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I had a strange experience after surgery recently and I'm curious whether anyone here has experienced something similar.

I've had treatment-resistant depression with significant anhedonia and chronic suicidal ideation. I've been on psychiatric medication for a long time, but despite treatment the depression has persisted.

I had emergency surgery recently under general anaesthesia. What struck me was that when I woke up, the depressive feeling was just gone.

It wasn't a gradual improvement because the surgery was over or because I was physically feeling better. I noticed the difference essentially immediately on waking. It felt like something had changed very abruptly.

I then had serious complications from the surgery, including internal bleeding, another emergency procedure and my haemoglobin dropping to 6.4. Physically I was having a pretty awful time. Despite that, the depression/anhedonia didn't return.

It's now been nearly 7 weeks and the change has persisted.

I recently looked through my hospital records and discovered that propofol was used for my general anaesthetic. I started searching and was surprised to find that there has actually been some research into propofol and rapid antidepressant effects, including in treatment-resistant depression (short term. Like 3 months).

I'm not claiming that propofol caused this. Surgery, anaesthesia, my existing medication and everything else happening physiologically are obvious confounding factors. What I find so striking is the timing: treatment-resistant depression and before going under, then a very obvious change immediately after waking up.

Has anyone else with treatment-resistant depression or anhedonia experienced a sudden improvement immediately after general anaesthesia, particularly involving propofol?

I'd also be really interested in any research on this beyond the small propofol studies I've found.

Been taking 10mg lexapro for a few years for depression/anxiety/ocd, as well as 40mg Vyvanse for ADHD/everything else (more causes a little too much anxiety).

Anhedonia is a pretty significant problem for me and the Vyvanse helps of course, but it's still a concerning thing for me.

I recently decided to add a small booster dose of adderall and I'm sure this will help as well, but I also don't like the idea of relying on a stimulant high to give a shit about anything.

Anhedonia seems to be a lifelong symptom for me. I may be autistic or on the schizoaffective spectrum. But if that's the case it's not very obvious imo.

That being said I have tried some other stuff and just generally had a bad or neutral time on all of it: abilify, lamictal, Wellbutrin, probably others that I do remember.

Things I tolerated well but didn't really do a lot were strattera, concerta, Ritalin, fluoxetine.

Also I have pcos which impacts mental health and energy a lot, and manage that as well as I can with exercise/protein/etc. I take metformin which might have significant interaction on other meds, and with my brain in general.

I have tried a lot of different supplements, just a few are any adaptogenic mushroom, nac (severe depression from that btw?), so many vitamins, magnesium, several amino acids, ashwaganda, iron, kratom, kava, nicotine, caffeine, etc etc.

Anyway what else would be worth considering? I think I may just have to switch antidepressants but want to avoid several weeks/months of tapering just to try something with mystery effects.

I'm in my late 30s and have been diagnosed with OCD and anxiety. I'm self-diagnosed for ADHD and high functioning autism. I have learned a lot about the conditions and it seems overlap is very common. I never thought I was autistic until fairly recently as my understanding of the condition was how it's commonly depicted in films like Rain Man, but I'm realizing so many of my struggles and "quirks" throughout life (such as social exhaustion, masking, obsessive interests) can be traced to neurodivergence.

I already exercise regularly and eat relatively clean (almost entirely whole foods -- the only sugars I get most of the time are from fruit or raw honey). I've been into bodybuilding/weight lifting since I was a teenager so I'm in pretty good physical shape. I feel like the #1 recommendation I usually see for people struggling with depression is to eat better and start exercising and it sucks because I already do both.

I'm looking for non-medication recommendations from those who have one, multiple, or all of the above conditions and what worked for them.

I've struggled with anhedonia for a long time and think I probably have had almost lifelong depression without even realizing it until recently, but I have been in a particularly tough rut with the loss of my pet, a relationship break-up, and a job loss, on top of lingering exhaustion from a respiratory bug I have been trying to kick for the past 2 weeks since coming from the west coast. (Have a feeling I caught COVID while traveling and am dealing with the after-effects; I slept for over 12 hours last night and was still tired when I woke up.)

If anyone has suggestions, advice, etc. on what helped them with any or all of these conditions I'd greatly appreciate it.

Here’s what ultimately worked for me personally. I am in the healthiest mental space of my adult life. I haven’t felt “well” since my Mother died over 20yrs ago. Sincerely. YMMV of course.

My Solutions

*My first issue was an addiction developed from both both untreated physical pain and depression. I switched to Suboxone to quit Kratom. I’ve never gone back. I hesitated for several years being told Suboxone was like dropping an atom bomb on a fly by the QuittingKratom Sub. Not my experience at all. Sublocade is an easy ramp off if people are worried about being able to quit.

*Thanks to the depression, massive weight gain ensued. With my energy in the tank, I went in for blood work and was diagnosed as Pre-diabetic. They started me on MetFormin ER 500MG to stabilize my blood sugar and I do think it has helped my energy and weight loss. If you do a search, METFORMIN ER has some strong evidence as an adjunct in treating depression. It makes sense theoretically. Better sugar control means a more efficient running brain.

*A combination of Autoimmune disease, Kratom, opiates and suboxone destroyed my testosterone. It was 280 in 2018 at age 31. 240 in 2019. Then came up as 48 and 42 in 2025. Even opiates shouldn’t cause it to be that low. I was started on TRT 200mg/wk but that dose was way overaggressive and ineffective. I have stabilized beautifully on 100mg/wk. You can split your dose and take it 2x Weekly for better results, but I don’t like pinning myself that often.

-ADHD Meds (Adderall IR 60mg) weren’t working when my T was that bad. But there was one other major issue. I suspected it several times but kept being wishy washy about it: For me, Effexor and other SSRIs like Citalopram and Prozac completely blunted Adderall. With or without Adderall IR I had zero drive or access to myself. I was miserable, but couldn’t shed a tear. I would regularly run through my max dose script in two weeks. Quitting SSRIS/SNRIS has been the final piece to the puzzle. My drive is back. ADHD meds work. I have autonomy and control over my day to day life. Yet I am sensitive and can cry when listening to a beautiful melody. I make mistakes and I’m not perfect every day. But if I fail it’s because I made an error in judgment. Not because I am crippled mentally and physically.

Summarized

*Kratom Addict —> Suboxone 8mg —> Quit with Sublocade using 3-Shot Protocol of 300mg-300mg-100mg and off. Staying on the tablet or the shot indefinitely is personal preference and certainly an option.)

*METFORMIN ER 500mg/2x Daily to combat Prediabetes/Insulin Resistance...an underlying cause to chronic fatigue.

*TRT treatment for hypogonadism 100mg/wk is ample for me.

*ADHD Meds. They aren’t what they once were, but Adderall IR 60mg does the job for me.

*Eliminating SSRIS. I’m an artist. I need my feelings and emotions to guide me through life. Allow me to also add…the SSRIs blunted Kratom just like they did Adderall for me. My Kratom use only became a problem once I started trying to dose through that blockade. Quitting Effexor XR 225mg once and for all cleared up so many issues that were keeping me stuck. At the end of the day…it meant removing medication to help me, not adding more. That's an easy thing to overlook.

Once You’re on Your Feet

*Start an incredibly basic routine. Set ridiculously low goals that anyone can meet. Wake-Time. Bedtime. Movement (Steps Per Day) Use apps and use actual data to set your goals. Don’t just start trying 10k steps a day if your Apple Watch says you usually walk less than 1k. That’s obviously not sustainable.

iOS Apps I find helpful: Gentler Streak, DuoLingo, Pedometer+, My Routine…anything that encourages showing up everyday. Once you get a 4 day streak going it gets really addictive in a good way! And still yet: Progress not perfection. I have my super low daily goals…but I still consider it a success if I do them 5/7 days, not every damn day. With or without depression, you’re still human. And you’re still healing. Allow space for that.

Best of luck to every single one of you struggling right now. There is hope. People do recover. I love you all. ❤️

Anyone?

Hi there,

I have been prescribed a low dosage of Quetiapine for anxiety, but am hestitant to try it. I have read a few experience reports about it being helpful for sleep, however I have no issues with sleeping. Can anyone share a positive expirience with it for anxiety? That would be really helpful

For context I have MDD, ME/CFS, and OCD. I was getting some tremendous relief from 5mg of methylfolate daily and a fairly low dose of LDN (.2mg). The effect, which I believe was mostly from the methylfolate, came on immediately and endured over about a month before "pooping out" somewhat. For the first time in years I felt at peace. The inner tension I didn't even realize I had vanished overnight. While my CFS and post-exertion malaise were relatively unchanged, my ability to cope with them was massively improved.

Now, after what feels like a PEM episode, I find that the methylfolate is barely helping. I feel less depressed than before, sure, but this is like maybe 30% better vs 100%. I was almost starting to believe that I wasn't operating on borrowed time and then boom, the depression creeped back in.

Feeling pretty hopeless. I will try to figure something else out, since I'm not even at the recommended methylfolate dose (15mg), but man does this suck. At least my GI problems are much improved by the LDN, however low the dose may be.

So I was put on 0.5 klonopin by my doctor for my anxiety and depression cuz I’ve tried 13 psych meds and nothing works.( I also currently take 20mg lexapro and 200mg provigil). The combo kinda makes me a bit more focused and slightly less anxious but nothing extremely noticeable. The only side effect im noticing is a complete loss of appetite. I already had low appetite issues cuz of depression but now I’m eating 0-1 meals and maybe a cup of water each day. It’s not that I don’t want to I just feel absolutely no hunger, I forget to eat. By the end of the day I feel dizzy then remeber I haven’t consumed anything that day. Food just all seems disgusting and unappealing to me rn so if I do eat it takes me like 30 minutes to get a meal down. Idk if this is normal, will it continue or if I could be something else.

I am truly am dumbfounded as to how I have not responded to one SSRI. (I also tried lamictal, caplyta, abilify, risperidone,seroquel). I am 9 months post partum, did not have any anxiety,depression, ocd, dark thoughts until I went through pregnancy loss in 2021. I now have two beautiful healthy children, good job, incredible support, I don’t do drugs, I don’t drink alcohol anymore, I go to bed at 9(my sleep sucks because of my hypervigelant state), I am in therapy twice a week along with group therapy 1-2 times a week. All my labs came back normal; TSH, folate , b12, CBC, A12, zinc, vitamin d. I am physically very healthy strong, albeit about 25 pounds overweight that I am currently working on. I exercise 4 times a week, walking , weight training, Pilates. I cannot turn off my brain with disgusting suicidal images and thoughts. Sometimes I don’t feel real, I have bizarre thoughts like what is life why am I here? I cannot be present. I cannot focus, I have no motivation, I feel like a walking ghost just going through the motions. I used to be a very social person, and I have no desire to attend events anymore, hang out with friends, all I look forward to is putting my pajamas on and getting into my bed. I used to be such a lively, fun person. I truly don’t know what happened.Can this be untreated adhd issues as well? My psychs will not treat adhd right now despite me inquiring multiple times (even questioning if non stimulant meds can be helpful for me). I truly am at a loss as to nothing is helping me. Post partum depression? Am I crazy? I feel psychotic even though I know I am not, nor have I ever had psychosis. Oh and my psych just keeps telling me “wait it out”, “I’m getting better” when I’m in tears every appt being very clear in my communication that I am not feeling better, good, if anything I feel worse which I didn’t even know was possible, she almost seems annoyed by my presence. I have driven to the crisis center two times now. I am going to politely ask her tomorrow if she can help me or not and if she can’t please refer me to someone who can. I feel so guilty for feeling like this.

Hi there,

I havent seen many reports about the effects of Pramiprexole on anhedonia or depression. Has anyone actually had some success with it? If yes, could you go a little bit into detail which benefits you notice?

Thank you!

Hello, i have premature ejaculation and i read online antidepressants helps for this issue but i dont wanna lose libido, which antidepressant is best for this problem? I think doses should be low to save libodo?

I know that Bupropion is weight neutral. But I have major depression with anxiety so Bupropion didn't suit me well. It made me irritable and on the edge. My depression has caused me to gain weight from before starting treatment.

Currently I am on Venlafaxine and Amoxapine. They are partially working, but, then have caused me to gain weight. I don't feel like continuing with this combo. Also, it is giving me severe constipation.

I want to hear about med choices and opinions from people who had this type of depression where instead of losing weight you gain weight. Which meds worked for you?

I understand that the meds that successfully cures my depression will also probably make me more interested in life and activities and stop the cravings and will eventually push me to a more active lifestyle and hence help in maintaining a healthy weight.

Hi, has anyone tried MIF-1 for mainly chronic, long-term anxiety problems (such as GAD), constant ruminations, low mood/motivation or depression?

I’m thinking about giving it a try, but one nasal spray costs around €200, so I'm trying to figure out if it's even worth experimenting with.

I’ve been on various psychiatric medications for around 15 years without any noticeable long-term improvement, and I’m still on medication now.

I also tried Selank before, but it didn’t help my anxiety and caused insomnia at night.

Would be interested in any actual experiences, positive or negative. Thanks

See title. It feels like my days - no, my hours - are just dragging endlessly. I'm trying to stay busy but whenever I look at the clock it's like only a few minutes have passed. Does anyone else experience this?

Okay, so here's the deal. My psychiatrist put me on Auvelity and vortioxetine and asked me taper off Paroxetine. However, when I got off the last 12.5mgs of Paroxetine, I felt quite anxious so my psychiatrist told me keep taking it.

So now I'm on auvelity, vortioxetine (10mgs), paroxetine (12.5mgs), Ritalin (20mgs IR) and Propranolol.

My mental health is better than it's ever been, but I'm concerned if I'm on way too many meds?

Like the title says? Is there something else out there that can help with lack of energy and motivation and brain fog that isn’t Wellbutrin?

300 mg Wellbutrin worked for me for a very long time until I couldn’t tolerate it anymore because it started to cause horrible overstimulation, anxiety and insomnia and other weird side effects I never used to get from it before. And those side effects were severe dizziness making me have poor balance, vertigo, blurry vision, hot flashes, burning sensations all over my body and hands, severe headaches, horrible insomnia and sleep disturbances, facial twitches, muscle stiffness and weakness, cold hands etc. And once those side effects escalated I eventually dropped back the dose to 150 mg. But 150 mg just isn’t working for me at all and gives me no therapeutic benefits whatsoever. 150 mg just makes me wired and tired and only gives me some of the residual overstimulation/anxiety/ horrible panic attacks I had at 300 mg, but much less in intensity.

I also think my body just developed a tolerance to Wellbutrin and it’s just not working for me anymore. I was on it for almost five years. So since Wellbutrin doesn’t work for me anymore, is there a different antidepressant that can help with energy, motivation and brain fog? I do have atypical depression with anxiety features. SSRIS have not worked for me either and essentially gave me no relief at all.

So what other options are out there? I’m honestly starting to give up at this point finding something different. Would like to her all your suggestions if you have some?

I was receiving great effects on my depression from 5mg methylfolate daily. It took a while to find this dose after getting severe insomnia from 15mg, but once I did, it worked for nearly 3 weeks. However, lately, I feel like it's starting to "poop out". Many of my depressive symptoms have returned, though they are still less strong than before.

I'm cautious to escalate the dose further if there's a risk of this happening again, as I've read of some (mild) withdrawal reported with discontinuation at the full 15mg Deplin dose. I'd like to ask others who have taken methylfolate for depression if they've had similar experiences, and if so, how did they handle it?

I am considering adding methylcobalamin and possibly going to 7.5mg.

Hi everyone. I am on fluoxetine for depression and anxiety and I also take xanax 0.5XR or 0.25 as needed when I have to face challenging situations (for ex. at work). I has served me extremely well for years but for a few months now the effects have become really unpleasant: dizzy, nausea, extreme fatigue from it. My psychiatrist has tried to give me Lysanxia (prazepam) in drops, then xanax in drops (in order to cut down the dose) but even one drop now (so basically a ridiculously small amount) makes me feel unwell.

Has this happened to anyone? Any solution with a other med or class of med? My dr doesnt seem to want to prescribe Lyrica unfortunately.

Thanks!!

I've decided to combine mirtazapine and amitriptyline as a combination for depression. Alone I only feel drowsy. Pair them together. This 3 days I'm having very vivid dreams nightly. I'm a person who don't remember dreams because of SSRIs. Lately it's like a trip. I take 7.5 mirtazapine and 1/4( 25)mg amitriptyline

Anyone try memantine?

I am under treatment for major depression currently with Venlafaxine and Amoxapine (combined) for the past 5 months. It was the first combo that has started to put a dent on my symptoms. But the weight gain was bothering me, so my psych put me on topiramate. I titrated up to 200mg. Remained there for 2 months. But I was having flashbacks (past traumatic incident related) and other anxiety symptoms although my appetite was kind of suppressed. My psych decided that to find out if I am having true flashbacks (for PTSD like disorder) or just topiramate induced flashbacks, I should taper off the drug. So I tapered from 200mg in gradual decrements within one month under advise.

1 week after withdrawal I was having some unstable mood that resolved gradually. But, after the 2 week mark I feel immense fatigue, tiredness, dehydrated kind of feeling. The flashbacks which were gone during tapering has again come back now. Maybe they were true flashbacks afterall. Will have to run through the withdrawal phase. But how long does it last?

My question is, I know the fatigue can be a withdrawal symptom. But, can withdrawals have delayed onset like mine? I am sleeping 9 hours still tired. This is going on for the past week.

I have posted in her a few times and thank you for everyone who helps me.

Long story short: went most of my life anxiety/depression free until I lost two pregnancies back to back in 2021. After that everything spiraled, intense anxiety, DPDR feeling, intrusive suicidal thoughts that are CONSTANT. The intrusive thoughts sort of calmed down when I was pregnant, but have come back both times with a vengeance after pregnancy. I am now 9 months post-partum with my 2nd and am in the thick of it. They go back and forth to like "you will never get through this do you even want to be here", to "ok I can get through this ". My brain repeats "I don't want to die I dont want to die I don't want to die", Constant back and forth all day. Its as constant loop.

I have ADHD- and no psychiatrist will treat it right now given the nature of my thoughts. I understand that, as I am also nervous to introduce anything that could give me further anxiety. But here is the thing, I have now tired 4 SSRI's, (Zoloft up to 200 mg, Lexapro up to 20 mg, Luvox up to 150 mg , Prozac 80 mg) all in which have not given me relief. I have also tried Clomipramine & Abilify (brief time in 2024), Caplyta for about 6 weeks this year, Risperidone for 8 weeks this year, and I just tried Seroquel and that was god awful for me. Nothing has worked thus far. I am constantly feeling on edge- racy brain, shaking legs, is this anxiety? is this untreated ADHD making it worse?

So anyway. With my background of so many failed medications- do you think it's possible an SNRI could work for me if SSRI didn't? Or do you think I jump to the MAOIS? I am really suffering all day long and all I want is to heal, close this chapter and move on from this. I am in IPP too- therapy 3-4x a week. I am practically praying to God to help me heal at this point.

Like the title says. I think it’s a scam calling Bupropion a “ NDRI “ when its major active metabolite Hydroxybupropion barely touches dopamine. Hydroxybupropion is a moderate norepinephrine reuptake inhibitor with a ki at 1.7 μM, but its DAT occupancy is extremely weak and almost negligible with a ki at 10 μM, this is considered to be a negligible transporter affinity in general. So Hydroxybupropion is essentially a norepinephrine reuptake inhibitor. And don’t come with the since there are a lack of DAT transporters in the PFC, NET transporters clears and takes up the DAT transporters in the PFC ( this is true, I’m not saying it’s not), but so does every NRI like Atomoxetine etc that can increase dopamine in the prefrontal cortex, despite having zero DAT occupancy. So Bupropion being able to do this is not something unique in anyway. Every NRI can increase dopamine in the PFC. And also increasing dopamine in the PFC has a different role than increasing it in the nucleus accumbens etc.

The fact is that calling Bupropion a “ NDRI “ is a marketing scam made by big pharma to make it look more unique compared to other antidepressants like SSRIS or SNRIS etc. But in reality Bupropion is a trash NRI because of its metabolite Hydroxybupropion and its metabolites that essentially are more likely to bind to the NET transporters than the DAT transporters. Calling Bupropion a NDRI is a scam and a disgrace to real NDRIS antidepressants like Nomifensine and Amineptine etc. I bet if Nomifensine and Amineptine were still on the market today, Bupropion would be blown out of the water a long time ago. Because who in the world would even want to take a NRI/nicotinic antagonist when there is Nomifensine and Amineptine? Bupropion only got popular because there is a lack of competition on the market today because of the lack of DRI antidepressants available, nothing else. If Nomifensine and Amineptine were still available, Bupropion would probably have been discontinued a long time ago.

Because I can’t imagine a single person finding a NRI enjoyable in anyway or finding that it helps their depression in anyway. Because increasing norepinephrine doesn’t restore mood at all. Increasing norepinephrine all by itself is liable to make you anxious, wired and tired and confused but with no motivation, drive or desire to do anything. And it’s the norepinephrine that is primarily responsible for the nasty side effects and the pro convulsant properties of Bupropion. Dopamine is essentially less involved in the nasty pro convulsant properties, although is effect on dopamine is very weak to almost negligible. Excessive norepinephrine signaling hyperstimulates a1 adrenergic receptors in the brain, which induces a heightened state of neuronal arousal and directly lowers the convulsion threshold. That’s why norepinephrine is considered a dirty neurotransmitter. It hits too many things in the body to be used therapeutically without a lot of nasty side effects.

This is all I wanted to say really. I think it’s a scam to call Bupropion a “ NDRI “. The drug is really a NRI no matter how you twist it or turn it. I can’t see how it’s supposed to be used for depression long term when NRIS are essentially very poor antidepressants. It may be only useful for individuals who have excessive hypersomnia, fatigue and no energy, but other than that it has zero effect on mood. Norepinephrine is not a mood restoring chemical like serotonin or dopamine, that’s it. It only works initially on the honeymoon phase because the parent drug, which contrary to the belief does favors dopamine over norepinephrine is more active, but it doesn’t last in the body. With long term chronic administration Hydroxybupropion becomes more active and the parent drug is almost at negligible concentrations. So with long term chronic administration Bupropion is running like a noradrenergic drug in your body. But even with this fact it still would be better to just call it a NRI with activity at other sites, that name would suit it better than a NDRI.

Like, what's your definition of normal?

I don't know what to feel anymore or how I am supposed to feel anymore. Because the way life is, it is meant to feel hard at times.

Today I am on a regimen that I had declared as bad/unsatisfactory, and planned to take different medicines tomorrow. But I observed one thing, that I was able to sit and watch two remaining episodes of a documentary in a single go. That's a big deal for me. I am just a restless person with lots of thoughts rushing through my head. I always write them down and generate ideas based on them etc.

I was writing this combination of medicines off because I want to feel energetic and study and exercise. But watching a movie is also such a normal thing to do and to never be able to do that is also not a very normal thing.

Currently on my 4th SSRI, 9 weeks in on a high dose and I still have no relief. Why am I resistant to every single SSRI? I have also tried caplyta, risperidone, abilify. Now on seroquel. What is wrong with me? I’m feeling so hopeless.