Amitriptyline: the good,bad and ugly
 

If you talk to ten people about their experience with this drug, you'll get 10 different answers. Amitriptyline is a "dirty" drug in that it modulates many receptors in the body both inside and outside the central nervous system. On the one hand, it explains why it is used for so many different medical problems. It also explains the long list of side-effects.

Amitriptyline functions at higher doses as a Serotonin>Noradrenalin reuptake inhibitor and results in an increase in availability of these neurotransmitters in the brain (Dopamine may also be involved to a lesser extent). Hence the reason why this class of drug was the "go to drug" for depression and anxiety until the late 1980s.

They have also become popular for pain modulation because of their ability to modulate pain perception (many proposed mechanisms of action including its ability to block sodium channels, antagonize NMDA, reduce Substance P, modulate the GABA and opioid receptor, induce an anti-inflammatory effect via prostaglandins, etc....)

Unfortunately, it's the fact that this drug wears multiple hats that leads to the troublesome side-effects. This is especially true in its ability to modulate the anti-histamine receptors in the brain (drowsiness) and the anti-cholinergic receptors everywhere (dry mouth, constipation, perhaps even memory....which is why it's not commonly used in the elderly). It's the "anti- histamine" side-effect of drowsiness that is used therapeutically to help with sleep maintenance (as opposed to sleep induction).

One has to also remember that the same dose can cause different degrees of "drowsiness" which can persist for different amounts of time for different people. There are many explanations for this phenomenon. For one, Amitriptyline is metabolized through the liver through a special enzyme pathway called the P450 cytochrome system. Within that system, there are many enzymes (proteins that help break down or deactivate a drug). In the case of Amitript., the enzymes 2C19 and 2D6 do most of the work. Anything that affects the function of these 2 enzymes will affect the blood levels of the drug and thus the side-effects.

The most common example of this is when other medications are used that affect the way 2C19 and 2D6 work. The result can be higher or lower levels of Amitriptyline in the blood stream. We also know that people can genetically have different levels of efficiency to their cytochrome enzymes again resulting in higher or lower blood levels for the "same" dose. (An example is the pain-killer "codeine" where almost 20% of the population are genetically "rapid-metabolizer". What they will tell you is that when they take the drug, it does nothing for their pain.) People may also have a sensitivity to this drug for reasons we can't explain yet.

Bottom line: Amitriptyline is a reasonable choice for assisting people with sleep difficulties in the setting of mTBI (especially if headaches are present). People generally do not develop tolerance to the anti-histaminic effect (sedation) hence the reason it can be used long-term without having to escalate the dose. However, it will not be suitable for everyone. The reasons for this are multi-factorial. One might however try smaller doses to determine if their intolerance is dose-dependent.

Cheers, Canadoc

I didn't like it because it made me very tired, and I was fatigued to start with. Prefered using an SNRI and then Lyrica.

Canadoc, thanks for your good explanation.

If I understood you right, amitryptiline can on the one hand supress TBI symptoms (because of it's effect on the receptors), but on the other hand it also acts sedative. This means that some people could indeed miss the point where they healed their TBI because the drug makes them still feel tired, exhausted or dazed(I often heard the term 'zombie feeling').

At the moment, I feel like I'm in no man's land, because I feel like a zombie, not knowing wether it comes from my injury or the drug.

And because of that I'm definately planning to stop taking the drug by slowly reducing the dose over a few weeks. (how long does this sedative effect last, after one has stopped to take it?)

You talked about genetic factors. Well my father also took it, maybe he had the same feelin as I have. I will talk to him.

Hey guys,

I'm about to start taking amitriptyline, hope you don't mind me asking a few quick questions.

What specific improvements have you noticed since taking it?

I'm being prescribed this for post traumatic migraines (which i don't think I'm getting, but I'm willing to try), my neuropsychologist thinks it's this because of my light/sound sensitivity. Has anyone noticed improvements in these after taking it?

Sorry for hijacking....

Abilee,

If it's any use to you I had headaches and light/noise sensitivity and took Imigran (Sumatripen) for this and it really helped.

Been on a 100 mg for over a year. Just stopped taking it and noticed no difference incept for being in a better mood. Was supposed to be helping my migraines and sleep and did neither.

Also please don't complain about sleep 7 hours is a ton. Im lucky to get a half hour to an hour even on meds like klonopin

I am on amitriptyline to help with sleeping. I am almost unable to sleep without taking it. I have been on it for a year at a low dose of 100 mg. I found that most of the fatigue went away after 2-3 months.

It takes about an hour for me to feel sleepy. I also need to fall into a deep sleep, it stopped the running dream feeling I had. I went weeks feeling like I never slept until the doctor gave me amitriptyline.

I take 100 mg of Topamax for the headaches (again a low dose).

This are both clear cut for me. I don't sleep without the amitriptyline and I have daily headaches with the Topmax.

Oh the jealousy I have for you all.

I didn't do it long because obviously it's counterproductive for my other issues but for about a two weeks straight I took 40mg melatonin, 6 zzzquills and two unisoms plus normal scripts. Still couldn't fall asleep. Never got over 2 hours sleep in that time frame either.

It's weird. I average ill say an hour a sleep for a 24 hr period but I never feel tired. No clue why. But it's been this way for a while. I wish I could say it is anxiety and im thinking but its not. Sure doesnt help that when I close my eyes it looks like a laser show is going off. Yet again cluster headaches at 930 at night a few times a week dont help.

Can I ask what you mean by running dream feeling? I've been having vivid, emotional dreams what feels like all night every night and it's really messing with my head, finding it hard to distinguish some stuff which happens in my dreams with what has actually happened in reality.
Has anyone found that amitriptyline helps this?

ABSOLUTELY HATED THIS DRUG!!

Slept the entire nest day, was wicked out of it, and that feeling lasted way too long to be an effective employee the following day! Not to mention I had VERY disturbing dreams that night before and didnt like it at all- even after dropping the dose down in half i still didnt feel good the next day. This is NOT the drug for me at all. NO WAY !