Cymbalta (duloxetine) Side Effects: Critical Safety Info

Alternative to Meds Editorial Team

What is Cymbalta, generic duloxetine, and what is it prescribed for?

Cymbalta is an SNRI antidepressant, the patents of which expired back in 2013. Its generic equivalent, duloxetine hydrochloride has been widely available for more than a decade.  However, in 2024, and again in 2025 the FDA issued safety recalls due to a cancer-causing element found in the duloxetine formulation. Duloxetine has become hard to find in some areas, as a quarter of a million bottles have been recalled so far, according to industry reports.

Seek medical assistance if this has become a problem for you or a loved one, as abrupt cessation of any antidepressant is not recommended. Alternatives may be available that could help avoid this potential problem.

Sometimes duloxetine is called an SSNRI, meaning Selective Serotonin Norepinephrine Reuptake Inhibitor. It is a time-released drug. It’s mechanism of action is unknown, but regulators believe it selectively targets certain neurotransmitters such as serotonin, norepinephrine (adrenaline), dopamine to a lesser degree, and possibly others.

What are the reported side effects of Cymbalta and duloxetine?

Side effects for Cymbalta/duloxetine make a very long list. Some are severe enough to warrant the highest level warnings issued by the FDA, including a black box warning.

Black box statements for Cymbalta/duloxetine include:

• Suicidality in children, and young adults.
• Not approved for use in pediatric patients

Warnings and Precautions prominently listed on the drug label include:

• Toxic to liver, can cause liver failure and fatality
• Orthostatic hypotension (low blood pressure) and syncope (fainting, falls from sudden drop in blood pressure)
• Increases in high blood pressure compared to placebo
• Serotonin syndrome (can be fatal)
• NMS (neuroleptic malignant syndrome) life-threatening drug reaction: very high fever, rigidity, altered mental state, suddenly can’t speak or swallow, rapid breathing, loss of bladder/bowel control, excessive sweating, fluctuations in blood pressure and heart rate, renal failure, sepsis, cardiac arrest.
• Abnormal bleeding, may be worsened by aspirin, NSAIDS, other drugs affecting coagulation of blood
• Mania, or hypomania (mania of shorter duration or intensity)
• Seizures
• Duloxetine causes dilated pupils, which is a risk for narrow angle glaucoma
• Glycemic dysregulation found in a study on diabetic patients (fluctuating blood sugar levels)
• Urinary retention, may require use of a catheter
• Slowed gastric emptying
• Hyponatremia (low sodium levels) leads to headache, nausea, confusion, loss of energy, restlessness, irritability, muscle spasms, cramps, seizures, swelling in the brain, coma, hallucination, respiratory arrest, can be fatal if not treated promptly
• Withdrawals when Cymbalta or duloxetine is stopped, include seizures and other reactions.

For more information on Cymbalta/duloxetine withdrawal symptoms and treatment please see:

Cymbalta Withdrawal, Tapering & Alternatives (Safe Duloxetine Guide)
Antidepressant Withdrawal Help | Professional Effective Support

Adverse reactions observed in clinical trials according to the drug’s label include:

• Nausea/vomiting
• Dizziness
• Headache
• Physical weakness (asthenia)
• Dry mouth
• Mood swings
• Irritability
• Apathy
• Disorientation
• Daytime sleepiness
• Constipation
• Excessive sweating
• Cold sweats, chills
• Hot flushes, reddening of the skin (erythema)
• Decreased appetite
• Stomach ulcers
• Dysregulated or elevated fats in the blood, high cholesterol (hyperlipidemia, dyslipidemia))
• Halitosis (bad breath)
• Bruxism (grinding, clenching of teeth)
• Sensitivity to light
• Anorexia
• Indigestion
• Flatulence
• Passage of bright red blood from rectum (hematochezia)
• Pain when urinating (dysuria)
• Abnormal smell of urine
• Frequent nighttime urination (nocturia)
• Polyuria (urinating more than 3 L per 24 hr)
• Black tarry stools (melena)
• Thirst, dehydration
• Abdominal pain
• Weight loss
• Insomnia
• Abnormal dreams
• Jittery, tension, nervousness, restlessness, malaise
• Agitation, psycho-motor agitation
• Anxiety
• Erectile dysfunction in males
• Anorgasmia (inability to orgasm in females)
• Influenza, laryngitis
• Viral or bacterial infection of the stomach/intestines
• Cough
• Muscle spasms
• Gait disturbance
• Tremor, muscle twitching, muscle tightness
• Bruises easily (ecchymosis)
• In animal studies duloxetine caused reactions in the newborns similar to serotonin syndrome and possibly related to withdrawal syndrome.

Additional Cymbalta Side Effects Categorized and Clearly Defined

In addition to the above list, other adverse effects of Cymbalta/duloxetine are categorized by disorder type, and are listed as frequent, or infrequent.

Cardiac Disorders associated with Cymbalta include:

• Frequent heart palpitations
• Infrequent heart attack, tachycardia (elevated heart rate when body is at rest)

Ear and inner ear disorders associated with Cymbalta include:

• Frequent vertigo
• Infrequent ear pain, tinnitus

Endocrine disorders associated with Cymbalta include:

• Infrequent hypothyroidism (insufficient thyroid hormones) can lead to depression, fatigue, weight gain, intolerance to cold, inability to sweat, brittle fingernails and toenails, hair loss or thinning, puffy face, irregular menses in women, infertility, enlarged thyroid or goiter, joint or muscle pain)

Eye disorders associated with Cymbalta include:

• Frequent blurred vision
• Infrequent diplopia (double vision) and visual disturbance

Nervous system disorders associated with Cymbalta include:

• Frequent distorted sense of taste, parasthesia (pins and needles), numbness
• Infrequent nerve damage causing speech impairment, involuntary movement, disturbed attention

Some Post-Marketing Adverse Side Effects of Cymbalta/duloxetine Listed on the Drug Label

• Stevens Johnson Syndrome, or other severe rashes and anaphylactic reactions, which can be life-threatening and need immediate medical intervention
• Aggression, anger, particularly early in treatment or when Cymbalta is discontinued
• Sudden or rapid swelling under the skin of the face, neck, or other areas, can block the airway, impair quality of life due to unpredictable onset (angioneurotic edema)  
• Hives, itchy red welts that are raised on the skin, swelling (urticaria)
• Appearance of target-like lesions with red rings around a pale center, can be fatal (multiforme)
• Extrapyramidal disorders, not specified on the label, can be immediate as in restless legs, and seizures, especially on discontinuation of the drug, or tardive as in tardive dyskinesia
• Hallucinations
• Painful spasms in the jaw muscles (trismus)
• Supraventricular tachycardia — an elevated heart rate which can cause cardiac arrest, stroke, unconsciousness, decrease the pumping action of the heart muscle, or increase risk of blood clots.

Cymbalta/duloxetine Drug-Drug Interactions to Avoid

Certain drugs should be avoided while taking Cymbalta/duloxetine because of the way they interact. Some, but not all of the drugs to avoid, are listed on the drug’s label.  

Examples of drugs to avoid while taking Cymbalta/duloxetine include:

• Other drugs or substances that elevate serotonin levels, such as St. John’s Wort, tryptophan, Prozac, other SSRIs, other SNRIs, lithium, and tricyclic antidepressants such as amitriptyline
• The antipsychotic thioridazine, when combined with duloxetine can result in sudden death.
• Combining duloxetine with heavy alcohol use can lead to severe liver injury
• Combining duloxetine with aspirin, NSAIDs, warfarin, or other drugs that affect blood coagulation should be avoided
• Smoking cigarettes while taking Cymbalta/duloxetine can decrease the concentration of duloxetine by 30%.

Please ensure your doctor and you are on the same page before combining duloxetine with any other substances to avoid these and other dangerous side effects. You may have to do the research yourself, as doctors are rushed and time-constraints can lead to unintended errors in judgement.

for Help with Cymbalta/duloxetine Side Effects

Cymbalta Side Effects FAQs

Although the patents have expired on the brand name drug Cymbalta, duloxetine hydrochloride remains on the market, Cymbalta’s generic equivalent. The side effect profile is reportedly similar, if not identical, between brand name and generic drugs.

Sources:

1. FDA label and prescribing information Cymbalta (duloxetine hydrochloride) Delayed Release Capsules for Oral Use last reviewed 2026, first approval 2004 [cited 2026 Aug 13]

2. Knadler MP, Lobo E, Chappell J, Bergstrom R. Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. PMID: 21366359. [cited 2026 Aug 13]

3. Carter NJ, McCormack PL. Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. PMID: 19480470. [cited 2026 Aug 13]

4. Shelton RC. Serotonin and Norepinephrine Reuptake Inhibitors. Handb Exp Pharmacol. 2019;250:145-180. doi: 10.1007/164_2018_164. PMID: 30838456. [cited 2026 Aug 13]

5. Gosmann NP, Costa MA, Jaeger MB, Frozi J, Spanemberg L, Manfro GG, Cortese S, Cuijpers P, Pine DS, Salum GA. Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis. Psychol Med. 2023 Jul;53(9):3783-3792. doi: 10.1017/S0033291723001630. Epub 2023 Jun 6. PMID: 37278215. [cited 2026 Aug 13]

6. Carter NJ, McCormack PL. Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. PMID: 19480470. [cited 2026 Aug 13]

7. FDA Adverse Event Reporting System [cited 2026 Aug 13]

8. Health Canada Summary Basis of Decision for Cymbalta updated 2026 [cited 2026 Aug 13]

9. Allgulander C, Hartford J, Russell J, Ball S, Erickson J, Raskin J, Rynn M. Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment from a pooled analysis of three clinical trials. Curr Med Res Opin. 2007 Jun;23(6):1245-52. doi: 10.1185/030079907X182202. Epub 2007 Apr 25. PMID: 17559726. [cited 2026 Aug 13]

10. Lentacker, A. Epistemology of the side effect: anecdote and evidence in the digital age. BioSocieties 19, 84–111 (2024). https://doi.org/10.1057/s41292-022-00293-5 published Dec 22, 2022 [cited 2026 Aug 13]

11. Gerlach, A FDA Recalls 233,000 Bottles of Duloxetine over Risk of Cancerous Chemical, published December 19, 2024, Pharmacy Times [cited 2026 Aug 13]

12. Urits, I., Peck, J., Orhurhu, M.S. et al. Off-label Antidepressant Use for Treatment and Management of Chronic Pain: Evolving Understanding and Comprehensive Review. Curr Pain Headache Rep 23, 66 (2019). https://doi.org/10.1007/s11916-019-0803-z [cited 2026 Aug 13]

13. FDA label Cymbalta/duloxetine approval 2004, revised 2008, 2009 & 2010 [cited 2026 Aug 13]

14. Safer DL, Arnow KD. Suprathreshold duloxetine for treatment-resistant depression, anorexia nervosa binge-purging type, and obsessive-compulsive disorder: a case report. Innov Clin Neurosci. 2012 Mar;9(3):13-6. PMID: 22567604; PMCID: PMC3342990. [cited 2026 Aug 13]

Originally Published August __, 2026 by Diane Ridaeus

This content has been reviewed and approved by a licensed physician.

Dr. John Motl, M.D.

Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona.  He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine.  Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.

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Diane Ridaeus

Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.