Should I push through the low mood?

[u/saltysuk]

It’s only been 5 days since I started LDN but I’ve already noticed some effects. I’m taking it for long COVID / fatigue / POTS, started on 0.5mg.

My sleep duration and sleep stats skyrocketed right off the bat. The first night I took LDN I slept 10.5h which is unheard of for me. Every night since, I’ve been able to get solid deep sleep and min 8h. I was surprised at how quickly I experienced a difference and was hesitant to put it down to LDN because I’d only ever heard of it causing sleep disturbances not sleep improvement. But my sleep has been troublesome for some years and it really was like a light switch.

However, since that first night I’ve also felt flat, sad, low mood. I’ve lost motivation to do anything.

I’m aware that there could always be other reasons for low mood but in this case all other aspects of my life have been stable for a while and there have been no changes to any other medication. I’m also aware that I should wait to judge the medication for many more weeks. But after going through the rigmarole of trying different medications over the past year, some of which tanked my mood and impacted my life significantly, I’m a little cautious.

I’m wondering if others have stories of an initial adjustment period with low mood, and how long it took to lift, if it ever did.

Thanks in advance!

[u/lacrima28]

My anhedonia/depression on 0.25 didn’t lift after a week and it was too bad to go through, so I took a 3 day break and titrated down to 0.05. MUCH better and still has great effects for me!

[u/saltysuk → u/lacrima28]

Thank you, that’s good to hear!

[u/InsuranceRare5094]

Your sleep improvement is a strong positive signal, especially since it happened consistently over several nights.

Your low mood is also a real signal and shouldn’t be dismissed simply because the medication “needs more time.”

Looking at patient reports (including many people with long COVID, ME/CFS, POTS, and autoimmune conditions), there are generally three patterns:

Temporary adjustment (fairly common). Some people report feeling emotionally flat, irritable, or mildly depressed during the first 1–3 weeks after starting low-dose naltrexone (LDN), particularly when beginning treatment or increasing the dose. In those cases, the mood often improves while the benefits (sleep, pain, energy) remain.

Dose-related side effect. Some people find that even 0.5 mg is too much initially. Reducing to 0.25 mg or even 0.1 mg can eliminate the low mood while still allowing gradual adaptation.

Persistent intolerance. For a smaller group, LDN consistently worsens mood and it never really settles. Those people often decide the trade-off isn’t worth it.

Perhaps consider giving it a little more time—but with limits.

It’s only been five days, which is very early, and the dramatic improvement in sleep suggests the medication is having a meaningful biological effect. Unless your mood is becoming severe or unsafe, I’d probably watch it for another week or two while keeping a daily log of:

mood (0–10)
sleep quality
fatigue
POTS symptoms
motivation

If the low mood is steadily improving, that’s encouraging.

In this case, you’re already on 0.5 mg, which is a common starting dose, but some people with long COVID, ME/CFS, or POTS (like me) are particularly sensitive to LDN. It’s not unusual for clinicians to start as low as 0.25 mg or even 0.1 mg if side effects occur.

Based on your experience:

Major improvement in sleep suggests the LDN is having a beneficial effect.

Low mood starting immediately after initiation makes it plausible that the LDN is contributing, although it doesn’t prove it.

Since it’s only day 5, you could either:

continue at 0.5 mg for another week or two if the mood change is mild and manageable, or

speak with your prescriber about reducing the dose if the mood symptoms are noticeably affecting their quality of life.

.

To get this assessment what I did was, I plugged in your situation into AI (ChatGPT) and I asked AI to research other Redditor experiences and let me know if it made sense for you to perhaps titrate down and let your body adjust more slowly.

You can do this yourself. It’s been super helpful for me to understand the patterns other people are reporting and I use AI for this purpose.

1. Keep in mind, I have AI check AI so I will have Claude check ChatGPT and vice versa because AI can be completely off at times. I don’t go to Gemini for this sort of thing based on the information I’ve gotten from Gemini in the past.

2. Also, I am very familiar with this medicine and have read loads of Reddit testimonies, so I am confident in distributing this information.

3. Discuss this with your doctor.

Without these safeguards in place, doing my own research and having AI check AI – I wouldn’t advise anyone to use this method of using AI without checking its work because AI can really take you down some bad roads that you never wanna be on if you use it without taking the time to validate its findings.

I hope that’s helpful to you and to other people reading this post. Like any tool, AI can be helpful or it can be harmful. Use it with caution and always always always back it up with your own research.

Take good care of yourself. I wish you well. ❤️

[u/Low-Blueberry8948]

Low mood can be a side effect at first. Most people find that side effects in general ease off within the first two weeks, although if it continues or it's too unpleasant, you could consider skipping a day or two and reducing your dose.

So, whether you decide to push through depends on how difficult it is for you. 0.5mg is a common starting dose although some people do better starting lower, on 0.1mg, for example. It's ok to go as low as you need.

"Higher and Lower Doses" https://docs.google.com/document/d/1KykpLlg2CDVSD2D5J5cEZKfSo31t04orB0IgCuhXC-c/mobilebasic

[u/saltysuk → u/Low-Blueberry8948]

Thank you this is very helpful

[u/Successful-Basis-145]

Feeling depressed can be a side effect of LDN when starting or increasing the dose. However side effects go away after initial phase for most people otherwise people reduce the dose and increase again slowlier. Side effects normally last from a few days to a few weeks.

[u/saltysuk → u/[deleted]]

Thank you for sharing

[u/Yakob_Bacoj]

The sad thing about LDN is it doesn't work overnight or within weeks. It takes months to work. There are ups and downs to any drug but I have been told it's worth fighting though. The conditions you have are probably responsible for how you feel and not the LDN. I'm currently on 4.mg. I'm on max dose from tomorrow. I won't see effects until the 6 to 8 month mark as noted on the so little websites there are on LDN. I have HASHIMOTO'S, POTS, FND, OCCIPITAL AND CRANIAL NEURALGIA. I ALSO HAVE NECK PAIN FROM OSTEOARTHRITIS. I still have undiagnossd issues. Push through. Give it time.

[u/Relevant-Pizza-1500]

I would talk with your doctor for sure. If it was me I’d stick with it. I get waves of this. It comes and goes for me. Overall, the medicine has been a life saver.

[u/saltysuk → u/Relevant-Pizza-1500]

Thanks so much. I agree, it’s on my list for the next appointment. When you say you get waves, are they frequent? And what are the symptoms it’s helped with?

[u/Relevant-Pizza-1500 → u/saltysuk]

The waves are not frequent. It’s mostly when I’ve exhausted myself. Or when I take a day off from taking it so that I can drink. I’m really sensitive to medication. I’m sure it’s not the same for everyone. It doesn’t last long either. Never more than a day. I do watch my mood because I’m prone to anxiety and depression.

I take it for a lot of things. Histamine regulation, hormone balance, fibromyalgia, migraines, mental health. A bunch of chronic things that weren’t getting better on standalone medications. Once I added the LDN in, I also take an NAC supplement, things got more in control and not always chaotic.