Cymbalta (duloxetine) vs. Effexor (venlafaxine), what is the difference?

What is Cymbalta? What is Effexor? How do they work (mechanism of action)?

Cymbalta (duloxetine), Effexor, and Effexor XR (venlafaxine) are selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants. Cymbalta and Effexor XR are both used for the treatment of pain and major depressive and anxiety disorders (for example, general anxiety, panic, and social disorders). Cymbalta also treats diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain. Other SNRIs include milnacipran (Savella) and desvenlafaxine (Pristiq).

Cymbalta prevents reuptake of the neurotransmitters serotonin and epinephrine by nerves after they have been released, thereby increasing the effect of serotonin and norepinephrine in the brain. Effexor XR works in the same way as Cymbalta; however, it prevents the reuptake of the neurotransmitters serotonin and norepinephrine.

What are the uses for Cymbalta vs. Effexor?

Cymbalta (duloxetine) uses

Cymbalta is used for the treatment of:

Effexor (venlafaxine) uses

Effexor is used for the treatment of depression, depression with associated symptoms of anxiety, generalized anxiety disorder, and social anxiety disorder; and for the treatment of adults with panic disorder.

What are the differences in the side effects of Cymbalta and Effexor?

Cymbalta side effects

The most common side effects of duloxetine include:

Effexor side effects

Effexor, like most antidepressants, can cause:

Cymbalta and Effexor serious side effects

  • Sexual dysfunction (decreased sex drive and delayed orgasm and ejaculation)
  • Seizures
  • An increase in blood pressure, blood pressure should be monitored.
  • Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with depression and other psychiatric disorders. Anyone considering the use of venlafaxine or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.

What are the withdrawal symptoms of Cymbalta and Effexor?

Cymbalta, Effexor XR, and any other antidepressants can cause withdrawal symptoms if they are stopped suddenly (abruptly) without gradually reducing the dosage. Withdrawal symptoms may occur even if a few doses are missed. Withdrawal symptoms include:

  • Dizziness
  • Headache
  • Nausea
  • Changes in mood
  • Changes in the sense of smell and taste

What are the differences in the dosages of Cymbalta vs. Effexor?

Cymbalta dosage

  • The recommended dose for treating depression is 20 or 30 mg twice daily or 60 mg once daily. Patients may be started with 30 mg once daily for one week before increasing the dose to 60 mg daily because it may help patients adjust to the drug.
  • The recommended dose is 60 mg daily for anxiety disorder, pain associated with diabetic neuropathy, fibromyalgia, or chronic musculoskeletal pain.
  • There is no evidence that doses greater than 60 mg/day provide additional benefits. However, the maximum dose for depression or anxiety disorder is 120 mg/day.

Effexor dosage

Venlafaxine should be taken with food at doses specifically directed by a doctor since individual doses can vary greatly.

  • The antidepressant effects are not maximal for 1-2 weeks. The dose of Effexor XR gradually should be reduced under the direction of a doctor to avoid withdrawal symptoms.
  • For people with difficulty swallowing tablets or capsules, Effexor XR capsules can be opened and the contents sprinkled onto a spoonful of applesauce or other food; however, removing the capsule contents will immediately release of the drug, so it is no longer extended release.
  • The dose for treatment of depression using the immediate release formulation is 75 to 375 mg daily divided in 2 or 3 doses and given every 8 or 12 hours. The extended release dose is 37.5 mg to 225 mg once daily. Dosing is usually begun with low initial concentrations and adjusted as needed by the treating doctor.
  • Generalized anxiety and panic disorder are treated with 37.5 mg to 225 mg once daily using the extended release formulation.
  • Social anxiety is treated with 75 mg daily using the extended release formulation.

What are the drug interactions of Cymbalta vs. Effexor?

Cymbalta drug interactions

  • Duloxetine should not be used in combination with a monoamine oxidase inhibitor (MAOI) such as phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), and selegiline (Eldepryl), or within 14 days of discontinuing the MAOI. At least 5 days should be allowed after stopping duloxetine before starting an MAOI. Combinations of SNRIs and MAOIs may lead to serious, sometimes fatal, reactions including very high body temperature, muscle rigidity, rapid fluctuations of heart rate and blood pressure, extreme agitation progressing to delirium, and coma. Similar reactions may occur if duloxetine is combined with antipsychotics, tricyclic antidepressants or other drugs that affect serotonin in the brain. Examples include tryptophan, sumatriptan (Imitrex), lithium, linezolid (Zyvox), tramadol (Ultram), and St. John’s Wort.
  • Fluoxetine (Prozac, Sarafem), paroxetine (Paxil, Paxil CR, Pexeva), fluvoxamine (Luvox), and quinidine increase blood levels of duloxetine by reducing its metabolism in the liver. Such combinations may increase adverse effects of duloxetine.
  • Combining duloxetine with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin) or other drugs that are associated with bleeding may increase the risk of bleeding, because duloxetine itself is associated with bleeding.
  • Duloxetine has an enteric coating that prevents dissolution until it reaches a segment of the gastrointestinal that has a pH higher than 5.5. In theory, drugs that raise the pH in the gastrointestinal system (for example, Prilosec) may cause duloxetine to be released early while conditions that slow gastric emptying (for example, diabetes) may cause premature breakdown of duloxetine. Nevertheless, administration of duloxetine with an antacid or famotidine (Axid) did not significantly affect the absorption of duloxetine.
  • Duloxetine may reduce the breakdown of desipramine (Norpramin), leading to increased blood concentrations of desipramine and potential side effects.

Effexor drug interactions

  • Venlafaxine should not be used in combination with a monoamine oxidase inhibitor (MAOI) such as phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), and selegiline (Eldepryl), or within 14 days of discontinuing the MAOI. At least 5 days should be allowed after stopping venlafaxine before starting an MAOI. Combinations of SNRIs and MAOIs may lead to serious, sometimes fatal, reactions including very high body temperature, muscle rigidity, rapid fluctuations of heart rate and blood pressure, extreme agitation progressing to delirium, and coma. Similar reactions may occur if venlafaxine is combined with antipsychotics, tricyclic antidepressants or other drugs that affect serotonin in the brain. Examples include tryptophan, sumatriptan (Imitrex), lithium, linezolid (Zyvox), tramadol (Ultram), and St. John's Wort.
  • Combining venlafaxine with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin) or other drugs that are associated with bleeding may increase the risk of bleeding, because venlafaxine is associated with bleeding.
  • Most medications affecting the brain such as venlafaxine have the potential to slow reflexes or impair judgment. Therefore, caution is advised especially early in the course of treatment.
  • Safety has not been established in children below the age of 18 years.

Are Cymbalta or Effexor safe to take if I am pregnant or breastfeeding?

Cymbalta safety

  • Duloxetine is excreted into the milk of lactating women. Because the safety of duloxetine in infants is not known, breastfeeding while on duloxetine is not recommended.

Effexor safety

  • The effects of venlafaxine on the fetus during pregnancy are unknown.
  • It is not known if venlafaxine is secreted in breast milk, and therefore, if it may have an effect on nursing infants.

Summary

Cymbalta, brand name duloxetine, and Effexor XR brand name venlafaxine (Effexor has been discontinued) are antidepressants belonging to a drug class called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). Cymbalta and Effexor are used for the treatment of chronic depression, anxiety disorders (for example, general or social), and pain. Cymbalta also treats fibromyalgia, and musculoskeletal or diabetic neuropathy (nerve pain).

Similar side effects of Cymbalta and Effexor include headaches, insomnia, anxiety, nausea, and dry mouth. Both Cymbalta and Effexor can cause serious side effects like increased blood pressure, erectile dysfunction (ED, impotence) and seizures. They also may increase the risk of suicidality.

Side effects that occur with Cymbalta that do not occur with Effexor include constipation, diarrhea, and fatigue. Effexor may cause side effects like sleepiness, loss of appetite, weight loss, and sweating. If Cymbalta or Effexor are stopped abruptly they may cause withdrawal symptoms like irritability, insomnia, anxiety, nervousness, dizziness, nausea, vomiting, and diarrhea.

The brand name Effexor is no longer available in the US; however, Effexor XR is.

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Medically Reviewed on 2/22/2018
References
REFERENCE: FDA Prescribing Information for Cymbalta and Effexor and Effexor XR.
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