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Prozac Vs. Zoloft: Drug Comparison

Compare common side effects, interactions, warnings, and more.

Medical Review byMike Bohl, MD, MBA, MPH, MS, ALMNov 4, 2024

Medication Name

Prozac

*image for illustrative purpose only

Zoloft

*image for illustrative purpose only

Summary

Prescription only

Prozac® (fluoxetine) is a selective serotonin reuptake inhibitor (SSRI) used to treat depression, anxiety, and other mood disorders by increasing available serotonin levels in the brain, which helps improve mood and reduce anxiety. Its FDA-approved indications include major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa, panic disorder, and premenstrual dysphoric disorder (PMDD). Off-label uses may include managing post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and borderline personality disorder. Prozac is available in capsule, tablet, and liquid form, typically taken once daily. Common side effects include nausea, insomnia, headache, and sexual dysfunction. It has a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults during the early stages of treatment.

Prescription only

Zoloft® (sertraline) is a selective serotonin reuptake inhibitor (SSRI) used to treat mood disorders by increasing available serotonin levels in the brain, which helps improve mood and reduce symptoms of anxiety and depression. Its FDA-approved indications include the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD). Off-label uses may include the treatment of eating disorders and generalized anxiety disorder (GAD). Zoloft is available in tablet and oral solution forms, typically taken once daily. Common side effects include nausea, dizziness, insomnia, and sexual dysfunction, and it carries a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults, particularly during the initial treatment period.

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Drug Category

Selective serotonin reuptake inhibitor (SSRI)

Selective serotonin reuptake inhibitor (SSRI)

Approved Uses

Prozac (fluoxetine hydrochloride) is a indicated for:

  • Acute and maintenance treatment of major depressive disorder (MDD)

  • Acute and maintenance treatment of obsessive compulsive disorder (OCD)

  • Acute and maintenance treatment of bulimia nervosa

  • Acute treatment of panic disorder, with or without agoraphobia

Prozac and olanzapine in combination for treatment of:

  • Acute depressive episodes associated with bipolar I disorder

  • Treatment resistant depression

Zoloft (sertraline hydrochloride) is indicated for the treatment of:

  • Major depressive disorder (MDD)

  • Obsessive-compulsive disorder (OCD)

  • Panic disorder (PD)

  • Posttraumatic stress disorder (PTSD)

  • Social anxiety disorder (SAD)

  • Premenstrual dysphoric disorder (PMDD)

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Dosage

  • Typically taken orally once daily

  • Comes in 10 mg, 20 mg, and 40 mg Pulvules®

  • Typically taken orally once daily

  • Comes in 25 mg, 50 mg, and 100 mg tablets and 20 mg/mL oral solution

Known Common Side Effects

Most common adverse reactions (≥5% and at least twice that for placebo) associated with:

Major depressive disorder, obsessive compulsive disorder, bulimia, and panic disorder:

  • Abnormal dreams

  • Abnormal ejaculation

  • Anorexia

  • Anxiety

  • Weakness

  • Diarrhea

  • Dry mouth

  • Indigestion

  • Flu syndrome

  • Impotence

  • Insomnia

  • Libido decreased

  • Nausea

  • Nervousness

  • Inflammation of the throat

  • Rash

  • Inflammation of the sinuses

  • Sleepiness

  • Sweating

  • Tremor

  • Vasodilatation

  • Yawn

Prozac and olanzapine in combination:

  • Also refer to the adverse reactions section of the package insert for Symbyax

Most common adverse reactions (≥5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were:

  • Nausea

  • Diarrhea/Loose stool

  • Tremor

  • Indigestion

  • Decreased appetite

  • Excessive sweating

  • Ejaculation failure

  • Decreased libido

Interactions & Contraindications

  • Serotonin syndrome and MAOIs

  • Pimozide

  • Thioridazine

  • When using Prozac and olanzapine in combination, also refer to the contraindications section of the package insert for Symbyax

  • Drug interactions: monoamine oxidase inhibitors (MAOIs), drugs metabolized by CYP2D6, tricyclic antidepressants (TCAs), CNS acting drugs, benzodiazepines, antipsychotics, anticonvulsants, serotonergic drugs, drugs that interfere with hemostasis (e.g., NSAIDs, aspirin, warfarin), drugs tightly bound to plasma proteins, olanzapine, drugs that prolong the QT interval

  • Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs

  • Concomitant use of pimozide

  • Known hypersensitivity to sertraline or excipients

  • Zoloft oral solution only: Concomitant use of disulfiram

  • Drug interactions: protein-bound drugs, CYP2D6 substrates

Warnings & Precautions

  • Suicidal thoughts and behaviors in children, adolescents, and young adults

  • Serotonin syndrome

  • Allergic reactions and rash

  • Activation of mania/hypomania

  • Seizures

  • Altered appetite and weight

  • Increased risk of bleeding

  • Angle-closure glaucoma

  • Low blood sodium

  • Anxiety and insomnia

  • QT prolongation

  • Potential for cognitive and motor impairment

  • Long half-life

  • Prozac and olanzapine in combination: When using Prozac and olanzapine in combination, also refer to the warnings and precautions section of the package insert for Symbyax

  • Sexual dysfunction

  • Pregnancy: SSRI use, particularly later in pregnancy, may increase risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate

  • Serotonin syndrome

  • Increased risk of bleeding

  • Activation of mania/hypomania

  • Seizures

  • Angle closure glaucoma

  • QTc prolongation

  • Sexual dysfunction

  • Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the neonate

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Boxed Warning

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.

Monitor for worsening and emergence of suicidal thoughts and behaviors.

When using Prozac and olanzapine in combination, also refer to Boxed Warning section of the package insert for Symbyax.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients.

Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors.

References

*This information is from the label for brand name Prozac®. See the Full Prescribing Information for more complete information. Fluoxetine, the active ingredient in Prozac, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient fluoxetine.

*This information is from the label for brand name Zoloft®. See the Full Prescribing Information for more complete information. Sertraline, the active ingredient in Zoloft, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient sertraline.

The information provided here is NOT MEDICAL ADVICE and is for informational and educational purposes only. The drug comparison tool does not determine eligibility for medications or treatments provided via the Hims/Hers platform. Consultation with a healthcare provider is required to assess suitability for any medical treatment based on individual health and medical history. All product names and associated trademarks are the property of their respective owners.

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