Medication approval journey
diazepam (Valium)
Approved for Anxiety disorders; short-term relief of anxiety symptoms
page first published · last updated
Also answers to “the mid century lounge chair” — 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 diazepam dose
Stopping abruptly can be dangerous — never do it without medical supervision
Do not stop a benzodiazepine abruptly. Abrupt withdrawal can cause seizures, delirium, and can be fatal. Physical dependence develops within weeks of daily use and is not the same thing as addiction. Coming off safely is a prescriber-supervised taper measured in months, sometimes far longer, and going slower is not failure.
How long the diazepam trials actually ran
We could not establish a longest trial length for diazepam. That is a gap in what we can show you — not evidence that the trials ran long.
Approved before the Physician Labeling Rule, so no clinical studies section was ever required. The absence is the state of the public record, not a gap in our research.
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 label does not say how long any trial ran, because it does not describe any trial.
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: risks from use with opioids
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 diazepam boxed warning covers risks from use with opioids; abuse, misuse, and addiction; dependence and withdrawal reactions.
The warning below covers three things. First, taking this drug with an opioid can cause deep sedation, slowed breathing, coma, and death. Second, it can be abused and misused. That can lead to addiction, overdose, and death. Third, taking it day after day can lead to physical dependence. Stopping fast after that can set off withdrawal. The label says that withdrawal can be life threatening, so it says to come off slowly.
The FDA’s own words follow, copied exactly.
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation (see WARNINGS and PRECAUTIONS ). The use of benzodiazepines, including VALIUM, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing VALIUM and throughout treatment, assess each patient's risk for abuse, misuse, and addiction (see WARNINGS ) . The continued use of benzodiazepines, including VALIUM, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of VALIUM after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue VALIUM or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS ) .
FDA label effective August 11, 2026 — read the full label on DailyMed
What diazepam is FDA approved for, and what the record shows
Approved for the management of anxiety disorders or the short-term relief of the symptoms of anxiety; the label also covers acute alcohol withdrawal, skeletal muscle spasm, and adjunctive use in convulsive disorders in 1963, under application NDA 013263. Source: FDA Drugs@FDA.
Diazepam was approved in 1963, and the FDA has never published its review of the application — Drugs@FDA carries review documents mainly for approvals from the late 1990s onward. How many trials supported the approval, how long they ran, and how many patients took part are not on the public record, and the current label describes none of it.
The label describes no clinical trials for any indication: it has no clinical studies section, and its adverse reactions section reports no trial sizes, durations, or comparative rates. Its only trial-related statement is that effectiveness in long-term use — more than 4 months — has not been assessed by systematic clinical studies.
The largest gap on this page. This drug was approved in 1963, and the FDA has never published its review. Drugs@FDA holds review papers mostly for approvals from the late 1990s on.
How many trials backed the approval is not on the public record. Nor is how long they ran, or how many people took part. The label sold today describes none of it.
The FDA approved diazepam in 1963. The approved use was managing anxiety disorders. It also covers short-term relief of anxiety symptoms. The label covers alcohol withdrawal, muscle spasm, and added help in seizure disorders too. The file number is NDA 013263. The source is Drugs@FDA, the FDA's own database.
The label describes no trial for any use. It has no clinical studies section. Its side effect section gives no group sizes, no trial lengths, and no side-by-side rates.
Its one statement about tested evidence is a negative one. It says that use beyond 4 months has not been looked at in planned studies.
The effectiveness of Valium in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
Verbatim from the diazepam FDA label, Indications and Usage section, effective August 11, 2026 — read the full label on DailyMed.
Side effects of diazepam listed on the FDA label
The label reports no incidence figures from clinical trials — for diazepam or placebo — in any population. It names the side effects most commonly reported, without saying by whom, at what doses, or over what durations, so the list below carries no percentages and cannot be compared with the trial-based rates shown for newer drugs.
Read the limits first. The label gives no trial rates at all. It gives none for the drug and none for a placebo, in any group of people.
It names the side effects reported most often. It does not say who reported them. It does not say at what dose, or over how long.
So the list below carries no percentages. It cannot be compared with the trial rates shown for newer drugs.
- Drowsiness
- Fatigue
- Muscle weakness
- Ataxia
Side effects most commonly reported were drowsiness, fatigue, muscle weakness, and ataxia.
From the diazepam FDA label, Adverse Reactions section, effective August 11, 2026 — DailyMed.
More from the diazepam label: drug abuse and dependence
Schedule IV controlled substance
Diazepam is a Schedule IV controlled substance. The label describes it as a benzodiazepine and CNS depressant with a potential for abuse and addiction, noting that even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse.
FDA label, Drug Abuse and Dependence section.
Stopping requires a gradual taper
Continued therapy may produce physical dependence, and abrupt discontinuation or rapid dose reduction can precipitate acute withdrawal reactions, including seizures, which can be life-threatening. The label describes a protracted benzodiazepine withdrawal syndrome that persists beyond 4 to 6 weeks and may last weeks to more than 12 months.
FDA label, Drug Abuse and Dependence section.
Response can fade with prolonged use
The label states that some loss of response to the effects of benzodiazepines may develop after repeated use of diazepam for a prolonged time, and that tolerance to the therapeutic effect may develop — while little tolerance develops to the amnestic and other cognitive impairments benzodiazepines cause.
FDA label, Precautions section.
How many Americans take diazepam
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.
- 3,346,944
- prescriptions in the United States (2024), refills included
- 1,047,987
- people filling them (2024), ± 347,230 (95%)
Prescriptions are down 63% from 2014 to 2024, a change larger than the survey’s margin of error. Whatever you decide about diazepam, you are deciding alongside about 1,047,987 other people in 2024.
Prescriptions by year: 2014 9,134,522 · 2015 8,899,752 · 2016 6,606,346 · 2017 5,184,806 · 2018 6,448,085 · 2019 5,711,207 · 2020 4,972,397 · 2021 3,898,004 · 2022 3,093,210 · 2023 2,711,268 · 2024 3,346,944.
Prescriptions are down 63 percent since 2014. About 1.0 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.
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 diazepam
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.
- 121,002
- reports mentioning diazepam, all time
- 98,058
- 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
- Toxicity to various agents9,514
- Drug ineffective7,286
- Drug abuse7,212
- Nausea6,288
- Fatigue5,838
- Pain5,269
- Anxiety5,086
- Somnolence5,077
- Headache5,071
- Off label use4,809
“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 diazepam 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
Drug Interactions Opioids The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid- related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation. Centrally Acting Agents If Valium is to be combined with other centrally acting agents, careful consideration should be given to the pharmacology of the agents employed particularly with compounds that may potentiate or be potentiated by the action of Valium, such as phenothiazines, antipsychotics, anxiolytics/sedatives, hypnotics, anticonvulsants, narcotic analgesics, anesthetics, sedative antihistamines, narcotics, barbiturates, MAO inhibitors and other antidepressants. Alcohol Concomitant use with alcohol is not recommended due to enhancement of the sedative effect. Antacids Diazepam peak concentrations are 30% lower when antacids are administered concurrently. However, there is no effect on the extent of absorption. The lower peak concentrations appear due to a slower rate of absorption, with the time required to achieve peak concentrations on average 20 - 25 minutes greater in the presence of antacids. However, this difference was not statistically significant. Compounds Which Inhibit Certain Hepatic Enzymes There is a potentially relevant interaction between diazepam and compounds which inhibit certain hepatic enzymes (particularly cytochrome P450 3A and 2C19). Data indicate that these compounds influence the pharmacokinetics of diazepam and may lead to increased and prolonged sedation. At present, this reaction is known to occur with cimetidine, ketoconazole, fluvoxamine, fluoxetine, and omeprazole. Phenytoin There have also been reports that the metabolic elimination of phenytoin is decreased by diazepam.
FDA label for diazepam, effective August 11, 2026 — DailyMed.
Label history: when this label changes, it is recorded in What changed.
Who pays for diazepam
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. 939,381 beneficiaries filled 3,011,861 claims in 2024 — 714,054 aged 65 and over, and 225,327 under 65.
- Medicaid
- At least 1,304,365 prescriptions in 2024 — a floor, because 166 of 567 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 64 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 3,346,944 purchases and 1,047,987 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 diazepam 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 diazepam, 2019–2024
Medicare Part D
Claims, all ages — the one payer with a public per-drug series.
3,431,247 → 3,011,861 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.
301,399 → 225,327 beneficiaries
Medicaid
A floor each year — small-cell rows are suppressed federally and excluded from the sum.
1,431,769 → 1,304,365 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 diazepam 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?
Our reading
Approved in 1963 — one year after the law first required efficacy evidence at all — and the current label carries no clinical studies section. Valium became, for a stretch of the 1970s, the most prescribed drug in America; whatever trial record sat under that phenomenon has never been printed on the document patients see. Sixty submissions have been filed against the application in six decades, and the application itself has changed hands from Roche to a company most people have never heard of, which is what the end of a blockbuster looks like in regulatory records.
Step 2
The approval
When was it approved, under what application, and by whose review?
- Approved
- November 15, 1963
- Application
- NDA013263
- Review
- STANDARD
- Original sponsor
- Roche
- Holds it now
- Waylis Therapeutics
- Label submissions since
- 60
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?
The FDA strengthened the benzodiazepine warning in 2020
57 years after approval
In September 2020 the FDA required the boxed warning on every benzodiazepine to be rewritten. The wording matters: physical dependence can develop even when the medication is taken exactly as prescribed, and stopping abruptly or dropping the dose quickly can cause withdrawal reactions that include seizures and can be life-threatening.
This is not a claim that the medication is bad or that you should stop taking it. It is the opposite. It is the reason not to stop on your own. The FDA's own instruction to prescribers is to taper gradually rather than stop, and to reassess dose and duration over time.
Worth asking
How long is the plan for me to be on this, what does my taper look like if we decide to come off, and how will we tell withdrawal apart from my original anxiety coming back.
Step 4
What independent research has found since
What has been learned by people who were not selling it?
Opioid users who also filled a benzodiazepine had about twice the odds of an overdose visit
54 years after approval
The label says the combination is dangerous. This is the study that put a number on it, in the year before the FDA required the boxed warning.
Significant findings
Sun and colleagues (BMJ, 2017) analysed claims for 315,428 privately insured people aged 18 to 64 who filled at least one opioid prescription between 2001 and 2013. Concurrent use meant the two prescriptions overlapped by at least one day. "9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users."
On the outcome: "Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users." The odds ratio was 1.42 for intermittent opioid users and 1.81 for chronic users.
The authors' own conditional: "If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16)."
Worth asking
Two things this study is not. It is not a trial, so it cannot prove the benzodiazepine caused the overdoses; people prescribed both may differ in ways claims data cannot see. And it is not about street drugs; every exposure was a filled prescription from a doctor. That second point is the useful one. Both drugs came through a pharmacy, which means a pharmacist can see both. If you take either, ask the pharmacist to check for the other.
Benzodiazepines were present in a third of prescription opioid overdose deaths in 2017; alcohol in one in seven
57 years after approval
The label says benzodiazepines plus opioids kill. This is the count.
Significant findings
Tori, Larochelle and Naimi (JAMA Network Open, 2020) analysed every opioid-involved poisoning death in the CDC's WONDER database from 1999 to 2017: "399 230 poisoning deaths involved opioids, of which 263 601 (66.0%) were male, and 204 560 (51.2%) were aged 35 to 54 years."
Alcohol: "Alcohol co-involvement for all opioid overdose deaths increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. By opioid subtype, deaths involving heroin and synthetic opioids (eg, fentanyl; excluding methadone) had the highest alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017."
Benzodiazepines: "Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017."
The state-level pattern: "State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r = 0.34; P = .02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r = 0.57; P < .001)."
Worth asking
Co-involvement means the drug was found at death, not that it caused the death, and death certificates undercount what was not tested for. Even so, one in three prescription opioid deaths with a benzodiazepine present is the number behind the boxed warning. If you take a benzodiazepine and any opioid is in your life, prescribed or not, the question for your prescriber is whether naloxone is in the house and whether the people around you know how to use it.
Higher benzodiazepine doses went with non-response to ketamine for depression, above 8 mg diazepam-equivalent
57 years after approval
Ketamine, from a clinic or from the street, works on the same brain systems benzodiazepines quiet. This study asked whether the sedative blunts the antidepressant.
Significant findings
Andrashko and colleagues (Frontiers in Psychiatry, 2020) analysed 47 patients with major depression who had not responded to at least one antidepressant and received a single infusion of racemic ketamine, 0.54 mg per kilogram, on top of their existing medication. "Thirteen patients (28%) reached ≥ 50% reduction in MADRS within one week after ketamine administration. Nineteen (40%) patients took concomitant benzodiazepines on a daily basis."
"The doses of BZDs were significantly higher in nonresponders (p=0.007). ROC analysis distinguished responders from nonresponders by a criterion of >8mg of diazepam equivalent dose (DZ equivalent) with a sensitivity of 80% and a specificity of 85% (p<0.001)." Patients above that dose had "a significantly worse outcome" on day 3 and day 7.
"The results of the study indicate that concomitant benzodiazepine treatment in higher doses may attenuate ketamine's antidepressant effect." A 2015 letter by Frye, Blier and Tye in the Journal of Clinical Psychopharmacology, read for this wave, reported the same pattern under the title "Concomitant benzodiazepine use attenuates ketamine response".
Worth asking
Forty seven patients and a retrospective split, so the cut-off is a hypothesis, not a rule. The direction is consistent across the two reports, and it matters in both settings: a person paying for ketamine treatment while on a moderate benzodiazepine dose may be paying for less effect, and a person using street ketamine on top of a benzodiazepine is combining two sedatives, which the esketamine label in this wave addresses directly. If ketamine treatment is on the table, the question for the clinic is what your benzodiazepine dose is in diazepam-equivalents and whether that changes the plan. Any change to the benzodiazepine is the prescriber's, with a taper; the same drugs cause dangerous withdrawal if stopped abruptly.
Withdrawal from these medications can take months, and NICE says so
59 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.
Step 5
What still is not known
Which questions you might reasonably have has nobody answered yet?
- Once the most prescribed drug in the country, and the label never printed the trials. What was the evidence at approval?
- The class boxed warning on dependence arrived in 2020, fifty-seven years after approval.
- Like lorazepam, the label describes short-term use. What is the plan if this prescription is in its fifth year?
Deciding about diazepam?
- Side-effect rates from diazepam's own label — drug vs placebo, with every caveat the label attaches
- How long every medication's approval trials ran — diazepam 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 diazepam (Valium) in veisund
The app has the full approval journey, the resources behind it, and people working through the same questions.
