Duloxetine (Cymbalta) and venlafaxine (Effexor): uses, side effects and what to know

Duloxetine and venlafaxine are serotonin and norepinephrine reuptake inhibitors (SNRIs). Per their FDA labels, exactly how they work is not known; they are believed to boost the action of two brain messengers, serotonin and norepinephrine, which affect mood and anxiety. The Cymbalta label also links this effect to pain control.

Cymbalta is the brand name of duloxetine (delayed-release capsules). Effexor XR is the brand name of extended-release venlafaxine; per MedlinePlus, venlafaxine also comes as regular tablets. Both are sold as generics.

Both are prescription medicines and neither is a controlled substance: the Effexor XR label says so outright, and the Cymbalta label assigns it no controlled-substance schedule.

According to the FDA label for Cymbalta, duloxetine is approved for:

According to the FDA label for Effexor XR, venlafaxine is approved in adults for major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. The label states that it is not approved for patients under 18.

Off-label use: MedlinePlus notes that it is sometimes used for hot flashes in menopause or in women taking breast cancer treatment. That use is not on the FDA label; if it applies to you, the doctor explains the benefits and risks.

Of the two, duloxetine is the one with FDA-approved pain uses: diabetic nerve pain, fibromyalgia and chronic musculoskeletal pain. If you have burning, tingling or numbness in your feet, read about numbness and tingling; if you have diabetes, see type 2 diabetes. For back pain, read the low back pain guide.

The Effexor XR label lists no pain use. If a doctor uses venlafaxine for pain, that is off-label. Other medicines are used off-label for nerve pain, such as amitriptyline; the doctor evaluates your case and decides what is appropriate.

Duloxetine. Per the FDA label, adults take 30 to 60 mg a day depending on the use, and for depression and generalized anxiety the maximum is 120 mg a day. It can be taken with or without food. Swallow the capsule whole: do not open, chew or crush it.

Venlafaxine (Effexor XR). Per the FDA label, it starts at 37.5 to 75 mg once a day, with food and at about the same time, and the maximum is 225 mg a day (75 mg a day for social anxiety). Regular tablets are taken two or three times a day with food, per MedlinePlus.

The doctor decides the dose and adjusts it gradually based on how you respond and on your liver and kidney function. Do not change it on your own.

How long they take. MedlinePlus says duloxetine can take 1 to 4 weeks or longer to reach its full effect. Keep taking it even when you feel better.

Duloxetine. Per the FDA label, the most common side effects in adults are nausea, dry mouth, sleepiness, constipation, decreased appetite and excessive sweating.

Venlafaxine. Per the Effexor XR label, the most common are nausea, sleepiness, dry mouth, sweating, decreased appetite, constipation, ejaculation problems, erectile dysfunction and lower sex drive.

Both labels warn about sexual side effects. Both can cause sleepiness or dizziness: do not drive or use machinery until you know how they affect you. If a side effect bothers you, talk with the doctor before stopping the medicine.

The FDA labels for both medicines carry a boxed warning: antidepressants increased the risk of suicidal thoughts and behavior in children, teenagers and young adults. Per the Effexor XR label, in studies the increase was seen in people under 18 and in adults aged 18 to 24, and not in people over 24.

At any age, speak up right away about new or worse depression, anxiety, agitation, insomnia, irritability or thoughts of harming yourself, especially in the first months or when the dose changes. If that happens, call Línea PAS at 1-800-981-0023 or 988.

Liver (duloxetine). The label warns of liver injury. Duloxetine is not prescribed to people with substantial alcohol use or chronic liver disease, and the Medication Guide says to avoid heavy drinking while taking it.

Blood pressure. Venlafaxine can cause sustained increases in blood pressure, and duloxetine can raise it too. The labels call for checking blood pressure before starting and during treatment. If you have high blood pressure, the doctor takes it into account.

Dizziness on standing and falls (duloxetine). It can lower blood pressure when you stand up and cause dizziness, fainting or falls, mostly when starting or raising the dose.

Other label warnings: serotonin syndrome; a higher risk of bleeding; angle-closure glaucoma; low blood sodium, especially in older adults; seizures; mania in people with bipolar disorder; with duloxetine, trouble urinating and severe skin reactions; and with venlafaxine, interstitial lung disease and eosinophilic pneumonia, which show up as shortness of breath, cough or chest pain.

Do not combine them with MAO inhibitors (MAOIs), or close to starting or stopping one, per the waiting periods in each label. Nor are they started in someone receiving linezolid or intravenous methylene blue.

Serotonin syndrome. The risk rises when they are combined with other medicines that raise serotonin, such as other antidepressants, triptans for migraine, tramadol or St. John's wort.

Bleeding. Taking them with aspirin, anti-inflammatories such as ibuprofen or naproxen, or warfarin raises the risk of bleeding.

Duloxetine only: the label says to avoid potent inhibitors of the CYP1A2 enzyme, such as fluvoxamine, and not to combine it with thioridazine. It is also avoided when kidney function is very low (filtration below 30 mL/min).

Tell the doctor about every medicine, supplement and natural product you take.

If you are pregnant, planning a pregnancy or breastfeeding, the decision is made with the doctor. Per the FDA labels, use late in the third trimester can cause problems in the newborn, such as trouble breathing or feeding, tremor or unstable temperature. Use in the month before delivery is linked to a higher risk of bleeding after delivery, and the venlafaxine label mentions a possible higher risk of preeclampsia.

Both pass into breast milk. The duloxetine label describes infants with sleepiness, poor feeding or poor weight gain. Untreated depression carries risks too: do not stop the medicine on your own if you become pregnant; talk with the doctor first.

Both labels warn about a discontinuation syndrome when the medicine is stopped abruptly. For duloxetine, the label lists dizziness, headache, nausea, diarrhea, tingling, irritability, vomiting, insomnia, anxiety, sweating and fatigue.

The venlafaxine list is long: it includes dizziness, nausea, anxiety, confusion, nightmares, tremor, flu-like symptoms and electric-shock sensations. That is why the label recommends lowering the dose gradually. If you want to stop or switch, the doctor tells you how.

SSRIs such as sertraline (Zoloft) and escitalopram (Lexapro) act mainly on serotonin; SNRIs act on serotonin and norepinephrine. Their approved uses differ: for example, duloxetine has pain uses those SSRIs do not, and the SNRI labels call for watching blood pressure. Neither group is “better” for everyone: the doctor chooses with you based on your symptoms, history and other medicines.