what does the fluoxetine black box warning mean?

the boxed warning says antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents and young adults in short-term trials. the label’s own table gives the size: 14 additional people per 1,000 treated under 18, 5 additional at 18 to 24, 1 fewer at 25 to 64 and 6 fewer at 65 and older. no suicides occurred in the pediatric trials. the warning asks for close observation, especially in the first months and after dose changes; it is not an instruction to stop the drug.

what are the most common fluoxetine side effects?

in the label’s pooled placebo-controlled trials (2,869 on fluoxetine, 1,673 on placebo): nausea 22% vs 9%, insomnia 19% vs 10%, nervousness 13% vs 8%, anxiety 12% vs 6%, sleepiness 12% vs 5%, decreased appetite 10% vs 3%, diarrhea 11% vs 7%, tremor 9% vs 2%, sweating 7% vs 3% and decreased libido 4% vs 1%. the label says sexual side effects are undercounted because people rarely raise them; a questionnaire-based meta-analysis found rates of 25.8% to 80.3% across antidepressants.

does fluoxetine work for teenagers with depression?

it beats placebo, by less than its reputation suggests. the label’s two pediatric trials (315 children and adolescents, 8 to 9 weeks) found it better than placebo, and in the tads trial 61% of 439 adolescents responded to fluoxetine against 35% on placebo, 71% with cbt added. two lancet network meta-analyses put its edge at a standardised 0.51 with very low confidence; the 2021 cochrane review found 2.84 points on a 17 to 113 point scale, about 0.20, and called it "small and unimportant". a 2026 re-analysis traced the gap to one small 2006 trial with implausible results; without it the lancet estimates fell to 0.26 and 0.29, close to cochrane’s. every analysis still finds some benefit. the boxed warning applies most strongly to this age group.

why did the reviews of fluoxetine for children disagree?

because of one trial. a 2026 re-analysis by lyus and colleagues found that a 2006 single-site trial of 40 children comparing fluoxetine with nortriptyline, which reported an effect of about 4.2 standard deviations, fed into the two lancet reviews through an indirect comparison and roughly doubled fluoxetine’s estimated effect. the 2021 cochrane review excluded tricyclics, so it never included that trial. removing it brought all three to a small effect. the re-analysis was exploratory, with no pre-registered protocol, and the authors say guidelines should be updated; they do not say anyone should stop.

how long does fluoxetine stay in your system?

a long time. the label gives a half-life of 4 to 6 days for fluoxetine after regular use and 4 to 16 days for its active metabolite norfluoxetine, so a dose change is not fully reflected in the blood for several weeks, and an maoi cannot be started until 5 weeks after the last dose. the slow fall is also why the label says discontinuation symptoms may be less of a risk with this drug, though a gradual taper is still what it recommends.

what happens if you stop fluoxetine suddenly?

the label lists dysphoric mood, irritability, agitation, dizziness, electric-shock sensations, anxiety, confusion, headache, lethargy, insomnia and hypomania as reactions reported on stopping ssris, particularly abruptly, and recommends a gradual reduction whenever possible, going back up a step if symptoms are intolerable. it adds that fluoxetine’s blood level falls slowly, which may lessen the risk. in a 2021 trial, 56% of people randomised to stop a long-term antidepressant relapsed within a year against 39% who stayed on. a taper plan is a conversation with a prescriber.

Medication approval journey

fluoxetine (Prozac)

Approved for Major depressive disorder, acute and maintenance

page first published 2026-08-31 · last updated 2026-10-13

Also answers to “the vintage vinyl” — its codename in our videos and posts. The full codebook

FDA approvedSSRI antidepressantTaper risk: moderate

How this page reads

The page as written, with the clinical terms

Plain language uses the same facts, the same numbers and the same caveats. It does not leave anything out. Quotes from the FDA label are never reworded in either setting.

Before you stop or change your fluoxetine dose

Stopping abruptly causes withdrawal effects that can be severe

Stopping or reducing an SSRI too fast commonly causes withdrawal symptoms — dizziness, electric-shock sensations, insomnia, agitation. These are often more severe and far longer-lasting than the "one to two weeks" many people are told. Any change should be a slow, prescriber-supervised taper.

what the fluoxetine warnings mean

label facts below are read from the fluoxetine capsules FDA label on DailyMed, set id 23899405-007b-48d9-82a9-a530b8e90784, version 16, effective august 20, 2026. the section numbers in brackets are the label’s own. every source is linked at the end of this section. last checked 2026-10-13.

fluoxetine was approved for depression in december 1987, and about 6.2 million americans filled a prescription for it in 2024 [meps]. its label carries one boxed warning and sixteen further numbered warnings, and it is approved for depression from age 8 and for ocd from age 7 [label 8.4]. this section says what each warning means in plain words, what the approval trials measured and for how long, which side effects the label counts and how often, and what independent research has found since, in both directions. every number is from the label or from a study in the library, and each source is linked at the end.

the legal and safety record for this drug, including court and regulator records, has its own page on this site and is not repeated here [legal-record]. this is information to take to a prescriber. nothing here is a reason to start, stop or change a dose on your own; the label itself says stopping suddenly is the thing to avoid.

the boxed warning: suicidal thoughts and behaviors, by age

the boxed warning says antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents and young adults in short-term studies, that the studies did not show an increase over age 24 and showed a reduction at 65 and older, that everyone started on the drug should be watched closely for worsening, and that fluoxetine is not approved under age 7 [label, boxed warning and 5.1].

the numbers come from pooled placebo-controlled trials: 24 short-term trials of 9 antidepressants in more than 4,400 children and adolescents, and 295 trials of 11 antidepressants in more than 77,000 adults. the label gives the difference against placebo per 1,000 people treated: under 18, 14 additional people with suicidal thoughts or behaviors; 18 to 24, 5 additional; 25 to 64, 1 fewer; 65 and older, 6 fewer [label 5.1, table 2]. no suicides occurred in any of the pediatric trials, and the adult trials had too few to say anything about suicide itself. the label says it is unknown whether the risk extends beyond several months [label 5.1]. the age ceiling is the part most people never hear [age-ceiling].

what the warning asks for is observation: families and caregivers watching daily, especially in the first months and after any dose change, for agitation, irritability, panic, insomnia, hostility, impulsivity, restlessness or mania, and reporting them at once [label 5.1]. the fda web page that explained how the warning came to be added now returns a 404; the warning itself is on the live label, which is where to read it [fda-page-gone].

the sixteen other warnings, in plain words

the warnings section runs from 5.1 to 5.17; 5.16 only points to the label of the olanzapine combination product. none of the rest is boxed. where the label gives a number, it is here.

serotonin syndrome [5.2]: a potentially life-threatening reaction, more likely with other serotonergic drugs (the label names triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines and st john’s wort) and with maois, which are contraindicated. because fluoxetine lingers, an maoi cannot be started until 5 weeks after the last dose [label 4.1, 2.9]. the signs clinicians use to recognise it are the hunter criteria: muscle twitching, agitation, sweating, tremor, overactive reflexes, and in severe cases rigidity and fever [hunter-2003].
rash and allergic reactions [5.3]: 7% of 10,782 people in us trials developed a rash or hives, and almost a third of them stopped the drug because of it. two trial patients developed a serious systemic illness, and since marketing there have been rare systemic reactions involving the lung, kidney or liver, some fatal. the label says to stop fluoxetine if a rash appears with no other explanation.
mania or hypomania [5.4]: 0.1% on fluoxetine and 0.1% on placebo in the depression trials; 0.8% against none in the ocd trials. in children and adolescents it was 2.6% (6 of 228) against 0 of 190 on placebo, and it was the most common reason a child left a trial [label 8.4]. the label says to screen for bipolar disorder before starting an antidepressant.
seizures [5.5]: 0.1% on fluoxetine against 0.2% on placebo in the depression trials, and 0.2% of all 10,782 trial patients.
appetite and weight [5.6]: 11% reported decreased appetite against 2% on placebo in the depression trials; weight loss 1.4% against 0.5%. in the 16-week bulimia trial people on 60 mg lost 0.45 kg on average while placebo gained 0.16 kg. in a 19-week pediatric trial, children on fluoxetine gained 1.1 cm less in height and 1.1 kg less in weight than children on placebo, and the label says height and weight should be monitored in children [label 8.4].
bleeding [5.7]: ssris may increase bleeding, more so with aspirin, nsaids or warfarin; the label adds that exposure in the month before delivery has been associated with a less than twofold increase in postpartum hemorrhage. a 2014 meta-analysis of 393,268 people put the odds of an upper stomach bleed at 1.66 times on an ssri alone and 4.25 times with an nsaid as well, which is one extra bleed for roughly every 3,177 low-risk people [anglin-2014].
angle-closure glaucoma [5.8]: the pupil dilation many antidepressants cause can trigger an attack in people with anatomically narrow angles.
low sodium [5.9]: hyponatremia, sometimes severe (below 110 mmol/l), mostly in older people and people on diuretics; headache, confusion, unsteadiness and falls are the signs the label lists.
anxiety and insomnia [5.10]: 12% to 16% on fluoxetine against 7% to 9% on placebo in the depression trials; insomnia 33% against 13% in the bulimia trials at 60 mg.
qt prolongation [5.11]: post-marketing reports of qt prolongation and torsade de pointes. pimozide and thioridazine are contraindicated with fluoxetine [label 4.2], and the label says to avoid other qt-prolonging drugs and consider an ecg in people with risk factors. in routine trial ecgs a qtcf of 450 ms or more was a "frequent" finding, the label’s word for at least 1 in 100 [label 6.1].
concomitant illness [5.12]: people with a recent heart attack or unstable heart disease were excluded from the trials; in diabetes, fluoxetine can lower blood sugar during treatment and raise it after stopping.
thinking and driving [5.13]: as with any cns-active drug, caution with machinery and cars until the effect is known.
the long half-life [5.14]: fluoxetine’s half-life is 4 to 6 days with regular use and its active metabolite norfluoxetine’s is 4 to 16 days, so a dose change is not fully reflected in the blood for several weeks [label 12.3]. this cuts both ways: it is why the label expects milder discontinuation symptoms than with shorter-acting ssris, and why interactions can persist for weeks after stopping.
stopping [5.15]: dysphoria, irritability, agitation, dizziness, electric-shock sensations, anxiety, confusion, headache, lethargy, insomnia and hypomania have been reported on stopping ssris, particularly abruptly, and the label recommends a gradual reduction whenever possible. it adds that fluoxetine’s slow fall in blood level may minimise the risk with this drug in particular.
sexual dysfunction [5.17]: delayed or absent ejaculation, decreased libido and erectile problems in men; decreased libido and delayed or absent orgasm in women. the label asks prescribers to ask about it before and during treatment, because people rarely volunteer it, and says symptoms occasionally persist after stopping [label 6.1].

what the approval trials measured, and for how long

the depression approval rests on 7 short-term and 2 long-term placebo-controlled trials in adults and in children aged 8 to 18 [label 14]. the adult trials ran 5 and 6 weeks and the label does not say how many adults were in them; it reports that fluoxetine beat placebo on the hamilton depression scale, and that studies of 20, 40 and 60 mg found 20 mg enough for most people [label 14.1, 2.1]. two 6-week trials in 671 people aged 60 and over found 20 mg effective, with 12% leaving for side effects against 9% on placebo [label 14.1].

two trials of 8 to 9 weeks in 315 children and adolescents (170 aged 8 to 12, 145 aged 13 to 18) found a larger fall on the children’s depression rating scale than placebo [label 14.1]. the maintenance evidence is a randomised-withdrawal design: 298 adults who had responded during 12 weeks of open-label fluoxetine were randomised to continue or to switch to placebo, and over the next 38 weeks fewer relapsed on fluoxetine. a second study randomised responders after 13 weeks and followed them for 25 weeks with the same result [label 14.1]. the label gives no relapse percentages for either.

the other indications have their own trials. for ocd, two 13-week trials at fixed doses of 20, 40 or 60 mg: yale-brown scores fell about 4 to 6 and 4 to 9 points against 1 point on placebo, and 27% to 28% of completers were "much improved" on each dose against 8% on placebo, with a further 8% to 19% "very much improved" against 3% [label 14.2, table 6]. for bulimia, 60 mg but not 20 mg beat placebo, cutting binges by 1 to 2 a week and vomiting by 2 to 4 a week; for most people the benefit was a partial reduction, not an end [label 14.3]. for panic disorder, 42% against 28% and 62% against 44% were free of panic attacks at 12 weeks [label 14.4].

side effects, with the label’s numbers

across the placebo-controlled trials for depression, ocd, bulimia and panic combined (2,869 on fluoxetine, 1,673 on placebo), the label’s table 4 gives: nausea 22% against 9%, insomnia 19% against 10%, nervousness 13% against 8%, anxiety 12% against 6%, sleepiness 12% against 5%, decreased appetite 10% against 3%, diarrhea 11% against 7%, weakness 11% against 6%, tremor 9% against 2%, dry mouth 9% against 6%, sweating 7% against 3%, decreased libido 4% against 1%. headache was 21% against 19%, which is to say mostly not the drug [label 6.1, table 4].

the sexual numbers are the ones the label itself says are undercounted. decreased libido was the only sexual effect reported by at least 2% of people in the depression, ocd and bulimia trials (4% against under 1%); among men in the ocd trials 7% reported abnormal ejaculation against none on placebo [label 6.1, table 3]. the label says such estimates "are likely to underestimate their actual incidence" because neither patients nor clinicians raise them. when researchers asked with a questionnaire instead of waiting for a complaint, sexual dysfunction ran from 25.8% to 80.3% across antidepressants, with fluoxetine fifth of the ten drugs ranked [serretti-2009].

in 322 children and adolescents the side-effect profile was similar to adults, with thirst, hyperactivity, agitation, nosebleeds and frequent urination also reported at 2% or more [label 6.1]. the label’s own caveat applies to all of these numbers: trial rates "may not reflect or predict the rates observed in practice".

what the research says, in both directions

in favour. in the largest comparison of antidepressants, a 2018 network meta-analysis of 522 trials and 116,477 adults, fluoxetine beat placebo and was among the better tolerated drugs, though several others ranked higher for effect [cipriani-2018]. a cochrane review pooling 171 trials and 24,868 people found it as effective as the older tricyclics and better tolerated [cochrane-2013]. in children and adolescents it has the strongest record of any antidepressant tested: in a 2016 network meta-analysis of 34 trials and 5,260 young people, fluoxetine was the only one of 14 drugs statistically better than placebo [cipriani-2016], and in the nimh-sponsored tads trial of 439 adolescents, 61% responded to fluoxetine alone and 71% to fluoxetine with cbt, against 43% for cbt alone and 35% for placebo; the combination also produced the biggest drop in suicidal thinking [tads-2004]. in a 2021 trial of 478 primary-care patients who felt well enough to stop a long-term antidepressant, including fluoxetine 20 mg, 56% of those who stopped relapsed within a year against 39% who stayed on [antler-2021].

against, or smaller than it sounds. the same reviews limit it. the cochrane review found fluoxetine slightly less effective than sertraline, mirtazapine and venlafaxine [cochrane-2013], and in the 2018 ranking it sat mid-pack for effect [cipriani-2018]. the pediatric margin over placebo "nearly touched zero", the evidence was rated very low quality in most comparisons, and the trials were mostly industry funded and 8 to 12 weeks long [cipriani-2016]. the 2021 cochrane network meta-analysis of 26 trials in 6 to 18 year olds put fluoxetine’s effect at 2.84 points on a 17 to 113 point scale (moderate certainty), which the reviewers called "small and unimportant"; on suicide-related outcomes it found low-certainty evidence that fluoxetine "may at least slightly increase" the odds (odds ratio 1.27, 95% ci 0.87 to 1.86), and that children judged at risk of suicide were usually excluded from the trials [hetrick-2021]. a 2026 re-analysis found that one small 2006 trial roughly doubled fluoxetine’s apparent effect in under-18s in the two lancet reviews; the next block sets it out [lyus-2026]. in a 122-person trial of bright light for non-seasonal depression, fluoxetine alone did not beat placebo (effect size 0.24) while light did, and the combination did best; with about 30 people per arm, that null is one small trial’s result, not a verdict [lam-2016].

the warnings, measured. the sexual warning has a european postscript: in may 2019 the eu safety committee ordered every maker of fluoxetine and nine other ssris and snris to warn that sexual dysfunction can persist after the drug is stopped, acting on case reports rather than a prevalence study, so how often it happens is unknown [prac-2019]. the size of the bleeding warning is in the 2014 meta-analysis above [anglin-2014], and the diagnostic rules behind the serotonin syndrome warning are the 2003 hunter criteria, built from 2,222 overdose admissions [hunter-2003].

children and teenagers: why three big reviews disagreed, and what a 2026 re-analysis found

fluoxetine is the antidepressant guidelines most often name first for depression under 18, and that rests mainly on two network meta-analyses in lancet journals: cipriani 2016, which is in this library [cipriani-2016], and a 2020 analysis by zhou and colleagues with an overlapping author team, which is not. both put fluoxetine ahead of placebo by a standardised effect of 0.51 (95% credible intervals 0.03 to 0.99, and 0.18 to 0.84), and both rated confidence in that result very low [lyus-2026]. the 2021 cochrane review found a gap of 2.84 points on the 17 to 113 point cdrs-r scale (95% ci 1.56 to 4.12, moderate certainty), about 0.20 in the same standardised units, and called it "small and unimportant" [hetrick-2021]. its authors also wrote that fluoxetine "is currently the only treatment recommended for first-line prescribing", and that sertraline, escitalopram and duloxetine as well as fluoxetine "could be considered as a first option" [hetrick-2021].

in 2026, lyus, naudet, van valkenhoef and plöderl re-ran both lancet analyses on their published data. each carried an inconsistency between the direct and indirect evidence in the fluoxetine, nortriptyline and placebo loop that the original authors could not explain, and the re-analysis traced it to one trial: a 2006 single-site study of 40 children and adolescents comparing fluoxetine with the older drug nortriptyline, with no placebo arm, which reported a standardised effect of about 4.2 in fluoxetine’s favour. the cochrane review had left it out only because it excluded tricyclics such as nortriptyline [lyus-2026]. without that one trial, fluoxetine’s edge over placebo fell to 0.26 (0.09 to 0.43) in the cipriani data and 0.29 (0.07 to 0.50) in the zhou data, close to the cochrane figure, and the inconsistency disappeared. in the authors’ words: "discrepancies between the three nmas were explained by the indirect influence of a single small trial with extreme and unreliable results" [lyus-2026]. they also judged the trial itself of low trustworthiness: ethics approval is not mentioned, dropouts were replaced with new cases, and score changes were nearly uniform within each arm [lyus-2026].

the other direction, and the limits. even without that trial, all three analyses still put fluoxetine ahead of placebo beyond chance; the dispute is about how big the effect is, not whether there is one [lyus-2026]. the re-analysis was exploratory and had no pre-registered protocol, and because the full dataset behind the 2021 cochrane review had not been retained, the authors rebuilt it starting from a partial dataset the cochrane authors provided; their rebuilt estimate, 0.27, sat close to cochrane’s own [lyus-2026]. one author is a cochrane employee, and the paper states cochrane had no role in the work. the authors do not tell anyone to stop the drug; they write that clinicians and patients "should be informed of fluoxetine’s actual efficacy, and treatment guidelines should be updated accordingly" [lyus-2026]. the re-analysis concerns how the pooled reviews sized the effect; it does not re-score the label’s two pediatric trials or tads, which are reported above as published [label 14.1; tads-2004]. if a child is taking fluoxetine, this is a question for their prescriber, not a reason to stop.

questions to ask your prescriber about fluoxetine

each one comes from a warning or a study above. they are questions, not instructions; the answers depend on a history nobody here has.

which side of the age line in the boxed warning am i on, what exactly should the people around me watch for in the first two months, and who do we call if it appears?
the label says a dose change takes several weeks to show in the blood. how long should we wait before judging whether a dose is working?
the trials that got fluoxetine approved ran 5 to 9 weeks, and the maintenance study 38 weeks. how long do you expect me to take it, and when will we review that?
the label says sexual side effects are undercounted because nobody asks. can we agree now how we will track them, and what we would do if they appeared?
i take ibuprofen, aspirin or a blood thinner. the label and a large meta-analysis both say the bleeding risk rises with the combination; does that change anything for me?
decreased appetite was about five times more common than on placebo in the trials, and children gained less height and weight. if weight changes, what is the plan?
if we ever stop, the label says taper rather than stop and that fluoxetine’s slow clearance helps. what would the taper look like, and how would we tell withdrawal from relapse?
for a child or teenager: the reviews now agree the average benefit over placebo is small. what change would tell us it is working for this child, how will we measure it, and by when?

questions people ask

what does the fluoxetine black box warning mean?: the boxed warning says antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents and young adults in short-term trials. the label’s own table gives the size: 14 additional people per 1,000 treated under 18, 5 additional at 18 to 24, 1 fewer at 25 to 64 and 6 fewer at 65 and older. no suicides occurred in the pediatric trials. the warning asks for close observation, especially in the first months and after dose changes; it is not an instruction to stop the drug.
what are the most common fluoxetine side effects?: in the label’s pooled placebo-controlled trials (2,869 on fluoxetine, 1,673 on placebo): nausea 22% vs 9%, insomnia 19% vs 10%, nervousness 13% vs 8%, anxiety 12% vs 6%, sleepiness 12% vs 5%, decreased appetite 10% vs 3%, diarrhea 11% vs 7%, tremor 9% vs 2%, sweating 7% vs 3% and decreased libido 4% vs 1%. the label says sexual side effects are undercounted because people rarely raise them; a questionnaire-based meta-analysis found rates of 25.8% to 80.3% across antidepressants.
does fluoxetine work for teenagers with depression?: it beats placebo, by less than its reputation suggests. the label’s two pediatric trials (315 children and adolescents, 8 to 9 weeks) found it better than placebo, and in the tads trial 61% of 439 adolescents responded to fluoxetine against 35% on placebo, 71% with cbt added. two lancet network meta-analyses put its edge at a standardised 0.51 with very low confidence; the 2021 cochrane review found 2.84 points on a 17 to 113 point scale, about 0.20, and called it "small and unimportant". a 2026 re-analysis traced the gap to one small 2006 trial with implausible results; without it the lancet estimates fell to 0.26 and 0.29, close to cochrane’s. every analysis still finds some benefit. the boxed warning applies most strongly to this age group.
why did the reviews of fluoxetine for children disagree?: because of one trial. a 2026 re-analysis by lyus and colleagues found that a 2006 single-site trial of 40 children comparing fluoxetine with nortriptyline, which reported an effect of about 4.2 standard deviations, fed into the two lancet reviews through an indirect comparison and roughly doubled fluoxetine’s estimated effect. the 2021 cochrane review excluded tricyclics, so it never included that trial. removing it brought all three to a small effect. the re-analysis was exploratory, with no pre-registered protocol, and the authors say guidelines should be updated; they do not say anyone should stop.
how long does fluoxetine stay in your system?: a long time. the label gives a half-life of 4 to 6 days for fluoxetine after regular use and 4 to 16 days for its active metabolite norfluoxetine, so a dose change is not fully reflected in the blood for several weeks, and an maoi cannot be started until 5 weeks after the last dose. the slow fall is also why the label says discontinuation symptoms may be less of a risk with this drug, though a gradual taper is still what it recommends.
what happens if you stop fluoxetine suddenly?: the label lists dysphoric mood, irritability, agitation, dizziness, electric-shock sensations, anxiety, confusion, headache, lethargy, insomnia and hypomania as reactions reported on stopping ssris, particularly abruptly, and recommends a gradual reduction whenever possible, going back up a step if symptoms are intolerable. it adds that fluoxetine’s blood level falls slowly, which may lessen the risk. in a 2021 trial, 56% of people randomised to stop a long-term antidepressant relapsed within a year against 39% who stayed on. a taper plan is a conversation with a prescriber.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

we went and looked

confirmedis fluvoxamine fda approved for major depression? no, its u.s. labels list only ocdsaid on Psychopharmacology and Psychiatry Updates, 2026-10-03; the host is right. every current FDA label we read for fluvoxamine, both the immediate-release tablets and the extended-release capsules, lists obsessive compulsive disorder as the only indication. major depressive disorder isn't there.
confirmeddoes the aripiprazole label call for half the dose with a strong cyp2d6 inhibitor like bupropion?said on PsychEd: Educational Psychiatry Podcast, 2026-09-01; the speaker has the label right. the current aripiprazole prescribing information tells prescribers to "administer half of usual dose" when aripiprazole is taken with a strong CYP2D6 inhibitor, and FDA's own reference table lists bupropion as a strong CYP2D6 inhibitor.

every check quotes one sentence, links the original at the timestamp, and takes each assertion to the primary record. the full list: /checked.

How long the fluoxetine trials actually ran

We could not establish a longest trial length for fluoxetine. That is a gap in what we can show you — not evidence that the trials ran long.

The label carries a clinical studies section describing the trials the approval rested on.

The gap between how long the trials ran and how long people actually take these medications is the single most important thing on this page. It is not evidence that longer use is unsafe or ineffective. It is evidence that longer use was not what got tested.

People often stay on these drugs for far longer than the trials ran. The short adult trials behind the approval ran 5 and 6 weeks.

That does not mean longer use is unsafe. It does not mean the drug stops working either. It means longer use was never the thing that got tested.

If you have been on it a long time, that is a fair thing to ask your prescriber about.

Boxed warning: suicidal thoughts and behaviors

The strongest warning the FDA puts on a label, often called a black box warning. It is reproduced below word for word, not summarised.

This is the strongest warning the FDA can put on a drug label. Some people call it a black box warning. We copied it word for word. We did not shorten it and we did not soften it.

The warning below is about suicidal thoughts. In short studies, antidepressants raised the risk of suicidal thoughts and behavior. That was in children, teens, and young adults. The same studies did not show that added risk in people over 24. In people aged 65 and older the risk went down. The label tells prescribers to watch every patient closely when treatment starts.

The FDA’s own words follow, copied exactly.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions (5.1) ] . In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber [see Warnings and Precautions (5.1) ] . Fluoxetine is not approved for use in children less than 7 years of age [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4) ] . When using fluoxetine and olanzapine in combination, also refer to Boxed Warning section of the package insert for Symbyax. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants ( 5.1 ). Monitor for worsening and emergence of suicidal thoughts and behaviors ( 5.1 ). When using fluoxetine and olanzapine in combination, also refer to Boxed Warning section of the package insert for Symbyax.

Symbyax Sarafem

FDA label effective August 20, 2026 — read the full label on DailyMed

What fluoxetine is FDA approved for, and the trials behind it

Approved for major depressive disorder, acute and maintenance treatment in 1987, under application NDA 018936. Source: FDA Drugs@FDA.

The label does not state how many adults took part in the acute 5- and 6-week depression trials; enrollment figures are given only for the elderly studies (N=671), the pediatric trials (N=315), and the maintenance study (N=298).

The label describes 7 short-term and 2 long-term placebo-controlled trials for depression across adults and pediatric patients. The acute adult trials ran 5 and 6 weeks against placebo; two 6-week studies randomized 671 patients aged 60 and older. In a maintenance study, 298 patients who had responded to 12 weeks of open-label fluoxetine were randomized to continued fluoxetine or placebo, with a lower relapse rate on fluoxetine over the following 38 weeks.

One gap first. The label does not say how many adults took part in the short 5-week and 6-week depression trials.

It gives enrollment only for three groups. Those are the studies in older adults (671 people), the studies in children and teens (315 people), and the longer study (298 people).

The FDA approved fluoxetine in 1987. The approved use was major depression. That covers treating an episode and keeping it from coming back. The file number is NDA 018936. The source is Drugs@FDA, the FDA's own database.

The label describes 7 short and 2 long trials against a placebo for depression. They cover adults and young patients.

The short adult trials ran 5 and 6 weeks against a placebo. Two 6-week studies split 671 people aged 60 and older by chance.

In a longer study, 298 people had done well over 12 open weeks. They were split by chance. Fewer of those who stayed on the drug got ill again over the next 38 weeks.

Trials: 7 short-term and 2 long-term trials
Duration: 5 and 6 weeks (acute adult trials)
Compared against: Placebo

The efficacy of fluoxetine was studied in 5- and 6-week placebo-controlled 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. Fluoxetine was shown to be significantly more effective than placebo as measured by the Hamilton Depression Rating Scale (HAM-D).

Verbatim from the fluoxetine FDA label, Clinical Studies section, effective August 20, 2026 — read the full label on DailyMed.

Side effects of fluoxetine in the approval trials

Incidence among 1,728 patients on fluoxetine versus 975 on placebo in US placebo-controlled trials in major depressive disorder; the label pools other indications separately. It cautions that trial rates cannot be directly compared with rates for other drugs and may not reflect or predict the rates observed in practice.

Read the limits first. These numbers come from US depression trials against a placebo. 1,728 people took the drug and 975 took a placebo. The label pools the other approved uses on their own.

It warns that you cannot line these rates up against another drug’s rates. It warns that real life may not match or predict them either.

Nausea (21% vs 9% on placebo)
Insomnia (16% vs 9%)
Nervousness (14% vs 9%)
Somnolence (13% vs 6%)
Anxiety (12% vs 7%)
Diarrhea (12% vs 8%)
Anorexia (11% vs 2%)
Dry mouth (10% vs 7%)
Tremor (10% vs 3%)
Asthenia (9% vs 5%)
Sweating (8% vs 3%)
Dyspepsia (7% vs 5%)

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, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido decreased, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawn

From the fluoxetine FDA label, Adverse Reactions section, effective August 20, 2026 — DailyMed.

More from the fluoxetine label: drug abuse and dependence

Dependence not systematically studied
Fluoxetine has not been systematically studied in animals or humans for abuse, tolerance, or physical dependence. Premarketing experience showed no withdrawal syndrome or drug-seeking behavior, but the label notes these observations were not systematic and advises evaluating patients for a history of drug abuse.
FDA label, Drug Abuse and Dependence section.
Discontinuation adverse reactions
Reactions reported on stopping, particularly abruptly, include dysphoric mood, irritability, dizziness, sensory disturbances such as electric shock sensations, insomnia, and hypomania; gradual dose reduction is recommended whenever possible. The label adds that fluoxetine and norfluoxetine levels fall gradually after stopping, which may minimize the risk of discontinuation symptoms.
FDA label, Warnings and Precautions section.

How many Americans take fluoxetine

Survey-based federal estimates, published with a lag of about two years. They count prescriptions filled, not outcomes.

These are federal survey numbers. They come out about two years late. They count prescriptions filled. They do not tell you if the drug helped.

29,517,276
prescriptions in the United States (2024), refills included: 6,177,252
people filling them (2024), ± 896,149 (95%)

From 2014 to 2024 the estimate moved up 24%, but that is within the survey’s margin of error, so we do not call it a rise or a fall. Whatever you decide about fluoxetine, you are deciding alongside about 6,177,252 other people in 2024.

Prescriptions by year: 2014 23,867,189 · 2015 28,311,454 · 2016 23,729,287 · 2017 21,913,276 · 2018 25,619,277 · 2019 27,110,302 · 2020 23,403,050 · 2021 22,686,839 · 2022 24,014,263 · 2023 27,518,944 · 2024 29,517,276.

Prescriptions are not clearly up or down since 2014. About 6.2 million people in the United States took it in 2024.

Correction (29 September 2026). An earlier version of this section took its numbers from ClinCalc DrugStats, a third-party site that republishes this survey; we now compute them from AHRQ’s public-use files ourselves. It said prescriptions were up 24% since 2014; that change is within the survey’s margin of error, so we no longer state a direction.

Source: AHRQ Medical Expenditure Panel Survey (MEPS), Prescribed Medicines public-use files, 2014 (HC-168A) through 2024 (HC-254A), computed by veisund. People with at least one purchase where the Multum generic name (RXDRGNAM) equals the drug, weighted by the year’s person weight; purchases include refills. Standard errors by Taylor linearization on VARSTR/VARPSU. AHRQ’s reliability rule: a year is not shown when fewer than 60 survey respondents reported the drug or the relative standard error is over 50%. AHRQ cautions that its 2018 questionnaire redesign and the 2020–2022 pandemic years make year-to-year comparisons less certain.

What people report to the FDA about fluoxetine

Read this before the numbers.

Anyone can file an adverse event report — patients, doctors, manufacturers — and nobody verifies that the drug caused what was reported. There is no denominator: tens of millions of prescriptions generate reports at an unknowable rate, and reporting rises with news coverage, not necessarily with harm. Counts below are report volumes, not rates, and cannot be compared between drugs. The FDA itself says not to use this data to make medical decisions — we show it because you deserve to see what is in the public record, with its limits stated plainly.

Read this before the numbers.

Anyone can send a report to the FDA. Patients can. Doctors can. Drug makers can. Nobody checks that the drug caused what the report describes.

There is also no bottom number. Tens of millions of prescriptions turn into reports at a rate nobody knows. Reports go up when a drug is in the news, and that is not the same as more harm.

So these are counts of reports. They are not rates. You cannot use them to compare one drug with another. The FDA itself says not to use this data to make medical choices.

We show it because it is on the public record, and you should get to see it with its limits named.

131,850
reports mentioning fluoxetine, all time: 94,043
filed as serious (a report-level flag covering every drug and outcome in the report) filed as serious. That flag covers the whole report, and one report can name more than one drug and more than one outcome.

Most-reported reactions

Drug ineffective8,385
Nausea7,751
Fatigue7,713
Headache6,586
Depression6,136
Anxiety5,974
Dizziness5,412
Diarrhoea5,372
Off label use5,201
Pain5,185

“Drug ineffective” ranking this high is worth noticing: a report of not being helped counts as an adverse event too, and people file them in large numbers.

It is worth noticing how high “drug ineffective” ranks. A report that the drug did not help counts as an adverse event too. People file a lot of them.

Source: FDA Adverse Event Reporting System (FAERS), via openFDA, openFDA dataset refreshed 2026-07-30 (the refresh date of the query endpoint, not the date reports run through).

Drug interactions listed on the fluoxetine label

The FDA label’s interactions section, verbatim. A pharmacist checking your actual medication list beats any published list — including this one.

Below is the part of the FDA label that lists other drugs. It is copied word for word.

No list on the web can see what else you take. A pharmacist can. Ask one to check your full list.

Read the label’s interactions section

7 DRUG INTERACTIONS As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility. Monoamine Oxidase Inhibitors (MAOIs): ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( 7.7 ) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued ( 5.2 , 7.7 ) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs ( 7.2 ) Benzodiazepines: Diazepam – increased t½, alprazolam - further psychomotor performance decrement due to increased levels ( 7.7 ) Antipsychotics: Potential for elevation of haloperidol and clozapine levels ( 7.7 ) Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) Serotonergic Drugs: ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs that Interfere with Hemostasis (e.g. NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding ( 7.4 ) Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations ( 7.6 , 7.7 ) Olanzapine: When used in combination with fluoxetine, also refer to the Drug Interactions section of the package insert for Symbyax ( 7.7 ) Drugs that Prolong the QT Interval: Do not use fluoxetine with thioridazine or pimozide. Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.7 , 7.8 )

7.1 Monoamine Oxidase Inhibitors (MAOI) [See Dosage and Administration (2.9 , 2.10) , Contraindications (4.1) , and Warnings and Precautions (5.2) ].

7.2 CNS Acting Drugs Caution is advised if the concomitant administration of fluoxetine and such drugs is required. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status [see Clinical Pharmacology (12.3) ] .

7.3 Other Serotonergic Drugs The concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) with fluoxetine increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of fluoxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2) ].

7.4 Drugs that Interfere with Hemostasis (e.g., NSAIDS, Aspirin, Warfarin) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SNRIs or SSRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when fluoxetine is initiated or discontinued [see Warnings and Precautions (5.7) ] .

7.5 Electroconvulsive Therapy (ECT) There are no clinical studies establishing the benefit of the combined use of ECT and fluoxetine. There have been rare reports of prolonged seizures in patients on fluoxetine receiving ECT treatment.

7.6 Potential for Other Drugs to affect Fluoxetine Drugs Tightly Bound to Plasma Proteins — Because fluoxetine is tightly bound to plasma proteins, adverse effects may result from displacement of protein-bound fluoxetine by other tightly-bound drugs [see Clinical Pharmacology (12.3) ] .

7.7 Potential for Fluoxetine to affect Other Drugs Pimozide — Concomitant use in patients taking pimozide is contraindicated. Pimozide can prolong the QT interval. Fluoxetine can increase the level of pimozide through inhibition of CYP2D6. Fluoxetine can also prolong the QT interval. Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QT prolongation. While a specific study with pimozide and fluoxetine has not been conducted, the potential for drug interactions or QT prolongation warrants restricting the concurrent use of pimozide and fluoxetine Thioridazine — Thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued, because of the risk of QT Prolongation [see Contraindications (4.2) , Warnings and Precautions (5.11) , and Drug Interactions (7.8)]. In a study of 19 healthy male subjects, which included 6 slow and 13 rapid hydroxylators of debrisoquin, a single 25 mg oral dose of thioridazine produced a 2.4-fold higher Cmax and a 4.5-fold higher AUC for thioridazine in the slow hydroxylators compared with the rapid hydroxylators. The rate of debrisoquin hydroxylation is felt to depend on the level of CYP2D6 isozyme activity. Thus, this study suggests that drugs which inhibit CYP2D6, such as certain SSRIs, including fluoxetine, will produce elevated plasma levels of thioridazine. Thioridazine administration produces a dose-related prolongation of the QT interval, which is associated with serious ventricular arrhythmias, such as Torsades de Pointes-type arrhythmias, and sudden death. This risk is expected to increase with fluoxetine-induced inhibition of thioridazine metabolism. Drugs Metabolized by CYP2D6 — Fluoxetine inhibits the activity of CYP2D6, and may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index (see list below) should be initiated at the low end of the dose range if a patient is receiving fluoxetine concurrently or has taken it in the previous 5 weeks. Thus, his/her dosing requirements resemble those of poor metabolizers. If fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued [see Contraindications (4.2)]. Tricyclic Antidepressants (TCAs) — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ]. Benzodiazepines — The half-life of concurrently administered diazepam may be prolonged in some patients [see Clinical Pharmacology (12.3)] . Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels. Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment. Lithium — There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine. Cases of lithium toxicity and increased serotonergic effects have been reported. Lithium levels should be monitored when these drugs are administered concomitantly [see Warnings and Precautions (5.2)]. Drugs Tightly Bound to Plasma Proteins — Because fluoxetine is tightly bound to plasma proteins, the administration of fluoxetine to a patient taking another drug that is tightly bound to protein (e.g., Coumadin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect [see Clinical Pharmacology (12.3)]. Drugs Metabolized by CYP3A4 — In an in vivo interaction study involving coadministration of fluoxetine with single doses of terfenadine (a CYP3A4 substrate), no increase in plasma terfenadine concentrations occurred with concomitant fluoxetine. Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam. These data indicate that fluoxetine’s extent of inhibition of CYP3A4 activity is not likely to be of clinical significance. Olanzapine — Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. When using fluoxetine and olanzapine and in combination, also refer to the Drug Interactions section of the package insert for Symbyax.

7.8 Drugs that Prolong the QT Interval Do not use fluoxetine in combination with thioridazine or pimozide. Use fluoxetine with caution in combination with other drugs that cause QT prolongation. These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). Fluoxetine is primarily metabolized by CYP2D6. Concomitant treatment with CYP2D6 inhibitors can increase the concentration of fluoxetine. Concomitant use of other highly protein-bound drugs can increase the concentration of fluoxetine [see Contraindications (4.2) , Warnings and Precautions (5.11) , Drug Interactions (7.7) , and Clinical Pharmacology (12.3) ].

FDA label for fluoxetine, effective August 20, 2026 — DailyMed.

Label history: when this label changes, it is recorded in What changed.

Who pays for fluoxetine

Two claims datasets and one survey, covering different populations with different instruments — they cannot be reconciled by arithmetic, and where their sum crowds the all-payer estimate, that is a finding about the estimates rather than a percentage.

Medicare Part D · claims · 2024Medicaid · claims floor · 2024All-payer · survey · 2024Commercially insured adults · not publishedChildren · no per-drug data

Medicare Part D: Read the under-65 group correctly before the numbers: Medicare before 65 means the disabled and dual-eligible population — among the sickest, highest-need people in the program — and reading their utilization as typical adult use would be a category error. The beneficiary total sums brand-level rows, so treat it as an upper bound on distinct people. 1,487,371 beneficiaries filled 7,496,788 claims in 2024 — 1,146,172 aged 65 and over, and 341,199 under 65.
Medicaid: At least 6,359,320 prescriptions in 2024 — a floor, because 143 of 1,157 national data rows are suppressed for privacy and contribute zero. Medicaid covers more children than any insurer in the country and publishes no age split — how much of this number is pediatric use is not knowable from public data.
All payers (survey estimate): A survey estimate from 351 respondents, which we computed from AHRQ’s MEPS 2024 Prescribed Medicines file (people with at least one purchase, weighted; purchases include refills), puts the whole country at 29,517,276 purchases and 6,177,252 people in 2024. Subtracting the public programs from it would produce a number for everyone else — and we do not print that number, because subtracting a survey from claims counts manufactures precision that does not exist.
The population nobody counts: The commercially insured working-age adult — statistically, the likeliest person to be reading this page — is the one population with no public per-drug count anywhere. Private claims data exists and is sold, but nothing a patient can check is published. For children the record is thinner still: no public source counts pediatric use of fluoxetine specifically; the closest the public record comes is condition-level treatment rates for children, which we have traced for one condition in how childhood ADHD got counted.

Sources: Medicare Part D Prescribers — by Geography and Drug, data.cms.gov, National rows, data year 2024 (published with ~17-month lag). Medicaid State Drug Utilization Data 2024, data.medicaid.gov, national aggregate rows. Retrieved 2026-09-01.

Who has been paying for fluoxetine, 2019–2024

Medicare Part D

Claims, all ages — the one payer with a public per-drug series.

20192024

6,885,834 → 7,496,788 claims

Medicare under 65

Beneficiaries, not ordinary working-age adults: Medicare before 65 means the disabled and dual-eligible population. A gap is a suppressed split, not zero.

20192024

366,772 → 341,199 beneficiaries

Medicaid

A floor each year — small-cell rows are suppressed federally and excluded from the sum.

20192024

5,838,131 → 6,359,320 prescriptions (floor)

Commercially insured adults

No public dataset publishes per-drug commercial claims for any year — the absence is the finding, and it is rendered, not interpolated. The population this library most wants to inform is the one with no public per-drug series, in any year — insurers and PBMs hold that data privately. What the federal surveys do measure — how many adults take these medications at all — is on the adult-usage page.

Sources: Medicare Part D Prescribers by Geography and Drug (data.cms.gov, national rows, per data year); Medicaid State Drug Utilization Data (data.medicaid.gov, national rows). Claims, fills and beneficiaries are different units — compare each series only with itself.

The fluoxetine approval, step by step

Step 1
What the approval was actually based on
Which studies did the FDA rely on, how long did they run, and who was in them?
Efficacy for PROZAC was established for the: Acute and maintenance treatment of Major Depressive Disorder in adults, and children and adolescents (8 to 18 years) in 7 short-term and 2 long-term, placebo-controlled trials [see Clinical Studies 14.1].
FDA-approved labelling, 14 CLINICAL STUDIES — read the label on DailyMed
Our reading
A stronger package than most: nine trials, two of them long-term, and the FDA gave it priority review. Fluoxetine is the drug in this class with the most approval-era evidence behind it, which is worth knowing if you are comparing options rather than comparing a drug against nothing.
Step 2
The approval
When was it approved, under what application, and by whose review?
Approved
December 29, 1987
Application
NDA018936
Review
PRIORITY
Original sponsor
Eli Lilly and Company
Holds it now
Eli Lilly and Company
Label submissions since
89
Source: openFDA Drugs@FDA, original application ORIG-1
Step 3
What was added after it was on the market
Which warnings arrived only after millions of people were already taking it?
- PRAC recommendations on signals adopted at the 13-16 May 2019 PRAC meeting, section 1.3: SNRIs and SSRIs - persistent…
  32 years after approval
  On 16 May 2019 the EU drug regulator's safety committee ordered every manufacturer of citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, desvenlafaxine, and milnacipran to add this warning within two months: "There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRI." The patient leaflet wording is "In some cases, these symptoms have continued after stopping treatment." This is a regulator acting on case reports and pharmacovigilance data, not a prevalence study — how often it happens is still unknown, and that uncertainty cuts both ways.
  Worth asking
  European regulators require a label warning that sexual side effects can persist after stopping an SSRI or SNRI — how would you and I tell that apart from the depression itself if it happened to me?
  PRAC recommendations on signals adopted at the 13-16 May 2019 PRAC meeting, section 1.3: SNRIs and SSRIs - persistent sexual dysfunction after drug withdrawal (EMA/PRAC/265212/2019). — Pharmacovigilance Risk Assessment Committee (PRAC), European Medicines Agency. Rapporteur: Gross-Martirosyan L. (2019)
- The antidepressant suicidality warning has an age ceiling most people never hear about
  Antidepressants carry a boxed warning about suicidal thoughts and behaviour in children, adolescents and young adults. It came from pooling 24 short-term placebo-controlled trials of nine antidepressants in more than 4,400 young patients: suicidality was reported in about 4% on drug against 2% on placebo. There were no completed suicides in those trials.
  The part that usually gets lost is the age boundary, which is in the label itself. The studies did not show an increased risk above age 24, and in patients 65 and older the risk went in the other direction — it was reduced. The warning is real and it is specific, not a blanket statement about everyone who takes one.
  Worth asking
  Given my age, which side of that line am I on, what specifically should I or the people around me watch for in the first two months, and who do I call if it happens.
  PROZAC (fluoxetine) prescribing information — Boxed Warning: Suicidal Thoughts and Behaviors — U.S. Food and Drug Administration (approved labelling)
Step 4
What independent research has found since
What has been learned by people who were not selling it?
- Cochrane 2021: newer antidepressants cut depression in children and teens by a small and unimportant amount
  34 years after approval
  The Cochrane review of newer antidepressants for depression in children and teenagers, and the one that disagreed with the Lancet reviews on fluoxetine.
  Significant findings
  Hetrick and colleagues pooled 26 randomised trials of newer antidepressants in 6 to 18 year olds with major depression, searched to March 2020. Older drugs (tricyclics and MAO inhibitors) were not included. On the clinician-rated CDRS-R scale (17 to 113 points), most drugs gave a "small and unimportant" drop in symptoms compared with placebo. Fluoxetine: 2.84 points (95% CI 1.56 to 4.12), moderate certainty. Sertraline (3.51), escitalopram (2.62), duloxetine (2.70) and paroxetine (1.43) were in the same range. Differences between most of the drugs were also "small and unimportant".
  No trial reported the two primary outcomes, diagnosis by clinical interview and suicide. Suicide-related outcomes were uncommon and the estimates wide. For fluoxetine the odds ratio was 1.27 (0.87 to 1.86): low certainty that it may at least slightly raise those odds. Most trials excluded young people at risk of suicide, so the review cannot speak for them.
  The other direction
  The review does not say these drugs are useless. Averages hide people who respond more. The authors say sertraline, escitalopram, duloxetine and fluoxetine "could be considered as a first option", with close monitoring of treatment effects and suicide-related outcomes, and that therapy, particularly CBT, remains important. They also say methodological shortcomings in the trials make the findings hard to interpret.
  Why it matters now
  Because it left out tricyclics, this review did not include a small 2006 trial of fluoxetine against nortriptyline. A 2026 re-analysis (Lyus and colleagues, in this library) found that trial is what made fluoxetine look larger in the two Lancet reviews, including Cipriani 2016 (also in this library). Without it, all three land close to this review's estimate.
  What this does not show
  It does not tell any family whether to start, keep or stop a medicine. If your child takes fluoxetine, this is a question for their prescriber, not a reason to stop.
  Worth asking
  What size of change should we expect, how will we measure it, and how will suicide-related thinking be watched?
  New generation antidepressants for depression in children and adolescents: a network meta-analysis — Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, Cox GR, Merry SN, Meader N (2021)
- SSRIs raise the odds of a stomach bleed by about two thirds; with an NSAID as well, about fourfold
  27 years after approval
  Serotonin is needed for platelets to clump. Antidepressants that block its reuptake reduce the platelet store, and this meta-analysis measured what that does to the risk of bleeding from the stomach, alone and with an anti-inflammatory painkiller.
  Significant findings
  Anglin and colleagues (American Journal of Gastroenterology, 2014) searched to April 2013 and included "Fifteen case-control studies (including 393,268 participants) and four cohort studies". "There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50)."
  The absolute numbers: "The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881." And the combination: "The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42)."
  The authors' conclusion: "SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients."
  Worth asking
  The number needed to harm is the one to hold on to: on an SSRI alone, one extra bleed for roughly every three thousand low-risk people, or every nine hundred high-risk. The combination with regular NSAID use is where the risk stops being modest. If you take an SSRI and buy ibuprofen or naproxen for pain, the question for the pharmacist is what the alternative is, and whether you count as high risk (prior ulcer, older age, anticoagulants, steroids).
  Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis — Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI (2014)
- Serotonin toxicity is diagnosed by seven signs, and the rules were built from 2,222 overdoses
  16 years after approval
  Half the labels in this wave warn about serotonin syndrome. This is the paper that defined how a clinician recognises it.
  Significant findings
  Dunkley and colleagues (QJM, 2003) studied "all patients admitted to the Hunter Area Toxicology Service (HATS) following an overdose of a serotonergic drug from January 1987 to November 2002 (n = 2222)." A learning set of 473 SSRI-alone overdoses was used to find which clinical features predicted a toxicologist's diagnosis of serotonin toxicity.
  "Numerous clinical features were associated with serotonin toxicity, but only clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were needed for accurate prediction of serotonin toxicity as diagnosed by a clinical toxicologist. Although the learning dataset did not include patients with life-threatening serotonin toxicity, hypertonicity and maximum temperature > 38 degrees C were universal in such patients; these features were therefore added."
  The result: "These new criteria were simpler, more sensitive (84% vs. 75%) and more specific (97% vs. 96%) than Sternbach's criteria."
  Worth asking
  The everyday value of this paper is the symptom list in plain words: muscle twitching or jerking that a doctor can trigger by flexing your ankle, restlessness, sweating, tremor, overactive reflexes, and in severe cases stiffness and fever. Nausea or a headache after starting a second serotonergic drug is not on the list. If you have been told to watch for serotonin syndrome, these seven signs are what to watch for, and they are a reason to seek care the same day.
  The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity — Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM (2003)
- Fluoxetine versus other types of pharmacotherapy for depression
  26 years after approval
  Pooling 171 randomised trials with 24,868 people, fluoxetine was as effective as older tricyclic antidepressants and better tolerated, though slightly less effective than sertraline, mirtazapine, and venlafaxine.
  Worth asking
  Fluoxetine trailed a few alternatives slightly on effectiveness in this review - what made it the better fit for me over sertraline?
  Fluoxetine versus other types of pharmacotherapy for depression — Magni LR, et al. (2013)
- Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major…
  31 years after approval
  Across 522 randomised trials with 116,477 adults, fluoxetine beat placebo for major depression and was among the better-tolerated antidepressants, though other drugs ranked higher on effectiveness in head-to-head comparisons.
  Worth asking
  Fluoxetine ranked mid-pack for effect but high for tolerability in this huge comparison - which of those mattered more in choosing it for me?
  Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis — Cipriani A, et al. (2018)
- In children and teenagers, only one antidepressant clearly beat placebo
  29 years after approval
  Cipriani, Zhou and colleagues pooled every double-blind trial of antidepressants for major depression in under-18s. They searched regulator websites and trial registers too, to catch unpublished results.
  Significant findings
  34 trials, 5,260 young people, 14 drugs - and one drug that beat placebo. Fluoxetine's margin nearly touched zero.
  Tolerability separated the drugs more than benefit did. Imipramine, venlafaxine and duloxetine all caused more dropouts for side effects than placebo, imipramine at over five times the placebo rate.
  The caution runs both ways. Evidence quality was rated very low in most comparisons - small trials, mostly industry-funded, at high or unclear risk of bias.
  That makes the negative results about individual drugs almost as uncertain as the positive one. The honest reading is that the evidence here is thin, not that these drugs are known to fail.
  This covers acute treatment only, typically eight to twelve weeks. It says nothing about staying on them.
  Worth asking
  What did we try before this, what exactly are we measuring, and is therapy running alongside? Never stop or change a prescribed antidepressant on your own. Abrupt stops can be dangerous, and any change needs a prescriber-supervised taper.
  Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis — Cipriani A, et al. (2016)
- Withdrawal from these medications can take months, and NICE says so
  35 years after approval
  NICE guideline NG215 covers safe prescribing and managed withdrawal for five groups of medication: opioids, benzodiazepines, gabapentinoids, Z-drugs and antidepressants. It is the closest thing there is to an official answer on how coming off actually goes.
  It states that withdrawal can be difficult and may take several months or more, that symptoms vary widely in type and severity, that they affect both physical and mental health, and that they can be delayed in onset and can persist. Two recommendations are worth quoting to a prescriber. Do not stop a medicine abruptly except in exceptional medical circumstances. And taper using a slow, stepwise reduction proportionate to the current dose, so the decrements get smaller as the dose gets lower — not a fixed cut each time.
  That last detail is the one most commonly missed. Gabapentinoids are the exception in the guideline and are reduced by a fixed amount at each step.
  Worth asking
  Can we write the taper down, what size are the steps near the end, and how long do I hold at each step before the next reduction.
  Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults (NG215) — National Institute for Health and Care Excellence (2022)
- Maintenance or Discontinuation of Antidepressants in Primary Care
  34 years after approval
  Among 478 primary-care patients who felt well enough to stop long-term antidepressants (including fluoxetine 20 mg), 56% of those randomised to stop relapsed within a year versus 39% of those who stayed on their medication.
  Worth asking
  If I feel well and want to come off fluoxetine, what taper schedule and follow-up would you recommend given the relapse rates in this trial?
  Maintenance or Discontinuation of Antidepressants in Primary Care — Lewis G, et al. (2021)
- In 2019 the Royal College of Psychiatrists changed its position on withdrawal
  32 years after approval
  For years people reporting long, severe antidepressant withdrawal were told it lasted a week or two. In May 2019 the Royal College of Psychiatrists published a position statement conceding the point: while withdrawal symptoms are often mild and self-limiting, there is substantial variation, and for some patients symptoms last much longer and are more severe.
  It went further and asked for changes — that guidelines and patient information recognise the potential for severe and long-lasting withdrawal, that pharmacologically-informed tapering guidance be developed, that discontinuation be tapered at a rate the patient can tolerate over potentially several months, and that clinicians actively work to tell withdrawal apart from relapse.
  One thing it explicitly does not say, and it is worth being accurate about: the College states that from a clinical perspective antidepressant use is not associated with dependence in the addiction sense. Withdrawal and dependence are not the same claim.
  Worth asking
  If I feel bad three weeks after a dose reduction, how will we decide whether that is withdrawal or my depression returning, and what do we do differently in each case.
  Position statement on antidepressants and depression (PS04/19) — Royal College of Psychiatrists (2019)
- One flawed 2006 trial roughly doubled fluoxetine's apparent benefit for childhood depression, a 2026 re-analysis finds
  39 years after approval
  Why two influential reviews and a Cochrane review disagreed about fluoxetine for depression in children and teenagers, traced to one small trial.
  Significant findings
  Fluoxetine (sold as Prozac) is the antidepressant most guidelines name first for depression in under 18s. That rests mainly on two network meta-analyses in Lancet journals, Cipriani 2016 (in this library) and Zhou 2020. Both put fluoxetine ahead of placebo by a standardised effect of 0.51 (95% credible intervals 0.03 to 0.99, and 0.18 to 0.84), with confidence rated "very low". The 2021 Cochrane review (Hetrick, in this library) found a gap of 2.84 points on a 17 to 113 point rating scale, about 0.20 in the same units, and called it small and unimportant.
  Lyus, Naudet, van Valkenhoef and Plöderl re-ran both Lancet analyses on their published data. Each carried an unexplained clash between direct and indirect evidence in the fluoxetine, nortriptyline and placebo loop. They traced it to one trial: Attari A, Moghaddam FY, Hasanzadeh A, et al., "Comparison of efficacy of fluoxetine with nortriptyline in treatment of major depression in children and adolescents: a double-blind study", Journal of Research in Medical Sciences 2006;11:24-30. Cochrane had left it out only because it excluded older tricyclic drugs such as nortriptyline.
  Without that trial, fluoxetine's edge fell to 0.26 (0.09 to 0.43) in the Cipriani data and 0.29 (0.07 to 0.50) in the Zhou data, close to Cochrane, and the clash went away. In the authors' words: "Discrepancies between the three NMAs were explained by the indirect influence of a single small trial with extreme and unreliable results."
  The trial
  Forty children and teenagers at one site in Iran, 20 on each drug, no placebo arm. It reported an effect of about 4.2 for fluoxetine; the next largest in the Cipriani dataset was 0.9. Scored from end-of-trial scores instead of changes, the effect was 0.93. To produce the reported figure, before and after scores would have to correlate almost perfectly (r above 0.97): score changes were nearly uniform within each arm. Ethics approval is not mentioned, dropouts were replaced with new cases, and one p-value does not match its data. The authors did not answer two emails. The journal editor forwarded the concerns; the publisher, MedKnow, had not replied when the paper was written. Lancet Psychiatry peer reviewed an earlier version, rejected it and considered the matter closed.
  The other direction
  Even without the trial, all three analyses still put fluoxetine ahead of placebo beyond chance. The dispute is about size, not existence. The re-analysis was exploratory, had no preregistered protocol, could not exactly reproduce every original estimate, and rebuilt the Cochrane dataset because the full original was not kept. One author works for Cochrane, which the paper says had no role. Andrea Cipriani, a co-author of the 2016 and 2020 reviews, told Nature he agrees the 2006 data are problematic. He said the teams discussed it at the time but had no protocol then for excluding untrustworthy trials, and that both reviews noted concerns and rated confidence in the fluoxetine finding "very low". MedKnow told Nature it has asked the journal's editors to look into it.
  What this does not show
  The authors do not tell anyone to stop fluoxetine. They say clinicians and patients should know its actual effect and that guidelines should be updated. If your child takes fluoxetine, this is a question for their prescriber, not a reason to stop.
  Worth asking
  Given the smaller benefit these reviews now agree on, what do we expect fluoxetine to do for my child, and how will we know if it is working?
  A Re-Appraisal of Three Network Meta-Analyses to Explain the Discrepancy in Findings for the Efficacy of Fluoxetine for the Treatment of Depression in Children and Adolescents — Lyus R, Naudet F, van Valkenhoef G, Plöderl M (2026)
- Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for…
  17 years after approval
  In 439 adolescents with depression, 71% responded to fluoxetine plus CBT, 61% to fluoxetine alone, 43% to CBT alone, and 35% to placebo after 12 weeks; combining CBT with fluoxetine also gave the biggest drop in suicidal thinking.
  Worth asking
  This landmark trial found fluoxetine works best for teens when paired with CBT - can we add talk therapy alongside the prescription?
  Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial — March J, et al. (TADS Team) (2004)
- Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.
  22 years after approval
  When sexual function is actually asked about with a questionnaire rather than waited for as a spontaneous complaint, treatment-emergent sexual dysfunction ranged from 25.8% to 80.3% of patients across antidepressants, all significantly above placebo. In descending order of impact the drugs were sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine. Agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone showed no significant difference from placebo.
  Worth asking
  Where does the antidepressant I'm on sit on the sexual side-effect ranking, and is there a drug with a lower rate that would still treat my condition?
  Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. — Serretti A, Chiesa A. (2009)
Step 5
What still is not known
Which questions you might reasonably have has nobody answered yet?
- The boxed warning about suicidal thoughts in under-25s arrived in 2005, eighteen years after approval. What changed — the drug, or what was measured?
- What does "long-term" mean in the two long-term trials, and does it match how long you have been taking it?

The fluoxetine legal and safety record

Settled and adjudicated matters only, from primary sources — including the litigation that was decided for the manufacturer, and the cases this drug is verifiably not part of.

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Side-effect rates from fluoxetine's own label — drug vs placebo, with every caveat the label attaches
How long every medication's approval trials ran — fluoxetine beside every other drug in the library, from the same FDA record
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Already on it? The 10-question annual review — including the honest case for staying
How long every drug here was tested before approval — one chart, all medications

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fluoxetine (Prozac)

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what the research says, in both directions

children and teenagers: why three big reviews disagreed, and what a 2026 re-analysis found

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