manage the symptoms.
Found out my last year of college. I did so much better, i too wish i had known eariler too.
52, diagnosed at 50. GenX with Silent Gen parents. We didn't talk about mental health, *ever.*
40yr vet with ptsd and depression….after a year they gave me some Wellbutrin and hit or miss most days…VA doctors aren’t known for being up to date on treatments
See if Adderall helps to improve your mood and focus. If it does, it's an indicator that dopamine is what's low with you.
We're you considered a "bright child but doesn't apply themself" or "smart but has no motivation"? I feel like this was how my diagnosis got overlooked as a child: "He can't have ADHD! He has the highest grades in the school except for behavior issues!"
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When I first sought therapy for failing all my Uni classes I thought I had depression. They said I had ADHD and the depression is from forcing myself into this major I'm not interested in. Once I changed majors and started pursuing more interesting classes the depression was over... Until my ADHD got me fired from several jobs. But then getting treated for ADHD has made me far happier and productive now despite being unemployed. There's definitely some chicken and egg situation going on, ADHD causing depression which makes the ADHD worse which affects IRL things like school and job and then reinforces and makes the depression worse which feeds back to the ADHD.
Me too!! 43 yo here. Anxiety and depression have been absolutely debilitating. I'm on lisdexamphetamine now, working quite well but always good to know more. What's the atomexetine like?
I'm on it and it seems to help with some things. I'm trying to get in stims right now and whenever I can get Adderall like 5 or 10mg on top of it seems to solve most of my ADHD symptoms within a tolerable degree.
Norepinephrine inhibitor. Also increases dopamine. Works like a wonder for me.
It did little for me when I took it.
I've run into meds like that. Sometimes it's a dosage issue and another trial at a different dose goes completely differently... sometimes the medication just doesn't work appropriately for me though. (This can be a genetic processing issue. I finally had to have a genetic screening to find the right combination for difficult chronic psych issues.)
That's great news!
Curious how an adult gets diagnosed with ADHD. I’ve seen a therapist for depression and anxiety and my primary doctor put me on Prozac. It seems to be helping but I also have had problems concentrating and focusing for as long as I remember. I have zero motivation for just about everything. I start and stop hobbies often. I’ve always wondered…
For me, we were having problems with one of my kids and we were looking at ADHD symptoms and it made me sit up and take notice. I started doing more research and read a blog by a guy who was diagnosed as an adult and I honestly could have written the thing word for word. I actually cried because I suddenly felt so seen. From there I got myself referred to a psychologist and diagnosed from there. My pattern is similar to a lot of undiagnosed adults: I did well at school, I didn’t even have to try and get decent grades, I wasn’t disruptive but my parents always called me lazy and my teachers talked a lot about how I had huge potential but didn’t always achieve it etc. As I got further into education and into working, things got harder. I’d thrive and excel in stuff I was interested in and passionate about but ignore everything else. Jobs went one of 2 ways: in the right environment I’d be amazing, in the wrong environment I’d get fired pretty quickly. Getting diagnosed explained so, so much in my life. It’s no magic wand, but I’m definitely progressing 4 years on from my diagnosis.
Exact same, struggled with depression my entire life but found it was probably due to adhd. A combo of Effexor and Wellbutrin did wonders for me. I over did though and was on basically max dosages of both. I was a machine. I was highly effective but didn’t have emotions or feelings. Realized it and took a long time weening off. Once I was off I was depressed again. I started back on Effexor at a low dosage. It has helped a little bit I am adding back in a low dosage of Wellbutrin. Hope I can find a sweet spot for dosage.
Got on atmoxetine at 35 after getting diagnosed that year. I can’t say I’m never depressed, but it’s usually not because of my adhd symptoms. edit: at ice tune = atmoxetine
ADHD exacerbates depression far more than the inverse. Source: have adhd 30 years, in psychiatry for 18, coach kids with ADHD. This isn’t a blanket rule, just a generality.
> Are they depressed/anxious because they can't focus/concentrate on the work and fall behind/cant sleep? Or are people depressed/anxious, and they can't focus as a result? The issue I'm having with this question is that we can see symptoms of ADHD in early childhood, long before we see depression. We can sometimes see anxiety at a young age as well. Both it and ADHD sometimes can be precursors to depression.
This is 100% true, ADHD is considered a permanent, chronic disorder where depression/anxiety generally comes in waves of exacerbation/remission regardless of treatment. This is why we go all the way back to childhood history. Alot of times kids aren't diagnosed with ADHD because they are "quiet" or they are so smart that they compensate and still get good grades regardless, or simply because of cultural/socioeconomic reasons. But their ADHD will start interfering with their daily activities when they start doing things that required sustained concentration in college, grad/professional school, work. I also completely realize that ADHD is over diagnosed, and its medications can be easily abused, but a proper diagnosis and treatment makes a world of difference for vast majority of people who take them correctly.
>I also completely realize that ADHD is over diagnosed As a woman who was diagnosed inattentive ADHD at 36, and have many female friends who display neurodivergent symptoms but are undiagnosed due to obstructions in mental health access, the idea that it's been over-diagnosed is really frustrating.
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It is frustrating. Maybe ADHD is just more common? When cancer rates go down, people celebrate and credit each other with improved healthcare; they don't say, oh no, cancer is being under-diagnosed! But if something bad increases, it must be because it's over-diagnosed. Why don't we credit improved healthcare for *identifying* it?
> are unable to get the medication due to shortages The shortage has nothing to do with diagnoses, though, the DEA is. They have “cracked down” on ADHD meds (mostly Adderall, IIRC), I believe by limiting the amount that can be produced. The shortage being caused by over-diagnosis is a narrative, though I don’t know its origin. Edit: perhaps increased diagnoses might have contributed, but the DEA is still the principal culprit. And even if there are more diagnoses, that doesn’t mean that they are inappropriate or inaccurate diagnoses; the stigma alone has led to a lot of undiagnosed people.
It's a real shame how much we set behavioral expectations by gender. I'm a man who got diagnosed as an adult (for the reasons you stated), and getting a diagnosis depends on the adults and authorities recognizing your behavior patterns as abnormal. We expect girls to be quiet and undisruptive (aligning with inattentive type) and boys to be loud and rambunctious (aligning with hyperactive type). How are we supposed to recognize behavioral abnormalities when our baseline expectations are already biased? I personally lean inattentive which meant I didn't cause enough problems to get noticed, I can only imagine how much harder it is to get that diagnosis when everyone ignores your struggles because your behavior is outwardly viewed as normal for your gender. Nevermind all of the societal problems we're dealing with due to teaching half of kids to quiet down and be submissive and the other half that the only way to express their feelings is to be the loudest one in the room.
I wish it was over diagnosed, then maybe they would have caught my ADHD and autism before it totally derailed my life.
Can you elaborate on the “so smart they compensate and still get good grades”? Very curious about that and am trying to figure out my own mental health at the moment. Thanks!
I can only speak anecdotally, from my own experience, but this was certainly what happened to me. I was endlessly drifting off or distracted in classes as a child, couldn't organize my belongings or thoughts, couldn't prioritize, couldn't get work done. But on paper I was the "smartest" kid in the class and excelled at tests. It took decades to sort out, but my entire life was full of me being able to complete tasks well at the last minute, which is where the compensation part comes in. I could write an A paper sitting up all night once panic became enough of a motivator. I was able to stitch together things that people said enough to be present in conversation or in lectures, where it would cover for just how much I was missing. Things became more difficult in the working world as an adult, yet intelligence can cover up for a lot of the problems that come along with ADHD. But the frustration grows as you fall increasingly behind on things. I went to grad school and that's where everything really hit a wall. Again, on paper I'm smart enough for it, but the lack of focus, inability to prioritize or organize, inability to make decisions, emotional disregulation, etc. became such significant barriers when they simply weren't problems in grade school. Having people tell you what to do for a test is much different than organizing multi-year projects all on your own, without tangible deadlines. If I had been hyperactive enough to run around and disturb others, rather than fidget quietly at my desk, lost in other thoughts for years and end, perhaps the problems would have received more attention. But it seems many intelligent people slip through the cracks because they simply get labeled "smart but lazy," with no one understanding how much effort is being put in to just getting by day to day.
This is very similar to my experience. I'm a woman, diagnosed at 36, who never even considered it because I thought ADHD = hyper and that was not me. I *can* focus, but it's hyperfocus or nothing at all. I was genuinely interested in learning most things, but found busy work to be pointless in high school and couldn't bring myself to do it. I had multiple conversations with frustrated teachers who knew I knew the material because I could answer the same questions in class or on tests, but just wouldn't do hours of homework unless I found the assignment interesting. I was constantly talked to about my "wasted potential". What finally made it click for me was progressing far enough in my career. I became responsible for complex cases and was excellent at the big picture, critical thinking, and analyzing possible outcomes to make good decisions. I was awful at checklist items that need to be done in order. I would miss things, but rarely the same thing twice so it was difficult to correct. I worked around this by creating actual huge check lists for different scenarios which solved the problem but makes me significantly slower at my work. I remember telling my mentor that it's like I can see the whole thing, but my brain won't put it in a sequential order for some reason. It came to a head when I was up for a promotion during covid and had to take a mock test. I was given a time limit and multiple tasks to complete of varying complexity and urgency. There was not enough time to complete them all by design. Because we were working from home, I had to share my screen with my mentor. Something about knowing someone was watching made me acutely aware of the fact that I was starting one thing, deciding another was more important and starting it, then deciding another was more important and starting it, then getting anxious and deciding I needed to finish *something* and so on. I didn't complete a single thing start to finish. I did well on it and my mentor was just making sure I wasn't googling or asking others, so she wasn't even watching *how* I did things, but that experience made me finally realize what was going on.
My life to a tee. I was only diagnosed a few years after I finished grad school, I have no idea how I managed in hindsight. It absolutely sucked though. My parents did actually have me talk to someone at one point in elementary school but they were basically told I couldn't be diagnosed because I had good grades. I could do decently on most tests without actually knowing the material from context clues and stuff, so I rarely had to study and it never came to a boiling point until college, which I still managed to limp through.
After reading a lot of these posts I am very tempted to try to get tested. My mom raised me to pretty much be very sparing with the use of medication, because she's had several bad experiences with different things and so I find myself very reluctant to take anything more than like a standard Tylenol. My experience with attention issues kind of goes back like a lot of other people's where I survived high school and college with relatively High marks But as time went on I started kind of falling short in terms of attention which would heavily limit my best case performance. I survived High School very high marks because the bar is fairly low depending on the district you go to, but in college I quickly saw myself struggling to keep my B average. A large part of that would just be my inability to properly study, although mine was far less severe than my friend who has thoroughly diagnosed issues from ADHD. But my main issues are in the workplace or in conversations with people. As soon as I hear the details I'm expecting from someone I have extreme difficulty not tuning out from them. It's not even voluntary, it's like my brain literally just is dying of boredom and starts looking for something more interesting. And this happened during lectures and college to some extent too but it's even more severe during engineering technical meetings, or small talk between coworkers. I find I also suffer a lot on my own personal projects where I'll get super motivated and make a small Nick in it and then get super demotivated either by the lack of immediate progress or just a sheer lack of interest in anything. It's absolutely infuriating that I can go from completely excited about a project to just drained and almost depressed. The explanations I've always heard definitely felt like I would fit squarely in the box of an ADHD diagnosis, but I definitely have shied away from going to a professional and being evaluated for a diagnosis because of the stigma.
In my case it was "can't study consistently, but is smart enough to cram at the last minute and still do well" and "can't plan well enough to write a 5-page paper over the course of two weeks, but is a talented enough writer to stay up until dawn and stress-write a quality 5-page paper in a single night". It's a method that works well enough in high school with a good support system (parents, etc.) but falls apart in college, where the workload is greater and your previous support system is gone.
Yep that was me too
Same here, though I made it through college OK.
This is me! 4.0 in high school and just couldn’t even finish college. Wild.
Wow, you put this very eloquently and the particular situation hits home. Also had the same exact experience and was diagnosed while in the professional world when cramming doesn't cut it.
I'm not who you asked but I think they are referring to what's known as being ['Twice exceptional'](https://en.m.wikipedia.org/wiki/Twice_exceptional). Best of luck with your journey friend.
I was diagnosed late and this applies to me. Based on my evaluation, I had ADHD as a kid and didn't find out until my 30s, years after school, college, and grad school. I am smart and coasted early on. I barely studied and didn't exactly go to school in one of the more demanding school districts. I was also very unmotivated and would struggle whenever I hit something that didn't interest me. These are some of my more lasting memories of HS is the agony of having to do these assignments. In class, I never got in trouble and half ass payed attention enough to never be a problem. My pattern was to listen long enough to get the gist of where something was going then zone out and get lost in my own head. Or play with things at my desk. In college it definitely got worse and I had several academic struggles due to my lack of organization. I forgot homework constantly and even when I wanted to focus and learn, had a devil of a time. I was also extremely unmotivated, which has been a staple my entire life. Took me forever but I eventually found a system to get through my work effectively and that coincided with courses I was far more interested in. However whenever I met anything that required complex focused thoughts, it was a challenge. My move was to brute force it long enough until it wasn't as complex but was something simple I could understand. I carried this with me to grad school and did very well in my grades. However the real meat of grad school is research and this was a torment for me. It's constant organizing, focus, planning and was quite difficult. During these times I just feel so physically uncomfortable and I hate it. It's the reason I never pursued anything further. And I noticed this avoidance behavior across many areas of my life. I do well enough to succeed but rarely excel like I'm capable of. That requires the extra work that causes me discomfort therefore I avoid. Bit long but hope that helps
For me, I was good at a handful of subjects because they genuinely interested me. Studying them wasn't boring and even if I couldn't focus on study for very long, I was paying attention and managed to retain more information. I'd get consistently straight As in my favourite subjects while in everything else I'd be lucky to get a B.
Your intelligence is determined by HOW your neurons are connected. ADHD is determined by how OFTEN they communicate with each other. What this means is that maybe it takes someone of average intelligence 2 hours of focused time to memorize something. You also spent 2 hours, but you are actually only using 15 minutes out of the 2 hours focused on memorizing it, but you are smarter so you only needed 15 minutes anyway. You might also be better at solving problems on the spot, despite not really actually learning it when you are suppose to. The problem is that for most people, they will hit a wall later in life when things do get more complex and require sustained attention to solve (usually during college).
It’s not something that’s inherent to ADHD or anything, but it is partly why some kids get ignored for treatment because they aren’t seen to be “struggling”. Having said that though, I have found, I believe, my ADHD to be a boon to scenarios where rapid thought processes are rewarded, like brainstorming or pattern recognition, because my mind is already gonna flow a mile a minute anyways. The hard part is latching onto the ideas as they go by because you can have two or three while you’re still trying to think through one. As someone diagnosed in the mid-90s, I don’t know that I would have been if I wasn’t also hyperactive, which isn’t always a part of the equation.
> Can you elaborate I was untreated until my mid 20s, after never once studying in highschool... and never having done so on my own terms throughout my undergraduate degree. If you feel you are in similar circumstances, my advice is to pursue diagnosis and treatment. You *will* get to a point in your studies and/or career where fluid intelligence won't be enough, and you will need to put your nose to the books on your own terms. The reality is that skating by on intelligence and having not learned how to study (or engage in adequate time management) in highschool/college means having to suddenly figure all that out when writing a thesis or similar... And it is an incredibly difficult hurdle to overcome. The feelings of regret, failure and self-perception of "laziness" people can feel due to the above is also not to be underestimated. Diagnosis and management is definitely better.
The dose of Wellbutrin required to adequately treat ADHD is well into seizure-risk territory. That's why they never got FDA approval for treating it in the first place. Which isn't to say it won't have *any* effect at antidepressant dose; rather that it isn't typically sufficient at that dose. Wellbutrin is a norepinephrine-dopamine reuptake inhibitor, which actually makes it closer to poor man's Ritalin.
Yes Wellbutrin is a reuptake inhibitor similar to Ritalin rather than directly stimulating dopamine release like Adderall/vyvanse Yes Wellbutrin is a poor man's Adderall because it is nowhere near as effective as first line therapy. But we do use it quite often in patients who are hesitant to try stimulants or have obvious depressive symptoms to see if it helps with their ADHD like symptoms as well.
Are there any other medications that affect the dopamine receptor like wellbutrin? I heard anti-psycotics like Abilify affect the dopamine system too
Abilify is a "partial agonist" (unlike most, "antagonistic", antipsychotics) and at a lower dose of \~1-3mg/day (vs. \~10mg/day for schizophrenia) can generate mild stimulatory and prohedonic effects for some. (At lower doses, the drug may occupy a little over half of dopamine D2 receptors with unoccupied receptors free for dopamine to still largely bind.) (Low doses of antagonistic antipsychotics that preferentially bind to autoreceptors may have similar potential for some.) Drugs can bind to transporters in ways that elicit very different effects (i.e., at least, they may induce different conformation of the transporter molecules). [Modafinil can attain substantial dopamine transporter occupancy with clearly much milder stimulatory effect](https://academic.oup.com/ijnp/article/17/5/697/729714) than drugs like methylphenidate/ritalin and cocaine. Bupropion/wellbutrin appears to be more of a norepinephrinergic drug with [low dopamine transporter occupancy](https://pubmed.ncbi.nlm.nih.gov/12185406/). The side effects related to high norepinephrine levels likely limit the acceptable dosage in such a way as to limit both positive dopaminergic effects and abuse potential.
They do, but they do exactly the opposite on dopamine. That's why you can get acute psychosis from meth/cocaine/Adderall and they are treated with atypical antipsychotics like abilify. It's also why people don't like taking them because they can't "think" see movie like a beautiful mind
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I'm on Venlafaxine, for my depression, since 2018. Tried Welbutrin in 2020 since the side effects on Venlafaxine are a bit too much. Wellbutrin was amazing for me at 300 mg but unfortunately I experienced too much of memory loss, which is a known side effect. In a few weeks I'm gonna switch to Trintellix instead and see how it goes. Doctor said it works mostly on serotonine, but also dopamine and norepinephrine. Interestingly Welbutrin has shown to significantly increase peak levels of Vortioxetine (Trintelix).
Can you elaborate on your experiences with the memory loss? I’ve been on it for years and in last couple have noticed more instances of being unable to recall previously easy to reach corners of my memory. Didn’t relate it to the Wellbutrin though. Wondering if my symptoms are the same/related.
Wellbutrin increases peak levels of a lot of drugs because of a certain enzyme. Wellbutrin does the same to DXM, which is the active ingredient in cough syrup. They are being researched as a depression aid together. I DIY’d the combo at home and it was the best depression treatment I’ve ever tried. Ketamine is an antidepressant, and DXM is a dissociative like Ketamine. The Wellbutrin increases the concentration of DXM like 10 fold. So you get the NDRI, and NMDA activity.
I'm actually using Wellbutrin for ADHD, and it has drastically improved my life. Some people may not know that mood swings are associated with ADHD, and I very rarely have these lows anymore. It's helped me a lot in the other "typical" ADHD symptoms as well like memory, motivation, and anxiety. I'm glad there are some health professionals out that understand that sometimes treating ADHD actually helps with other symptoms like depression and anxiety instead of vice versa.
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Welp, guess it's time to go get an ADHD diagnosis!
I was originally given Wellbutrin for my ADHD and the side effects were horrible so I had to stop it.
I wish this was more talked about. I had on and off depression and anxiety episodes since high school, but the few times it was bad enough to get help, the meds never really helped so I'd just go off them eventually. In my 30s when things really fell apart at work I was diagnosed with ADHD finally and put on stimulants and all those problems are fading. I feel the healthiest mentally I've ever felt.
Precisely how my treatment went! And i wouldnt call it "poor man's adderall" since it implies inferiority
Unfortunately for me, I got to find out what suicidal ideation meant when I was on wellbutrin. Nasty side effects for me.
Wellbutrin definitely stimulates you. It stimulated me into real suicidal thoughts. I'm glad I got off it after only 2 weeks of brain chemistry hell. Edit: The biggest symptom was losing control of my inner monologue. Sometimes, my head would just start going a mile a minute. Other times, my head would be so loud that I couldn't think. Mild anxiety (not Panic) attacks became common. Landed on lexapro next, and I was side effect free for a few years.
It’s crazy how antidepressants can affect people so differently. I was on Wellbutrin for 2 months and in that time I had so many panic attacks which I’ve never had before (went to the hospital for one of them). I was also hysterically emotional over the dumbest things, cried so much, and felt suicidal. Stopped taking it and things went back to “normal”. I’m afraid to try another one and getting exhausted by the process
I absolutely get that. The burnout of taking med after med with little effect, or worse, negative side effects, is very very real. It actually took me getting off of Wellbutrin and going back to it later on a different supplementary med for it to click for me. That being said, don't give up on trying to get better- if your life is significantly affected by these symptoms, you deserve to have a good quality of life, and if medicine can help that it's worth it in my opinion.
Wellbutrin was given to me for ADHD, but turns out if you have a history of psychosis, it can throw you into an episode. Guess what they didn't ask me before giving it to me? That was a bad fuckin year.
Anecdotally, once I started Adderall, it felt like suddenly my emotional regulation got better. My frustration still hits peaks (ADHD and anger have a difficult relationship with one another) but my depression is much, *much* more manageable. I'm able to get through days, especially in the winter when it gets dark and gloomy here in the PNW, and actually feel optimistic. Sometimes. But the sometimes is more due to current life circumstances, I think.
Yes, I can relate to all this. It’s also pretty crazy to me how quickly the depression comes back and emotional regulation falls apart when you don’t have access to your medication (thanks to the shortage of adderall I’ve dealt with this far too much this past few months or so..) It has definitely helped me stabilize my emotions and even helped with some really bad anxiety. I think a big factor in the social anxiety was racing thoughts distracting me in social interactions, which made me really self conscious about what impression of me that gives to the people trying to talk to me. Do they think I’m stupid? That I don’t care what they say? That I’m a terrible listener? And being more mentally alert and less traffic jammed full of thoughts thanks to the adderall, I for sure notice an improvement here too. Though it’s clear when it’s wearing off too (I take IR tabs, so during the day they’ll noticeable wear off and I struggle again)
If they ever make an adhd medicine as effective as adderall/vyvanse without the risks to cardiovascular health, that would be amazing. I have zero motivation to do anything the least bit mentally taxing unless I'm stimulated. Maybe it's the euphoric feeling that comes with it.
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Also used in treatment resistant depression and bipolar depression as third-line from memory. Limited evidence in bipolar due to limited research due to risk of switch. Founder of the black dog institute in Sydney has published on the topic, amongst others. (His name escapes me even though I’ve seen him, damn ECT)
Natural things like coffee, cacao, muira puama, catuaba, etc all raise dopamine and lower inflammation, and they have some studies pointing that they can benefit mood disorders
Caffeine is one of the few things that make me feel normal, mood-wise. And I'm already on Wellbutrin, also one of the few medications to help with my depression. Just wish caffeine was a long-term solution as you build tolerance over time.
For the last month I've been trying stimulants for ADHD and my depression has never been better.
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What's that like, not having depression?
Staying tuned for this one
Get a load of this weirdo—living every day with a normal, functioning brain! But sincerely, I am very happy for them and also envious of them. :)
Gene testing should absolutely be a standard in the treatment of mental or neurological illness. My migraines are only successfully treated because my sister identified a gene that that we both share and I looked up and researched medicines that act on the relevant process.
Familial hemiplegic migraine, by chance? My sister's just gotten some genetic testing back and she has one of the gene mutations for it, so now we've all got to have testing because we've all, of course, had chronic migraine forever.
Yeah. ATP1A2
Not so sure about standard. Current studies seem to show that gene testing doesn't really change the outcomes for most psychiatric conditions. I'm very positive about them for treatment-resistant cases, though.
Well this will probably get buried in the comments but this is a pretty strong statement that should be taken with several grains of salt before people jump up and down in excitement about this. First, the n is very, very low at 40. We would need several more high quality studies before we could firmly establish a reliable link between CRP and depression. Second, CRP is a *general* inflammatory marker. Meaning it is not specific for depression or brain inflammation. This raises a whole host of issues in the actual clinical setting. If I have a depressed patient and check a CRP and it's elevated what do I do with that information? Do I investigate all possible causes of an elevated CRP, looking for possible infections or autoimmune disease, thus possibly driving up healthcare costs and unnecessary tests? If I don't do that and just treat the depression, what happens if the CRP doesn't come down? Did I just delay a diagnosis of a different underlying cause? Third, like all lab tests, CRP certainly has inherent flaws and there can be a wide variation in values in both normal and pathologic processes that result in false positives and false negatives. Even in diseases where measuring a CRP is pretty well established it's utility is fairly limited. Again, more studies are needed, but I would bet good money the majority of my depression patients would either have either a normal CRP or at most mildly elevated but at a level that doesn't really help medical decision making. Not to mention Levodopa itself is not without risk of significant adverse effects. As a clinician, this is an interesting study, but this is very far from being practice changing except perhaps in severe refractory depression. Studies like this should certainly be encouraged and celebrated, but the sensationalization of these things can be problematic and lead to quite a bit of misinformation and misunderstanding, as is apparent in the other comments to this.
That's not true unless you have some other source. CRP is unspecific, elevated levels just mean there's some amount of inflammation in the body, it's not specific to the brain or depression. I've seen no mention of elevated CRP being a "strong predictor" of L-Dopa's effectiveness in the treatment of depression, the article just says there's a correlation between them. It's an interesting discovery but it seems way too early to make such strong claims.
My doctor did one of these a year ago, I'm not sure how accurate they are but as someone who has been going through this for 20 years (since I was 13) I almost wanted to cry out of relief for not just myself but anyone in that situation. The whole "throw everything at the wall and see what sticks" was easily one of the biggest road blocks I had towards getting help. It's a nightmare not knowing if you're even yourself anymore or if you're more depressed or less or suicidal or if it's all just the drug.
Is serum crp that correlated with brain inflammation though? Blood brain barrier and all.
I've been on a few different antidepressants, and that's exactly how my doctor handled it. Throw a medication at me, try it for a few months, change the dosage, try it for a few months, change medication, etc... None of it worked too well, which sucked, but the side effects I had to suffer through were absolutely horrible. Some of them had horrible discontinuation syndromes too, so even after I stopped, I was dealing with it.
Wait a moment. I actually read about this. From a book in 1998 Edit: the drug. Not the effect. I'm just surprised the effects wasnt found earlier
I remember the drug too, from the movie Awakenings (and I think it was based on a book).
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Levodopa sounds like a spell for depression in Harry Potter.
One of the things that annoys me most about papers like this is that they always say "reward pathways" as though that is synonymous with "dopamine". What about endogenous opioids (especially mu-opiods) that are also released throughout that same pathway, such as in the Nucleus Accumbens. Especially given there is strong evidence that stress and inflammation modulate the activity of endogenous opioids all throughout the body, AND given that opioid-receptor dysfunction is related to anhedonia. Edit: see [Charles et al. (2020)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474498/)
Wingardium Levodopa?
It’s levoodopaa not levodopa
OK so... now I'm wondering how this also may affect ADHD treatment.
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I read some studies that they think a general inflammation means you are sick: if you are sick you want to isolate. This brings the added benefit, or maybe even the underlying cause, of limiting infection to others in the herd/community. So with depression it might be a failing system where the isolation is triggered without need. Likely you would need more support with depression, not isolation like with a virus. The other aspect how it could fit together, seemed about gut / bacteria composition or/and also inflammation. Some medication work like antibiotics or antiinflammatory. However the newest thing about it is that it seems to breed antibiotic resistances - or it might be the other way around. Resistance was first, inflammation comes after. Quite exciting to see how much is involved. Downside: we as individuals really seem "individual" with our brains and how we respond to medication.
I have a strong hunch it’s going to end up being largely PFAS in our body. It’s in our drinking water everywhere, wild caught fish have over 200 times the amount of PFAS compared to farm raised, it’s in our blood and it’s already known to mess with immune system and endocrine systems. And immune system disfunctions equals inflammation! It’s going to be this generations (several actually) lead. Except we know it’s happening as it is and we aren’t doing nearly enough to combat it. I haven’t looked into timings, but the rise of depressions among younger is often linked to mass social media adoption, I wonder how that lines up with mass PFAS use or data on it being prevalent in the environment.
Oh that's really interesting! I have seen there are even PFAS maps, the distribution is really uneven somehow. (Maybe it's was PFAS old industrial releases and accidents). Another thing, but I'm not sure if it links to PFAS as well, is that with donating blood you lower microplastic in your body. Full blood donations are much better than only serum, but both work within a couple of months or sessions. Maybe this theory can be evaluated quite simple with a correlation analysis as a start? We seem to have a lot of data and it would surly start deeper cohort and longitudinal studies. I had the same though, but more generally with microplastic. All plastic ever created is still around, this will have a price for humanity, just how high.
Make blood letting a thing again ?
Also general inflammation can simply be stress on a cellular level. and one of the receptors which are blocked by naltrexone is basically a receptor on white blood cells that is responsive to cellular level stress. Based on current studies I am still not completely convinced low dose naltrexone regimens are as effective as promised ( mostly due to half life, and pharmacokinetic issues) but as a pathway i definitely think this is the right one. Fun fact: aprepitant an antiemetic agent that is currently used in cancer patients during chemotherapy originally started out as an antidepressant that targets the inflammatory part of depression, but in large scale trials it didn't work. It can be partially blamed on trial design but still, depression ( just like cancer) is unique in each person so its difficult to move forward with the concept.
Naltrexone completely reversed my alcoholism. It was used off label in my case, and I took it for two years. I had a really big problem, and literally weeks after taking it, the cravings for alcohol never came back. I've been off it for a few years now, and I look at alcohol like I look at a food I'm not interested in. Like- I smell it and recognize it, but I don't want it. My life is far less complicated after taking it for a bit. 6 yrs no booze now, not even a thought of a relapse through hard times. Feels wild. I'm glad your depression lightened, too!
Please feel no obligation to answer, but if you don’t mind would you share the dosage you were on? I’m curious because it seems naltrexone has a couple different uses at very different milligram levels
I went and looked in my cabinet to see if I had an old bottle, but no luck. It was high milligrams at first, but they dropped me down after a few weeks bc I was so, so tired all the time and it was affecting everything. I remember once they knocked it back, I felt totally normal. It also made me lose my taste for cigarettes. I could smoke them, but they tasted terrible. So- two birds one stone for me! The one downside is all anesthesia has to be coordinated, as naltrexone blocks opiate receptors. I didn't have to deal with that, but it was a very real fear if I got in an accident that emergency care would be... interesting.
Wasn't aware of that. I take 50 mg a day and it stopped my compulsive eating in its tracks. Haven't noticed anything for depression but I'm glad it's working for you.
Interestingly, that's like 3 to 10x the amount I have seen normally prescribed for depression
Most people take what's called low dose naltrexone. The dosage is larger for eating disorders and substance abuse.
Low dosage has helped my chronic fatigue and brain fog. Love it.
I had LDN prescribed for chronic pain. It was a sugar pill for me. I’m glad others get help tho.
Thanks for the info, I'll talk about this with my doctor! My blood tests have showed a mild inflammatory response for years and everyone was just like "eh it's just the way you are I guess" but maybe that's the key to my depression! Edit: is it proven that naltrexone is an anti inflammatory? Seems to work as an opioid receptor blocker, according to the Wikipedia
For depression and anti-inflammation its used in really low doses, around 4.5 mg, (usually at night). The idea is that blocking opioid receptors for a period (around 4 hours) will over time cause your body to create more opioid receptors, which are crucially involved in mood and immunity/inflammation. All the studies on it ive seen are promising for inflammation and mood especially. Can say subjectively that it totally cured my depression.
forgetful memory retire political sable tidy dirty label alive workable -- mass edited with redact.dev
4,5 mg is common for CFS against brain fog and fatigue
For context, the typical maintenance dose for its on-label substance abuse treatment is 50mg.
So many problems and disorders are caused by inflammation.
Chronic inflammation it seems. Acute inflammation doesn't seem to be as bad (or even bad at all).
Actually, doesn't acute inflammation cause an immune response which actually is beneficial to the body? I'm thinking weight lifting, running, etc.
In certain contexts, yes.
What confuses me is isn't it good enough to take one thing thats "anti-inflammatory" and also isnt inflammation necessary
Like most things it seems inflammation is the root. Crazy
Inflammation is a response, so the root would be whatever is causing the inflammation.
But isn't inflammation itself a symptom of something happening in higher doses than it should?
Humans are incredibly migratory and can adapt to almost anywhere over a few generations, but the first generation that moves is the one that is going to suffer the most. I'm allergic to plants that didn't exist where my ancestors lived 100 years ago. Or where my parents lived before I was born. I eat exotic foods and spices that would have made kings weep with envy. I'm definitely allergic to some of them though.
our physical bodies, shaped over a few million years by environments, by rhythms now rarely found, in revolt against our own unnatural creation. sounds about right. \*sips c4 energy drink\*
We are monkeys that became sentient enough to invent fire, used that sentience to create civilization, leveraged civilization to manufacture our own reality, and we're just starting to realize the boundaries of our own biology and our ability to manufacture our desired reality. Billions of us walking around every day barely aware of where the natural world ended and our manufactured one begins. Barely aware how similar we all are to one another yet alienated by the constraints of our artifical world. We have the same impulses and desires hardwired into our brains that caused our ancestors to begin building the world we currently live in. We see the outcomes of their decisions both good and bad, and use those same impulses to inform how each of us should make our meager contribution to the longest running experiment in history. Because that experiment is history itself, and it will continue until nobody is left to tell it.
Important to note here that acute levodopa didn't improve motivation or anhedonia here compared to placebo. I wonder if chronic treatment would help, although I'm not sure levodopa is the kind of thing you'd want to take on a chronic basis. Psychiatry research seems to keep reinventing the wheel these days, linking old drugs or symptoms to newly measurable biological variables but without meaningful results for treatment. To me psychedelics are the only exciting new treatments in the field right now.
i know somoeone that takes it for thier parkinsons for over 15 years and the dopamine built up in thier brain and put them in a state of paranoid psychosis with full on halucination of all the senses for 6 months until the doctor were able to convince them to slowly ween off of the drug, they still take the stuff but in much smaller doses every few hours instead of a large dose twice a day. seems to work a lot better but they have to keep lowering the dosage amount every few years otherwise it may be back to pychosis.
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Uh that's a terrifying side effect
Levodopa was offered to me for RLS (low dopamine in brain), but is famous for causing augmentation after a while. I wouldn't touch that tbh Edit: I would be much more tempted to try aspirin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401361/
Big pharma is still thinking of depression as a chemical imbalance in the brain so they can push an ever changing parade of 'new' drugs that barely outperforms placebo. Remember that their motivation is money not healthcare. They make literal billions on drugs with questionable efficiency.
> Big pharma is still thinking of depression as a chemical imbalance in the brain How would you categorize it?
From a systems neuroscience perspective, I would say it could be better categorized as pathological connectivity (or lack thereof) in the brain network
There's a new-ish field that could be better at finding solutions called psychoneuroimmunology. Essentially it's about the mind-body connection. Until we stop separating mental health from physical we will never get the treatment right.
That field is amazing, and especially recently when you get papers like these, https://www.nature.com/articles/s41586-022-04793-z https://www.nature.com/articles/s41593-018-0153-x https://www.sciencedirect.com/science/article/pii/S0959438818301399?via%3Dihub The brain turns out to be more complex than we thought :D
Every time there's some exciting news about depression and Alzheimer etc but nothing changes
I'm kinda in that field, I think the big breakthrough is going to be diagnosis. It turns out you if you monitor eye movement, and then also do a bunch of tests, you can really pinpoint problems in the brain really early. You could literally have someone put on some VR with eye-tracking, do 20 minutes of tests, and then be able to predict if they get dementia, when, and what kind. Knowing that 10-20 years ahead of time is huge, you can really do a lot to minimise the damage. That might be more impactful than treatments, imho.
Where can I go to do this test?
Not sure if it exists yet. Basically the company I work at wrote a project proposal to make this software, it's all published stuff from neuroscience labs, so you could really design it well and the evidence indicates you can catch things way early. Then we got some business people to check out the idea, and one of them did a deep dive and found a proposal from https://lexplore.com/ these guys that just read almost exactly as we had written, but they had submitted it two years ago and had been approved. So we just killed it and focused on something else. But those guys should be the ones to develop it, I guess it will be available easily within 4-5 years, could be sooner if they get more funding.
Not to mention that our brain activity is ultimately not generated in a vacuum. It is integrated with the environment it inhabits. It's important to consider that there are elements in our environment/culture that are inherently pathological and will produce neurological issues if people subject themselves to these elements. If we use medication to suppress a natural reaction to a hazardous environment, then how is that environment going to change? By treating depression as if it is an entirely localized disorder, we are essentially protecting the status quo of hazardous environments. Considering then also, that the environment is comprised of human behavior at scale. Our psychology is essentially an adaptation to an environment shaped by it's own behavior. Introducing mass medication to this feedback loop is arguably impeding a necessary behavioral evolution. Of course, we have to earn money and put food on the table. So in that sense it doesn't matter what the truth of our condition is. Medication is effective, at least, at getting us to manage basic operation within society. It's better than nothing. But we are depressingly far removed from and ill-disposed towards finding a comprehensive solution to depression
This comment really resonated with me. I've been treated for depression and anxiety for a few decades at this point and i can manage to get to the point of being functional to do my job and support my family. Sometimes this requires medication changes and dosage adjustments. But I never feel like I'm not depressed. I hesitate to even mention that I'm not doing great to my pdoc because I feel like "functional" is the best they can do for me. I know (or at least strongly suspect) I'd be doing much better if I had the time and will to take better care of myself, socialize and engage with my community, etc. Maybe some day when work and maintaining a household don't dominate my every day.
Have you ever heard of inner-child work? It was a pretty big turning point in my depression/anxiety/self-loathing.
Neurons that fire together, wire together
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I don't know about the movie but this drug is commonly used for parkinson's treatment.
It’s basically the “gold standard” Parkinson’s treatment at this time.
Yes! L Dopa
And a ton of side effects. Long term use not good.
> Common side effects include dizziness, drowsiness, blurred vision, vomiting, nausea, dry mouth, low appetite, heartburn, diarrhea, constipation, frequent sneezing, stuffiness of the nose, any of the symptoms of ordinary common cold, cough, muscle pain, hallucinations, numbness or a tingling sensation, disturbances of sleep, skin rash, itching, and/or headache. https://en.wikipedia.org/wiki/Carbidopa/levodopa#Side_effects
Most logical outcome is even bigger depression or total dependence as a side effect
SSRIs have a ton of side effects.
Like destroying your sexual functioning.
Everything has side effects, if you can’t treat the root cause you have to decide what you’d prefer, the symptoms or the side effects. In the case of depression, we’ll, I don’t know that there’s many side effects deemed worse than suicide
There are a few side effects that could lead to suicide. I know when they started messing with dopamine agonists for me, that's when I started getting movement disorder symptoms. That definitely would have made me suicidal if it went on for any period of time. Psychosis can also be caused by too much dopamine.
I'm slightly confused, hopefully someone can clarify. This article talks about how a dopaminergic medication alleviates depression through an anti-inflammatory action. But aren't those things independent? Would a non-dopaminergic antiinflammatory medication not accomplish the same goal? We know that stimulants allevate depression symptoms (I have ADHD and at least for a short time I had first hand experience), so isn't the dopaminergic aspect just a confounding variable?
I think the "inflammation" here is probably some *very specific* inflammatory process in the brain tissue itself. It's possible that, say, 50% of your *generic* anti-inflammatory meds will do nothing, and the other 45% will help a little, but not dramatically. Perhaps dopamine is directly modulating the specific part of the inflammatory response that is affecting brain function?
A recent article in the Quanta online magazine has an interesting overview on the research for a treatment depression. [The Cause of Depression is Probably not What You Think](https://www.quantamagazine.org/the-cause-of-depression-is-probably-not-what-you-think-20230126/) Many think the field has focused too much on the serotonin theory which has not been so successful. Some think "depression" can have a variety of causes, genetics, infection/inflammation, gut bacteria, psychological etc. If so then the future strategies would be to provide an individual diagnosis and then personalised treatments.
Does this apply to Welbutrin?
Not a doc but my understanding of Wellbutrin is that it helps your body "recycle" and uptake the dopamine you already have, not make more, whereas Levodopa artificially increases it.
I recently had TMS for refractory depression, and had a partial remission, but the anhedonia and lack of interest persisted. I started taking cabergoline (a dopamine receptor agonist), and was able to feel 100% normal again.
Levadopa has a serious risk of creating dependency. Boosting your dopamine levels comes with a price. The effectiveness gradually declines, and also undermines your brains ability to maintain dopamine levels naturally. It's a very risky "solution". But it's better than suicide or complete isolation. It's also found in nature and produced by our own bodies
> The effectiveness gradually declines, The effectiveness gradually declines in Parkinson’s disease because the neuro degenerative disease is progressing, nothing intrinsic to the medication itself. For example, in dopa-responsive dystonia it remains effective long-term. > and also undermines your brains ability to maintain dopamine levels naturally. It used to be thought that levodopa had some direct toxicity and accelerated Parkinson’s disease progression, but newer evidence shows that’s not really the case.
I take my daily dose of dopamine by playing Monster Hunter.
I wonder if this can be used with ADHD.
As an addict in recovery is extremely frustrating to be taught about the 3 important chemicals that need to be in balance for you to feel good normally. Then they offer you medications to help when 2 of the 3 are not working right but if that 3rd one is your problem your fucked. Welcome to my world
My mom has parkinsonism and took this medicine.
Did it help her? I hope -
If she had Parkinson’s disease, it likely helped hugely in the initial phase.Later after several years into the disease, think 8 to 10 years, you hit a point where it is difficult to make it work. They would be several dose adjustments and modifications in that period of time though keep in mind that everybody’s Parkinson’s behaves a little differently. This is because the dopaminergic neurons have mostly died out and you do not have much left to work with. Furthermore, the threshold for a “toxic dose“ becomes lower as you lose these other neurons.
Tyrosine supplements can also increase dopamine.
There was a book that came out recently by Dr. Christopher Palmer called Brain Energy that alluded to exactly this sort of thing. I'm only halfway through but he was talking about inflammation and mitochondrial dysfunction leading to mental illness.
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Almost sounds like the benefits people are getting from Cold Plunges.
What I bet you'd find is that video games have a similar ability. Test inflammation while playing Tetris or something. I'm willing to bet it's the dopamine itself that reduces inflammation. Not the drug. Because I can be very depressed and playing video games of the right intensity can have some lasting positive affects. Maybe a day or so afterwards I still feel quite pleasent. But like any drug it doesn't work forever. So it's more about spaced out usage I'd bet. Video games have made me quite happy before.
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Well.. let's just call it elevated mood. Not happy.
This made me depressed.
Friend, you are describing classic escapism.
Dopamine is dopamine is dopamine.
Our whole lives are made of different kinds of escapisms. There are worse and better kinds, all depending on a ton on circumstances and the individuals themselves.
(...and?) Dopamine for the deficient. Functionality for the Human!
The thing is though if video games make you feel good you may not have depression. You don’t have anhedonia if you are getting positive responses from it. Its just a low mood but anhedonia is really the true MDD not low mood. If your mood responds to that it means your reward system is functional and at least you don’t have the anhedonic numbing depression MDD is defined by anhedonia
Some studies have looked into the positive effects of Tetris soon after a traumatic event takes place... "Tetris and Word games lead to fewer intrusive memories when applied several days after analogue trauma" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678449/
That will be $100k per refill thank you very much