Milnacipran - completely stopping my brain fog

[hurray]

You dont take it regulary, yust before , after O ?

Hi hopeoneday,

No, I don't take it regularly. I take one dose approximately 1-1.5 hours before O.

[hurray]

Milnacipran inhibits the reuptake of norepinephrine. Is this having an effect on my immune system, and stopping my POIS symptoms after O?

The sympathetic effects of norepinephrine include:

Multiple effects on the immune system. The sympathetic nervous system is the primary path of interaction between the immune system and the brain, and several components receive sympathetic inputs, including the thymus, spleen, and lymph nodes. However the effects are complex, with some immune processes activated while others are inhibited.

https://en.wikipedia.org/wiki/Norepinephrine

[hurray]

"There are several drugs which boost norepinephrine, so why is milnacipran any different?"

Well, I have already tried several NRIs:

atomoxetine (Strattera) - uncomfortable feeling during O, brain fog remained
buproprion - made me feel jittery, brain fog remained
ritalin - gave me energy and focus before quickly building up tolerance, did not stop the brain fog
duloxetine - felt like bad flu, could not drive or work, withdrawal symptoms, too sick to accurately gauge brain fog
venlafaxine - felt like bad flu, could not drive or work, bad withdrawal symptoms, too sick to accurately gauge brain fog

The effects of duloxetine and venlafaxine (both SNRIs) were interesting. They made me feel terrible - there was no way that I could take them every day. But my POIS felt a bit different while I was on both drugs.

I read that duloxetine and venlafaxine don't have a powerful effect on norepinephrine at low doses. There was only a substantial norepinephrine reuptake inhibition effect at high doses.

Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819762/

Trying milnacipran, I was surprised  to find that a low one-off dose was sufficient to completely stop the POIS brain fog that I have been accustomed to for so many years. I attributed this to the powerful effect that milnacipran has on norepinephrine reuptake inhibition.

Milnacipran also has multiple reports that it cured the brain fog of fibromyalgia sufferers.

[kingfisher]

Hi hurray, quite encouraging to hear this. Thanks a lot for sharing this.

One member in this forum found beta blockers effective. Beta blockers block beta adrenergic receptors. How different would this be from a noradrenaline reuptake inhibitor I don't know. But it seems the noradrenaline/adrenaline pathways are key for POIS symptoms to occur.

It's also interesting that the brain fog / fatigue symptoms of POIS could be using the same biochemical pathways as fibromyalgia.

[kingfisher]

Have you tried amitriptyline before and also is it safe to take only before O and not regularly, as that is the case with most antidepressants.

I was considering asking my doctor for amitriptylene, but since milnacipran is working so well for me I may not have the opportunity now.

A doctor told me it takes amitryptiline about 3 weeks to get into our system and become effective. So amitryptiline may not be as effective as a single dose option like milnacipran.

[hurray]

Hi hurray, quite encouraging to hear this. Thanks a lot for sharing this.

One member in this forum found beta blockers effective. Beta blockers block beta adrenergic receptors. How different would this be from a noradrenaline reuptake inhibitor I don't know. But it seems the noradrenaline/adrenaline pathways are key for POIS symptoms to occur.

It's also interesting that the brain fog / fatigue symptoms of POIS could be using the same biochemical pathways as fibromyalgia.

Hi Kingfisher. The milnacipran is still working as of 2 days ago 

That's an interesting comparison between beta blockers and NRIs. I agree that noradrenaline (norepinephrine) pathways could be an important part of understanding POIS symptoms. Amitriptyline has potential, but as you point out, you would have to take it all the time for it to become effective.

I found a couple of interesting articles discussing brain fog, fatigue, norepinephrine and milnacipran:

Fibrofog and fibromyalgia: a narrative review and implications for clinical practice

First and foremost, patients’ experiences of cognitive impairment/mental fogginess should be acknowledged. Fibrofog is real, and appropriate neurocognitive testing can reveal these deficits.

Recognizing that fibromyalgia is associated with a CNS dysfunction, serotonin and norepinephrine reuptake inhibitors have been recommended for and used to treat the pain and other neuropsychological symptoms.

https://pubmed.ncbi.nlm.nih.gov/25583051/

Effects of Milnacipran on the Multidimensional Aspects of Fatigue and the Relationship of Fatigue to Pain and Function: Pooled Analysis of 3 Fibromyalgia Trials

Factors that may contribute to central fatigue include elevation of proinflammatory cytokines and activation of nitric oxide synthase pathways dysfunction of the hypothalamic-pituitary-adrenal axis and low levels of neurotransmitters such as serotonin, norepinephrine, and dopamine. As an SNRI, milnacipran is thought to act on the central nervous system by increasing levels of serotonin and norepinephrine, which may alleviate some of the neurotransmitter deficits associated with fatigue.

In placebo-controlled studies, treatment with milnacipran resulted in statistically significant and clinically meaningful improvement in mean fatigue levels and in a higher proportion of ‘‘responders’’ (ie, patients with Q30% reduction in fatigue).

https://pubmed.ncbi.nlm.nih.gov/24847745/

[Mushnikk]

Have you tried amitriptyline before and also is it safe to take only before O and not regularly, as that is the case with most antidepressants.

I was considering asking my doctor for amitriptylene, but since milnacipran is working so well for me I may not have the opportunity now.

A doctor told me it takes amitryptiline about 3 weeks to get into our system and become effective. So amitryptiline may not be as effective as a single dose option like milnacipran.

This latency applies to basically all antidepressants, but only for the serotonergic antidepressive component and not this pharmacological action. It is simply a differing pharmacological receptor binding profile between the two antidepressants and milnacipran has a higher affinity for the adrenergic receptor I guess.

[Mushnikk]

A case study whose subject found relief with Milnacipran both with premature ejaculation und postcoital headaches. Took 50mg, and tried a beta blocker and indomethacin without success.

[hurray]

A case study whose subject found relief with Milnacipran both with premature ejaculation und postcoital headaches. Took 50mg, and tried a beta blocker and indomethacin without success.

I think I've found the case study you mention. Very interesting, thanks 

https://journals.lww.com/americantherapeutics/Citation/2019/10000/Milnacipran_for_Postcoital_Cephalgia_and_Premature.37.aspx

[demografx]

Thanks, hurray

[Mushnikk]

A case study whose subject found relief with Milnacipran both with premature ejaculation und postcoital headaches. Took 50mg, and tried a beta blocker and indomethacin without success.

I think I've found the case study you mention. Very interesting, thanks 

https://journals.lww.com/americantherapeutics/Citation/2019/10000/Milnacipran_for_Postcoital_Cephalgia_and_Premature.37.aspx
[/quote

[hurray]

No POIS for over 2 months now. Milnacipran continues to work 

[demografx]

Great, hurray!

[hurray]

Great, hurray!

Thanks Demo 

[Mushnikk]

No POIS for over 2 months now. Milnacipran continues to work 

Awesome, congrats! I will try this also, I have a feeling it might be the right thing for me. Did the quality of your orgasms change?

[hurray]

No POIS for over 2 months now. Milnacipran continues to work 

Awesome, congrats! I will try this also, I have a feeling it might be the right thing for me. Did the quality of your orgasms change?

Thanks Mushnikk 

Yes indeed, my Os became a lot more intense, and lasted for longer. I've never experienced this effect with any other medicine or supplement. A very pleasant side-effect.

If you do decide to give it a try, good luck! Milnacipran is quite cheap

[Vandemolen]

I was considering asking my doctor for amitriptylene, but since milnacipran is working so well for me I may not have the opportunity now.

I took amitriptylene for a few years, but it did not help me. I stopped because of the side effects like sweating. Do not stop cold turkey, but ask your doctor.

A doctor told me it takes amitryptiline about 3 weeks to get into our system and become effective. So amitryptiline may not be as effective as a single dose option like milnacipran.

[hurray]

I was considering asking my doctor for amitriptylene, but since milnacipran is working so well for me I may not have the opportunity now.

I took amitriptylene for a few years, but it did not help me. I stopped because of the side effects like sweating. Do not stop cold turkey, but ask your doctor.

A doctor told me it takes amitryptiline about 3 weeks to get into our system and become effective. So amitryptiline may not be as effective as a single dose option like milnacipran.

Hi Vandemolen!

The side effects of amitriptylene do sound nasty, I doubt that I will try it now. Milnacipran has its own side effects, I felt some nausea the first few times I tried it. It has also been known to increase blood pressure for some people.

But it also stops me getting brain fog 

After O, I feel more relaxed and cheerful, but I have no difficulty having a conversation, going shopping, or going for a drive. The fog does not descend on my brain any more. Feeling good after an O is nice after all these years 

[hurray]

Once again, milnacipran has prevented me from having any brain fog following an O.

It is by far the most effective thing I have ever tried in order to get rid of my POIS. And I have tried many, many different drugs and supplements over the last 20 years.

[Aladin]

Hi
That sounds so promising!  Please, tell me, i understand brain fog was your main symptom. Did you not suffer from depression/anxiety when on pois?
If so, did these symptoms disappear also?