Medication approval journey
sertraline (Zoloft)
Approved for Major depressive disorder in adults
Before changing anything
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.
How long the 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.
The boxed warning
The strongest warning the FDA puts on a label, reproduced word for word — not our summary of it.
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
How many Americans take sertraline
Survey-based federal estimates, published with a lag of about two years. They count prescriptions filled, not outcomes.
- 44,634,055
- prescriptions in the United States (2024)
- 10,233,568
- people filling them (2024)
Prescriptions are up 18% since 2014. Whatever you decide about sertraline, you are deciding alongside about 10,233,568 other people this year.
Source: ClinCalc DrugStats (Medical Expenditure Panel Survey (MEPS), Agency for Healthcare Research and Quality), CC BY-SA 4.0, release 2026.08.
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.
- 218,320
- reports mentioning sertraline, all time
- 156,310
- filed as serious (a report-level flag covering every drug and outcome in the report)
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.
Source: FDA Adverse Event Reporting System (FAERS), via openFDA, data through 2026-07-30.
Known interactions, from the label
The FDA label’s interactions section, verbatim. A pharmacist checking your actual medication list beats any published list — including this one.
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.
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)
- The MEPS-based estimate above puts the whole country at 44,634,055 prescriptions and 10,233,568 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.
The 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?
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?
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)
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 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?
- 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 Resolv
The app has the full approval journey, the resources behind it, and people working through the same questions.
