Table 1. Study characteristics.
| ID | Indication | Total number of subjects | Age in years (both sexes) | Dosage amitriptyline per day (mg) | Accepted concomitant medications | Excluded concomitant medications | Dry mouth-related ADRs | Digestion-related ADRs | Genitourinary-related ADRs | Vision-related ADRs | Thermoregulation-related ADRs | Cardiovascular-related ADRs | Fatigue-related ADRs | Attention-related ADRs | Memory-related ADRs | Restlessness-related ADRs | Coordination-related ADRs | Unspecifically reported Ach-ADRs | Gastrointestinal-related ADRs | ADRs related to hypersensitivity | ADRs related to the endocrine system | Unspecifically reported NACH-ADRs | Unspecifically reported G-ADRs | ADRs overall | Discontinued due to ADRs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rickels 1970 | neurotic depression | 136 | 100 (flexible dosing) |
X | X | X | X | ||||||||||||||||||
| Feighner 1979 | depression | 143 | 75–150 (flexible dosing) |
X | X | X | X | X | X | ||||||||||||||||
| Goldberg 1980 | neurotic depression | 122 | 18–60 | 75–200 (flexible dosing) |
X | X | X | ||||||||||||||||||
| Rickels 1982 | depression | 136 | 100–200 (flexible dosing) |
X | X | X | |||||||||||||||||||
| Roffman 1982 | depression | 214 | 18–65 | 75–150 (flexible dosing) |
chloral hydrate | X | X | X | X | X | X | X | |||||||||||||
| Claghorn 1983 | major depression | 172 | 18–65 | 75–300 (flexible dosing) |
chloral hydrate | X | X | X | X | X | X | X | X | X | X | X | X | X | |||||||
| Amsterdam 1986 | depression/ anxiety | 105 | 21–67 | 100–300 (flexible dosing) |
chloral hydrate | sedative/hypnotic, anxiolytic medication | X | X | |||||||||||||||||
| Reimherr 1990 | major depression | 299 | 18–65 | 50–150 (flexible dosing) |
chloral hydrate, given as infrequently as possible and not on nights before psychiatric scale ratings, as a sleeping aid; estrogens, progesterone, and diuretics | concurrent psychotherapeutic medication or concomitant medications, receiving another investigational drug within 4 weeks of enrolling in this study | X | X | X | X | X | X | X | X | X | X | X | X | X | ||||||
| Carman 1991 | major depression | 100 | ≥ 19 | 120–300 (flexible dosing) |
contraception | X | X | X | X | X | X | X | X | X | X | ||||||||||
| Bakish 1992 | major depression | 112 | 18–65 | 50–150 (flexible dosing) |
chloral hydrate, short-acting benzodiazepine | antihypertensive, diuretic, anticholinergic or sympathomimetic agents, psychotropic medication, foods rich in tyramine | X | X | X | X | X | X | X | ||||||||||||
| Pfaffenrath 1993 | tension type headache | 131 | 18–65 | 25–75 (flexible dosing) |
analgesics, mixed analgesics, ergotamine tartrate, dihydroergotamine, acetylsalicylic acid, paracetamol | X | X | X | X | X | X | X | X | X | |||||||||||
| Carette 1994 | fibromyalgia | 126 | ≥ 18 | 10–50 (flexible dosing) |
acetaminophen | nonsteroidal anti-inflammatory drugs, hypnotic drugs, antidepressant agents | X | X | |||||||||||||||||
| Bremner 1995 | major depression | 100 | ≥ 18 | 40–280 (flexible dosing) |
chloral hydrate | X | X | X | X | X | X | X | X | X | X | X | X | ||||||||
| Lydiard 1997 | major depression | 260 | ≥ 18 | 50–150 (flexible dosing) |
chloral hydrate, temazepam | X | X | X | X | X | X | X | X | ||||||||||||
| Montgomery 1998 | depression | 386 | ≥ 18 | 40–280 (flexible dosing) |
chloral hydrate | medication that might interfere with the action of mirtazapine, or the use of any psychotropic agent | X | X | X | X | X | X | X | ||||||||||||
| Kautio 2009 | chemotherapy-induced neuropathic symptoms | 114 | 20–75 | 25–100 (flexible dosing) |
medication for neuropathic symptoms or contraindications for amitriptyline | X | X | X | |||||||||||||||||
| Couch 2010 | migraine headache | 391 | 18–70 | 25–100 (flexible dosing) |
X | X | X | X | X | X | X | X | X | X | X | X | X | ||||||||
| Foster 2010 | interstitial cystitis/painful bladder syndrome | 271 | ≥ 18 | 10–75 (flexible dosing) |
X | X | X | X | X | ||||||||||||||||
| Goldman 2010 | arm pain associated with repetitive use |
118 | ≥ 18 | 12.5–25 (flexible dosing) |
anti-inflammatory medications, NSAIDs, antidepressants, other non-study treatments | starting new treatments during the study | X | X | X | ||||||||||||||||
| Dinat 2015 | HIV-associated sensory neuropathy | 124 | ≥ 18 | 25–150 (flexible dosing) |
acetaminophen, non-steroidal anti-inflammatory drugs, codeine phosphate | X | X | X | |||||||||||||||||
| Talley 2015 | functional dyspepsia | 194 | 18–75 | 25–50 | X | X | X | X | X | X | X | X | X | ||||||||||||
| Goncalves 2016 | migraine | 131 | 18–65 | 25 | acute migraine medication | X | X | X | X | X | X | X | X | ||||||||||||
| Maarrawi 2018 | chronic neck pain | 332 | 18–75 | 5 | X | X | X |
Seventeen studies [10, 30, 32, 33, 36, 47–59] had a high, four studies [34, 60–62] a medium, and two studies [35, 63] a low overall RoB score. Fifteen of the seventeen studies with a high overall RoB score had an attrition rate of 20% or more. The results of the RoB assessment are shown in the S2 and S3 Tables.