Table 1.

Inclusion and exclusion criteria for study selection

PICOS framework	Inclusion criteria	Exclusion criteria
Population	Adult humans, age ≥ 18 any ethnicity, any sex, any indication, or healthy	Not applicable
Intervention	Amitriptyline monotherapy: any dose, frequency, duration, and oral mode of administration (tablets, capsules or liquid form)	Amitriptyline in combination with another active therapy, topical use of amitriptyline
Comparator	Passive placebo (an inert substance that may mimic the ADRs of amitriptyline, i.e., nocebo effects).	Comparing amitriptyline with active drugs or other forms of therapy
Outcome	Quantification of ADRs for each group, e.g., absolute numbers (frequency and severity (mean/sd)), associated with amitriptyline (i.e., negative effects): (a) caused by its anticholinergic properties and negative effects (b) not caused by anticholinergic properties	No outcomes relating to adverse drug reactions.
Study design	Randomized, double-blind, placebo-controlled trials (RCTs) with ≥ 100 subjects in total for the amitriptyline and placebo arm at baseline: no limitation on publication date, language, setting, time of follow up. Only the first period of crossover trials will be extracted (to avoid carry-over effects [31]. We will include trials with more than two arms, as long as we can identify an amitriptyline and a placebo arm.	Any other study design
Type of publication	Full publication	Abstract, conference presentation, provisional papers without complete results