Medication approval journey
sertraline (Zoloft)
Approved for Major depressive disorder in adults
page first published · last updated
Also answers to “the blue fish” — its codename in our videos and posts. The full codebook
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 sertraline 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 sertraline warnings mean
label facts below are read from the sertraline hydrochloride FDA label on DailyMed, set id 1afd0016-d0ee-4e25-a1a4-b66f228e2f9c, version 3, effective august 27, 2026. the section numbers in brackets are the label’s own. every source is linked at the end of this section. last checked 2026-10-05.
sertraline was approved for depression in 1991, and about 10.2 million americans filled a prescription for it in 2024 [meps]. its label carries one boxed warning and ten further warnings. this section says what each one 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.
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, and that everyone on the drug should be watched for worsening, especially in the first months and after a dose change [label, boxed warning and 5.1].
the number behind it comes from pooled placebo-controlled trials of antidepressants covering about 77,000 adults and more than 4,400 children. the label states 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]. no suicides occurred in any of the pediatric studies, and the adult studies had too few to conclude anything about suicide itself.
so the warning is specific, not blanket. it describes thoughts and behaviors, not deaths; it describes the first months, not years (the label says the longer-term risk beyond four months is unknown); and above age 24 the pooled trials did not show an increase at all [label 5.1; age-ceiling row]. for someone under 25 the question is who is watching and what they are watching for. for someone over 65 the number in the label runs the other way.
the ten other warnings, in plain words
the label’s warnings and precautions section runs from 5.2 to 5.11. none is boxed. each is a mechanism the fda considers real enough to print; how often it hurts anyone is a separate question, and where a study has measured that, it is in the research section below.
- serotonin syndrome [5.2]: too much serotonin signalling, which can be life-threatening. the risk rises with other serotonergic drugs (the label names triptans, tricyclics, fentanyl, lithium, tramadol, buspirone, amphetamines and st john’s wort, among others) and the combination with an maoi is contraindicated. it can also happen on sertraline alone. the signs are agitation or confusion, racing heart, sweating, fever, tremor, muscle jerking and overactive reflexes.
- bleeding [5.3]: drugs that block serotonin reuptake make platelets less effective. the label says aspirin, nsaids such as ibuprofen and naproxen, and blood thinners add to the risk, and that ssri use in the month before delivery has been linked to a less than twofold rise in postpartum bleeding.
- activation of mania or hypomania [5.4]: in someone with bipolar disorder an antidepressant can tip a depressive episode into a manic one. people with bipolar disorder were generally excluded from the trials; mania or hypomania was still reported in 0.4% of patients on sertraline. the label tells prescribers to screen for a personal or family history first.
- discontinuation syndrome [5.5]: stopping, particularly abruptly, can bring nausea, sweating, low mood, irritability, dizziness, electric-shock sensations, tremor, anxiety, confusion, headache, insomnia, tinnitus and, rarely, seizures. the label recommends gradual reduction rather than abrupt cessation whenever possible.
- seizures [5.6]: people with a seizure history were excluded from the studies, so the label simply says to prescribe with caution.
- angle-closure glaucoma [5.7]: the pupil dilation many antidepressants cause can trigger an attack in an eye with narrow drainage angles that has not been treated.
- low sodium [5.8]: hyponatremia, with cases below 110 mmol/l reported. early signs are headache, poor concentration, confusion, weakness and unsteadiness; severe cases have included seizures and death. the label says older people, people on diuretics and anyone dehydrated may be at greater risk.
- false-positive drug screens [5.9]: sertraline can trigger a false positive on urine immunoassay tests for benzodiazepines, for several days after stopping. a confirmatory lab test tells them apart.
- qtc prolongation [5.10]: a heart-rhythm interval that lengthened with blood level in a thorough qt study of 54 healthy adults, and post-marketing reports of qtc prolongation and torsade de pointes, most confounded by other risk factors. the label says caution in people with existing risk factors, not avoidance.
- sexual dysfunction [5.11]: delayed or absent ejaculation, erectile dysfunction and reduced desire in men; reduced desire and delayed or absent orgasm in women. the label tells prescribers to ask before starting and to ask again during treatment, because people do not volunteer it.
what the trials measured, and for how long
the depression approval rested on two placebo-controlled trials in adult outpatients aged 18 to 65. study mdd-1 ran 8 weeks and compared sertraline (126 people) with amitriptyline (123) and placebo (130). study mdd-2 ran 6 weeks and compared fixed doses of 50, 100 and 200 mg (82, 75 and 56 people) with placebo (76); the label says that study was not readily interpretable for whether a higher dose works better [label 14.1]. the outcome was a depression rating scale score, not whether people recovered or returned to work.
a third study took 295 people who had responded to 8 weeks of open-label sertraline and randomised them to keep taking it or switch to placebo for 44 weeks. relapse was 8% on sertraline and 39% on placebo [label 14.1]. that design cannot separate relapse from withdrawal effects, because the placebo group had just stopped the drug; the open-questions step further down this page says so.
the arithmetic that matters: the longest controlled measurement behind the approval was 44 weeks, the efficacy trials were 6 and 8 weeks, and the trials excluded people with bipolar disorder, seizures and anyone under 18 or over 65. the people taking it today number about 10.2 million a year in the united states. how long people stay on it is on the longest-trial page linked below.
the most common side effects, with the label’s numbers
the label pools 3,066 people on sertraline against 2,293 on placebo from 8- to 12-week trials across all six approved conditions, and reports the reactions that were at least 5% and twice placebo: nausea 26% vs 12%, diarrhea or loose stools 20% vs 10%, insomnia 20% vs 13%, dry mouth 14% vs 9%, fatigue 12% vs 8%, dizziness 12% vs 8%, sleepiness 11% vs 6%, tremor 9% vs 2%, indigestion 8% vs 4%, sweating 7% vs 3%, decreased appetite 7% vs 2% [label 6.1, table 3]. the full list is in the side-effects section lower on this page.
sexual side effects have their own table. in men (1,316 on sertraline, 973 on placebo): ejaculation failure 8% vs 1%, decreased libido 7% vs 2%, erectile dysfunction 4% vs 1%. in women (1,750 vs 1,320): decreased libido 4% vs 2% [label 6.1, table 4]. the label adds, in its own words, that these estimates "may underestimate their actual incidence" because patients and clinicians are reluctant to raise them. the research section below has what happens when someone asks with a questionnaire.
two cautions the label attaches to all of these: rates from trials cannot be compared directly with rates for other drugs, and they may not match what happens in ordinary practice, where people are older, sicker and on more medicines than trial volunteers.
what independent research says, in both directions
in favour. the largest comparison of antidepressants ever done, 522 randomised trials with 116,477 adults, found every antidepressant beat placebo for acute depression and placed sertraline among the drugs with the better combination of effectiveness and tolerability in head-to-head trials [cipriani-2018]. the same group’s earlier analysis of 117 trials and 25,928 adults put sertraline among the four most effective of 12 newer antidepressants, sharing the best tolerability with escitalopram, and suggested it as a sensible first choice [cipriani-2009]. the cochrane review pooling 59 trials and about 10,000 people found a small effectiveness edge over fluoxetine and better tolerability than several older drugs, at the cost of more diarrhoea than its comparators [cochrane-2010]. on staying versus stopping, a 2021 trial of 478 primary-care patients who felt well enough to stop their long-term antidepressant (sertraline 100 mg among them) found 56% of those randomised to stop relapsed within a year against 39% of those who stayed on [antler-2021].
against, or at least smaller than the badge suggests. the one large independent trial of sertraline in ordinary primary care, 653 uk patients, found no clear reduction in depressive symptoms at 6 weeks compared with placebo; anxiety symptoms did improve, and people on it were more likely to say their mental health had improved [panda-2019]. when sexual function is measured with a questionnaire instead of waited for as a complaint, treatment-emergent sexual dysfunction across antidepressants ran from 25.8% to 80.3%, and sertraline sat at the top of the ranking [serretti-2009]. in may 2019 the european regulator’s safety committee ordered every maker of sertraline and nine related drugs to add a warning that sexual dysfunction can continue after the drug is stopped; how often is unknown, and that uncertainty cuts both ways [prac-2019]. a post hoc analysis of 276 people found each previous antidepressant course cut the odds of responding to sertraline by about a fifth (odds ratio 0.81), with the caveats that it was not the question the trial was built to answer and that harder-to-treat depression could produce the same numbers [amsterdam-2009].
where the warnings have been measured. the bleeding warning is real but modest: a meta-analysis of 15 case-control and 4 cohort studies put the odds of an upper-gi bleed on an ssri at 1.66 times, which is one extra bleed for roughly every 3,177 low-risk people or 881 high-risk people; with an nsaid as well the odds rose to 4.25 times [anglin-2014]. the triptan interaction, listed on every ssri label, produced two definite cases of serotonin syndrome in 30,928 person-years of combined use in one health system, about 0.6 per 10,000 years [orlova-2018]. serotonin toxicity itself has a seven-sign definition built from 2,222 overdoses: inducible muscle jerking, agitation, sweating, tremor, overactive reflexes, and in severe cases rigidity and fever [hunter-2003]. on withdrawal, the uk guideline nice ng215 says coming off can take months, that medicines should not be stopped abruptly except in exceptional circumstances, and that tapers should get smaller as the dose gets lower [nice-2022]; the royal college of psychiatrists conceded in 2019 that for some people withdrawal is severe and long-lasting, while stating that antidepressant use is not dependence in the addiction sense [rcpsych-2019].
questions to ask your prescriber about sertraline
each one comes from a warning or a study above. they are questions, not instructions; the answers depend on a history nobody here has.
- given my age, which side of the boxed warning’s line am i on, and what exactly should i or the people around me watch for in the first two months?
- the primary-care trial found sertraline helped anxiety before it helped low mood. how many weeks do we wait before judging whether it is working for me?
- i take ibuprofen or naproxen for pain, or a blood thinner. does the bleeding warning change what i should use instead?
- the label says to ask about sexual function before starting and during treatment. can we do that now, and how would we tell a drug effect from the depression itself?
- if i ever want to stop, what would the taper look like, how small are the steps near the end, and how would we tell withdrawal from relapse?
- do i have any of the risk factors the qtc warning refers to, and does anything else i take lengthen the interval?
- how many antidepressant courses have i had, and does that number change what you would try?
questions people ask
- does sertraline have a black box warning?
- yes. the fda label carries one boxed warning, on suicidal thoughts and behaviors in children, adolescents and young adults in short-term studies. the label’s pooled numbers per 1,000 people treated are 14 additional cases under age 18, 5 additional at 18 to 24, 1 fewer at 25 to 64 and 6 fewer at 65 and over. no suicides occurred in the pediatric studies.
- what are the most common sertraline side effects?
- from the label’s pooled trials of 3,066 people on sertraline and 2,293 on placebo: nausea 26% vs 12%, diarrhea 20% vs 10%, insomnia 20% vs 13%, dry mouth 14% vs 9%, fatigue and dizziness 12% vs 8% each, sleepiness 11% vs 6%, tremor 9% vs 2%. in men, ejaculation failure was 8% vs 1% and decreased libido 7% vs 2%; in women, decreased libido was 4% vs 2%.
- does sertraline cause sexual side effects, and do they go away?
- the label has a dedicated warning (5.11) and says its own trial figures may underestimate the true rate. when researchers asked with a questionnaire, sexual dysfunction across antidepressants ranged from 25.8% to 80.3%, with sertraline at the top of the ranking. in 2019 the european regulator required a label warning that sexual dysfunction can persist after stopping; how often that happens has not been measured.
- what happens if you stop sertraline suddenly?
- the label lists a discontinuation syndrome after abrupt stopping: nausea, sweating, low mood, irritability, dizziness, electric-shock sensations, insomnia and, rarely, seizures, and recommends gradual reduction whenever possible. 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, not something to decide from a web page.
- does sertraline affect the heart rhythm (qt prolongation)?
- the label’s warning 5.10 reports post-marketing cases of qtc prolongation and torsade de pointes, most confounded by other risk factors, and a thorough qt study in 54 healthy adults in which the interval lengthened with blood level. the label calls for caution in people with risk factors for qtc prolongation; it does not say to avoid the drug.
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.
- sertraline hydrochloride prescribing information, fda label on dailymed (set id 1afd0016-d0ee-4e25-a1a4-b66f228e2f9c, version 3, effective august 27, 2026): boxed warning; sections 5.1 to 5.11, 6.1 tables 3 and 4, 14.1
- ahrq medical expenditure panel survey, prescribed medicines public-use file 2024 (hc-254a): people with at least one sertraline purchase, weighted; computed by veisund, method on the usage section of this page
- the antidepressant suicidality warning has an age ceiling most people never hear about (fda boxed warning, read off the label) (library row)
- cipriani a, et al. comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder. lancet 2018 (library row)
- cipriani a, et al. comparative efficacy and acceptability of 12 new-generation antidepressants. lancet 2009 (library row)
- cipriani a, et al. sertraline versus other antidepressive agents for depression. cochrane database of systematic reviews 2010 (library row)
- lewis g, et al. the clinical effectiveness of sertraline in primary care (panda). lancet psychiatry 2019 (library row)
- lewis g, et al. maintenance or discontinuation of antidepressants in primary care (antler). new england journal of medicine 2021 (library row)
- serretti a, chiesa a. treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. journal of clinical psychopharmacology 2009 (library row)
- european medicines agency, pharmacovigilance risk assessment committee. recommendations on signals, 13 to 16 may 2019, section 1.3: ssris and snris, persistent sexual dysfunction after drug withdrawal (library row)
- anglin r, et al. risk of upper gastrointestinal bleeding with ssris with or without concurrent nsaid use: a systematic review and meta-analysis. american journal of gastroenterology 2014 (library row)
- orlova y, rizzoli p, loder e. coprescription of triptans and ssri or snri antidepressants and serotonin syndrome. jama neurology 2018 (library row)
- dunkley ej, et al. the hunter serotonin toxicity criteria. qjm 2003 (library row)
- amsterdam jd, et al. tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder. neuropsychobiology 2009 (library row)
- national institute for health and care excellence. medicines associated with dependence or withdrawal symptoms (ng215), 2022 (library row)
- royal college of psychiatrists. position statement on antidepressants and depression (ps04/19), 2019 (library row)
How long the sertraline trials actually ran
We could not establish a longest trial length for sertraline. 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 trials behind the depression approval ran 6 and 8 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 and young adults. The label tells prescribers to watch every patient closely for this. It also tells them to watch for the illness getting worse.
The FDA’s own words follow, copied exactly.
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [See Warnings and Precautions (5.1) ]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients ( 5.1 ) • Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 )
FDA label effective August 27, 2026 — read the full label on DailyMed
What sertraline is FDA approved for, and the trials behind it
Approved for major depressive disorder in adults in 1991, under application NDA 019839. Source: FDA Drugs@FDA.
The label reports enrollment per treatment arm rather than an overall total, so no single participant count is quoted here; the depression trials are otherwise documented in full in the clinical studies section.
Two randomized, double-blind, placebo-controlled trials in adult outpatients aged 18 to 65 established efficacy for depression. Study MDD-1 ran 8 weeks and compared sertraline (N=126) with amitriptyline (N=123) and placebo (N=130); study MDD-2 ran 6 weeks and compared three fixed sertraline doses (N=82, N=75, N=56) with placebo (N=76). A third study randomized 295 responders to open-label sertraline to continued sertraline or placebo for 44 weeks, with relapse in 8% versus 39%. The label's clinical studies section separately covers the later OCD, panic disorder, PTSD, social anxiety disorder, and PMDD indications.
One gap first. The label gives the number of people in each trial group. It does not give one total. So there is no single number of people to report here. The depression trials are otherwise written up in full in the label.
The FDA approved sertraline in 1991. The approved use was major depression in adults. The file number is NDA 019839. The source is Drugs@FDA, the FDA's own database.
Two trials backed the approval. In both, people were sorted into groups by chance and nobody knew who got the drug (randomized, double-blind). Everyone was an adult aged 18 to 65.
The first ran 8 weeks. It gave the drug to 126 people. It gave an older drug called amitriptyline to 123 people. It gave a placebo to 130 people.
The second ran 6 weeks. It tested three set doses, in 82, 75, and 56 people, against a placebo in 76 people.
A third study took 295 people who had already done well on the drug. Some stayed on it and some moved to a placebo for 44 weeks. 8 out of 100 got ill again on the drug. 39 out of 100 got ill again on the placebo.
The label covers the later uses in its own section. Those are OCD, panic disorder, PTSD, social anxiety disorder, and PMDD.
- Trials
- 2 placebo-controlled trials
- Duration
- 6 and 8 weeks
- Compared against
- Placebo and amitriptyline
The efficacy of sertraline hydrochloride as a treatment for MDD was established in two randomized, double-blind, placebo-controlled studies and one double-blind, randomized-withdrawal study following an open label study in adult (ages 18 to 65) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria for MDD (studies MDD-1 and MDD-2).
Verbatim from the sertraline FDA label, Clinical Studies section, effective August 27, 2026 — read the full label on DailyMed.
Side effects of sertraline in the approval trials
Incidence among 3,066 patients on sertraline versus 2,293 on placebo, pooled from 8- to 12-week placebo-controlled trials across all six approved indications, not depression alone. The label itself cautions that trial rates cannot be directly compared with rates for other drugs and may not reflect the rates observed in practice.
Read the limits first. These numbers come from trials that ran 8 to 12 weeks. 3,066 people took the drug and 2,293 took a placebo.
The trials covered all six approved uses, not depression alone. The label warns that you cannot line these rates up against another drug’s rates. It warns that real life may not match them either.
Ejaculation failure on the sertraline label
The sertraline FDA label names ejaculation failure in its Adverse Reactions section, in the list below.
- Nausea (26% vs 12% on placebo)
- Diarrhea/loose stools (20% vs 10%)
- Insomnia (20% vs 13%)
- Dry mouth (14% vs 9%)
- Fatigue (12% vs 8%)
- Dizziness (12% vs 8%)
- Somnolence (11% vs 6%)
- Tremor (9% vs 2%)
- Dyspepsia (8% vs 4%)
- Ejaculation failure (8% vs 1%, male patients)
- Hyperhidrosis (7% vs 3%)
- Decreased appetite (7% vs 2%)
The most common adverse reactions (≥5% and twice placebo) in all pooled placebo-controlled clinical trials of all sertraline hydrochloride-treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3).
From the sertraline FDA label, Adverse Reactions section, effective August 27, 2026 — DailyMed.
More from the sertraline label: drug abuse and dependence
Not a controlled substance
Sertraline is not scheduled under the Controlled Substances Act. In a placebo-controlled study of comparative abuse liability, sertraline did not produce the positive subjective effects, such as euphoria or drug liking, that were observed with alprazolam and d-amphetamine.
FDA label, Drug Abuse and Dependence section.
Discontinuation syndrome
The label lists adverse reactions after stopping serotonergic antidepressants, particularly abruptly, including nausea, sweating, irritability, dizziness, sensory disturbances such as electric shock sensations, insomnia, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.
FDA label, Warnings and Precautions section.
How many Americans take sertraline
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.
- 44,634,056
- prescriptions in the United States (2024), refills included
- 10,233,569
- people filling them (2024), ± 1,261,627 (95%)
From 2014 to 2024 the estimate moved up 18%, 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 sertraline, you are deciding alongside about 10,233,569 other people in 2024.
Prescriptions by year: 2014 37,723,879 · 2015 38,877,836 · 2016 37,105,238 · 2017 38,296,630 · 2018 38,383,043 · 2019 37,157,934 · 2020 38,219,814 · 2021 39,206,398 · 2022 39,891,990 · 2023 42,578,019 · 2024 44,634,056.
Prescriptions are not clearly up or down since 2014. About 10.2 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 18% 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 sertraline
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.
- 218,320
- reports mentioning sertraline, all time
- 156,310
- 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
- Nausea13,865
- Drug ineffective13,616
- Fatigue12,822
- Headache11,106
- Anxiety10,369
- Diarrhoea10,339
- Dizziness9,602
- Depression9,506
- Off label use8,420
- Pain8,284
“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 sertraline 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 • Protein-bound drugs: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs (e.g., warfarin) as warranted. ( 7.1 , 12.3 ) • CYP2D6 substrates: Reduce dosage of drugs metabolized by CYP2D6. ( 7.1 , 12.3 )
7.1 Clinically Significant Drug Interactions Table 5 includes clinically significant drug interactions with sertraline hydrochloride [ See Clinical Pharmacology (12.3) ]. Table 5. Clinically-Significant Drug Interactions with Sertraline Hydrochloride Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of SSRIs including sertraline hydrochloride and MAOIs increases the risk of serotonin syndrome. Intervention: Sertraline hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [ See Dosage and Administration (2.5) , Contraindications (4), Warnings and Precautions (5.2) ]. Examples: selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide Clinical Impact: Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention: Concomitant use of pimozide and sertraline hydrochloride is contraindicated [ See Contraindications (4) ]. Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs with sertraline hydrochloride increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of sertraline hydrochloride and/or concomitant serotonergic drugs [ See Warnings and Precautions (5.2) ]. Examples: Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact: The concurrent use of an antiplatelet agent or anticoagulant with sertraline hydrochloride may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [ See Warnings and Precautions (5.3) ]. Examples: aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact: Sertraline hydrochloride is highly bound to plasma protein. The concomitant use of sertraline hydrochloride with another drug that is highly bound to plasma protein may increase free concentrations of sertraline hydrochloride or other tightly-bound drugs in plasma [ See Clinical Pharmacology (12.3) ]. Intervention: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs as warranted. Examples: warfarin Drugs Metabolized by CYP2D6 Clinical Impact: Sertraline hydrochloride is a CYP2D6 inhibitor [ See Clinical Pharmacology (12.3) ] . The concomitant use of sertraline hydrochloride with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention: Decrease the dosage of a CYP2D6 substrate if needed with concomitant sertraline hydrochloride use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if sertraline hydrochloride is discontinued. Examples: propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thioridazine, tolterodine, venlafaxine Phenytoin Clinical Impact: Phenytoin is a narrow therapeutic index drug. Sertraline hydrochloride may increase phenytoin concentrations. Intervention: Monitor phenytoin levels when initiating or titrating sertraline hydrochloride. Reduce phenytoin dosage if needed. Examples: phenytoin, fosphenytoin Drugs that Prolong the QTc Interval Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of other drugs which prolong the QTc interval [ See Warnings and Precautions (5.10) , Clinical Pharmacology (12.2) ] . Intervention: Pimozide is contraindicated for use with sertraline. Avoid the concomitant use of drugs known to prolong the QTc interval. Examples: 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).
7.2 Drugs Having No Clinically Important Interactions with Sertraline Hydrochloride Based on pharmacokinetic studies, no dosage adjustment of sertraline hydrochloride is necessary when used in combination with cimetidine. Additionally, no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, and drugs metabolized by CYP3A4, when sertraline hydrochloride is administered concomitantly [ See Clinical Pharmacology (12.3) ] .
7.3 False-Positive Screening Tests for Benzodiazepines False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines.
FDA label for sertraline, effective August 27, 2026 — DailyMed.
Label history: when this label changes, it is recorded in What changed.
Who pays for sertraline
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
- 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. 3,200,756 beneficiaries filled 16,155,695 claims in 2024 — 2,690,736 aged 65 and over, and 510,020 under 65.
- Medicaid
- At least 9,178,192 prescriptions in 2024 — a floor, because 138 of 936 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 595 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 44,634,056 purchases and 10,233,569 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 sertraline 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 sertraline, 2019–2024
Medicare Part D
Claims, all ages — the one payer with a public per-drug series.
13,880,278 → 16,155,695 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.
561,151 → 510,020 beneficiaries
Medicaid
A floor each year — small-cell rows are suppressed federally and excluded from the sum.
8,430,980 → 9,178,192 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 sertraline 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?
The efficacy of ZOLOFT as a treatment for MDD was established in two randomized, double-blind, placebo-controlled studies and one double-blind, randomized-withdrawal study following an open label study in adult (ages 18 to 65) outpatients who met the Diagnostic and Statistical Manual of Mental Disorders...
FDA-approved labelling, 14 CLINICAL STUDIES — read the label on DailyMed
Our reading
Two short placebo-controlled trials plus one randomised-withdrawal study — a design where people already doing well on the drug are switched to placebo, which measures relapse-or-withdrawal rather than fresh benefit. Sixty-nine submissions have been filed against this application since 1991, so the label you read today is not the label it was approved on.
Step 2
The approval
When was it approved, under what application, and by whose review?
- Approved
- December 30, 1991
- Application
- NDA019839
- Review
- STANDARD
- Original sponsor
- Pfizer (now Viatris)
- Holds it now
- Viatris
- Label submissions since
- 69
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…
28 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?
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.
Step 4
What independent research has found since
What has been learned by people who were not selling it?
Triptans with SSRIs or SNRIs: 14 years of records found two definite cases of serotonin syndrome in 30,928 person-years
27 years after approval
The labels list triptans among the drugs that raise serotonin syndrome risk with antidepressants. This is the study that measured the combination and found the risk close to zero.
Significant findings
Orlova, Rizzoli and Loder (JAMA Neurology, 2018) searched electronic health records of the Partners system in greater Boston for patients diagnosed with anything compatible with serotonin syndrome who had also been co-prescribed a triptan and an SSRI or SNRI, from January 2001 to December 2014. "A total of 19 017 (±3) patients were coprescribed triptans and antidepressants during the study, with a total of 30 928 person-years of exposure."
"Serotonin syndrome was suspected in 17 patients. Only 2 patients were classified as having definite serotonin syndrome (incidence rate, 0.6 cases per 10 000 person-years of exposure; 95% CI, 0.0-1.5). Five patients were classified as having possible serotonin syndrome (incidence rate with these 5 cases added to the 2 definite cases, 2.3 cases per 10 000 person-years of exposure; 95% CI, 0.6-3.9)."
The advisory did not change practice: "The proportion of patients with triptan prescriptions who were coprescribed an SSRI or SNRI antidepressant was relatively stable during the study, ranging from 21% to 29%." The conclusion, verbatim: "The risk of serotonin syndrome associated with concomitant use of triptans and SSRIs or SNRIs was low. Coprescription of these drugs is common and did not decrease after the 2006 FDA advisory. Our results cast doubt on the validity of the FDA advisory and suggest that it should be reconsidered."
Worth asking
This is the row that keeps the rest of the wave honest. A listed interaction is a warning that a mechanism exists, not a measurement of how often it hurts anyone; here, when someone measured, the answer was about one definite case per 15,000 years of combined use. If you have migraines and depression, the combination is common, and the question for the prescriber is what symptoms would prompt a call, not whether the two can be prescribed together at all.
Cochrane 2021: newer antidepressants cut depression in children and teens by a small and unimportant amount
30 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?
SSRIs raise the odds of a stomach bleed by about two thirds; with an NSAID as well, about fourfold
23 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).
An SSRI blocked most of MDMA's psychological effects in a placebo-controlled study of 16 volunteers
9 years after approval
"Will my antidepressant stop ecstasy from working" has a measured answer from a Swiss laboratory, and it also explains why the combination is not simply safe.
Significant findings
Liechti and colleagues (Neuropsychopharmacology, 2000) gave MDMA 1.5 mg per kilogram by mouth to 16 healthy volunteers in a double-blind, placebo-controlled study, with or without pretreatment with citalopram 40 mg intravenously.
"MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram."
The mechanism, from the abstract: "The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site." The finding "suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier".
Worth asking
Two consequences follow, in opposite directions. The first is that a person on an SSRI who takes MDMA and feels little may take more, and the dose that goes up is the dose whose heart and temperature effects were not blocked. The second is that MDMA and an SSRI both raise serotonin, and every SSRI label lists amphetamines among the drugs that raise serotonin syndrome risk. The Vuori 2003 row in this wave is what happened when MDMA met an MAOI antidepressant. A person on an antidepressant who is going to use MDMA anyway should know that "it did nothing" is not the same as "it was safe".
Each previous antidepressant course cut the odds of responding to sertraline by about a fifth
18 years after approval
The closest measurement to "does it work the second time," from a trial that counted how many drugs each person had already tried.
Significant findings
Amsterdam and colleagues treated 276 patients with major depressive disorder with sertraline at 150 to 200 mg a day for eight weeks. People who were still depressed were then randomised to eight more weeks of sertraline plus atomoxetine (72 people) or sertraline plus placebo (74). The question added afterwards was whether a longer history of antidepressant trials predicted a weaker response.
It did. "The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial."
In the second phase the pattern disappeared: "the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy."
The conclusion: "This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials."
The other direction
The abstract calls this a post hoc analysis, meaning the trial was designed to test atomoxetine, not this question, and the finding was extracted afterwards. An odds ratio of 0.81 per prior course is a slope, not a cliff: it does not say what fraction of people with two or three prior courses responded, and the abstract gives no absolute rates. The second phase found no association at all. And people with more prior courses may simply have had harder-to-treat depression, which would produce the same numbers without the drug being to blame; the abstract cannot separate those.
What this does not show
It does not measure the case people ask about most: restarting the same drug that worked before. It does not say a drug will not work after several courses, only that the odds shift. It is not a reason to avoid, restart or stop anything; how a treatment history should shape the next step is a prescriber's judgment.
Worth asking
How many antidepressant courses have I had, and does that number change what you would try?
Half of people on an SSRI or SNRI reported weaker mushroom effects, lasting up to three months after stopping
32 years after approval
People taking mushrooms while on an antidepressant report a specific thing: it does less. This survey measured how often, and for how long after stopping.
Significant findings
Gukasyan and colleagues (Journal of Psychopharmacology, 2023) ran an online retrospective survey of people who had used psilocybin mushrooms with an antidepressant or within two years of stopping one, comparing the strength of effects with the same dose before the antidepressant or with companions not on one.
"In reports (n = 611) of taking mushrooms with an antidepressant, probabilities [95% CI] of weaker than expected drug effects were 0.47 [0.41-0.54] (selective serotonergic reuptake inhibitors, SSRIs), 0.55 [0.44-0.67] (serotonin norepinephrine reuptake inhibitors, SNRIs) and 0.29 [0.2-0.39] (bupropion)."
After stopping: "Following SSRI/SNRI discontinuation (n = 1,542 reports), the probability of reduced drug effects was not significantly different from the earliest post-discontinuation timepoint (within 1 week) until 3-6 months, probability = 0.3 [0.20-0.46], p = 0.001." Removing fluoxetine, which lingers in the body, did not change that. "SSRI/SNRIs appear to weaken psilocybin drug effects relative to a non-serotonergic antidepressant. This dampening effect may last as long as 3 months following antidepressant discontinuation."
Worth asking
A survey of people who chose to answer cannot give a true rate, and "weaker than expected" is a memory. What it does show is the shape: serotonergic antidepressants blunt psilocybin, bupropion much less, and the blunting outlasts the drug by weeks to months. The Becker 2022 row beside this one is the controlled trial, which found the good effects intact and the bad ones reduced after two weeks of escitalopram. The two are not in conflict; they measured different things over different durations. What neither supports is stopping an antidepressant to make mushrooms work, which trades a known risk for an unmeasured one.
Serotonin toxicity is diagnosed by seven signs, and the rules were built from 2,222 overdoses
12 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.
Sertraline versus other antidepressive agents for depression
19 years after approval
Pooling 59 randomised trials (about 10,000 people), sertraline had a small effectiveness edge over fluoxetine and was better tolerated than several older antidepressants, though it caused diarrhoea more often than comparator drugs.
Worth asking
Sertraline causes diarrhoea more often than similar antidepressants - if that happens to me, how long does it usually last and when should we switch?
Sertraline versus other antidepressive agents for depression — Cipriani A, et al. (2010)
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major…
27 years after approval
Across 522 randomised trials with 116,477 adults, every antidepressant beat placebo for major depression, and sertraline was among the drugs with a better combination of effectiveness and tolerability in direct head-to-head comparisons.
Worth asking
Sertraline scored well on both effectiveness and tolerability in the largest antidepressant comparison ever done - is that part of why you chose it for me?
The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a…
28 years after approval
In 653 UK primary-care patients, sertraline did not clearly reduce depressive symptoms at 6 weeks compared with placebo, but it did reduce anxiety symptoms and people on it were more likely to say their mental health had improved.
Worth asking
This trial found sertraline helped anxiety before it helped low mood - how many weeks should I wait before we judge whether it is working for me?
Withdrawal from these medications can take months, and NICE says so
31 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.
Maintenance or Discontinuation of Antidepressants in Primary Care
30 years after approval
Among 478 primary-care patients who felt well enough to stop long-term antidepressants (including sertraline 100 mg), 56% of those randomised to stop relapsed within a year versus 39% of those who stayed on their medication.
Worth asking
If I ever want to stop sertraline, this trial showed a real relapse risk - what taper plan and check-ins would you want in place first?
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
28 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.
Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis
18 years after approval
Across 117 randomised trials with 25,928 adults, sertraline was among the four most effective of 12 newer antidepressants and shared the best tolerability profile with escitalopram; the authors suggested it as a sensible first choice for moderate-to-severe depression.
Worth asking
This analysis called sertraline a good first choice on both effect and cost - does that match how you rank it against newer options today?
Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.
18 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?
Step 5
What still is not known
Which questions you might reasonably have has nobody answered yet?
- A randomised-withdrawal design cannot separate relapse from withdrawal effects. Which was being measured?
- What is the evidence for continuous use beyond the first year?
- Sixty-nine label submissions in three decades — which of those added a warning rather than an indication?
The sertraline 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.
Deciding about sertraline?
- Side-effect rates from sertraline's own label — drug vs placebo, with every caveat the label attaches
- How long every medication's approval trials ran — sertraline beside every other drug in the library, from the same FDA record
- 12 questions to ask before starting a psychiatric medication — each with the study behind it
- 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
Open sertraline (Zoloft) in veisund
The app has the full approval journey, the resources behind it, and people working through the same questions.
