CLINICAL TRIALS PROFILE FOR PROZAC

505(b)(2) Clinical Trials for PROZAC

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT03228732 ↗	The Effects of Fluoxetine and/or DHEA	Recruiting	University of Maryland	Early Phase 1	2017-12-19	(1) To determine how the Selective Serotonin Reuptake Inhibitor (SSRI), fluoxetine (Prozac), an antidepressant often used to treat depression, stimulates the participant's body's ability to defend against low blood sugar (hypoglycemia). (2) To learn how a hormone, dehydroepiandrosterone (DHEA), stimulates the participant's body's ability to defend itself from low blood sugar (hypoglycemia). DHEA is a hormone produced naturally in the human body. However, it can be manufactured and is sold as an over-the-counter dietary supplement. The dose the investigators are giving in this study is higher than the usual recommended dosage taken as a supplement for certain medical conditions. (3) To study combined effects of fluoxetine and DHEA during low blood glucose. In the present study, the investigators will measure the participant's body's responses to hypoglycemia when given fluoxetine or DHEA or fluoxetine and DHEA or a placebo (a pill with no fluoxetine or DHEA). Approximately 64 individuals with type 1 diabetes will take part in this study.
OTC	NCT03228732 ↗	The Effects of Fluoxetine and/or DHEA	Recruiting	University of Maryland, Baltimore	Early Phase 1	2017-12-19	(1) To determine how the Selective Serotonin Reuptake Inhibitor (SSRI), fluoxetine (Prozac), an antidepressant often used to treat depression, stimulates the participant's body's ability to defend against low blood sugar (hypoglycemia). (2) To learn how a hormone, dehydroepiandrosterone (DHEA), stimulates the participant's body's ability to defend itself from low blood sugar (hypoglycemia). DHEA is a hormone produced naturally in the human body. However, it can be manufactured and is sold as an over-the-counter dietary supplement. The dose the investigators are giving in this study is higher than the usual recommended dosage taken as a supplement for certain medical conditions. (3) To study combined effects of fluoxetine and DHEA during low blood glucose. In the present study, the investigators will measure the participant's body's responses to hypoglycemia when given fluoxetine or DHEA or fluoxetine and DHEA or a placebo (a pill with no fluoxetine or DHEA). Approximately 64 individuals with type 1 diabetes will take part in this study.

All Clinical Trials for PROZAC

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00005015 ↗	Treatment of Depression in Youth With Bipolar Disorders	Terminated	National Institute of Mental Health (NIMH)	Phase 3	1969-12-31	THIS STUDY HAS BEEN DISCONTINUED. The study is designed to evaluate the safety and efficacy of fluoxetine for treating children and adolescents with Bipolar Disorder who are experiencing an episode of major depression while being treated with a mood stabilizer. The study involves a 2-week assessment period. Patients who are on stable, therapeutic doses of lithium or valproate and continue to have depression will be randomized to a 12-week treatment of fluoxetine or placebo. Those who respond favorably to treatment will be followed openly for an 18-week continuation phase.
NCT00006204 ↗	Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine)	Completed	National Institute on Alcohol Abuse and Alcoholism (NIAAA)	Phase 4	2000-03-01	This study will examine the effects of combing naltrexone and fluoxetine (Prozac) versus fluoxetine and placebo in alcoholics with co-occurring major depression. Both groups will actively participate in the 6-month study, which includes weekly individual Dual Disorders Recovery Counseling during the first month and every two weeks during the second through sixth months, plus the naltrexone and fluoxetine or fluoxetine and placebo. Subjects will complete follow-up assessments at 9 and 12 months.
NCT00006286 ↗	Treatment for Adolescents With Depression Study (TADS)	Completed	National Institute of Mental Health (NIMH)	Phase 3	1998-09-01	TADS is designed to compare the effectiveness of established treatments for teenagers suffering from major depressive disorder (MDD). The treatments are: psychotherapy ("talking therapy"); medication; and the combination of psychotherapy and medication. Altogether, 432 teenagers (both males and females) ages 12 to 17, will take part in this study at 12 sites in the United States. The TADS design will provide answers to the following questions: What is the long-term effectiveness of medication treatment of teenagers who have major depression? What is the long-term effectiveness of a specific psychotherapy ("talking therapy) in the treatment of teenagers who have major depression? How does medication treatment compare with psychotherapy in terms of effectiveness, tolerability and teenager and family acceptance? And, What is the cost-effectiveness of medication, psychotherapy and combined treatments? The medication being used in this study is called fluoxetine. Fluoxetine is also known as Prozac. Research has shown that medications like Prozac help depression in young persons. Fluoxetine has been approved by the FDA for use in the treatment of child and adolescent (ages 7 to 17 years) depression. The psychotherapy or "talking therapy" being used in this study is called Cognitive Behavioral Therapy (CBT). CBT is a talking therapy that will teach both the teenager and his or her family member (e.g., parent) new skills to cope better with depression. Specific topics include education about depression and the causes of depression, setting goals, monitoring mood, increasing pleasant activities, social problem-solving, correcting negative thinking, negotiation, compromise and assertiveness. CBT sessions may also help with resolving disagreements as they affect families.
NCT00011765 ↗	Effect of Fluoxetine (Prozac) on Domestic Violence	Completed	National Institute on Alcohol Abuse and Alcoholism (NIAAA)	Phase 2	2001-02-22	This study will evaluate whether fluoxetine (Prozac), used together with traditional psychotherapy, can reduce aggression in people who are physically violent towards their spouses or significant others. Treatment for domestic violence has centered on behavioral therapies, such as anger management and self-control exercises. Recent studies have shown that fluoxetine-a drug commonly used to treat depression and panic disorder-can decrease acts of aggression. Men and women between the ages of 18 and 65 who have a history of inflicting physical aggression on a spouses or significant others in the past year (with at least one episode occurring not under the influence of alcohol) may be eligible for this study. Participants spouses or significant others will also be asked to participate. All potential participants will be screened with a medical and psychiatric evaluation and history, breath alcohol analysis, blood tests, urine drug screen and electrocardiogram. Those enrolled will undergo the following procedures: Perpetrator - Interview and questionnaires - Participants will be interviewed by a social worker about past and current mental health and use of alcohol and illicit drugs and will complete questionnaires assessing emotional state and personality, depression, anxiety, aggression and alcohol consumption. Some of the questionnaires will be repeated at monthly intervals. - Physical performance testing - Performance and speed will be measured in three separate training sessions that involve repeatedly pressing a button on a button box console, earning points worth money. - Dyadic interaction paradigm - Participants will interact with their spouse/significant other in a small room, first discussing a neutral topic, such as the day's events, and then a subject that has been a source of conflict. - Fluoxetine administration - Participants will be randomly assigned to receive either 10 mg. of fluoxetine or placebo (identical capsules with no active ingredients) once a day for 3 days, then twice a day, increasing up to four capsules a day if there are no serious side effects. Blood will be drawn once a month to measure drug levels. At the end of 3 months, participants taking placebo may remain in the study and receive fluoxetine. - Clinic visits - Participants are followed in the clinic weekly for the first month, then twice a month for the next 2 months for adjustment of number of pills, evaluation of aggressive behavior and alcohol consumption, and therapy for issues of self-esteem, anger management and communication skills. Couples therapy aimed at conflict resolution and improving communication skills will be offered. - Genetic tests (optional) - Blood will be drawn to determine if there is a relationship between genes involved in a chemical process (serotonin reuptake) that is influenced by fluoxetine and the participant's response to the drug. Spouse/Significant other: Spouses/significant others will complete several questionnaires once a month (total 4 times) to rate their partners' behavior while in the study. They will also participate in the dyadic interaction paradigm described above at the beginning and end of the study.
NCT00018200 ↗	Effect of Antidepressants on Back Pain	Completed	US Department of Veterans Affairs	Phase 2	1999-04-01	The purpose of this study is to determine whether different types of antidepressant medicines relieve back pain that has lasted at least six months on a daily basis. Study participants will be assigned to treatment with either a antidepressant acting on the serotonin system in the brain (fluoxetine), one acting on the noradrenaline system (desipramine, or to a control medication not expected to relieve pain (benztropine). Each participant will be seen at least nine times during their 12 weeks on medication. This is a phase 2/3, outpatient study.

Clinical Trial Conditions for PROZAC

Condition Name

Condition Name for PROZAC
Intervention	Trials
Depression	23
Major Depressive Disorder	17
Healthy	7
Major Depression	6

Condition MeSH

Condition MeSH for PROZAC
Intervention	Trials
Depression	56
Depressive Disorder	47
Disease	30
Depressive Disorder, Major	28

Clinical Trial Locations for PROZAC

Trials by Country

Trials by Country for PROZAC
Location	Trials
United States	257
Canada	11
China	7
France	3
India	3

Trials by US State

Trials by US State for PROZAC
Location	Trials
New York	20
California	16
Pennsylvania	16
Texas	14
Ohio	11

Clinical Trial Progress for PROZAC

Clinical Trial Phase

Clinical Trial Phase for PROZAC
Clinical Trial Phase	Trials
PHASE1	1
Phase 4	27
Phase 3	20

Clinical Trial Status

Clinical Trial Status for PROZAC
Clinical Trial Phase	Trials
Completed	80
Recruiting	11
Terminated	9

Clinical Trial Sponsors for PROZAC

Sponsor Name

Sponsor Name for PROZAC
Sponsor	Trials
National Institute of Mental Health (NIMH)	24
University of Pittsburgh	6
Eli Lilly and Company	6

Sponsor Type

Sponsor Type for PROZAC
Sponsor	Trials
Other	143
NIH	34
Industry	26

Executive summary

Last updated: July 28, 2026

• PROZAC (fluoxetine) is an off-patent antidepressant with long-established generic competition; the core business question is not new exclusivity but ongoing lifecycle risk (label/indication breadth), formulary dynamics, and ongoing generic pricing pressure.
• Clinical trials for fluoxetine have shifted toward new combinations, comparative effectiveness, replication studies, and specialty cohorts rather than single-agent development intended to restart exclusivity.
• Market analysis and projections for PROZAC should be modeled as a mature, commodity-style antidepressant market where growth is driven primarily by volume/brand share changes, payer mix, and seasonal utilization, not by patent-driven supply constraints.

PROZAC (fluoxetine) clinical trials update: what studies are active, completed, and recruiting now?

Fluoxetine trial activity is typically concentrated in four lanes: comparative trials versus other SSRIs, trials in specific populations (adolescents, postpartum depression, OCD subtypes, treatment-resistant depression), safety/tolerability, and combination regimens.

What phase mix does fluoxetine development show?

Most fluoxetine “development” is late-stage, comparative, or academic. In practice, many postings are:

• Phase 4 comparative effectiveness or real-world evidence style interventional studies
• Phase 2/3 specialty cohorts (where endpoints are symptom scales and tolerability)
• Bioavailability/bioequivalence and formulation work that may appear as interventional studies in registries but does not create exclusivity

What trial designs dominate?

The most common endpoints for fluoxetine programs remain:

• MADRS/PHQ-9/HAMD style depression severity outcomes
• Response/remission rates using standard thresholds
• Anxiety and OCD-adjacent symptom scales where the indication scope is expanded

Where do trials cluster by geography and sponsors?

Fluoxetine trial records often show:

• Academic and government-backed sponsors for comparative and symptom-scale studies
• Industry-led trials when anchored to a combination strategy or a specific delivery/formulation objective
• Multi-country recruitment with heavier enrollment in regions that support larger depression cohort accrual

What market does PROZAC (fluoxetine) play in: antidepressant share, segment drivers, and payer impact?

PROZAC sits in the oral antidepressant segment within the broader SSRI class. Since fluoxetine is generic, the brand operates primarily on:

• Patient familiarity and prescriber inertia
• Formulary access (preferred vs non-preferred placement)
• Brand-to-generic substitution dynamics
• Plan-level switching rules and pharmacy benefit design

How does PROZAC compete inside the SSRI shelf?

Within SSRIs, fluoxetine competes on:

• Price positioning after generic entry
• Dosing convenience and clinician familiarity (long half-life is an adherence talking point)
• Switching tolerance and discontinuation considerations

What drives volume in mature antidepressant markets?

Model drivers for PROZAC-like mature oral antidepressants:

• Incidence and prevalence of depression in covered lives
• Adherence persistence after initiation
• Formulary step-therapy rules
• Seasonality (depression treatment utilization often shows periodic volume effects)
• Clinic practice patterns (first-line SSRI selection)

What is the commercial mechanism if patents are irrelevant?

In an off-patent setting, market performance tracks:

• Channel mix (retail vs mail order)
• PBM formulary design
• Brand rebates and contract coverage
• Generic penetration intensity

When does PROZAC lose exclusivity: what is the expiration status for fluoxetine patents and exclusivity?

Fluoxetine’s primary brand protection is no longer a meaningful constraint. Business relevance today is residual:

• Brand-specific line extensions (if any remain for particular dosage forms)
• Method-of-use and formulation tail patents that can affect specific products, strengths, or presentation formats
• Country-level legacy patents that may still affect a narrow product subset, not the active ingredient broadly

How to interpret “exclusivity” in a generic-dominant market

For mature molecules like fluoxetine:

• Hatch-Waxman exclusivity is typically exhausted
• Market access risk comes from Orange Book-listed patents tied to specific presentations rather than new active-ingredient exclusivity

What is the Orange Book status of PROZAC (fluoxetine) and which patents still matter?

The Orange Book analysis in a brand-to-generic environment must be presentation-specific. For PROZAC, the practical outcome for business planning is:

• Generic entry barriers are narrow and usually limited to specific listed patents tied to particular NDA presentations or manufacturing processes.
• If no currently enforceable patents cover a given presentation, the pathway is straightforward for generics to enter at approval.

What patent categories can still appear in Orange Book for fluoxetine presentations?

Even for off-patent actives, Orange Book listings can include:

• Formulation patents (e.g., specific compositions, coatings, or manufacturing processes)
• Method-of-use patents tied to a label-specific claim
• Proprietary manufacturing process claims limited to certain product lines

How strong is the patent estate for PROZAC (fluoxetine) across formulations and methods of use?

For fluoxetine’s business planning, “strength” generally means whether there are:

• Live, enforceable Orange Book patents covering particular dosage forms
• Ongoing litigation that blocks specific generic submissions
• Settlement agreements that delay entry for certain filers

In most cases for fluoxetine, the estate is not strong in the aggregate because generics already have widespread approvals for oral fluoxetine.

What generic entry risks exist for PROZAC (fluoxetine) products, dosage forms, and strengths?

Generic entry risks for a mature antidepressant are usually dominated by:

• Switching and contracting risk (not legal)
• Supply and manufacturing capacity risk for certain manufacturers
• Label-specific market carve-outs if a non-substitutable presentation remains protected

How do Paragraph IV challenges apply to fluoxetine?

Paragraph IV litigation can occur only when a generic filer challenges a listed patent on a specific NDA presentation. For fluoxetine, the typical reality is:

• Fewer new Paragraph IV events than for on-patent brands
• Remaining disputes, if any, are usually presentation-specific and time-bounded

What patent litigation affects PROZAC (fluoxetine): ongoing cases, settlements, and outcomes?

For mature fluoxetine brands, litigation events tend to be:

• Older disputes tied to specific Orange Book patents
• Less frequent new actions unless a new listed patent is asserted against a filer or a product presentation changes

Business relevance:

• If no active injunctions or settlement-based entry delays exist for a given presentation, the near-term legal risk to market supply is low.
• If settlements exist, they are typically limited to certain generics or certain presentations.

Which companies are challenging PROZAC (fluoxetine) and what does that mean for supply and pricing?

In off-patent categories, market share concentrates among:

• Early filers with robust distribution
• High-coverage generic manufacturers with strong PBM contracting
• Suppliers with dependable manufacturing capacity

Commercial impact:

• More filings and multiple approved ANDAs usually reduce price and increase substitution speed.
• Contracting and coverage determine near-term share more than patent posture.

How does PROZAC compare with other SSRIs (escitalopram, sertraline, citalopram) on clinical and market outcomes?

For business benchmarking:

• Fluoxetine often competes on prescriber familiarity and pharmacology perceptions (long half-life).
• Market outcomes are usually driven by PBM coverage rather than head-to-head superiority.

Clinical comparators used in trials:

• Escitalopram, sertraline, paroxetine, venlafaxine, and duloxetine are common comparators in depression comparative studies.

What FDA regulatory status applies to PROZAC (fluoxetine), including labeling and formulation considerations?

Key regulatory reality for fluoxetine:

• Broad, established labeling across depression and anxiety-spectrum conditions.
• Ongoing label maintenance, safety updates, and postmarketing commitments.
• Formulation changes can occur for specific presentations, but regulatory exclusivity remains limited given generic dominance.

How many PROZAC (fluoxetine) patents cover each presentation: capsules vs liquid vs other dosage forms?

A presentation-by-presentation patent count must be derived from current Orange Book listings. For fluoxetine, the business conclusion for planning is:

• Many presentations are already generic-available, so the number of enforceable, blocking patents is usually low relative to on-patent brands.
• Where patents remain, they tend to be narrow (formulation or method-of-use claims specific to a presentation).

What is the clinical pipeline outlook for fluoxetine: does it support new IP or new indications?

Fluoxetine’s pipeline posture is typically:

• No major “restart exclusivity” unless a combination or delivery platform creates a protected new product category
• Clinical activity focused on evidence generation rather than brand-restoration strategies

Where a new protected product might emerge:

• Specific combination products (fixed-dose or regimen-anchored)
• Specialty formulation technologies (where patents are tied to the specific platform)

Market projection for PROZAC (fluoxetine) 2026-2031: forecast scenarios and key sensitivities

A mature antidepressant model should use scenario structure anchored to:

1. Brand share drift (continuous generic substitution)
2. Pricing pressure (WAC-to-net compression and PBM dynamics)
3. Utilization growth (depression diagnosis and treatment rates)
4. Contract coverage (rebates, tier placement)
5. Supply stability (manufacturing disruptions, recalls)

Base-case projection framework (business-ready)

• Expect volume growth roughly tracking antidepressant class utilization, with brand declines or stagnation unless PROZAC retains preferred positioning.
• Expect net sales growth to be limited because brand net pricing offsets are capped by generic benchmark pricing.
• Key upside comes from contracted brand stickiness in specific formularies and product-line stability.

Downside case

• Faster brand share erosion due to aggressive tiering and mail-order substitution
• Continued generic price compression and reduced brand rebate support
• Any targeted tender shifts that favor alternative SSRIs

Upside case

• Stabilization of brand placement in high-volume plans
• Reduced generic competition via supply issues or manufacturing constraints
• Specialty-driven demand retention in populations that prefer fluoxetine

Key Takeaways

• PROZAC is a mature, generic-dominant antidepressant where clinical trial activity is mostly comparative or evidence-driven rather than exclusivity-restoring.
• Market performance is governed primarily by formulary access, PBM contracting, and generic substitution.
• Patent and Paragraph IV risk is narrow and presentation-specific; the biggest commercial determinants are channel, pricing, and coverage rather than new IP barriers.
• Forecasts should be modeled as scenario-based share and price dynamics, not as patent-expiration ramp-ups.

FAQs

1. Are there any currently recruiting clinical trials for fluoxetine (PROZAC) and what endpoints do they use?
2. Which PROZAC (fluoxetine) dosage form has the most Orange Book patent listings and why does that matter for generics?
3. How do settlement agreements in fluoxetine Paragraph IV cases typically affect entry timing for specific ANDA filers?
4. What payer and PBM levers most influence PROZAC brand share versus generic fluoxetine?
5. How does fluoxetine’s long half-life translate into adherence and discontinuation outcomes compared with other SSRIs in clinical studies?

References

1. FDA Orange Book. Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). U.S. Food and Drug Administration.
2. ClinicalTrials.gov. Fluoxetine (PROZAC) Search Results. National Library of Medicine.
3. FDA Drug Labeling (Dailymed). PROZAC (fluoxetine) Prescribing Information. U.S. National Library of Medicine.