How does fluoxetine (Prozac) work to treat symptoms of depression?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 8, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Fluoxetine (Prozac) works to treat symptoms of depression by increasing serotonin levels in the brain, as evidenced by its efficacy in decreasing depressive symptoms in patients, including youth, as shown in studies such as 1. The medication belongs to a class of medications called selective serotonin reuptake inhibitors (SSRIs), which block the reabsorption (reuptake) of serotonin into neurons, allowing more serotonin to remain available in the brain. Some key points about fluoxetine include:

  • It is effective in treating depression in various age groups, including youth, with a significant improvement in depressive symptoms compared to placebo, as seen in 1.
  • The full therapeutic effect usually takes 4-6 weeks to develop, though some improvement may be noticed earlier.
  • Common side effects include nausea, headache, insomnia, and sexual dysfunction.
  • Unlike some antidepressants, fluoxetine is less sedating and may even be slightly activating, which is why morning dosing is preferred.
  • It's essential to continue taking fluoxetine even when feeling better and to never stop abruptly without medical supervision, as this can lead to discontinuation symptoms. The study by Gibbons et al, as mentioned in 1, found that fluoxetine-treated patients had significantly greater improvement in depressive symptoms compared to those receiving placebo, with 46.6% of patients receiving fluoxetine achieving remission over 6 weeks, compared to 16.5% of those receiving placebo. Overall, fluoxetine is a valuable treatment option for depression, and its efficacy in decreasing depressive symptoms makes it a crucial medication for patients suffering from this condition.

From the FDA Drug Label

The efficacy of Prozac was established in 5– and 6–week trials with depressed adult and geriatric outpatients (≥18 years of age) whose diagnoses corresponded most closely to the DSM–III (currently DSM–IV) category of major depressive disorder The FDA drug label does not answer the question.

From the Research

Mechanism of Action

  • Fluoxetine, also known as Prozac, is a selective serotonin reuptake inhibitor (SSRI) that works by inhibiting the presynaptic reuptake of serotonin, a neurotransmitter in the brain 2.
  • This increase in serotonin levels is thought to improve mood, reduce anxiety, and enhance sleep quality.
  • Fluoxetine has essentially no effect on the reuptake of norepinephrine or other neurotransmitters, and it has negligible binding affinity for neurotransmitter receptor sites 2.

Efficacy in Treating Depression

  • Fluoxetine has been shown to be effective in treating major depression, with a response rate comparable to tricyclic antidepressants (TCAs) 2, 3, 4.
  • Studies have demonstrated that fluoxetine is safe and effective in the treatment of depression, with a favorable safety profile and improved patient compliance compared to TCAs 3, 4.
  • Fluoxetine has also been shown to be effective in treating other conditions, such as obsessive-compulsive disorder (OCD), bulimia nervosa, and anxiety-related disorders 2, 4.

Comparison to Other Antidepressants

  • Fluoxetine has been compared to other antidepressants, including sertraline, venlafaxine, and mirtazapine, and has been found to be less effective than some of these agents in certain studies 3.
  • However, fluoxetine has been shown to be better tolerated than some other antidepressants, including TCAs and certain newer agents 3.
  • The clinical meaning of these differences in efficacy and tolerability is uncertain, and treatment decisions should be based on individual patient characteristics and considerations of drug toxicity, patient acceptability, and cost 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fluoxetine versus other types of pharmacotherapy for depression.

The Cochrane database of systematic reviews, 2013

Research

Fluoxetine: a review on evidence based medicine.

Annals of general hospital psychiatry, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.