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Key takeaways
Effexor and Zoloft are FDA-approved for treating depression but differ in their classifications: Effexor is an SNRI, and Zoloft is an SSRI.
Both medications can be effective for depression with similar efficacy, but Zoloft is generally better tolerated and has fewer side effects. For example, Effexor may increase blood pressure.
Common side effects of Effexor include nausea, sleepiness, and sexual problems, while Zoloft may cause insomnia and diarrhea.
Effexor and Zoloft have serious warnings, including the risk of suicidal thoughts in young adults and serotonin syndrome. To avoid withdrawal symptoms, they should not be abruptly discontinued.
Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ
Effexor and Zoloft are two popular medications indicated for the treatment of depression, a common mental health condition, among other conditions. Both prescription drugs are approved by the United States Food and Drug Administration (FDA).
Effexor is part of a group of medications called SNRIs (serotonin-norepinephrine reuptake inhibitors). SNRIs increase levels of serotonin and norepinephrine in the brain.
Zoloft (sertraline) is an SSRI (selective serotonin reuptake inhibitor). An SSRI works by increasing levels of serotonin in the brain.
Treatment with Effexor or Zoloft is often accompanied by psychotherapy with a psychologist or doctor of psychiatry. Although Effexor and Zoloft are popular antidepressants, they are not the same. Continue reading to learn more about both medications.
What are the main differences between Effexor and Zoloft?
Effexor is an SNRI antidepressant and is available in brand (as Effexor XR) and generic form. The generic name is venlafaxine. Effexor is available in tablet form, and also as an extended-release capsule and extended-release tablet.
Zoloft is a selective serotonin reuptake inhibitor (SSRI) that is available in both brand and generic. The generic name is sertraline. Zoloft is available in both tablet and liquid form.
| Main differences between Effexor and Zoloft | ||
|---|---|---|
| Effexor | Zoloft | |
| Drug class | SNRI (serotonin-norepinephrine reuptake inhibitor) | SSRI (selective serotonin reuptake inhibitor) |
| Brand/generic status | Brand and generic | Brand and generic |
| What is the generic name? | Venlafaxine | Sertraline |
| What form(s) does the drug come in? | Tablet, extended-release capsules, extended-release tablets | Tablet and liquid |
| What is the standard dosage? | Typical dose is XR 75 or 150 mg daily
Taper gradually when discontinuing |
Adult dose: 50-200 mg daily (maximum 200 mg per day)
Taper gradually when discontinuing |
| How long is the typical treatment? | Varies | Varies |
| Who typically uses the medication? | Adults | Adults; children ages 6 years through 17 years for OCD only |
Conditions treated by Effexor and Zoloft
Effexor, in its immediate-release form, is indicated for major depressive disorder. Effexor XR (extended-release) is indicated for major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder.
Zoloft is indicated for treating major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder.
| Condition | Effexor | Zoloft |
| Major Depressive Disorder (MDD) | Yes (IR and XR forms) | Yes |
| Generalized anxiety disorder | Yes (XR form only) | Off-label |
| Obsessive-compulsive disorder (OCD) | Off-label | Yes |
| Panic disorder (PD) | Yes (XR form only) | Yes |
| Post-traumatic stress disorder (PTSD) | Off-label | Yes |
| Social anxiety disorder (SAD) | Yes (XR form only) | Yes |
| Premenstrual dysphoric disorder (PMDD) | Off-label | Yes |
Is Effexor or Zoloft more effective?
One study compared Effexor XR and Zoloft in the treatment of depression and found that both drugs had similar efficacy and similar effect on the quality of life, but that Zoloft had fewer side effects. Also, patients who took Effexor had an increased risk of high blood pressure.
An analysis in The Lancet reviewed many studies to look for the best antidepressant. The researchers looked at 21 antidepressants (including Effexor and Zoloft) and found all antidepressants to be more effective than placebo. Effexor was found to be one of the more effective antidepressants, but Zoloft was better tolerated.
The most effective drug for you should be determined by your healthcare provider, who can take into account your medical history, medical conditions, and other medications you take that could interact with Effexor or Zoloft.
Coverage and cost comparison of Effexor vs. Zoloft
Effexor XR, the more popularly prescribed type of Effexor, is covered by most insurance and Medicare prescription plans. The generic version will have a lower copay, and the brand name may have a higher copay or may not be covered. The out-of-pocket price of a typical prescription of 30, 150 mg generic capsules is about $140. You can use a free SingleCare card to buy the generic prescription for around $15.
Zoloft is usually covered by both insurance and Medicare prescription plans. Generic Zoloft will have a lower copay, whereas brand name may have a higher copay or may not be covered at all. The out-of-pocket cost of Zoloft is about $32 for 30 tablets of 100 mg generic sertraline tablets. You can use a free SingleCare card to lower the price to $10 for generic Zoloft.
As insurance plans vary and are subject to change, contact your health insurance plan for current coverage information.
| Effexor | Zoloft | |
| Typically covered by insurance? | Yes (generic) | Yes (generic) |
| Typically covered by Medicare Part D? | Yes (generic) | Yes (generic) |
| Quantity | 30, 150 mg extended-release capsules | 30, 100 mg tablets |
| Typical Medicare copay | $0-$20 | $0-$13 |
| SingleCare cost | $10-$40 | $9-$31 |
Common side effects of Effexor vs. Zoloft
The most common side effects of Effexor XR are nausea, sleepiness, dry mouth, sweating, sexual problems, decreased appetite, and constipation.
The most common adverse reactions of Zoloft are nausea, diarrhea, sexual problems, dry mouth, insomnia, and sleepiness.
Other adverse effects may occur. Consult your healthcare professional for a complete list of side effects.
| Effexor* | Zoloft | |||
| Side effect | Applicable? | Frequency | Applicable? | Frequency |
| Headache | Yes | 1.5% | Yes | % not reported |
| Nausea | Yes | 30% | Yes | 26% |
| Diarrhea | Yes | 8% | Yes | 20% |
| Constipation | Yes | 9% | Yes | 6% |
| Decreased appetite | Yes | 10% | Yes | 7% |
| Sweating | Yes | 11% | Yes | 7% |
| Ejaculation disorder/sexual problems | Yes | 5-10% | Yes | 8% |
| Dry mouth | Yes | 15% | Yes | 14% |
| Sleepiness | Yes | 15% | Yes | 11% |
| Insomnia | Yes | 18% | Yes | 20% |
| Dizziness | Yes | 16% | Yes | 12% |
*percentages listed are for Effexor XR, the more commonly prescribed formulation of Effexor.
Source: DailyMed (Effexor XR), DailyMed (Zoloft)
Drug interactions of Effexor vs. Zoloft
MAO inhibitors should not be used within 14 days of Effexor or Zoloft. The combination may increase the risk of serotonin syndrome, a life-threatening medical emergency due to excess serotonin. Triptans used to treat migraines, as well as other antidepressants, opioids, dextromethorphan, or St. John’s wort should not be used in combination with Effexor or Zoloft due to the risk of serotonin syndrome.
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as Advil, Motrin, and aspirin, or anticoagulants such as warfarin, should not be taken with Effexor or Zoloft because of increased bleeding risk.
Do not drink alcohol while taking Effexor or Zoloft.
Other drug interactions may occur. Consult your healthcare provider for a full list of drug interactions.
Aspirin
Celecoxib
Ibuprofen
Meloxicam
NaproxenNSAIDs (nonsteroidal anti-inflammatory drugs)YesYes
| Drug | Drug Class | Effexor | Zoloft |
| Phenelzine Rasagiline Selegiline Tranylcypromine |
MAOIs (Monoamine oxidase inhibitors) | Yes | Yes |
| Alcohol | Alcohol | Yes | Yes |
| Rizatriptan Sumatriptan Zolmitriptan |
Triptans | Yes | Yes |
| Dextromethorphan | Cough suppressant | Yes | Yes |
| Warfarin | Anticoagulant | Yes | Yes |
| St. John’s Wort | Supplement | Yes | Yes |
| Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline |
SSRI antidepressants | Yes | Yes |
| Desvenlafaxine Duloxetine Venlafaxine |
SNRI antidepressants | Yes | Yes |
| Amitriptyline Desipramine Imipramine Nortriptyline |
TCA (tricyclic antidepressants) | Yes | Yes |
| Baclofen Carisoprodol Cyclobenzaprine Metaxalone |
Muscle relaxants | Yes | Yes |
| Carbamazepine Divalproex sodium Gabapentin Lamotrigine Levetiracetam Phenobarbital Phenytoin Pregabalin Topiramate |
Anticonvulsants | Yes | Yes |
| Diphenhydramine | Sedating antihistamine | Yes | Yes |
Warnings of Effexor and Zoloft
- Effexor and Zoloft have a black box warning. A black box warning is the most severe warning required by the FDA (United States Food and Drug Administration). Children, adolescents, and young adults (up to age 24 years old) who take antidepressant medications have an increased risk of suicidal thoughts and behavior. All patients who take antidepressants should be carefully monitored.
- Patients who take Effexor or Zoloft are at risk of serotonin syndrome, a life-threatening medical emergency caused by too much serotonin. This is even more likely with dosage increases and/or if taking other medications that increase serotonin. Monitor for symptoms of hallucinations, fever, tremor, seizures, and/or agitation.
- Withdrawal symptoms, such as agitation, may occur when discontinuing Effexor or Zoloft. Patients should taper off the drug very slowly and never stop abruptly. Your healthcare provider can give you a tapering schedule.
- Use with caution in patients who have seizures or bipolar disorder.
- There is a risk of hyponatremia (low sodium) due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH symptoms may include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may cause falls. Seek immediate treatment if symptoms occur.
- Avoid Effexor or Zoloft in patients with angle-closure glaucoma.
- Effexor or Zoloft may increase the risk of bleeding. This risk increases with the concomitant use of NSAIDs or warfarin.
- Loss of appetite and/or weight loss may occur.
- Effexor or Zoloft should only be used in pregnancy if your healthcare provider determines that benefits outweigh risks. Effexor or Zoloft can cause serious complications to the baby, especially if taken in the third trimester. If you are already on Effexor or Zoloft and find out you are pregnant, contact your healthcare provider immediately.
- Zoloft oral solution contains 12% alcohol.
- Effexor may increase blood pressure. Monitor blood pressure before and during treatment with Effexor. Use with caution in patients with high blood pressure or heart problems.
Frequently asked questions about Effexor vs. Zoloft
What is Effexor?
Effexor is an SNRI antidepressant. Effexor treats depression (also called major depressive disorder or major depression) in adults. Effexor XR (extended-release) treats depression, social anxiety disorder, panic disorder, and generalized anxiety disorder. The generic name of Effexor is venlafaxine.
What is Zoloft?
Zoloft (sertraline) is an SSRI (selective serotonin reuptake inhibitor) indicated for the treatment of major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder.
Are Effexor and Zoloft the same?
Effexor and Zoloft are not the same. Effexor is part of a drug class called SNRIs, or serotonin-norepinephrine reuptake inhibitors. SNRIs work on serotonin and norepinephrine. Some other drugs in the SNRI class are Cymbalta (duloxetine) and Pristiq (desvenlafaxine).
Zoloft is part of a drug class called SSRIs, or selective serotonin reuptake inhibitors. SSRIs work on serotonin. Some other drugs in the SSRI class of medications are Prozac (fluoxetine), Celexa (citalopram), Lexapro (escitalopram), Luvox (fluvoxamine), and Paxil (paroxetine).
Other differences between Effexor and Zoloft are outlined above.
Is Effexor or Zoloft better?
Either drug can be effective, but everyone responds differently to different medications. The best medication can be determined by your healthcare provider, who can consider your medical history and other medications you take that could interact with Effexor or Zoloft.
Can I use Effexor or Zoloft while pregnant?
Taking Effexor or Zoloft in the third trimester can cause serious complications to the baby, resulting in prolonged hospitalizations, tube feeding, and breathing support. Effexor or Zoloft is only prescribed in pregnancy when the benefits outweigh risks and if no other safer alternative is available. If you are already taking Effexor or Zoloft and find out that you are pregnant, contact your healthcare provider for medical advice.
Can I use Effexor or Zoloft with alcohol?
No. Neither drug should be used with alcohol. Combining an antidepressant, like Effexor or Zoloft, with alcohol, can worsen depression or anxiety symptoms, impair thinking and alertness, and increase the effects of sedation and drowsiness.
Is Zoloft better for anxiety or depression?
Zoloft is indicated for major depressive disorder (depression). Zoloft is not indicated for generalized anxiety disorder, but it is indicated for panic disorder, social anxiety disorder, and OCD. Your healthcare provider can determine the best medication for you, depending on your diagnosis and other factors like your medical history and other medications you take that could interact with Zoloft.
Can Zoloft worsen anxiety?
Zoloft can treat depression and certain types of anxiety disorders. However, some people experience increased anxiety or agitation, especially when beginning treatment. If you take Zoloft and feel anxious or agitated, contact your healthcare provider for medical advice.
Also, suicidal thoughts can occur in some cases, and the risk is higher in patients up to age 24 years. If you are having suicidal thoughts, seek emergency treatment. Be sure that your loved ones know about the possibility of suicidal thoughts and/or behavior, so they can be alert for any potential issues and help you seek treatment if necessary.
Is it better to take Zoloft in the morning or at night?
The prescribing information for Zoloft does not specify the best time of day to take it. The best time of day is when you will remember to take it every day. Also, if Zoloft makes you drowsy, you may want to take it at night. For some people, Zoloft causes insomnia. If Zoloft causes insomnia, you may want to take it in the morning. You can ask your prescriber if he or she suggests a recommended time.