Zoloft vs Xanax: Usage, Differences, and Similarities

By Robynn Lowe
Medically reviewed checkmarkMedically reviewed
June 28, 2022

Both Zoloft and Xanax are prescribed to treat anxiety and major depressive disorder, but there are some major differences between the two medications.

In this article, we will compare Zoloft and Xanax, including their differences, what they treat, side effects, costs, and more.

Plus, we’ll cover how you should know when to see a doctor for signs of anxiety or depression.

Differences

The primary difference between Zoloft and Xanax is that they are in different drug classes because they work differently in the brain.

Zoloft (the brand name for sertraline) is a selective serotonin reuptake inhibitor (SSRI).

It increases levels of the neurotransmitter serotonin by blocking its reuptake (or removal).

This produces a calming effect on the brain. Zoloft is not a controlled substance. It comes in tablets and liquid forms. 

Xanax (the brand name for alprazolam) is a benzodiazepine.

It increases activity receptors in the central nervous system, affecting the neurotransmitter gamma-aminobutyric acid (GABA).

This also has a calming effect on the brain.

Xanax is a controlled substance because it has a greater potential for abuse or dependence.

It comes in tablet forms as immediate-release and extended-release. It is also available as an oral solution. 

Primary Differences Between Zoloft and Xanax

XanaxZoloft
Drug classBenzodiazepineSelective serotonin reuptake inhibitor (SSRI)
Generic drug nameAlprazolamSertraline
FormsImmediate-release tablet, extended-release tablet, oral solutionTablet, liquid
Standard dosageAdults: 0.25-1 milligrams (mg) taken 1-3 times dailyAdults: 50-200 mg daily
Does discontinuation require tapering?YesYes
Who it is prescribed forAdultsAdults; adolescents in some cases
Length of treatmentShort-term use; occasionally long-term use under close healthcare provider supervisionMonths or years

How quickly does each take to work?

Because Zoloft and Xanax work differently in the brain, their effects are noticed at different times.

  • Xanax: Benefits are typically felt within an hour.
  • Zoloft: Benefits may start being noticeable within two weeks, but full improvements may take 6-8 weeks.
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Conditions Treated

Zoloft is an SSRI that is FDA-approved for the treatment of:

Zoloft may also be used off-label for generalized anxiety disorder and other related conditions.

Xanax is FDA-approved for the short-term treatment of:

  • Anxiety
  • Panic disorder
  • Agoraphobia

Xanax is sometimes used off-label for depression and other anxiety disorders.

ConditionXanaxZoloft
Major depressive disorderOff-labelYes
Anxiety disordersYesYes
Post-traumatic stress disorder (PTSD)Off-labelYes
Obsessive-compulsive disorder (OCD)Off-labelYes
Short-term anxiety relief with or without depression symptomsYesNo
Panic disorderYesYes
Social anxiety disorderOff-labelYes
Premenstrual dysphoric disorder (PMDD)NoYes

Side Effects

Zoloft and Xanax may cause some common side effects.

In rare cases, they may lead to serious reactions.

Common side effects

Side effects that may commonly occur while taking Zoloft include:

Xanax side effects are dose-dependent, with higher doses likely causing more noticeable side effects.

These may include: 

Side EffectXanaxZoloft
NauseaYesYes
DiarrheaYesYes
Dry mouthYesYes
SleepinessYesYes (less common)
InsomniaYesYes
HeadacheYesYes
DizzinessYesYes
WeaknessYes (less common)No
Ejaculation disorder or sexual problemsYes (less common)Yes (less common)

More serious side effects

In rarer cases, both Zoloft and Xanax may cause serious side effects.

Xanax may worsen sleep apnea or obstructive pulmonary disease.

Both Zoloft and Xanax carry black box warnings, including an increased risk for suicidal thoughts or attempts.

Withdrawal symptoms

Both Xanax and Zoloft can cause withdrawal symptoms.

  • Xanax: It is possible to become dependent on Xanax even if you only take it for several days. Work with your doctor to discontinue Xanax use. Your medical provider will likely provide a tapered dose to help ease symptoms. If you have been taking Xanax long-term or multiple times a day, do not suddenly stop taking Xanax, as withdrawal symptoms can include serious effects such as seizures.
  • Zoloft: Do not stop taking Zoloft suddenly. Unless your healthcare provider tapers your dose, you may experience withdrawal symptoms. These range from nausea and vomiting to headaches, nightmares, dizziness, and tingling nerve pain.

Drug Interactions

Both Xanax and Zoloft can have some serious drug interactions.

Speak to your medical provider and pharmacist about other medications, over-the-counter drugs, or supplements you are taking.

This can prevent complications.

Drug ClassDrugsInteracts with Xanax?Interacts with Zoloft?
MAOIsPhenelzine
Selegiline
Rasagiline
Others
NoDo not take within 14 days of each other.
TriptansSumatriptan
Zolmitriptan
Rizatriptan
YesYes
Tricyclic antidepressantsAmitriptyline
Nortriptyline
Others
YesYes
SSRI antidepressantsCitalopram
Escitalopram
Fluoxetine
Paroxetine
Others
YesYes
SNRI antidepressantsVenlafaxine
Duloxetine
Others
YesYes
NSAIDsAspirinIbuprofen
Naproxen
Others
NoYes
AnticoagulantsWarfarinYesYes
Opioid painkillersCodeine
Hydrocodone
Methodone
Morphine
Tramadol
Others
YesYes
AlcoholAll typesYesYes
Sedating antihistaminesDiphenhydramineYesYes
AnticonvulsantsCarbamazepine
Gabapentin
Lamotrigine
Phenobarbital
Pregabalin
Topiramate
Others
YesYes
Herbal supplementsSt. John’s WortYesYes
Muscle relaxantsBaclofen
Cyclobenzaprine
Metaxalone
Others
YesYes
Macrolide antibioticsAzithromycin
Erythromycin
Others
YesYes
Azole antifungalsItraconazole
Ketoconazole
YesYes
ContraceptivesAnyYesYes

Coverage and Costs

Both Zoloft and Xanax have similar insurance and Medicare coverage.

Coverage for each typically includes: 

  • Most private insurance
  • Medicare Part D
  • Generic may be covered, brand name may not

Out-of-pocket costs for brand names and generics can differ significantly. Sertraline (generic Zoloft) may cost around $85 out of pocket.

A typical Medicare Part D copay for sertraline is between $0-13. Xanax generic (alprazolam) may cost $40 out of pocket or between $0-33 for a Medicare Part D copay.

XanaxZoloft
Covered by insurance?Yes (generic)Yes (generic)
Covered by Medicare Part D?Yes (generic)Yes (generic)
Typical Medicare Part D copay$0-33 (generic)$0-13 (generic)
Standard dosage60 tablets of 0.5 mg30 tablets of 100 mg

Warnings

Zoloft and Xanax can be effective treatments, but when used improperly or in certain populations, they come with serious warnings.

Zoloft

Zoloft carries a black box warning.

This is the most serious warning that the Food and Drug Administration (FDA) issues.

This means that this medication, particularly in younger adults, may carry a higher risk of causing suicidal thoughts and behavior.

Other warnings for Zoloft include increased risk of:

  • Serotonin syndrome
  • Agitation
  • Seizures
  • Electrolyte imbalance (hyponatremia)
  • Bleeding
  • Worsened episodes in patients with bipolar disorder

Additionally, individuals who are pregnant or breastfeeding should not take Zoloft unless a healthcare provider deems the benefits greater than the risk.

Xanax

Xanax also carries a black box warning because it may increase the risk of suicidal thoughts or behavior.

Xanax may also worsen:

  • Sleep apnea or COPD
  • Seizure disorders
  • Liver problems

Xanax may become habit-forming if used incorrectly or long-term.

Do not take Xanax with opioids due to risk of sedation, coma, or death.

Do not take Xanax if you are pregnant.

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When to See a Doctor

See a medical provider if symptoms of anxiety or depression affect your quality of life and functioning on a daily basis.

They can recommend appropriate medication as well as other treatments such as therapy and lifestyle changes.

If you already take Zoloft, Xanax, or other medication, let your healthcare provider know if your symptoms worsen, change, or you want to stop or change your regimen. 

How K Health Can Help

Think you might need a prescription for Zoloft (sertraline)?

K Health has clinicians standing by 24/7 to evaluate your symptoms and determine if Zoloft is right for you.

Get started with our free assessment, which will tell you in minutes if treatment could be a good fit. If yes, we’ll connect you right to a clinician who can prescribe medication and have it shipped right to your door.

K Health does not prescribe controlled substances such as xanax.

Frequently Asked Questions

Is Zoloft similar to Xanax?
Zoloft and Xanax may have similar effects on mental health conditions and similar side effects, but they are different drugs. Zoloft is meant to be taken long-term, whereas Xanax is a short-term medication. Xanax is a controlled substance and can be habit-forming. Both require tapering to discontinue, and both carry serious black box warnings. Your medical provider can determine which drug is appropriate for your health needs.
What is better than Zoloft for anxiety?
The best medication for anxiety depends on what type of anxiety you have, your other health conditions, and other medications you take. Zoloft is a longer-term treatment that may take 1-2 weeks before improving symptoms. Xanax is a short-term, fast-acting anxiety reliever, but it is habit-forming and cannot be taken regularly for a long period of time.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Robynn Lowe

Robynn Lowe is a board certified Family Nurse Practitioner with over 15 years in the medical field. Robynn received her Bachelor's and Master's degrees from Florida Atlantic University and has been practicing in rural family medicine since. Robynn is married to her college sweetheart, Raymond and they have three awesome children. When Robynn isn't with patients you can find her shopping, coaching her kids sports teams, or spending time on the water.

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