Prozac and Zoloft are common antidepressant drugs. Although they have similar effects on the body, their specific uses, side effects, and dosages are different.

Prozac and Zoloft are both selective serotonin reuptake inhibitors (SSRIs). This class of medication is among the first options for treating major depressive disorder, which people usually call depression.

Fluoxetine is the generic drug name for Prozac, and sertraline is the generic name for Zoloft.

In this article, we discuss the differences between Prozac and Zoloft.

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Taking either Prozac or Zoloft will increase the levels of serotonin in the brain.

Like other SSRIs, both Prozac and Zoloft work by increasing the levels of serotonin in the brain. Serotonin is one of the chemicals that play a role in regulating mood, and low levels seem to have an association with depressive symptoms.

The Food and Drug Administration (FDA) have approved both Prozac and Zoloft for treating:

In addition, the FDA have approved Prozac for the treatment of:

Doctors may also use Zoloft to treat post-traumatic stress disorder (PTSD) and social anxiety disorder.

Some doctors prescribe Prozac for social anxiety disorder in adults, borderline personality disorder, Raynaud's phenomenon, and selective mutism, but the FDA have not approved these uses.

Other SSRIs include:

  • escitalopram (Lexapro)
  • vortioxetine (Trintellix)
  • citalopram (Celexa)
  • fluvoxamine (Luvox)
  • paroxetine (Paxil)
  • vilazodone (Viibryd)

Both Prozac and Zoloft are available in the forms of a liquid oral solution, a tablet, and a capsule.

The following table lists the different forms of each drug along with the available dosages in milligrams (mg) and milligrams per milliliter (mg/ml).

ProzacZoloft
Capsule10 mg, 20 mg, 40 mg, 90 mg25 mg, 50 mg, 100 mg
Tablet60 mg25 mg, 50 mg, 100 mg
Liquid20 mg/5 ml20 mg/ml

When a person first starts taking antidepressants, they will typically begin on a smaller dosage and increase this over time. Doing this makes it possible to test how well the drug works and monitor its side effects, as the effectiveness and adverse effects can differ among individuals.

American Psychiatric Association guidelines report the following starting dosages and the usual effective dosages when treating MDD:

ProzacZoloft
Starting dosage20 mg/day50 mg/day
Usual effective dosages20–60 mg/day50–200 mg/day

Some people may see improvements in their symptoms in the first 1–2 weeks of treatment, whereas it may take 2–4 weeks for others to notice changes.

Some studies have shown that all antidepressants require at least 4–6 weeks before they reach their maximal clinical effectiveness.

There are three phases of MDD therapy:

  • The acute phase. The goal of the acute phase is for the person to recover from depressive symptoms and return to their baseline of functioning. This phase will last about 6–12 weeks.
  • The continuation phase. During the continuation phase, doctors will recommend that people continue treatment for 4–9 months to prevent symptoms from returning.
  • The maintenance phase. Some people may need to continue their medication for longer and complete a maintenance phase. The goal is to protect at-risk people from recurring depressive symptoms.

Doctors will usually recommend a maintenance phase for people with recurrent MDD or chronic depression.

If a person does not have a satisfactory response to medication, the doctor may try increasing the dosage. However, a higher dosage may cause more side effects, so doctors need to evaluate the risks and benefits of increasing it.

Another strategy to increase the effectiveness of the therapy is to add another medicine. A doctor may advise a person to combine Prozac or Zoloft with certain other antidepressants and other types of medication to improve their symptoms.

The doctor will determine which combinations are the most appropriate for each person while keeping in mind the possibility of drug interactions.

Doctors may also adjust medication dosages and regimens for people who are combining medication therapy and psychotherapy.

As Prozac and Zoloft are both SSRIs, people may experience similar side effects with these drugs.

Zoloft is more likely than Prozac to cause gastrointestinal tract side effects, such as nausea and diarrhea. Men taking Zoloft may also report more sexual dysfunction side effects, such as failure to ejaculate, than those using Prozac.

However, people taking Prozac more often experience headaches, nervousness, and a lack of energy.

The following table lists the most common side effects of Prozac and Zoloft, which occur in at least 5% of people.

ProzacZoloft
nausea22%26%
diarrhea11%20%
constipation5%6%
decreased appetiteno data available7%
anorexia10%no data available
acid reflux8%8%
dry mouth9%14%
sweating7%7%
insomnia19%20%
drowsiness12%11%
anxiety12%no data available
agitationno data available8%
nervousness13%no data available
dizziness9%12%
tremor9%9%
headache21%no data available
weakness/lack of energy11%no data available
flu-like symptoms5%no data available
decreased sex driveno data available6%
failure to ejaculateno data available8%

When people are ready to come off their antidepressant medications, they should do so gradually. Stopping Prozac, Zoloft, or any other antidepressant abruptly can cause discontinuation symptoms.

Discontinuation symptoms may include:

  • dysphoria, or general unease and dissatisfaction
  • irritability
  • agitation
  • dizziness
  • electric shock sensations
  • anxiety
  • confusion
  • headaches
  • lethargy
  • emotional lability, or rapid and exaggerated changes in mood
  • sleeplessness

Several short-term studies have shown that children, adolescents, and young adults under 24 years old have an increased risk of suicidal thoughts and behaviors when taking any antidepressants.

Doctors will monitor people taking Prozac, Zoloft, or any other antidepressant for worsening of depressive symptoms, suicidal thoughts, and unusual behaviors.

People with glaucoma and a history of seizures should use Prozac, Zoloft, and other SSRIs with caution because the drugs can make these conditions worse.

Suicide prevention

  • If you know someone at immediate risk of self-harm, suicide, or hurting another person:
  • Call 911 or the local emergency number.
  • Stay with the person until professional help arrives.
  • Remove any weapons, medications, or other potentially harmful objects.
  • Listen to the person without judgment.
  • If you or someone you know is having thoughts of suicide, a prevention hotline can help. The National Suicide Prevention Lifeline is available 24 hours a day at 1-800-273-8255.

SSRIs, including Prozac and Zoloft, have similar drug interactions.

Serotonin syndrome

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Feelings of agitation and restlessness can indicate serotonin syndrome.

Serotonin syndrome is a potentially life-threatening interaction that occurs as a result of combining drugs that increase serotonin in the body.

Doctors should avoid prescribing Prozac, Zoloft, and other SSRIs alongside the following drugs:

  • triptans
  • tricyclic antidepressants (TCAs)
  • fentanyl
  • lithium
  • tramadol
  • tryptophan
  • buspirone
  • amphetamines
  • St. John's wort
  • monoamine oxidase inhibitors (MAOIs)

Some of the signs and symptoms of serotonin syndrome include:

  • agitation
  • anxiety
  • restlessness
  • disorientation
  • sweating
  • a high body temperature
  • increased heart rate
  • nausea
  • vomiting
  • shaking
  • muscle rigidity
  • overactive reflexes
  • abnormal muscle contractions
  • dilated pupils
  • abnormal eye movements
  • dry mucous membranes
  • flushed skin
  • increased bowel sounds

MAOIs

People cannot take MAOIs, another type of antidepressant, with Prozac, Zoloft, or any other SSRIs because the risk of developing serotonin syndrome is very high.

Anyone taking an MAOI must stop taking it at least 2 weeks before starting SSRI treatment.

QT prolongation

Doctors have reported QT prolongation in people taking Prozac and Zoloft. QT prolongation is a potentially fatal heart rhythm dysfunction.

This heart condition is more common in people who take other drugs that can prolong the QT interval on an electrocardiograph. These include certain antipsychotics, antibiotics, and anti-arrhythmic medications.

Abnormal bleeding

Some people can experience abnormal bleeding when combining Prozac, Zoloft, and other SSRIs with drugs that can increase bleeding, such as:

  • aspirin
  • nonsteroidal anti-inflammatories (NSAIDs)
  • warfarin
  • anticoagulants

The following table compares the lowest available prices of Prozac and Zoloft:

fluoxetineProzacsertralineZoloft
Capsule (30 capsules)10 mg: $3.00
20 mg: $3.00
40 mg: $3.00
10 mg: $461.85
20 mg: $474.70
40 mg: $947.40
no information availableno information available
Tablet (30 tablets)10 mg: $4.00
20 mg: $26.76
60 mg: $96.35
no information available25 mg: $3.99
50 mg: $7.17
100 mg: $6.52
25 mg: $313.61
50 mg: $313.61
100 mg: $313.61
Liquid oral solution (1 bottle)120 ml: $12.81no information available60 ml: $25.1060 ml: $216.18

People should not take Prozac and Zoloft together. These drugs are in the same drug class and have the same actions. Taking both drugs will not improve symptoms but can cause additional side effects.

When people are not feeling the intended effects of either Prozac or Zoloft, the doctor may increase the dosage or alter the treatment regimen by adding another antidepressant or antipsychotic drug that has different actions on the brain.

Prozac and Zoloft are part of the same family of antidepressants, and both raise the levels of serotonin in the brain. Both drugs have FDA approval for the treatment of MDD, and they also have other approved and nonapproved uses.

The safe warnings relating to taking Prozac or Zoloft are similar, as are many of the side effects, although these can vary from person to person. Zoloft may be harsher on the stomach, while Prozac is more likely to cause headaches.

Both drugs are generally effective and safe, but people taking Prozac or Zoloft should follow up with their doctor to discuss their symptoms and side effects to ensure that they are taking the most effective dosage.

If treatment is successful, the doctor will slowly reduce the dosage if possible to eventually stop the medication. People should not abruptly stop taking Prozac or Zoloft.