Amitriptyline side effects: what 17,410 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Amitriptyline Hydrochloride (Amitriptyline Hydrochloride)
Who reports
17,410 reports · 80% serious · 1,314 with death outcome · 71% female
Used for
For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
What it is
DESCRIPTION Amitriptyline hydrochloride, USP, a dibenzocycloheptadiene derivative, is a white, or practically white, odorless, crystalline compound which is freely soluble in water and alcohol. It is designated chemically as 10,11-Dihydro-N,N-dimethyl-5 H -dibenzo[a,d] cycloheptene-Δ 5 , γ-propylamine hydrochloride.
Boxed warning
Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders.
Causality screen of the 40 strongest signals
What the badges mean
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,148 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Cardiospasm | 380 | 2,634.2 2,200.5–3,153.3ROR 2,692.8 · calibrated p 2e-22 ✓ | 785.6 EB05 721.5 · IC025 +8.5 3/3 methods agree | Not in label — unassessed | serious n=380 | not reported in cached trials |
| Cftr gene mutation | 15 | 1,975.6 864.7–4,513.9ROR 1,977.3 · calibrated p 4e-16 ✓ | 380.6 EB05 244.8 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=15 | not reported in cached trials |
| Immunisation | 256 | 1,764.3 1,455.1–2,139.1ROR 1,790.5 · calibrated p 4e-20 ✓ | 673.6 EB05 607.2 · IC025 +8.0 3/3 methods agree | Not in label — unassessed | serious n=256 | not reported in cached trials |
| Palmoplantar keratoderma | 373 | 1,308.1 1,129.9–1,514.4ROR 1,336.7 · calibrated p 1e-18 ✓ | 603.0 EB05 553.4 · IC025 +8.2 3/3 methods agree | Not in label — unassessed | serious n=373 | not reported in cached trials |
| Synovial fluid analysis | 42 | 1,131.5 741.5–1,726.5ROR 1,134.2 · calibrated p 1e-16 ✓ | 458.0 EB05 353.1 · IC025 +5.7 3/3 methods agree | Reporting / coding artifact | serious n=42 · ♀ 100% (drug 71%) · 100% clinician | not reported in cached trials |
| Heart sounds | 32 | 592.7 387.8–905.7ROR 593.8 · calibrated p 1e-13 ✓ | 319.8 EB05 237.2 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=32 · ♀ 100% (drug 71%) | not reported in cached trials |
| Device wireless communication issue | 56 | 347.5 258.1–468.0ROR 348.7 · calibrated p 6e-12 ✓ | 246.4 EB05 196.8 · IC025 +5.9 3/3 methods agree | Reporting / coding artifact | serious n=16 · 100% consumer | not reported in cached trials |
| Atrial tachycardia | 387 | 270.6 242.6–301.9ROR 276.8 · calibrated p 2e-11 ✓ | 218.2 EB05 200.5 · IC025 +7.3 3/3 methods agree | Not in label — unassessed | serious n=387 | not reported in cached trials |
| Sedation complication | 428 | 248.7 224.3–275.7ROR 254.9 · calibrated p 5e-11 ✓ | 203.9 EB05 188.2 · IC025 +7.2 3/3 methods agree | Reporting / coding artifact | serious n=428 · ♀ 100% (drug 71%) | not reported in cached trials |
| Pruritus genital | 377 | 232.5 208.4–259.4ROR 237.6 · calibrated p 9e-11 ✓ | 192.7 EB05 176.9 · IC025 +7.1 3/3 methods agree | Not in label — unassessed | serious n=377 | not reported in cached trials |
| Device maintenance issue | 80 | 198.8 157.0–251.8ROR 199.7 · calibrated p 7e-10 ✓ | 163.8 EB05 135.8 · IC025 +6.0 3/3 methods agree | Reporting / coding artifact | serious n=30 · 100% consumer | not reported in cached trials |
| Prolonged expiration | 32 | 165.6 114.5–239.7ROR 165.9 · calibrated p 6e-9 ✓ | 134.0 EB05 99.4 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=32 · ♀ 100% (drug 71%) | not reported in cached trials |
| Infusion site injury | 19 | 153.2 95.0–247.0ROR 153.4 · calibrated p 2e-8 ✓ | 119.7 EB05 81.0 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | – | NCT01581281: 1/145 (0.7%) on Amitriptyline (serious AE) |
| Neutropenia neonatal | 25 | 149.7 98.8–226.8ROR 149.9 · calibrated p 2e-8 ✓ | 120.9 EB05 86.1 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=25 · 100% clinician | not reported in cached trials |
| Creatinine renal clearance decreased | 434 | 145.2 131.6–160.2ROR 148.9 · calibrated p 5e-9 ✓ | 128.7 EB05 118.9 · IC025 +6.7 3/3 methods agree | Lab value / disease marker | serious n=432 · ♀ 100% (drug 71%) | not reported in cached trials |
| Carotid artery occlusion | 375 | 137.3 123.5–152.7ROR 140.3 · calibrated p 9e-9 ✓ | 122.4 EB05 112.4 · IC025 +6.6 3/3 methods agree | Not in label — unassessed | serious n=375 | not reported in cached trials |
| Multiple drug therapy | 63 | 119.3 92.1–154.5ROR 119.7 · calibrated p 5e-8 ✓ | 105.1 EB05 85.1 · IC025 +5.5 3/3 methods agree | Reporting / coding artifact | serious n=63 · ♀ 100% (drug 71%) | not reported in cached trials |
| Tenosynovitis stenosans | 50 | 118.1 88.3–157.8ROR 118.4 · calibrated p 6e-8 ✓ | 103.3 EB05 81.4 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious n=50 · ♀ 100% (drug 71%) | not reported in cached trials |
| Tension headache | 381 | 117.0 105.4–129.9ROR 119.6 · calibrated p 3e-8 ✓ | 106.0 EB05 97.4 · IC025 +6.4 3/3 methods agree | Labeled (related wording) related wording | serious n=380 | not reported in cached trials |
| Sleep terror | 372 | 116.7 105.0–129.6ROR 119.2 · calibrated p 3e-8 ✓ | 105.7 EB05 97.0 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious n=372 | not reported in cached trials |
| Infusion site discharge | 133 | 101.4 85.0–121.0ROR 102.2 · calibrated p 1e-7 ✓ | 92.3 EB05 79.8 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=44 · 100% consumer | not reported in cached trials |
| Infusion site induration | 99 | 90.0 73.4–110.3ROR 90.5 · calibrated p 3e-7 ✓ | 82.4 EB05 69.7 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | serious n=23 · 100% consumer | not reported in cached trials |
| Infusion site irritation | 83 | 86.0 68.9–107.4ROR 86.4 · calibrated p 5e-7 ✓ | 78.8 EB05 65.6 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=24 · 90% consumer | not reported in cached trials |
| Infusion site warmth | 77 | 82.2 65.3–103.5ROR 82.6 · calibrated p 6e-7 ✓ | 75.6 EB05 62.4 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | serious n=21 · 100% consumer | not reported in cached trials |
| Body tinea | 36 | 81.9 58.4–114.8ROR 82.1 · calibrated p 1e-6 ✓ | 73.8 EB05 55.7 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=36 · ♀ 100% (drug 71%) · 100% clinician | not reported in cached trials |
| Infusion site inflammation | 41 | 77.8 56.7–106.6ROR 77.9 · calibrated p 1e-6 ✓ | 70.7 EB05 54.4 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | serious n=12 · 100% consumer | not reported in cached trials |
| Infusion site discolouration | 52 | 77.2 58.4–102.2ROR 77.5 · calibrated p 1e-6 ✓ | 70.8 EB05 56.0 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious n=12 · 100% consumer | not reported in cached trials |
| Infusion site haemorrhage | 195 | 76.9 66.6–88.9ROR 77.8 · calibrated p 8e-7 ✓ | 71.8 EB05 63.8 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious n=54 · 96% consumer | not reported in cached trials |
| Patient dissatisfaction with device | 14 | 75.1 43.8–128.9ROR 75.2 · calibrated p 4e-6 ✓ | 64.7 EB05 41.0 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Infusion site infection | 130 | 73.1 61.3–87.3ROR 73.7 · calibrated p 1e-6 ✓ | 68.3 EB05 59.0 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=54 · 88% consumer | NCT01581281: 14/144 (9.7%) on Amitriptyline; 10/72 (13.9%) control |
| Infusion site nodule | 51 | 72.1 54.4–95.7ROR 72.3 · calibrated p 2e-6 ✓ | 66.4 EB05 52.5 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=12 · 100% consumer | not reported in cached trials |
| Anticholinergic syndrome | 88 | 70.2 56.7–87.1ROR 70.6 · calibrated p 2e-6 ✓ | 65.5 EB05 54.8 · IC025 +5.2 3/3 methods agree | Labeled (related wording) related wording | serious n=88 | not reported in cached trials |
| Creatinine renal clearance increased | 40 | 67.5 49.1–92.9ROR 67.7 · calibrated p 3e-6 ✓ | 62.1 EB05 47.6 · IC025 +4.6 3/3 methods agree | Lab value / disease marker | serious n=40 · ♀ 100% (drug 71%) · 100% clinician | not reported in cached trials |
| Infusion site pain | 673 | 66.9 62.0–72.2ROR 69.5 · calibrated p 2e-6 ✓ | 63.2 EB05 59.3 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=190 · 94% consumer | NCT00471445: 1/227 (0.4%) on Amitriptyline (serious AE) |
| Infusion site erythema | 421 | 64.3 58.4–70.8ROR 65.9 · calibrated p 2e-6 ✓ | 60.9 EB05 56.2 · IC025 +5.7 3/3 methods agree | Not in label — unassessed | serious n=119 · 95% consumer | not reported in cached trials |
| Infusion site swelling | 286 | 58.5 52.0–65.9ROR 59.5 · calibrated p 5e-6 ✓ | 55.6 EB05 50.4 · IC025 +5.5 3/3 methods agree | Labeled (related wording) related wording | serious n=71 · 96% consumer | not reported in cached trials |
| Device infusion issue | 112 | 57.6 47.7–69.6ROR 57.9 · calibrated p 6e-6 ✓ | 54.5 EB05 46.5 · IC025 +5.2 3/3 methods agree | Reporting / coding artifact | serious n=33 · 100% consumer | not reported in cached trials |
| Cerebellar stroke | 17 | 57.1 35.1–92.9ROR 57.1 · calibrated p 2e-5 ✓ | 51.5 EB05 34.1 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=17 | not reported in cached trials |
| Brain malformation | 16 | 56.1 34.0–92.6ROR 56.2 · calibrated p 2e-5 ✓ | 50.6 EB05 33.0 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Carbon dioxide abnormal | 14 | 56.1 32.8–95.8ROR 56.1 · calibrated p 2e-5 ✓ | 50.1 EB05 31.7 · IC025 +3.3 3/3 methods agree | Lab value / disease marker | serious n=14 | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Amitriptyline as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (3 of 40 signal terms matched).
- NCT01581281 — The Childhood and Adolescent Migraine Prevention Study (N=488, PHASE3; 21 AE terms posted; arms: Topiramate; Placebo; Amitriptyline)
- NCT00471445 — Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Pa (N=462, PHASE3; 85 AE terms posted; arms: Amitriptyline and Ketamine Hydrochloride; Placebo Cream)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Pain | 1,650 | 3.2 3.1–3.4ROR 3.5 · calibrated p 0.494 | 3.2 EB05 3.1 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 3.2 | NCT00471445: 1/227 (0.4%) on Amitriptyline (serious AE) |
| Nausea | 1,534 | 2.3 2.2–2.5ROR 2.5 · calibrated p 0.826 | 2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.6 | NCT00471445: 2/227 (0.9%) on Amitriptyline; 7/231 (3.0%) control |
| Headache | 1,475 | 2.8 2.7–3.0ROR 3.0 · calibrated p 0.624 | 2.8 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.3 | NCT00471445: 4/227 (1.8%) on Amitriptyline; 3/231 (1.3%) control |
| Fatigue (tiredness) | 1,449 | 2.2 2.1–2.4ROR 2.4 · calibrated p 0.876 | 2.2 EB05 2.1 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.5 | NCT01581281: 43/144 (29.9%) on Amitriptyline; 10/72 (13.9%) control |
| Dyspnoea (shortness of breath) | 1,439 | 3.1 2.9–3.2ROR 3.2 · calibrated p 0.551 | 3.1 EB05 2.9 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 2.7 | NCT00471445: 2/227 (0.9%) on Amitriptyline; 5/231 (2.2%) control |
| Dizziness | 1,225 | 3.0 2.8–3.1ROR 3.1 · calibrated p 0.591 | 3.0 EB05 2.8 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.3 | NCT01581281: 3/144 (2.1%) on Amitriptyline; 1/72 (1.4%) control |
| Diarrhoea (diarrhea) | 1,184 | 2.2 2.1–2.3ROR 2.3 · calibrated p 0.901 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 | NCT00471445: 2/227 (0.9%) on Amitriptyline; 6/231 (2.6%) control |
| Malaise (feeling unwell) | 1,092 | 3.0 2.8–3.2ROR 3.1 · calibrated p 0.587 | 3.0 EB05 2.8 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.3 | not reported in cached trials |
| Vomiting | 1,063 | 2.7 2.6–2.9ROR 2.8 · calibrated p 0.680 | 2.7 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.6 | NCT00471445: 2/227 (0.9%) on Amitriptyline; 4/231 (1.7%) control |
| Fall | 1,052 | 3.8 3.6–4.0ROR 4.0 · calibrated p 0.379 | 3.8 EB05 3.6 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.1 | not reported in cached trials |
| Off label use (used outside approved label) | 1,048 | 1.5 1.4–1.5ROR 1.5 · calibrated p 0.630 | 1.5 EB05 1.4 · IC025 +0.4 | Reporting / coding artifact | serious PRR 1.7 | not reported in cached trials |
| Arthralgia (joint pain) | 988 | 2.9 2.7–3.1ROR 3.0 · calibrated p 0.632 | 2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 3.4 | not reported in cached trials |
| Cognitive disorder | 955 | 25.2 23.7–26.8ROR 26.6 · calibrated p 5e-4 ✓ | 24.7 EB05 23.4 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious PRR 24.8 | NCT01581281: 14/144 (9.7%) on Amitriptyline; 8/72 (11.1%) control |
| Drug ineffective (drug did not work) | 896 | 0.8 0.8–0.9ROR 0.8 · calibrated p 0.189 | 0.8 EB05 0.8 · IC025 -0.4 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | serious PRR 1.3 | not reported in cached trials |
| Pruritus (itching) | 859 | 2.7 2.6–2.9ROR 2.8 · calibrated p 0.686 | 2.7 EB05 2.6 · IC025 +1.3 3/3 methods agree | Not in label — unassessed | serious PRR 4.1 | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Cardiospasm — n=380, PRR 2,634.2
- Immunisation — n=256, PRR 1,764.3
- Palmoplantar keratoderma — n=373, PRR 1,308.1
- Heart sounds — n=32, PRR 592.7
- Atrial tachycardia — n=387, PRR 270.6
- Pruritus genital — n=377, PRR 232.5
- Prolonged expiration — n=32, PRR 165.6
- Neutropenia neonatal — n=25, PRR 149.7
- Carotid artery occlusion — n=375, PRR 137.3
- Tenosynovitis stenosans — n=50, PRR 118.1
✓ A hand-written Bradford Hill causality assessment exists for this drug: Amitriptyline ↔ Tachycardia.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Amitriptyline?
In FDA FAERS, the most frequently co-reported reaction terms for Amitriptyline are pain, nausea, headache, fatigue, dyspnoea, dizziness. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Amitriptyline have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders.
Do FAERS signals prove that Amitriptyline causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 085baad2-d1c7-499e-b553-7477befd04d0, effective 20251217; matched on
openfda.generic_name.exact:"AMITRIPTYLINE HYDROCHLORIDE") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,188 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
AMITRIPTYLINE, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.