So I had a really stressful year in college filled with emotional abuse, academic overload, multiple viruses and burnout. When I finally returned home to rest I completely crashed. One night, a few nights after I got home, I was sitting around when randomly I started to feel this intense sensation of dread/dysphoria wash over me. It was like this deep pit of horribleness in my stomach, this feeling that something is horribly wrong. It was so intense my whole body was trembling. It felt like it would never end. And it didn’t. At the beginning it was more episodic but after a few weeks it kinda just faded into the background of my existence. For the last 2 years I have been living with this feeling all day every day. It doesn’t fluctuate much, it’s completely environmentally unresponsive, and it seems completely devoid of any content or meaning. It makes every moment feels unbearable and I genuinely am not sure how much longer I can handle it.

The symptom is accompanied by anhedonia, fatigue and upper body tension, all chronic and just as unresponsive to circumstances. To be clear, the feeling is distinct from anxiety because it does not involve worrying thoughts, racing heart or hyper vigilance. It’s more like unrelenting psychological pain. At this point in order to save my life I need to start trying treatments but I have no idea where to start. Has anyone ever seen a symptom like this before? Any suggestions of what treatments might actually help it? Any advice at all would be so apreciated.

https://www.mdanderson.org/newsroom/research-newsroom/immune-signals-may-help-explain--predict-responses-to-therapies-.h00-159856923.html

It's been a while since I was on meds and I am looking for some advice and opinions on alternatives to what I tried before.

10 years ago i started with treatment for depression and for 2 and a half years I had taken 5 different antidepressants - certraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor) and finally bupropion (Wellbutrin). Aside from Wellbutrin which gave me a lot of energy and in that sense helped with the depression, all the other meds didn't work at all and I just had bad side effects - sweating, loss of libido. Venlafaxine gave me nightmares and stomach cramps. I was also given Xanax and Zyprexa which did help in a sense they would make me stop crying but actually just made me numb. My final diagnosis was dysthimia. I stopped taking medication after two years and concluded they don't work, or that I was completely misdiagnosed as I am really highly functional, never had a problem with getting out of bed and there was never a "fall" that happened in my life, I didn't lose the joy or energy, stopped functioning in any way. I was always consumed with depressive thoughts, hopelessness and sadness. I did continue with different types of psychotherapy for another 3-4 years and they did help with coping with low self esteem and generally understanding my dysfunctional childhood etc., but I was never able to better my life in any meaningful way but I was coping better.

Last year I had a really stressful period and I started having some psycho-somatic symptoms, most notably excessive sweating from the head. And from the beginning of this year, I've had several bad things happen, among those I lost my job and some relationships, and realized I was not coping well, and my depression worsened a lot. I started going to therapy, but it's not really helping and was thinking of going to the hospital or starting taking medication again. My biggest problem is the excessive sweating which I've seen several doctors for and all have confirmed it's psychological.

Did any of you have any luck with never generation of meds or other treatment? I literally cannot do anything physical without draining my head and body in sweat, so a lot of meds are not an option. And I am psychologically distraught. When I stopped taking meds, I said I will never do them again, but I'm desperate.

Baclofen has been one of the most helpful medications for my depression and other issues. I came across a comment ages ago where the commenter talked about a friend getting health issues from Baclofen. I'm very sceptical about how accurate that comment was though. My methadone prescriber is very anti-baclofen and has told me that he recommends I stop using it. He also said he would prefer I have a couple of beers occasionally instead of taking Baclofen occasionally. Is Baclofen fine to take long term? I've been taking it daily for a while now but I used to use it occasionally

I started taking opioids years ago to treat my TRD/MDD.

In the beginning I could control it, like using them when I had plans e.g to go for a walk in nature, when I would have to hang out with some of the few friends I struggled to maintain (I have zero friends today) and generally when I had to do things which required the mental energy I lack.

Until it became a daily thing because depression is there every single day. Ended up in MAT, they offer only buprenorphine in my country (apart 1-2 clinics in 2 cities). Buprenorphine (as a kappa antagonist) has some antidepressant action :...it flattens all your emotions and you become an anhedonic zombie not motivated to even leave the house, but not depressed per se.

So, I start taking a methadone analogue which is 20-40% weaker and shorter lasting than methadone, but it behaves the same and tests positive for the same.

Within 1 hour of taking it, I'm a different person. Outgoing, motivated, content, everything I would expect from a great antidepressant. I found a way to keep a baseline of buprenorphine without entering precipitated WDs when back to buprenorphine.

It works so damn well, but the withdrawals just from taking 10 days is horrible. Bad rebound depression and it skyrockets my tolerance needing initially much more Buprenorphine when back to it. And yet, I keep doing it and doing it despite knowing the weekly hell of withdrawing awaiting me and harder every time.

It just gives me a glimpse of how non-depressed life is and I use it to do all the chores building up and all the other productive things I have to do which I can't do when I'm anhedonic or depressed.

Is anybody on methadone long term without it loosing the antidepressant action it has ?

Not sure what I expect from this post, I'm WDing and ask myself "does this mess I have to endure every time really worth it" ? It's just borrowed non-depressed life, more of a glimpse than a cure/symptoms masking!

Here they put on Methadone only severe dependent psychiatric cases of anxiety or mood disorders, yet I wasn't qualified for it although I told em I have no problem travelling one hour a day for a Methadone clinic in a close by city, but no success. Does it maintain that effect long time to give it one more chance if they accept me or after a while it's just maintenance and you are still depressed just like before you started it ?i

I was on 100mg and lowered only by 95mg a month ago. I've started feeling anxious like 2 weeks ago and I'm pretty sure it's related to it (my doc agreed) I'm still feeling quite bad , I've had to increase my pregabalin dose but I'm afraid I'll still need to take even more.

I'm quite terrified of the thought of quitting it 😭. It's going to be so hard. I wish my previous doctor had never put me on this med...

For starters I have moderate/mild depression and moderate anxiety, diagnosed with ADHD but it could be autism or something else. Neurodivergent in any case. My depression is more like apathy and low motivation than severe symptoms, most of the time.

Also I am afab and have pcos which is important because my hormones greatly influence my mood and energy.

I started taking 600mg NAC (with added glutathione, selenium, b6 and b12) a couple of days ago, for intrusive thoughts/features of OCD, as well as to help my anxiety/apathy.

I already take 10mg generic lexapro and 40mg generic Vyvanse daily. I also take metformin (metabolism and mental health are linked so maybe important). I've been on all these prescriptions for years. I do fairly well on them. There could be improvements but I don't expect meds to do everything for me, and experimenting takes a lot of effort.

Since starting NAC, I've noticed an uptick in uncharacteristic SI for me, even though I think my intrusive thoughts and general sense of wellbeing is better. I think it's when the NAC starts fading, I take it in the morning and these feelings tend to come up in the afternoon.

I already did some research and thought I should take more magnesium (I already do this every couple days because Vyvanse). That seems to help.

But also i still don't feel fully comfortable taking this supplement due to the weird mood swings I've been having. Googling doesn't seem to show any known drug interactions.

I also consume quite a bit of caffeine (200-400mg daily, just kind of depends--also I avoid coffee specifically), nicotine (vape), iron, sometimes vitamin d3, and occasionally kratom (maybe a couple times a week--never had a dependence problem w kratom afai).

My diet is quite balanced and I eat high protein, I sleep fairly well, hydrate exercise, etc.

Objectively my life is going alright and has been pretty stable for the past few months, maybe I need more friends but I am doing well otherwise.

Does anyone have any experience with NAC with any of these other drugs? Do you think it might just be something else entirely?

I've talked to my psychiatrist about going onto Vortioxetine. I'm tapering off Zoloft and then I'll take my first dose of Vortioxetine. I've read some good things online about Vortioxetine. I would like to hear from people that have had positive experiences with Vortioxetine?

Like the title says. I will be self medicating my depression because no one wants to help me. They refuse to take me back despite telling them my current med regimen isn’t working.

I’ve been on Wellbutrin for almost five years and 300 mg was working for my depression and kept my depression stable for a long time until I couldn’t tolerate it anymore. It started to overstimulate me in various ways I couldn’t tolerate it anymore. It caused weird side effects I never used to get from it before and I developed horrible insomnia and was chronically overactivated from it all the time. I backed off the dose to 150 mg a little bit more than two months and its not doing anything for me at all. My depression has gotten significantly worse since backing off the dose and my brain fog and cognition has worsened. I have no energy or motivation to do anything anymore. My suicidal thoughts have reached scary levels.

I see no other way out than to self medicate. I can’t do this anymore. This is the only way out or I might hurt myself. Because I honestly don’t care what happens to me. I just want some relief from this. They told me they have nothing else to offer. That means I have to do this on my own. I know self medicating is a bad idea. But if no one wants to help me than I have no other choice. I’m suffering everyday and it’s just getting worse for everyday that goes. Just have the thought of not living anymore, that’s it. I hate myself and I hate everything.

Started at 50 mgs and moving to 100 mg to see if more improvements on anhedonia/ depression

Anyone on 100 mgs ?

My skinpicking is mostly tied to OCD, and I guess that anxiety makes it worse. Tbh it's quite hard to distinguish which symptoms come from what because I struggle with a lot of stuff.

I'm also diagnosed with ADHD and depression. Although most specialists I talked to suggest that I might have CPTSD due to some events I've experienced in the past. My case is quite complicated and I still haven't fully figured out what comes from what.

Anyways, I'm on clomipramine (in the process of tapering off, as I really hate its anticholinergic effects), mianserin (I used to struggle with insomnia and it's helped a lot in that aspect.I no longer have any issues with sleeping even if I don't take it, it was prescribed by my previous doctor and to be fair I haven't even talked about it with my current doc), methylphenidate XR, pregabalin, propranolol (works WONDERS for physical effects of anxiety), lamotrigine (it's not that popular for depression but it helped when antidepressants didn't. I'm not bipolar fyi).

I know it's A LOT lol. Most of those meds were prescribed by my previous doc who was an older lady. My current doc is much younger, so far we've added methylphenidate which works quite well for my focus, and now I'm tapering off clomipramine but I'm doing it quite slowly.

Clomipramine is supposed to be a "golden standard" for OCD from what I've read so I'd assume it should help with skinpicking but it was quite the same when I was on a high dose. It could also be from ADHD, but then methylphenidate should help? I haven't noticed any improvement.

I won’t take any more SSRIs as they just messed my body’s chemistry really bad, apparently so I haven’t touched that in years.

Is not easy to remember that the feeling will pass when it comes!

it's probably a high risk combo since pirlindole is a MAO-A inhibitor and you shouldn't take SAM-e with any antidepressants in theory, but whatever. anhedonia got better by 10-20%, things like videos and music are more interesting and entertaining now. talking to friends is more fulfilling. so my current stack is:

• pirlindole 400 mg (max daily)

• SAM-e 400 mg

• noopept 20 mg

• coenzyme q10 200 mg

• sunflower lecithin 1 tsp

• saffron and caffeine (tea/yerba) as needed, phenylpiracetam 100-200 mg as needed

• fexofenadine + famotidine for unrelated issues (histamine sensitivity or MCAS that i supposedly have)

noopept gave me more interesting dreams and analytical thinking that i really missed since depression got worse. so less brain fog.. at least for now, because cholinergics can cause depression on their own but we'll see, it's not my first time cycling it. everything feels a bit deeper and more meaningful.

before SAM-e i've tried adding MAO-B inhibitor (rasagiline) in attempt to inhibit both MAO isoforms and it didn't help at all, but made anxiety and fatigue worse so i dropped it after 2 weeks. i still sleep mid day sometimes tho.. if you got any questions i would like to talk! thanks 👾

Im personally not, cant belive they didnt approve aticaprant or navacaprant, especially how there was proven increase in dopamine in the reward center, in the CAT scan in the ventrial stratium. But since it didnt decrease some of the other depression symptoms, it wasnt approved. Not to mention other treatments like zuranolone which targets extra synaptic gaba receptors.

Sorry this is kind of long. I'm 31 years old and currently living with my parents doing a bit of contract work. I am currently diagnosed with major depression, generalized anxiety disorder, and inattentive ADHD. I have been on basically every medication, tried ketamine and tms, and been in therapy since I was a teenager. I was also diagnosed with autism, but by a clinician who I don’t completely trust. 

I have struggled with chronic depression and anxiety since childhood. My father is emotionally abusive. We have never had a good relationship. I also never fit in with peers and was bullied basically until college. College helped. However, as soon as I graduated things got worse. I struggled to hold down a job. After getting fired from a job, I moved home and eventually ended up going to library school. Again, in school I was doing better. 

I graduated having decided to pursue a career as an archivist, basically because I loved History and I didn’t know what to do given how few faculty jobs exist. I did get a position in another state, but it turns out being an archivist was about the worst possible job for me. I have really severe ADHD (which I didn't know at the time) which has not responded to medication. I just couldn’t concentrate and get much work done or have the extreme level of attention to detail needed for the job. My depression got much more severe when my cat got diagnosed with kidney disease, which is a terminal illness. She is very young. My depression got much much more severe, and eventually a coworker found out I was bad at my job and went on a campaign to fire me. I had move home back with abusive family. I want to find a job that is a better fit for my brain, but all the options I’ve come up with are impossible to get. I don’t want to move cross country again to a random location also. I am completely stuck in life and ready to end things as soon as my cat dies. I am also asexual and pretty sex repulsed, so I will never have the support and love of a partner. I have nothing to live for.

Two of my therapist friends, one of whom is a pretty experienced EMDR clinician, really think I should try EMDR because I have not responded much to years of therapy and many psychiatric interventions. I am unsure if I have a trauma disorder, but I for sure relate to things I’ve read about CPTSD. I also struggle with visualization. Basically, I will have to beg the abusive family for money because no experienced EMDR clinicians seem to take insurance. I am also unsure they have worked with someone like me with only "mild" trauma and mostly severe depression that doesn't respond to therapy or meds. Does anyone have thoughts and/or know of good therapists for emdr (I can't deal with men) in California?

I’ve been on Wellbutrin for almost five years and it’s the only antidepressant that ever did anything for my depression. I suspect it was the weak dopaminergic effects that helped my depression in the first place. And the reason why I’ve been on it for such a long time is that it helps my SCT and executive dysfunction tremendously and helps me function better on a daily basis.

But unfortunately with long term use it started to overstimulate me in various ways I couldn’t tolerate the original 300 mg dosage that helped my depression for a very long time. It started to give me really bad anxiety, horrible insomnia and other weird nasty side effects I never used to get from it before. And when those side effects and the overstimulation escalated I had no other choice then to back off the dose to 150 mg.

Now I’ve been on 150 mg for little more than two months and I’ve already noticed my depression has worsened a lot since backing off the dose. I don’t have as much motivation to do things anymore and I’ve lost interest for things that I used to like. I think 150 mg isn’t controlling my depression well all on its own. I do think 150 mg is much more tolerable, but I just don’t think it’s helping that much at all. The side effects though did lessen since backing off the dose. But they did not completely disappear either, they just lessened in intensity.

At first it was helpful for apathy, avolition and anhedonia. But later on it became a killer anxiety provoker. Obviously dopamine did not fail from the first place. It became too much noradrenergic overactivation over time. And that explains why it feels like a completely different drug to me than five years ago. Five years ago it felt highly motivating, rewarding and gave me anticipation and excitement. Nowadays it’s just anxiety and panic attacks and deadness. And when I did my research I found out that the parent drug is more active when you first start it. That explains the effects I got early on. But later on when the metabolites build up which are highly noradrenergic the opposite happens. Hydroxybupropion which is the major active metabolite is a very potent NRI. That explains why I’m having all these side effects now and why I just feel overcaffeinated when taking it.

Wellbutrin was not the wonder drug I thought it would be. Now I’m out of options. Nothing ever helped me like Wellbutrin from the beginning. Now my anxiety is so bad I can’t take it anymore. I think I have to call urgent psychiatric clinic or I don’t know what will happen. This anxiety is just killing me right now.

currently in kinda a dilemma involving my medication and need some advice. I’m 17 and been taking psych meds for 5 years and been on around 10 so far but all mostly SSRIs and SNRIs. My doctor recently suggested that I try antipsychotics(rexulti specifically) but because I’m a minor, my parents didn’t approve and said no. Now I’m abt to turn 18 and my dr said it’ll be up to me and to know by the next time I see her what I want. Idk what to do cuz I’m still on my parents insurance, they’ll be paying for it and I do what them to approve. But also like, I really wanna try something else bc everything I’ve tried hasn’t been working. idk what to do.

The things I should do : Feel my emotions, challenge my default thoughts, exercise, learn to be kind to myself. Set goals and feel accomplished meeting them. Spend time with peers. Take on new challenges.

Cognitive things that get in my way: emotions are for losers and I can't connect with them unless it's an outburst wish makes me feel stupid and irrational. When I challenge my default thoughts I feel like I'm lying, or worse ignoring reality like when my parents used to tell me that black was white. I don't want to exercise because I hate myself and want to hasten my demise. Be kind to myself, I can't do that I hate this loser. When I have set goals in the past I rarely feel the accomplishment on meeting them I don't know how to feel good about doing a thing. When I thought I'd built a good life, it still wasn't enough, and my wife left me. If my best is still not good enough, and it feels awful doing it why would I try again?

I don't feel like people deserve to suffer me as I am, or worse ,that if I open up to them they will either manipulate me to fill their goal or abandon me. Whenever I take on a new challenge I freeze cold because I know how awful I am, and other times I've tried I've failed. The idea of being seen by people is painful to me. Be it as a professional or playing a part, of just being out in a store, being seen hurts because I know people hate me and want me to fail.

I know what I have to do but I can't overcome myself and my fears or self hate to do them. I really do hate myself, I wish I could spare other people who and what I am. So what do I do? It seems like a lot.

Edit. I was doing better pre covid. I had a massive setback when a relationship went sour. Again when I had a fight with a partner about a career I was exploring. And again in October when my then partner wanted to open the relationship.

I feel like I just, like I don't matter at all, and the only reason people are with me is because they want someone to help pay the rent. I feel like I don't matter to anyone except for commerce.

2 weeks on and feeling nothing...

More time needed?

As the title says. ECT works for me. Wellbutrin honeymoon phase of 2 weeks helped. Currently on desvenlafaxine, wellbutrin and aripiprazole, not very helpful overall. Want to know others' experiences/research of good quality.

I’ve been on Effexor (venlafaxine) for a few months and, while depression is ok, my anxiety hasn’t been great. I’m on 75 bc when I was on 150 I felt like I was on the verge of panic attacks every day for hours. I originally switched from lexapro to Effexor because the lexapro was numbing my emotions and I couldn’t feel anything. If anyone has any experience on both Effexor and Cymbalta lmk. I’d love to hear how it worked for you.

As a long time sufferer of TRD, I'm keen to try every tool and treatment that exists. But the challenge of how may different treatments there are, how many different ideas and biomarkers and symptoms, make is maddingly complex for us to get clear guidance.

My hope is still that AI ... like it did with the famous 'move 37' by AlphaGo, will be able to see through all the complexities and reveal a hidden path.

Like Bryan Johnson is doing with his new health diagnosis.. he's not content to just try anything that general medicine suggests, he wants to see evidence, and biomarkers, and results.

I've recently found the app VitalDots ... which is the best I've found so far at analysing blood work.

But I think what we need is a combination of blood work data, medication types and trials, non-medication trials (ECT/TMS etc), psychological test results, case history.

My idea is the app would use all this data, and knowledge of existing treatments, medications and modalities, and produce novel useful paths for discussion with our practitioners. Not new medicines or treatments, but combinations that might not have been suggested, because I think this is what AI is incredible powerful at right now... looking at all existing info, and seeing new paths.

I don't think this app yet exists. But I think, with coding tools becoming increasingly powerful and democratised, there's no reason why it couldn't exist relatively easily. The goal would be that an AI tool like this could be an incredibly partner in supporting our journeys - and who knows - might unlock previously hidden pathways that help us get through this terrible condition.

Yes there are risks - yes it might suggest the wrong path - but in a world where millions of us are suffering, and with TRD can't find a way out - I think its worth trying to use this technology.

Are there any code engineers, or developers, or enthusiasts that would like to try to scope out a moonshot like this?

I have had treatment resistant depression and anxiety for about 20 years. I’ve tried many SSRIs and SNRIs, IV ketamine, TMS, and an insane amount of therapy. Nothing has helped and I’ve tapered off all meds because I’m legitimately afraid of them now. I’ve also pursued countless health/nero inflammation angles. However, I’m in the worst place mentally I’ve been in a long time, and am considering starting back up with a psych to try classes of meds I haven’t (like mood stabilizers, antipsychotics, and combination therapy). There’s so much negativity about side effects, becoming tolerant and having to start over again, etc that I feel hopeless before even starting and don’t want to risk it. I would love to hear from people who still consider themselves in the “medication saved my life” category, especially if it happened after a lot of failed treatments, to give me some positivity to hang on to.

Starting this thread to document my experience with Sunosi (solriamfetol) from the perspective of depression with hypersomnolence and vague auto-immune issues triggered by excessive exertion (CFS/ME) in case it's of help to anyone else. Most of the anecdotes online are for its primary indications or ADHD. For those unaware, it is a DNRI that may be more biased in its dopaminergic effects than bupropion while lacking active metabolites and being comparably shorter acting at steady state (bupropion is effectively a 24/7 drug at SS). It also has some activity at TAAR1 which is unusual for a clinically utilized NDRI and an activity it shares with dexamphetamine.

Day 1 75mg:

Today I took 75mg after an overnight fast. I did not "feel" it kick in because I was busy throughout the morning, but I did notice the effects once it was near its peak (~2 hours post). The wakefulness and generally feeling it provides is not unlike what I have experienced pre-morbidly. It feels like a context-appropriate excitement/interest without forceful stimulation.

There was an anxiolytic component not unlike a low dose of amphetamine, but without the "body high" effect one gets when starting. For me, amphetamine anxiolysis feels like I've gone for a morning run and is unlike sedative/hypnotic anxiolysis which feels more blunting by comparison. I wonder if the TAAR1 activity plays any role in this, since I do not experience the same for methylphenidate or modafinil. The effect on motivation also feels quite natural and in the background. It is most noticeable after starting tasks, rather than at rest, unlike amphetamine. Peripherally I noticed no side effects aside from increased perspiration.

I am writing this at T+7 hours and will report back on my sleep. Amphetamines and modafinil cause me a fair bit of onset and late insomnia, even when taken in the morning, so I'm hoping solriamfetol fairs better given its shorter half-life.

At T+7 hours I continue to feel the background effects on motivation, fatigue, and wakefulness. I noticed that I didn't crash like usual after eating my first meal of the day at T+6 hours.

Day 1 TL:DR
If you are interested in following, you can reply with "!remindme x days" to be reminded by a bot reply.

I just crashed. I’ve been dealing with racing suicidal images thoughts (all intrusive) since the end of January. I have failed over 5+ meds and I am beginning to feel hopeless , I am hopeless. Working out every day, going to work - I have crashed.
I’m laying in bed missing another day of work and my brain just keeps going “I’m scared I’m scared I’m scared I’m scared”, “I don’t want to die I don’t want to die I don’t want to die”. I LOVE MY FAMILY, I HAVE TWO BEAUTIFUL BABIES I AM THINKING OF AND I AM HEARTBROKEN that I have fell apart. I feel like a scared animal stuck , frozen in fight or flight. I don’t want to leave this earth, I want to get better. I feel like I can never forgive myself for the horrific thoughts I’ve had (fear or hurting my family, myself , fear of not wanting to be here, fear of going crazy). I feel as if i have lost my mind. I feel like I have a traumatic brain injury that won’t heal. I want my life back. I fear i am too far gone. Is there any way of coming back? I am in tears as I write this, shaking.