Anhedonia and side effects while dosing tirzepatide or retatrutide

I'm already doing that kind of mixing, just looking for other ideas that might work. Being stuck in bed from anxiety sounds really rough.

In my experience time fixed it. I began on a higher Tirz dose than usual and felt off for the first few months, basically just sitting around with no drive. It passed on its own, though any dose increase brought it back briefly before fading again. I eventually reached 15 mg every four or five days and stopped noticing the flat feeling even at that level. Maybe the same will happen for you.

Thanks, but I couldn't handle feeling that way even temporarily so I switched to reta hoping it won't cause the same problem. Glad it eventually worked out for you, I might try Tirz again later since I have a big supply stored away.

I get it. I was so out of it I didn't even notice how off I was until things started feeling normal again and I wanted to do stuff. Hope reta treats you better than Tirz did.

Yeah, at first I didn't connect it to anything, but it kept getting worse so I started checking what side effects were listed.

I'm in the same spot with tirz and NAD+. Tried all three GLP-1s briefly and got anhedonia on each one. On sema it hit hard by week three so I stopped. That's why I keep trying the others at low partial doses. Three doses into tirz now with NAD a few times a week and it's mostly okay, though the flat feeling still shows up sometimes. The other morning I was making jokes early, which isn't usual for me at this age and stage. I already had some history with anhedonia turning into depression so that probably raises the risk. Not great at exercising regularly but even twenty minutes of walking helped my usual version of this. Not sure if it fixes the med-induced kind but worth trying. Energy is a bit better but probably not touching the dopamine side. When energy drops I get crankier. Also wondering about NAC.

From your experience I hope the same happens here. I've been ignoring how flat I've felt but I'm starting to admit it might be real. More workouts seem to help and it was already easing after my last dose increase, so maybe if I keep going it will stay gone while I stay healthy.

NAC as tablets or capsules? How much and how often? Would be nice to pick some up right away.

I think the mention was NAC, though I've seen NAD mentioned too for giving energy when feeling flat. Do you do the shots? I can't handle injections. I'm 49, perimenopausal, and have dealt with depression before, so probably more likely to get this side effect. Also read that ADHD can make it worse and I have some ADD traits without meds. Hope the tirz is going better for you now, go slow. Sorry it hit you too. I exercise six days a week and it helps a little with energy but didn't fix the total flatness. Switched to Reta at 5 mg.

N-acetylcysteine has been shown in animal studies to reverse anhedonic behavior in depression models by improving neurotransmitter balance and brain areas involved in reward. I stick with the standard 600 mg daily.

Thanks, I'll give it a try since it's inexpensive and easy to find.

Not a huge amount, started at 86 kg at 1.69 m and now at 76.6 kg. It felt odd not being able to enjoy the progress, like I wasn't sure if I should feel happy. I was usually around 65 kg before but became insulin resistant after having a kid and then again after covid when the weight came on.

I had mood changes too and thought it was perimenopause plus stress from an upcoming exam. Couldn't think of what to say when people talked to me and had no emotions at all, even though I'm usually the type who cries at everything. Got on sertraline but now that I'm feeling better and tapering off, the only change was lowering the tirz dose, so maybe that was the real cause.

NAC in pill form? How much?

Yes the lack of any emotion is terrible. I work with patients who cry and felt nothing, when normally I'm very emotional and can tear up over commercials especially now in perimenopause.

It's been a couple weeks, how are you doing now? NAD+ helps energy but not so much the flat feeling. I've noticed that forcing a laugh at a joke can sometimes bring the feeling back a little, unlike my usual anhedonia where if I wasn't going to laugh it just wasn't there. This version feels different. Still at a low dose, dropped to 1 mg last week. Used the light box yesterday and went to the gym three of the last four days, which usually perks me up. NAC was suggested somewhere. Open to more ideas. Starting to wonder if this just won't work or if I should wait for better weather.

Thanks for checking in. I'm actually back to normal because I lowered and stopped the tirz and switched to reta, which doesn't seem to cause the same flatness. I'm taking the NAC capsules every morning someone suggested, though I'm not sure if it's doing anything. Energy is fine with six days of exercise a week. Haven't tried NAD+ yet but want to look into Pinealon, Semax, and Selank since I have some ADD traits and sleep is often poor. Sorry it's still rough for you, maybe those brain peptides could help. I also tend to get a bit low in November when it's dark and cold and use a light therapy lamp. Heading somewhere sunny next week. If it's too much you could try Cagri instead since it works on a different receptor.

Thanks for explaining that. I watched an informative video on the same topic by Andrew Huberman on YouTube and recommend it. It covers how dopamine works and ways to improve it.

That one is excellent, though there are several good ones. The episode on controlling dopamine for motivation, focus and satisfaction is basically a masterclass. It explains what dopamine does, the circuits involved, peaks versus baseline, depletion, and gives fourteen tools for managing release to help with motivation, focus, addiction, and depression. It covers why stacking dopamine from chemicals and behaviors leads to feeling underwhelmed, how to raise baseline levels sustainably, things that harm or protect dopamine neurons like caffeine, and non-prescription supplements for dopamine along with their pros, cons, and synergy with acetylcholine boosters.

I didn't realize there were multiple, I just watched the one on motivation and focus.

Sorry that's happening. Do you take vitamin D3? That can help. I also make lemon balm tea for mood support. HRT helps when hormone drops affect me. Music I used to dance to really boosts mood, especially while exercising. Good luck.

I was looking into why I don't feel flat on Reta even at 7 mg while it started on Tirz around 8-10 mg. Maybe the glucagon part offsets the GLP-GIP effect on mood, though nobody really knows yet. Could also be because Reta hits the receptors differently.

Quick search shows the glucagon-serotonin link is indirect but they generally move together. The whole thing is odd and inconsistent, some feel better and some feel flattened, so probably no one knows for sure. Does reta slow the gut as much as the others? Meds seem less effective with slower gut movement. Will have to try the lemon balm. Always struggling with protein intake. Tryptophan as a serotonin precursor might matter, though not sure if all protein has it. My thoughts are scattered today.

I like semax in small doses. Started too high once and couldn't sleep. It helps wake my brain up but not sure it helps with staying on task. Selank made me too sleepy even with semax. Also curious about pinealon.

Yes I was just reading about those three peptides. What dose did you begin with? I saw 100-300 mcg mentioned. Also read about cortexin.

Began dosing at 300 mcg but discovered the reconstitution used far less bac water than intended, leaving me awake the whole night. For the current 10 mg vial I used 3 ml. Started at 4 units roughly 0.1 and have worked up to 6 units, a bit under 0.25. Nothing dramatic, just a gradual rise in mental energy. Won three Mahjong games yesterday so it appears helpful. Also taking Alpha GPC plus a mix that includes bacopa, ginkgo and lion's mane.

One way to find out. In my situation I take Wellbutrin, thyroid medication and ADHD meds. Most reports mention raising the dose. Levothyroxine gets absorbed right after the stomach and cannot handle the slowed passage through acid. My other two are extended release so I expect comparable issues since they are not formulated for that.

I take levothyroxine and have stayed at lower GLP doses so far. I keep hearing conflicting things about how these meds affect the thyroid and the medication itself. Some say it worsens the T4 situation, others say the medication stops working. It is confusing. I have not had recent labs so I simply do not know. Testing has become expensive for me lately.

A full hour sounds sensible, or taking it in the middle of the night as I do with my iron supplement when I get up to use the bathroom. For the ADHD meds, do you think they might need adjusting? Splitting the dose is worth trying. How is the HRT going?

Do you not get labs through your GP? I order tests for my patients when needed, though here in Denmark it is covered.

After four weeks since the adjustment it is time for bloodwork soon. Standard timing is five to six weeks, at least that is what I follow with patients. Who handles your ADHD treatment and what medication do you use?

Sorry you had to go through surgery; that is always difficult. I share many of the same worries. Splitting doses has worked well for me. I also have ADHD though never formally diagnosed or treated, along with age-related brain fog and memory issues, which is why I am looking into Semax. Hope everything improves for you. I have been on levo for years. It was stable until menopause disrupted things. I am on 88 now. It is best taken early in the morning two hours before anything else, but I have not been doing that, which may explain why the dose is now 88. I am also on HRT through my provider without labs, just going by how I feel. Curious about your experience with TRT. This stretch on Tirz and Reta has helped me stop drinking, start working out, drop nearly thirty pounds and feel much better overall. It seems to be helping but I should get the labs to confirm.

Generic extended-release Adderall at 20 mg, prescribed by my psychiatrist. The endocrinologist recommended checking thyroid levels eight weeks after any change. I am feeling better so far. I might ask the HRT provider to review things now anyway. Current weight suggests 88 could be appropriate but I am willing to try 75. Is there any downside if my TSH sits right around 1? The surgery felt like a win after years of feeling off; HRT helped and the thyroid medication is part of that. With levo the key is consistency and levels can be adjusted. Peri brain fog is real and everything shifts. My first HRT provider was the same one you mentioned, small world. After about a year and a half I reached 3 mg oral estrogen daily yet still had hot flashes, so something else was needed. It cleared 80-85 percent of the fog. Adding testosterone handled another 10 percent or so, which I count as progress. My work involves analysis and juggling projects and I received a couple of performance plans during the rough period. The HRT provider allowed me to finish my progesterone supply.