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