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Psychopharmacology book

Amitriptyline (ELAVIL)

Amitriptyline (ELAVIL)

“Elavil elevates your mood”. Introduced in 1961, amitriptyline (Elavil) was heavily prescribed prior to the arrival of SSRIs. Amitriptyline remains the most prescribed TCA and is the #88 most prescribed drug in the US. It appears to be more effective than newer antidepressants (Cipriani et al, 2018). Off-label uses include headache prevention, fibromyalgia, and insomnia.

Amitriptyline mnemonics

Amitriptyline tends to be anxiety-reducing (as opposed to drive-enhancing). Amitriptyline is not recommended for the elderly because it is more anticholinergic and antihistaminic than the average TCA. This can lead to falls. Of the tricyclics, it is the most likely to cause weight gain, averaging about 15 pounds over 6 months—“Am I fat now?”

TCA amitriptyline mechanism

Amitriptyline is highly anticholinergic. Dry mouth (an anticholinergic effect) occurs in almost everyone who takes 50 mg or more nightly. 


Although amitriptyline is not the deadliest TCA, it is the most prescribed. As a result, over 40% of all antidepressant fatalities are caused by amitriptyline. It should not be prescribed to patients with a history of overdosing on pills. Of 33,219 single-drug exposures to amitriptyline reported to Poison Control, there were 145 deaths (Nelson & Spyker, 2017). This equates to a mortality risk of 1 in 229. Multi-drug overdoses including amitriptyline are much more dangerous. 


Amitriptyline is metabolized to nortriptyline, which has fewer side effects and fewer interactions. So, why are more scripts written for amitriptyline than for nortriptyline? Possibly because the side effect of sedation is not a bug, it’s a feature—amitriptyline is often intended to double as a sleep medication. 


Dosing: For depression start 10 or 25 mg HS and titrate slowly due to sedative effects. The usual maintenance dose for depression is 50–150 mg HS. Maximum is 300 mg HS for depression and 150 mg for other uses. The target dose range for migraine prophylaxis is 10–100 mg HS. For neuropathic pain, consider dispensing a bottle of 10 mg tabs and instruct the patient to take 10 mg HS for one week and increase the dose by 10 mg weekly until pain is improved, up to 50 mg HS while they wait for their follow-up visit. Taper gradually to discontinue. Consider dispensing less than a 30-day supply if the patient is at risk of overdosing. 

Amitriptyline and nortriptyline (Elavil and Pamelor) tricyclic structures by Dr Jason Cafer MD
amitriptyline metabolised to nortriptyline

See Tricyclic antidepressants (TCAs)

Copyright 2024 CaferMed Publishing.  Intended for prescribers. 

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