Zoloft (Sertraline) and Prozac (Fluoxetine) both belong to the SSRI (Selective Serotonin Reuptake Inhibitors) group of antidepressants. The effect and working of most SSRI is fairly similar, but individual chemical composition of each drug determines which works best for a specific individual on specific symptoms. Prozac comes as a delayed release fluoxetine hydrochloride tablet or as ready-for-use liquid, while Zoloft is sertraline hydrochloride that comes as a coated tablet or as concentrated solution to be mixed with water.

Comparison chart

Prozac versus Zoloft comparison chart
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Generic Name Fluoxetine Sertraline
Prescription Required? Yes Yes
Description Anti-Depressant Anti-Depressant
Storage Conditions Away from Heat, Moisture & Light Room temperature with no light or moisture. Do not flush or wash down the drain.
Brand Name Prozac, Prozac Weekly, Sarafem Zoloft
Available as Capsules to be taken with water without being broken open Tablets to be taken with water & Liquid form to be diluted before consuming
Classification SSRI SSRI
Molecular Weight 345.79 342.7
Elimination Half Life Approximately 4-6 days NA
Storage Temperatures 59° - 86° F (15° - 30° C) 59° - 86° F (15° - 30° C)
Empirical Formula C17 H18 F3 NO.HCl C17 H17 NCl2 HCl
Chemical Name (±)-N-methyl-3-phenyl-3- [(a,a,a-trifluoro-p-olyl)oxy] propylamine hydrochloride (1S,cis)-4-(3,4-dichlorophenyl)- 1,2,3,4-tetrahydro-N-methyl- 1-naphthalenamine hydrochloride
Physical Properties White to off-white crystalline solid, with a solubility of 14 mg/mL in water White crystalline powder, slightly soluble in water and isopropyl alcohol and sparingly soluble in ethanol

Form and Consumption

Both Zoloft and Prozac should be taken exactly as prescribed, preferably at the same time each day. Because of the delayed relsease, it may take 4 weeks or longer for the effect to kick in. The use of these medicines should not be stopped before first talking to your doctor, as ceasing to take them suddenly may result in unpleasant side effects.

Both medicines need to be stored at room temperature, away from moisture and heat.

Tablet form

Zoloft: Should be taken with water. Sertraline (Zoloft) may be taken with or without food.

Prozac: An extended-release Prozac capsule should not be broken, chewed, or opened. The pill should be swallowed whole as it is designed to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.

Liquid form

Prozac and Zoloft both come in liquid form, but liquid Prozac is ready for intake as is, while Zoloft comes in a concentrated form and must be diluted before the intake. One dose of Zoloft may be mixed with 4 ounces of water, ginger ale, lemon/lime soda, lemonade, or orange juice - use of any other liquid to dilute the medication is not recommended.

How an SSRI Works

To understand why drugs like Zoloft and Prozac are prescribed, why it is important to neither exceed the dosage nor stop usage suddenly, and how it can be prone to substance abuse, it is important to understand how selective serotonin reuptake inhibitors work on the brain. This video explains the use of SSRI during depression:

Side Effects

Common side effects of SSRI drugs include allergic symptoms like skin rash or hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

More serious side-effects include mood or behavior changes, anxiety, panic attacks, trouble sleeping, impulsive/restless feeling, irritability, agitatation, hostility, aggression, hyperactivity (mentalor physical), more intense depression, suicidal thoughts.

Medical help should be sought at once at the sign of any new or worsening symptoms like:

Other less serious but more likely side effects include:

Prozac has a few more side effects in addition to the ones listed above:


SSRI should be taken in the precise prescribed amount; deviating from the dose amount can result in serious side effects.

Missing a dose

For either Prozac or Zoloft, a missed dose should be taken as soon as you remember, but skipped if it's almost time for the next scheduled dose. Do not take extra medicine to make up for the missed dose.


Seek emergency medical attention if you think you have taken too much of this Prozac or Zoloft.

Symptoms of a fluoxetine (Prozac) overdose may include nausea, vomiting, fever, sleepiness, rapid or uneven heartbeat, confusion, fainting, seizures, or coma.

Symptoms of a sertraline (Zoloft) overdose may include dizziness, drowsiness, nausea, vomiting, rapid heartbeat, agitation, tremor, confusion, seizures, and coma.

Other Precautions

Use of alcohol or other sleep inducing medicines (other medicines that make you sleepy (cold/pain medication, muscle relaxers, medicine for seizures, other medication for depression or anxiety, narcotic pain relievers) can increase the intensity of side effects of both Prozac and Zoloft, and should be avoided while on Prozac or Zoloft.

Zoloft and Prozac can both cause side effects that may impair your thinking or reactions. Actions that require focus and alertness (driving, operating machinery) should be avoided while on SSRI medication.

Do not take the liquid form of sertraline (Zoloft) if you are taking disulfiram (Antabuse). Liquid sertraline may contain alcohol and can initiate a severe reaction to disulfiram.


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