Effexor and Zoloft are two of many medications that can be used to help alleviate the symptoms of depression. Depression affects greater than 6 percent of adult males and greater than 10 percent of adult females in the United States. This incidence is even greater for people who report having 2 or more races. Genetics and family history are a large part of whether a person experiences a depressive episode. Often patients must suffer through several different trials of medication to find the one that works best for them. Unfortunately, many patients never find a medicine that works well.

Other commonly prescribed medications for depression or anxiety include citalopram, escitalopram, fluoxetine, paroxetine, duloxetine, bupropion, and dozens of others. Finding the best medication for you can be a daunting task.

What is Effexor?

Effexor, or venlafaxine, is a medication called an SNRI (serotonin-norepinephrine reuptake inhibitor). SNRI medications inhibit the reuptake of the neurotransmitters: norepinephrine, serotonin, and dopamine. When the reuptake of these neurotransmitters is blocked or delayed, they are allowed to remain available where they are needed, leading the person to have an improved mood. Dopamine, norepinephrine, and serotonin all help the body to function properly. Depression is sometimes associated with lower levels of these key neurotransmitters and allowing them to remain available longer can positively impact mood.

Effexor is used for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder, and panic disorder. It is often also prescribed to help with post-traumatic stress disorder (PTSD), cataplexy, diabetic neuropathic pain, and migraines.

What is Zoloft?

Zoloft, or sertraline, is an SSRI (selective serotonin reuptake inhibitor). This type of medication leads to the increased availability of serotonin. Serotonin helps to regulate attention, behavior, and body temperature. Serotonin is also critical in regulating digestion, blood flow and breathing. Normal levels of serotonin help you feel calmer and happier. Low serotonin levels are often associated with the symptoms of depression. Zoloft increases these levels leading a person to have an improved mood.

Zoloft is used for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder, PTSD, premenstrual dysphoric disorder, and social phobias. It has also been prescribed to manage premature ejaculation and vascular headaches.

Can I take Effexor and Zoloft Together?

No. Taking Effexor and Zoloft together can dangerously increase the levels of venlafaxine, increase the risk of serotonin syndrome, lead to life-threatening bleeding, low sodium levels, central nervous system depression, psychomotor impairment, and low platelets (further increasing the risk of bleeding).

Serotonin syndrome occurs when the levels of serotonin are too high in the body. Symptoms include confusion, hallucination, seizures, extreme changes in blood pressure, increased heart rate, fever, excessive sweating, shivering, or shaking, blurred vision, muscle spasms or stiffness, stomach cramps, nausea, vomiting, diarrhea, coma, and death. It is often misdiagnosed at first and can go untreated because the early signs and symptoms are not often obvious. Since many other medications can affect serotonin levels, not just anti-depressants, it is important that your physician and pharmacist know all the medications and herbals that you use.

Effexor vs Zoloft: Dosage Amounts


Effexor is supplied as either a capsule or tablet. It can be taken as an easy once-a-day extended-release capsule or tablet; or 2 to 3 times a day with the immediate-release tablets.

The extended-release doses available are: 37.5 mg, 75 mg, 150 mg, and 225 mg. Capsules can be opened and poured into apple sauce then swallowed, do not chew the beads. Tablets can be divided on the score line if needed. Extended-release is not approved for pediatric patients.

Immediate-release doses available are: 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg. Doses above 225 mg per day are not recommended. These tablets can be divided or crushed if necessary.

Dosage adjustments for Effexor are recommended for patients with kidney or liver disease depending on the severity of the disease. Poor CYP2D6 metabolizers are not able to efficiently change venlafaxine to the active metabolite, desvenlafaxine, and may experience little benefit from this medication with a potential for greater side effects, although dose adjustments may sometimes be recommended. Other genes, ABCB1, SLC6A4, HTR1B, and HTR2A, have also been shown to affect treatment response.


Zoloft is supplied as either a tablet or a solution. All doses are given once daily. Tablets come in 25 mg, 50 mg, and 100 mg; and the solution is 20 mg/milliliter. The maximum daily dosage should not exceed 200 mg.

Dosage adjustments for Zoloft are recommended for patients with liver disease. Patients with CYP2C19 variations may find Zoloft a poor choice. CYP2C19 metabolism inactivates sertraline, the active form of Zoloft. Patients who are ultrarapid metabolizers therefore may have low concentrations of Zoloft and find it either ineffective or find the effectiveness wears off earlier than expected. CYP2C19 poor metabolizers, on the other hand, lead to greater than expected concentrations of sertraline and a higher risk of adverse effects.

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Effexor vs Zoloft: Side Effects

*Both Effexor and Zoloft contain a Black Box Warning stating there is an increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. Closely monitor for clinical worsening, and emergence of suicidal thoughts and behaviors.


  • abnormal bleeding
  • angle closure glaucoma
  • constipation
  • decreased appetite
  • dry mouth
  • high blood pressure
  • low sodium levels
  • mania/hypomania
  • nausea
  • sexual dysfunction
  • sleepiness
  • sweating
  • weakness


  • abdominal pain
  • abnormal bleeding
  • agitation
  • angle closure glaucoma
  • constipation
  • decreased appetite
  • diarrhea/loose stool
  • dizziness
  • dry mouth
  • fatigue
  • indigestion
  • insomnia
  • low sodium levels
  • mania/hypomania
  • nausea
  • sexual dysfunction
  • sweating
  • tremor

Who Should Not Take Effexor?

Effexor has a Black Box warning for increased suicidal ideation. When starting any psychologically active medication it is important to regularly assess risks versus benefits and to monitor the patient closely whenever a dose is changed. Certain patients are unable to metabolize venlafaxine into the active metabolite and may find the medication less effective than expected. These same patients may also experience greater than predicted side effects. Discontinuing Effexor should be done under the supervision of a medical professional and may require tapering the dosage over time to avoid side effects.


  • bipolar disorder
  • Monoamine Oxidase Inhibitors use within 14 days
  • nursing mothers
  • pimozide
  • weight loss agents


  • alcohol use
  • drug testing – may lead to false positive
  • medications that affect clotting such (ex. aspirin, clopidogrel, NSAIDS, warfarin, etc.)
  • other central nervous system (CNS)-active medications
  • other serotonergic medications (ex. Other SNRIs, SSRIs, fentanyl, lithium, tramadol, buspirone, St John’s Wort, etc.). May lead to serotonin syndrome.
  • pregnancy (Category C)
  • seizures
  • sexual dysfunction

Who Should Not Take Zoloft?

Zoloft has a Black Box warning for increased suicidal ideation, assess regularly. Certain patients may metabolize sertraline more quickly than expected and therefore have decreased exposure to the active ingredient. This would mean that they may not have as effective control of their depression; more frequent dosing is not recommended presently. Slow discontinuation of Zoloft is recommended.


  • Monoamine oxidase inhibitor (MAOIs) use within 14 days
  • Use with pimozide
  • Zoloft oral solution only – use with disulfiram
  • Oral solution contains 12% alcohol


  • alcohol
  • CYP2D6 metabolized medicines (ex. flecainide, atomoxetine, dextromethorphan, metoprolol, tolterodine, venlafaxine, etc.)
  • false positive drug test for benzodiazepines
  • medications that affect blood clotting (ex. aspirin, clopidogrel, NSAIDS, warfarin, etc.)
  • medicines/herbals that affect serotonin levels (Ex. Other SSRIs, SNRIs, fentanyl, lithium, tramadol, buspirone, St John’s Wort, etc.). May lead to serotonin syndrome.
  • phenytoin
  • pregnancy
  • QTc prolongation
  • seizure disorders
  • sexual dysfunction

Effexor vs Zoloft: Which One Should I Take?

When choosing between Zoloft or Effexor it is important to consider which one would work best in your body. Knowing whether your genetics allow for the expected metabolism of the medication can easily reduce the need for trying multiple different medicines. You will want to avoid using Effexor if you are a poor CYP2D6 metabolizer. Avoid Zoloft if you have altered CYP2C19 metabolism.

Where Can I get Pharmacogenetics Testing?

ClarityX offers a Mindwell PGx test to help determine which psychological medications may work best for your body. A simple cheek swab can provide you and your provider an easy way to avoid multiple medication trials and can help you to feel better sooner with fewer side effects. It is possible to know which medications may work better in your body. You are a unique human being, and your medication therapy should reflect that uniqueness.

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