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.