Prozac vs. Zoloft


Prozac and Zoloft are the brand names for a category of medication known as selective serotonin reuptake inhibitors (SSRIs). They are both prescribed for the treatment of various mental health disorders, such as obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD).

While both these medications are considered first-line treatments for many disorders, neither is a cure. Both are more effective for long-term management when prescribed alongside other supplementary therapies such as psychotherapy and lifestyle changes.

Furthermore, Prozac and Zoloft have been shown to have different degrees of efficacy and varying side effects, despite directly increasing serotonin levels in the brain.

About Prozac and Zoloft

What is Prozac?

Prozac is the brand name for fluoxetine, an SSRI discovered in 1972 and FDA-approved in 1987 for treating mood disorders. Once absorbed into the body, fluoxetine is metabolized into desmethylfluoxetine and norfluoxetine, which are also SSRIs, thus prolonging the duration of action. Peak action is reached after 6 – 8 hours.

Prozac elimination is extremely slow as fluoxetine inhibits its metabolism. Therefore with long-term use, the half-life of Prozac increases from 1 – 3 days to 4 – 6 days.

Furthermore, long-term use of fluoxetine has been shown to improve myelination, a process that affects the connectivity of nerve cells within the central nervous system (CNS). Research suggests this may partially explain the long-term therapeutic benefit of continued use of this drug.

Interestingly, even though fluoxetine selectively reduces the reabsorption of serotonin, large doses also increase the levels of other neurotransmitters in the brain, such as dopamine and norepinephrine. While the exact mechanism is not fully understood, these research findings suggest that Prozac’s effective anti-depressive action in doses above 60 mg may be due to this supplementary action.

What conditions is Prozac approved to treat?

Prozac is FDA-approved as an acute treatment and management option for OCD, major depressive disorder (MDD), and bulimia nervosa. It is also approved for the acute treatment of certain types of panic disorders, with or without agoraphobia.

Prozac is also approved with olanzapine for treating an acute episode of depression associated with bipolar disorder and resistant depression.

How does Prozac work for Obsessive Compulsive Disorder (OCD)?

Clinical trials have shown that 40 – 60 mg of Prozac can manage OCD symptoms such as depressive episodes, suicidal intentions, and impulsiveness in those with abnormalities in serotonin-related neurotransmission.

However, it is significantly less effective in patients with a long history of OCD or who have more severe symptoms, including collective obsessions, washing compulsions, or comorbidities such as schizotypal personalities or vocal or motor tics.

What is Zoloft?

Zoloft is the brand name for the SSRI sertraline hydrochloride, also known as sertraline, that was FDA approved in 1991. Zoloft is considered a better-tolerated treatment for mood disorders with less severe side effects.

Sertraline is metabolized to desmethylsertraline, a monoamine reuptake inhibitor (MRI) that inhibits the reabsorption of serotonin as well as the neurotransmitters dopamine and norepinephrine. However, due to desmethylsertraline's stronger affinity to bind with serotonin receptors, it works with sertraline to increase serotonin levels.

Nevertheless, sertraline affects dopamine uptake to some degree, and research is still underway to understand this mechanism and the long-term significance of these findings.

Peak action of sertraline is noted between 4.5 – 8 hours, and its half-life is 26 hours, while desmethylsertraline is 62 – 102 hours. Research has shown that men metabolize sertraline faster than women, where half-life has been noted to be 22 hours and 32 hours, respectively.

What conditions is Zoloft approved to treat?

Zoloft is approved for MDD, OCD, panic disorders, PTSD, generalized or social anxiety disorders, and premenstrual dysphoric disorder (PMDD).

How does Zoloft work for Obsessive Compulsive Disorder (OCD)?

Zoloft is one of the most common treatments for OCD. While earlier research has shown that Zoloft is an effective treatment for OCD compared to a placebo, current studies recommend taking it with cognitive behavioral therapy.

This combination has been suggested to be more effective at managing symptoms, such as depressive episodes long term. Additionally, Zoloft is approved for pediatric use in children with OCD symptoms.


SSRIs increase the extracellular level of the neurotransmitter serotonin in the brain. Serotonin is a compound produced by the body and is colloquially known as the feel-good hormone because it plays a key role in several brain functions, including mood modulation, memory, cognition, reward, and learning.

Serotonin is also vital in many physiological processes, such as sleep, thermoregulation, vasoconstriction, gastrointestinal function, and sexual activity. The body self-regulates the level of serotonin in the system and reabsorbs excess in a process known as reuptake.

Research suggests that one of the reasons for mood disorders such as OCD is a deficiency of serotonin within the body and its inability to self-regulate. SSRIs inhibit the reabsorption of serotonin, thus increasing the level of serotonin and improving brain function, i.e., regulating mood and behavior.

How effective are Prozac and Zoloft for treating Obsessive Compulsive Disorder (OCD)?

Prozac and Zoloft bind to the brain's serotonin receptors, 5-HT1As. Over time, this leads to their downregulation, i.e., suppressing their action, so they can no longer respond to increased serotonin levels.

With more serotonin available, OCD patients with serotonin deficiencies have improved tolerance to passive stress and fewer depressive episodes.

Dosage information

Prozac and Zoloft do not show an immediate effect, and it can take up to eight weeks before either shows apparent changes in symptoms. Additionally, either therapy must be continued for at least one year.

It is important to note that even though SSRIs are not addictive, stopping treatment abruptly or missing dosages can lead to withdrawal-like symptoms, also known as discontinuation syndrome. These symptoms include:

  • Feelings of anxiety or uneasiness
  • Dizziness
  • Nausea
  • Flu-like symptoms
  • Lethargy

How is Prozac administered for Obsessive Compulsive Disorder (OCD)?

Prozac is given orally as a daily capsule that is swallowed whole and should not be crushed, chewed, opened, or broken in the mouth. Prozac is also available as a time-delayed capsule given weekly or as recommended by a doctor.

How is Zoloft administered for Obsessive Compulsive Disorder (OCD)?

Zoloft is given as oral tablets that are swallowed whole and as an oral solution that must be diluted before administering. Dosages are gradually increased by 25 – 50 mg increments once a week, depending on the tolerance to the medication.

For the oral solution, 25 or 50 mg of Zoloft can be mixed into 4 oz of water, lemon/lime soda, ginger ale, lemonade, or orange juice only. Patients must drink the solution immediately.

Side Effects

What are the most common side effects of Prozac?

  • Insomnia
  • Headaches
  • Drowsiness
  • Anxiety and nervousness
  • Flu-like symptoms
  • Nausea
  • Lower sex drive
  • Orgasm problems
  • Erectile dysfunction
  • Higher risk of bleeding
  • Altered Appetite and Weight
  • Allergic Reactions and Rash
  • Vision problems

Are there any potential serious side effects of Prozac?

  • Potential for Cognitive and Motor Impairment
  • Suicidal Thoughts and Behaviors Seizures
  • QT Prolongation
  • Angle-Closure Glaucoma
  • Antidepressant discontinuation syndrome
  • Serotonin syndrome

Are there the most common side effects of Zoloft?

  • Nausea
  • Headaches
  • Insomnia
  • Loss of appetite
  • Constantly tired, sleepy, or weak
  • Diarrhea
  • Dry mouth
  • Feeling dizzy
  • Agitation
  • Loss of bladder control
  • Allergic reactions

Are there any potential serious side effects of Zoloft?

  • QT prolongation
  • Suicidal thoughts and behaviors
  • Serotonin syndrome
  • Increased risk of bleeding
  • Angle-closure glaucoma
  • Activation of mania/hypomania
  • Discontinuation syndrome

Contraindications and Interactions

Warnings and general precautions for Prozac and Zoloft

Oral SSRIs such as Prozac and Zoloft are not recommended for patients with severe impairments in liver function as the body will be unable to metabolize the drugs, reducing their bioavailability.

Additionally, these medications are not advised for OCD patients with comorbidities of bipolar disorder, mania, or hypomania, as they can increase the risk of a manic/mixed episode.

Serotonin Syndrome

SSRIs such as Prozac and Zoloft should not be taken with monoamine oxidase inhibitors (MAOIs) such as intravenous methylene blue or linezolid because these medications increase the risk of serotonin syndrome.

Serotonin Syndrome is a life-threatening condition that can lead to death if not treated immediately. Symptoms range from mild to severe, including shivering, diarrhea, fever, muscle rigidity, and seizures.

It is recommended that treatment with MAOIs should be stopped 5 – 7 weeks before starting Prozac and 2 weeks before starting Zoloft treatment.

Alternatively, if patients are being taken off SSRI treatment, at least 5 weeks should be given for the body to eliminate Prozac and 2 weeks to eliminate Zoloft before starting MAOIs.

Suicidal Thoughts in OCD patients under the age of 25

Many psychiatric disorders, including OCD, have a depressive episodes where suicidal thoughts are known to increase. Clinical trials have shown that starting SSRI treatment may increase the likelihood of such thoughts in the initial phases.

While this mechanism is not fully understood, research has shown this is most common in patients under 25 with major depressive disorder (MDD). If OCD patients have co-morbidities of depression, health providers and caretakers must be vigilant for unusual changes in behavior or increased suicidal thoughts or tendencies.

Contraindications and important interactions for Prozac and Zoloft



Not recommended for any patient with impaired liver function, diabetes, and a history of bipolar disorder, manic and hypomanic disorder.


Not recommended for any patient with impaired liver function and a history of bipolar disorder, manic and hypomanic disorder.



Do not co-administer with other SSRIs, serotonergic drugs, or MAOIs such as tranylcypromine, selegiline, phenelzine, isocarboxazid, methylene blue, and linezolid as it increases the risk of serotonin syndrome.

Do not co-administer with drugs highly bound to plasma protein as that increases the free concentration of Prozac, thus increasing the risk of adverse symptoms.

Do not co-administer with pimozide, thioridazine, or specific antipsychotics such as ziprasidone, iloperidone, chlorpromazine, mesoridazine, or droperidol)

Do not co-administer with specific antibiotics such as erythromycin, gatifloxacin, moxifloxacin, or sparfloxacin)

Do not co-administer with Class 1A or Class III antiarrhythmics


Do not co-administer with other SSRIs, serotonergic drugs, or MAOIs such as tranylcypromine, selegiline, phenelzine, isocarboxazid, methylene blue, and linezolid as it increases the risk of serotonin syndrome.

Do not co-administer with anticoagulants or antiplatelet agents such as warfarin, heparin, clopidogrel, or aspirin, as it increases the risk of bleeding

Do not co-administer with drugs highly bound to plasma protein as that increases the free concentration of Zoloft, thus increasing the risk of adverse symptoms.

Do not co-administer with pimozide, tolterodine, propafenone, flecainide, perphenazine, atomoxetine, dextromethorphan desipramine, nebivolol, thioridazine, metoprolol, venlafaxine

Food/Beverage/Supplement Interactions


SSRIs are not to be taken with alcohol. They are not known to have any direct interaction with particular foods, beverages, or supplements.

Cost Comparison

How much do Prozac and Zoloft cost?

Prozac (fluoxetine) 40 mg tablets cost an average of $0.43 per tablet, approximately $3.01/per week for an adult taking 40 mg daily.

Zoloft (sertraline) 100 mg tablets cost an average of $0.366 per tablet, approximately $2.56/per week for an adult taking 100 mg daily.

Popularity of Prozac and Zoloft

Prozac and Zoloft are on the World Health Organization's List of Essential Medicines and are among the most popular SSRI medications in the US. In 2020, Prozac was the 25th most-prescribed drug, with over 23 million prescriptions. In the same year, Zoloft was the 12th most-prescribed drug, with over 38 million prescriptions.



Despite their similarity in mechanism, Zoloft is the superior medication for treating OCD. It has few side effects, precautions, and contractions. Additionally, it is a safer option for children with obsessive-compulsive tendencies.

However, patients must be closely monitored for mood and behavioral changes with either medication, which is why supplementary talk therapy is beneficial in both treatments.