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Effexor vs. Zoloft: Selected Neurotransmitters Make the Difference

Though Effexor and Zoloft both treat depression and anxiety as well as other selected disorders, they differ when it comes to how they work, how they affect the patient (i.e., side effects and caveats), and how they interact with other medicines.

For one, these two antidepressants come from different families of medicine. Effexor belongs to the serotonin-norepinephrine reuptake prohibitor (SNRI) group of antidepressants. It serves to balance the two neurotransmitters—serotonin and norepinephrine—that send messages to the brain and affect one’s mental health as it pertains to anxiety, panic, and depression.

Zoloft belongs to a family of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It does not act upon the neurotransmitter called norepinephrine. Instead, it addresses only the serotonin balance, more greatly associated with mood than norepinephrine, though both prove as actors in terms of mood.

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Both Address Many Common Conditions

According to Iodine.com, a mental health consumer-website, Zoloft and Effexor address many conditions in common:

  • Major depressive disorder (MDD)
  • Generalized anxiety disorder (GAD)
  • Social anxiety disorder (SAD)
  • Panic disorder (PD, the fight-or-flight dynamic in laymen’s terms)
  • Obsessive-compulsive disorder (OCD)
  • Premenstrual dysphoric disorder (PDD, a more severe, debilitating form of PMS)

Additionally, Effexor treats diabetic neuropathy (chronic pain due to diabetes), hot flashes, and migraines. Zoloft additionally treats bulimia nervosa (a binge-eating disorder) and post-traumatic stress disorder (PTSD).

How They Interact with Other Medicines

Both Effexor and Zoloft can be used while treating multiple disorders. However, Effexor can address any of its aforementioned treatments simultaneously while Zoloft is not designed to do so. Both stand to interact with many other drugs, and therefore, they should be monitored closely when a patient is using other medicines, especially those that affect liver enzymes or live diseases. As with any antidepressant medicines, they should not be taken with alcoholic beverages.

Effexor interacts with the following medicines: MAO inhibitors (isocarboxazid, phenelzine, selegiline, etc.), CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine), serotoneimipramines (fluoxetine, paratenolol, metoprolol trazodone, etc.), aspirin, NSAIDs, warfarin, desipramine, alcohol, and CNS drugs (phenobarbital, lorazepam, oxycodone, etc.).

Zoloft interacts with many of the same drugs as Effexor, plus: pimozide, other SSRIs, SNRIs such as Effexor, amiodarone, triptans, tricyclics (amitriptyline, nortriptyline, imipramine), beta-blockers (atenolo, metoprolol, etc.), fentanyl, tramadol, buspirone, amphetamines, St. John’s Wart, cimetidine, lamotrigine, phenytoin, carbamazepine, propafenone, and atomoxetine.

Neither drug should be taken with particular medications. Always defer to your personal physician about drug interactions and strictly follow doctor’s instructions when it comes to using other drugs simultaneously with either Effexor or Zoloft.

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During Pregnancy

As with all antidepressants, follow your doctor’s recommendations when using either Zoloft or Effexor. Such medicines can adversely affect the fetus in some individuals. However, according to research noted by Iodine.com, Zoloft “is the best choice among antidepressants if you are pregnant.”

Zoloft Side Effects

Comparatively, Zoloft hosts fewer side effects than Effexor and is considered a better-tolerated drug than many other antidepressants. This mostly results from the fact it manages only one neurotransmitter, serotonin. For example, it causes less sleepiness than other medicines.

Its side effects include nausea, diarrhea, dry mouth, drowsiness, insomnia, dizziness, shakes or tremors, fatigue, sweating, constipation, erectile dysfunction, stomachache, agitation, and loss of appetite.

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Effexor Side Effects

Effexor can cause dry mouth, dizziness, drowsiness, loss of appetite, and sweating. Additionally, it can cause headaches, insomnia, nausea, constipation, nervousness, fatigue, and anxiety. Less common side effects from Effexor include gas, tremors, sexual impotence, vomiting, seizures, blurred vision, increased blood pressure, chills, rash, abnormal dreams, muscle stiffness, chest pains, increased heart rate, diarrhea, indigestion, increased urination, agitation, confusion, pupil dilation, ringing in the ears, and blunting of the taste buds.


Effexor, which comes in capsule form as an extended-release medication, often requires dosages of 37.5-375 mg, taken 2-3 times a day or every 8-12 hours. To acclimate the patient to the drug, it can sometimes be prescribed for once a day or started on the lower end of the milligram scale. Tolerance for the drug can vary from one patient to the next, according to SingleCare, a healthcare group that offers prescription discount cards to consumers.

Release of Effexor XR usually takes at least two weeks. If the capsule is snapped and its contents sprinkled onto food, an immediate release of the medicine occurs, and its effects begin to materialize much sooner than two weeks.

Also serving as an extended-release medicine that takes as many as two weeks or more to begin acting and several weeks more to take full effect, Zoloft (generically known as sertraline) comes in an oral tablet form. It can be taken in doses of 25 mg, 50 mg, or 100 mg once a day.

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Cost and Insurance Coverage

Effexor costs almost twice as much as Zoloft (generically known as venlafaxine). Always check with your health insurance regarding any medications for mental health illnesses to make sure they are covered. Depending on the illness and the medications, some may not be covered.

To Sum It Up

It can be said that both Effexor and Zoloft share many commonalities, even though one (Zoloft) works on a single neurotransmitter while Effexor manages two neurotransmitters. Meanwhile, because of this difference, Zoloft is considered a bit gentler to the patient than Effexor and produces fewer side effects. However, as with all antidepressants, their effects can range from individual to individual. Therefore, patients should always defer to their physician in terms of which one will be more tolerable than the other.

Both drugs effectively treat depression and anxiety, but each one tackles particular disorders that the other does not treat.

Because of its capsule form, Effexor holds the distinction from many other antidepressants of being either an extended-release or immediate-release medicine—the latter when the capsule is snapped and sprinkled on food.

In terms of effectiveness, an article in WebMD suggests that any antidepressant that works on both the serotonin and norepinephrine neurotransmitters will likely produce a more solid result than medications such as Zoloft that address only one neurotransmitter.

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