Zoloft (sertraline) vs. Cymbalta (duloxetine): What's the difference?

What are Zoloft and Cymbalta?

Zoloft (sertraline) is an antidepressant in the selective serotonin reuptake inhibitor (SSRI) class used for treating depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD). Other examples of SSRIs include paroxetine (Brisdelle, Paxil, Paxil CR, Pexeva), fluoxetine (Prozac, Sarafem), citalopram (Celexa), and fluvoxamine (Luvox CR). Many experts believe depression may be caused by imbalances between serotonin and other neurotransmitters. Zoloft is thought to restore this chemical balance in the brain. Selective serotonin inhibitors block the reuptake of serotonin, changing the level of serotonin in the brain. A serotonin balance is reached between attachment to the nearby nerves and reuptake.

Cymbalta (duloxetine) is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant used to treat depression, anxiety disorder, and some types of pain. Other SNRIs include milnacipran (Savella), venlafaxine (Effexor), and desvenlafaxine (Pristiq). Cymbalta works by preventing the reuptake of the neurotransmitters serotonin and epinephrine by nerves after they have been released. The reduced uptake caused by Cymbalta increases the effect of serotonin and norepinephrine in the brain. The mechanism responsible for its effectiveness treating pain is not known but also is thought to involve its effects on serotonin and norepinephrine in the brain.

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Learn to Spot Depression: Symptoms, Warning Signs, Medication See Slideshow

What are the side effects of Zoloft and Cymbalta?

Zoloft

WARNING

  • As demonstrated in short-term studies, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Zoloft or any other antidepressant in a child or adolescent must balance this risk with the clinical need for the antidepressant. Patients who are started on therapy should be closely observed for clinical worsening, suicidal thoughts, or unusual changes in behavior.

The most common side effects of Zoloft are:

Possible serious side effects of Zoloft include:

Important side effects are irregular heartbeats, allergic reactions, and activation of mania in patients with bipolar disorder.

If Zoloft is discontinued abruptly, some patients experience side effects such as:

A gradual dose reduction of Zoloft is recommended when therapy is discontinued.

Cymbalta

WARNING

  • Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Cymbalta or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who begin therapy should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.

The most common side effects of Cymbalta are:

Increased blood pressure can occur and should be monitored. Seizures have been reported. Sexual dysfunction (decreased sex drive, and delayed orgasm and ejaculation) has been associated with Cymbalta.

Some patients may experience withdrawal reactions upon stopping Cymbalta. Symptoms of withdrawal include:

The dose of Cymbalta should be gradually reduced when therapy is discontinued to prevent symptoms of withdrawal.

What is the dosage of Zoloft vs. Cymbalta?

Zoloft

The recommended dose of sertraline is 25 to 200 mg once daily. Treatment of depression, OCD, panic disorder, PTSD, and social anxiety disorder is initiated at 25 to 50 mg once daily. Doses are increased at weekly intervals until the desired response is seen.

The recommended dose for PMDD is 50 to 150 mg every day of the menstrual cycle or for 14 days before menstruation.

Sertraline may be taken with or without food.

Cymbalta

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 the dose is advanced to 60 mg daily.

The recommended dose for anxiety disorder, pain associated with diabetic neuropathy, fibromyalgia, or chronic musculoskeletal pain is 60 mg daily. Starting at 30 mg daily for one week before increasing to 60 mg daily may help patients adjust to the drug. 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.

QUESTION

Depression is a(n) __________ . See Answer

What drugs interact with Zoloft and Cymbalta?

Zoloft

All SSRIs, including Zoloft, should not be taken with any of the monoamine oxidase inhibitor (MAOI) class of antidepressants, for example

  • isocarboxazid (Marplan),
  • phenelzine (Nardil),
  • tranylcypromine (Parnate),
  • selegiline (Eldepryl, Emsam, Elazar), and
  • procarbazine (Matulane).

Other drugs that inhibit monoamine oxidase include

Such combinations may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. (A period of 14 days without treatment should lapse when switching between Zoloft and MAOIs.) Similar reactions occur when Zoloft is combined with other drugs for example, tryptophan, St. John's wort, meperidine (Demerol, Meperitab), tramadol (ConZip, Synapryn FusePaq, Ultram) that increase serotonin in the brain.

Cimetidine (Cimetidine Acid Reducer, Tagamet HB ) may increase the levels in blood of Zoloft by reducing the elimination of Zoloft by the liver. Increased levels of Zoloft may lead to more side effects.

Zoloft increases the blood level of pimozide (Orap) by 40%. High levels of pimozide can affect electrical conduction in the heart and lead to sudden death. Therefore, patients should not receive treatment with both pimozide and Zoloft.

Through unknown mechanisms, Zoloft may increase the blood thinning action of warfarin (Coumadin, Jantoven). The effect of warfarin should be monitored when Zoloft is started or stopped.

Cymbalta

  • Cymbalta 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 Cymbalta 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 Cymbalta 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, Serafem), paroxetine (Paxil, Paxil CR, Pexeva), fluvoxamine (Luvox), and quinidine increase blood levels of Cymbalta by reducing its metabolism in the liver. Such combinations may increase adverse effects of Cymbalta.
  • Combining Cymbalta with aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), warfarin (Coumadin), or other drugs that are associated with bleeding may increase the risk of bleeding, because Cymbalta itself is associated with bleeding.
  • Cymbalta has an enteric coating that prevents dissolution until it reaches a segment of the gastrointestinal tract that has a pH higher than 5.5. In theory, drugs that raise the pH in the gastrointestinal system (for example, Prilosec) may cause Cymbalta to be released early while conditions that slow gastric empyting (for example, diabetes) may cause premature breakdown of Cymbalta. Nevertheless, administration of Cymbalta with an antacid or famotidine (Pepcid) did not significantly affect the absorption of Cymbalta.
  • Cymbalta may reduce the breakdown of desipramine (Norpramine), leading to increased blood concentrations of desipramine and potential side effects.

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Are Zoloft and Cymbalta safe to use while pregant or breastfeeding?

Zoloft

Cymbalta

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

Summary

Zoloft (sertraline) and Cymbalta (duloxetine) are antidepressants used to treat depression and anxiety disorders. Zoloft and Cymbalta belong to different classes of antidepressants. Zoloft is a selective serotonin reuptake inhibitor (SSRI) and Cymbalta is a selective serotonin and norepinephrine reuptake inhibitor (SNRI).

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Medically Reviewed on 6/24/2019
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