Zoloft vs Xanax: Usage, Differences, and Similarities

By Robynn LoweMedically reviewed

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

Xanax

Zoloft

Drug class

Benzodiazepine

Selective serotonin reuptake inhibitor (SSRI)

Generic drug name

Alprazolam

Sertraline

Forms

Immediate-release tablet, extended-release tablet, oral solution

Tablet, liquid

Standard dosage

Adults: 0.25-1 milligrams (mg) taken 1-3 times daily

Adults: 50-200 mg daily

Does discontinuation require tapering?

Yes

Yes

Who it is prescribed for

Adults

Adults; adolescents in some cases

Length of treatment

Short-term use; occasionally long-term use under close healthcare provider supervision

Months 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.

FEELING DOWN? TAKE OUR FREE ASSESSMENT AND LEARN ABOUT YOUR OPTIONS.

Get Started

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.

Condition

Xanax

Zoloft

Major depressive disorder

Off-label

Yes

Anxiety disorders

Yes

Yes

Post-traumatic stress disorder (PTSD)

Off-label

Yes

Obsessive-compulsive disorder (OCD)

Off-label

Yes

Short-term anxiety relief with or without depression symptoms

Yes

No

Panic disorder

Yes

Yes

Social anxiety disorder

Off-label

Yes

Premenstrual dysphoric disorder (PMDD)

No

Yes

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 Effect

Xanax

Zoloft

Nausea

Yes

Yes

Diarrhea

Yes

Yes

Dry mouth

Yes

Yes

Sleepiness

Yes

Yes (less common)

Insomnia

Yes

Yes

Headache

Yes

Yes

Dizziness

Yes

Yes

Weakness

Yes (less common)

No

Ejaculation disorder or sexual problems

Yes (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 Class

Drugs

Interacts with Xanax?

Interacts with Zoloft?

MAOIs

Phenelzine

Selegiline

Rasagiline

Others

No

Do not take within 14 days of each other.

Triptans

Sumatriptan

Zolmitriptan

Rizatriptan

Yes

Yes

Tricyclic antidepressants

Amitriptyline

Nortriptyline

Others

Yes

Yes

SSRI antidepressants

Citalopram

Escitalopram

Fluoxetine

Paroxetine

Others

Yes

Yes

SNRI antidepressants

Venlafaxine

Duloxetine

Others

Yes

Yes

NSAIDs

AspirinIbuprofen

Naproxen

Others

No

Yes

Anticoagulants

Warfarin

Yes

Yes

Opioid painkillers

Codeine

Hydrocodone

Methodone

Morphine

Tramadol

Others

Yes

Yes

Alcohol

All types

Yes

Yes

Sedating antihistamines

Diphenhydramine

Yes

Yes

Anticonvulsants

Carbamazepine

Gabapentin

Lamotrigine

Phenobarbital

Pregabalin

Topiramate

Others

Yes

Yes

Herbal supplements

St. John’s Wort

Yes

Yes

Muscle relaxants

Baclofen

Cyclobenzaprine

Metaxalone

Others

Yes

Yes

Macrolide antibiotics

Azithromycin

Erythromycin

Others

Yes

Yes

Azole antifungals

Itraconazole

Ketoconazole

Yes

Yes

Contraceptives

Any

Yes

Yes

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.

Xanax

Zoloft

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 dosage

60 tablets of 0.5 mg

30 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.

FEELING DOWN? TAKE OUR FREE ASSESSMENT AND LEARN ABOUT YOUR OPTIONS.

Get Started

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.