Milnacipran side effects: what 5,981 FDA adverse event reports show
Drug class
Selective serotonin and norepinephrine reuptake inhibitor (snri)
Label matched
Milnacipran Hydrochloride (Milnacipran Hydrochloride)
Who reports
5,981 reports · 42% serious · 152 with death outcome · 90% female
Used for
Milnacipran hydrochloride is indicated for the management of fibromyalgia. Milnacipran hydrochloride is not approved for use in pediatric patients . • Milnacipran hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia ( 1 ).
What it is
Milnacipran hydrochloride is a selective norepinephrine and serotonin reuptake inhibitor; it inhibits norepinephrine uptake with greater potency than serotonin. It is a racemic mixture with the chemical name: (±)-[1R(S),2S(R)]-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide hydrochloride.
Boxed warning
SUICIDALITY AND ANTIDEPRESSANT DRUGS Milnacipran hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders.
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- 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 flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 404 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 |
|---|---|---|---|---|---|---|
| Fibromyalgia | 152 | 22.1 18.9–25.8ROR 22.6 · χ² 3,021 / p <1e-300 | 21.9 EB05 19.1 · IC025 +4.1 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 25.5 | no trial data cached |
| Taste disorder | 74 | 13.0 10.4–16.3ROR 13.1 · χ² 805 / p 2e-177 | 12.8 EB05 10.5 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 34.8 | no trial data cached |
| Serotonin syndrome | 64 | 11.8 9.2–15.0ROR 11.9 · χ² 618 / p 9e-137 | 11.5 EB05 9.2 · IC025 +3.0 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 16.0 | no trial data cached |
| Bursitis | 37 | 10.8 7.8–14.9ROR 10.8 · χ² 318 / p 2e-71 | 10.3 EB05 7.6 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 16.2 | no trial data cached |
| Back injury | 28 | 9.1 6.3–13.2ROR 9.1 · χ² 193 / p 3e-44 | 8.3 EB05 5.9 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 15.1 | no trial data cached |
| Wound infection | 28 | 9.1 6.3–13.1ROR 9.1 · χ² 192 / p 5e-44 | 8.3 EB05 5.9 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 13.1 · 100% clinician | no trial data cached |
| Epilepsy | 75 | 8.6 6.9–10.8ROR 8.7 · χ² 498 / p 1e-110 | 8.3 EB05 6.8 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 11.7 | no trial data cached |
| Folliculitis | 25 | 8.5 5.7–12.6ROR 8.5 · χ² 158 / p 2e-36 | 7.7 EB05 5.3 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 13.5 · 92% clinician | no trial data cached |
| Hyperhidrosis (excessive sweating) | 286 | 7.8 7.0–8.7ROR 8.1 · χ² 1,693 / p <1e-300 | 7.7 EB05 7.0 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.1 · 70% consumer | no trial data cached |
| Migraine | 206 | 7.6 6.7–8.7ROR 7.9 · χ² 1,182 / p 2e-259 | 7.5 EB05 6.7 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 13.6 | no trial data cached |
| Sleep apnoea syndrome | 40 | 7.3 5.4–10.0ROR 7.4 · χ² 213 / p 2e-48 | 6.9 EB05 5.2 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 10.9 | no trial data cached |
| Hypercholesterolaemia | 20 | 7.3 4.7–11.4ROR 7.4 · χ² 103 / p 2e-24 | 6.4 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 10.6 | no trial data cached |
| Red blood cell sedimentation rate increased | 23 | 7.3 4.8–11.0ROR 7.3 · χ² 118 / p 8e-28 | 6.5 EB05 4.5 · IC025 +2.0 3/3 methods agree | Lab value / disease marker | serious PRR 10.7 · 91% clinician | no trial data cached |
| Crying | 75 | 7.2 5.8–9.0ROR 7.3 · χ² 396 / p 2e-88 | 7.0 EB05 5.7 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Synovitis | 37 | 7.2 5.2–9.9ROR 7.2 · χ² 191 / p 9e-44 | 6.7 EB05 5.0 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 10.2 · 100% clinician | no trial data cached |
| Suicidal ideation (thoughts of suicide) | 181 | 6.9 6.0–8.0ROR 7.1 · χ² 916 / p 2e-201 | 6.8 EB05 6.0 · IC025 +2.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.6 | no trial data cached |
| Pemphigus | 24 | 6.8 4.5–10.1ROR 6.8 · χ² 112 / p 1e-26 | 6.1 EB05 4.3 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.2 · 100% clinician | no trial data cached |
| Hot flush (hot flashes) | 142 | 6.6 5.6–7.8ROR 6.8 · χ² 672 / p 2e-148 | 6.5 EB05 5.6 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.5 | no trial data cached |
| Night sweats | 60 | 6.5 5.1–8.4ROR 6.6 · χ² 276 / p 3e-62 | 6.3 EB05 5.0 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 9.1 | no trial data cached |
| Pericarditis | 31 | 6.5 4.6–9.3ROR 6.6 · χ² 140 / p 2e-32 | 6.0 EB05 4.4 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.9 | no trial data cached |
| Laryngitis | 19 | 6.1 3.9–9.6ROR 6.2 · χ² 77 / p 1e-18 | 5.4 EB05 3.6 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious n=17 | no trial data cached |
| Gastrooesophageal reflux disease (acid reflux) | 140 | 6.1 5.2–7.2ROR 6.3 · χ² 597 / p 4e-132 | 6.0 EB05 5.2 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 10.9 | no trial data cached |
| Irritable bowel syndrome | 37 | 6.1 4.4–8.4ROR 6.1 · χ² 152 / p 3e-35 | 5.7 EB05 4.3 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.5 | no trial data cached |
| Heart rate increased | 165 | 5.8 5.0–6.8ROR 6.0 · χ² 661 / p 6e-146 | 5.8 EB05 5.1 · IC025 +2.3 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 6.1 · 71% consumer | no trial data cached |
| Joint range of motion decreased | 22 | 5.8 3.8–8.8ROR 5.8 · χ² 82 / p 6e-20 | 5.2 EB05 3.6 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 9.5 · 90% clinician | no trial data cached |
| Feeling jittery | 31 | 5.7 4.0–8.1ROR 5.7 · χ² 115 / p 3e-27 | 5.3 EB05 3.9 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious n=4 | no trial data cached |
| Helicobacter infection | 16 | 5.5 3.4–9.0ROR 5.5 · χ² 55 / p 8e-14 | 4.8 EB05 3.1 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.9 | no trial data cached |
| Autoimmune disorder | 15 | 5.5 3.3–9.1ROR 5.5 · χ² 51 / p 5e-13 | 4.8 EB05 3.1 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.0 | no trial data cached |
| Anger | 53 | 5.5 4.2–7.2ROR 5.5 · χ² 190 / p 2e-43 | 5.2 EB05 4.2 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.6 | no trial data cached |
| Systemic lupus erythematosus | 55 | 5.5 4.2–7.1ROR 5.5 · χ² 196 / p 9e-45 | 5.2 EB05 4.2 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 7.4 | no trial data cached |
| Dysuria (painful urination) | 57 | 5.4 4.2–7.0ROR 5.5 · χ² 202 / p 5e-46 | 5.2 EB05 4.2 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.6 · ♀ 37% (drug 90%) | no trial data cached |
| Osteoarthritis | 64 | 5.3 4.1–6.7ROR 5.3 · χ² 218 / p 1e-49 | 5.1 EB05 4.1 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 | no trial data cached |
| Palpitations (pounding heartbeat) | 168 | 5.0 4.3–5.9ROR 5.2 · χ² 542 / p 3e-120 | 5.0 EB05 4.4 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.3 | no trial data cached |
| Impaired gastric emptying | 18 | 5.0 3.1–7.9ROR 5.0 · χ² 53 / p 2e-13 | 4.4 EB05 3.0 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.1 | no trial data cached |
| Intervertebral disc degeneration | 13 | 4.9 2.8–8.4ROR 4.9 · χ² 37 / p 7e-10 | 4.2 EB05 2.7 · IC025 +1.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.0 | no trial data cached |
| Blood pressure increased | 208 | 4.8 4.2–5.4ROR 4.9 · χ² 619 / p 7e-137 | 4.7 EB05 4.2 · IC025 +2.0 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 4.6 | no trial data cached |
| Urinary retention | 45 | 4.7 3.5–6.3ROR 4.8 · χ² 129 / p 3e-30 | 4.5 EB05 3.5 · IC025 +1.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 · ♀ 32% (drug 90%) | no trial data cached |
| Vitamin d deficiency | 13 | 4.7 2.7–8.1ROR 4.7 · χ² 34 / p 3e-9 | 4.1 EB05 2.6 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.5 | no trial data cached |
| Drug hypersensitivity | 258 | 4.7 4.1–5.3ROR 4.8 · χ² 744 / p 3e-164 | 4.6 EB05 4.2 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 4.4 | no trial data cached |
| Obesity | 21 | 4.6 3.0–7.1ROR 4.6 · χ² 56 / p 4e-14 | 4.2 EB05 2.9 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.3 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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 |
|---|---|---|---|---|---|---|
| Nausea | 696 | 3.1 2.9–3.3ROR 3.4 · χ² 1,022 / p 1e-224 | 3.1 EB05 2.9 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 | no trial data cached |
| Pain | 518 | 3.0 2.7–3.2ROR 3.1 · χ² 687 / p 1e-151 | 2.9 EB05 2.7 · IC025 +1.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.5 | no trial data cached |
| Headache | 487 | 2.7 2.5–3.0ROR 2.9 · χ² 547 / p 2e-121 | 2.7 EB05 2.5 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 | no trial data cached |
| Vomiting | 360 | 2.7 2.4–3.0ROR 2.8 · χ² 390 / p 4e-87 | 2.7 EB05 2.5 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.0 | no trial data cached |
| Dizziness | 339 | 2.4 2.2–2.6ROR 2.5 · χ² 279 / p 8e-63 | 2.4 EB05 2.2 · IC025 +1.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.4 | no trial data cached |
| Insomnia (trouble sleeping) | 325 | 4.3 3.8–4.8ROR 4.5 · χ² 822 / p 5e-181 | 4.2 EB05 3.9 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.8 | no trial data cached |
| Depression | 299 | 4.6 4.1–5.1ROR 4.8 · χ² 845 / p 5e-186 | 4.6 EB05 4.1 · IC025 +2.0 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 6.0 | no trial data cached |
| Hyperhidrosis (excessive sweating) | 286 | 7.8 7.0–8.7ROR 8.1 · χ² 1,693 / p <1e-300 | 7.7 EB05 7.0 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.1 · 70% consumer | no trial data cached |
| Anxiety | 268 | 3.3 2.9–3.7ROR 3.4 · χ² 432 / p 3e-96 | 3.3 EB05 3.0 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.4 | no trial data cached |
| Drug hypersensitivity | 258 | 4.7 4.1–5.3ROR 4.8 · χ² 744 / p 3e-164 | 4.6 EB05 4.2 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 4.4 | no trial data cached |
| Rash | 215 | 1.7 1.5–2.0ROR 1.8 · χ² 68 / p 8e-17 | 1.7 EB05 1.6 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 2.1 | no trial data cached |
| Arthralgia (joint pain) | 213 | 1.8 1.6–2.1ROR 1.8 · χ² 77 / p 9e-19 | 1.8 EB05 1.6 · IC025 +0.6 | Not in label — unassessed | serious PRR 2.6 | no trial data cached |
| Malaise (feeling unwell) | 208 | 1.7 1.5–1.9ROR 1.7 · χ² 55 / p 6e-14 | 1.7 EB05 1.5 · IC025 +0.5 | Not in label — unassessed | serious PRR 2.2 | no trial data cached |
| Blood pressure increased | 208 | 4.8 4.2–5.4ROR 4.9 · χ² 619 / p 7e-137 | 4.7 EB05 4.2 · IC025 +2.0 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 4.6 | no trial data cached |
| Migraine | 206 | 7.6 6.7–8.7ROR 7.9 · χ² 1,182 / p 2e-259 | 7.5 EB05 6.7 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 13.6 | no trial data cached |
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.
- Taste disorder — n=74, PRR 13.0
- Bursitis — n=37, PRR 10.8
- Back injury — n=28, PRR 9.1
- Wound infection — n=28, PRR 9.1
- Epilepsy — n=75, PRR 8.6
- Folliculitis — n=25, PRR 8.5
- Sleep apnoea syndrome — n=40, PRR 7.3
- Hypercholesterolaemia — n=20, PRR 7.3
- Crying — n=75, PRR 7.2
- Synovitis — n=37, PRR 7.2
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 Milnacipran?
In FDA FAERS, the most frequently co-reported reaction terms for Milnacipran are nausea, pain, headache, vomiting, dizziness, insomnia. 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 Milnacipran have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: SUICIDALITY AND ANTIDEPRESSANT DRUGS Milnacipran hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI), similar to some drugs used for the treatment of depression and other psychiatric disorders.
Do FAERS signals prove that Milnacipran 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 b66b1850-0d2a-41d6-b0ad-c676166394c7, effective 20260319; matched on
openfda.generic_name.exact:"MILNACIPRAN 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, 444 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
Page generated 2026-10-08. 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.