Alprazolam

Is alprazolam safe?

It depends on how long and with what. Alprazolam, sold as Xanax, relieves severe anxiety and panic attacks within an hour, and an overdose of alprazolam alone is rarely fatal. Used for a short time at a low dose, by someone who does not drink heavily or take opioids, it can be reasonably safe.

The trouble is that those conditions often do not hold. Dependence builds within weeks of daily use, withdrawal can be dangerous, and combined with opioids or alcohol it can stop breathing. It is also the most prescribed benzodiazepine in the US: 38% of about 92 million benzodiazepine prescriptions in 2019, according to the FDA, and half of all patients given an oral benzodiazepine in 2018 took it for two months or longer. We score it 40, a point below lorazepam, above oxycodone and far below most medicines on our list.

Side effects at normal doses

Sedation is the side effect almost everyone notices. In 4-week anxiety trials at up to 4 mg a day, 41% of people on alprazolam felt drowsy against 22% on placebo. The panic disorder trials used higher doses, up to 10 mg a day, and the numbers rise with them:

Panic trials, up to 10 weeks	Alprazolam (1,388 people)	Placebo (1,231)
Drowsiness	77%	43%
Impaired coordination	40%	18%
Memory problems	33%	22%
Slurred speech	23%	6%

The label warns against driving or using machinery. Tolerance to the calming effect can develop, but the label notes that little tolerance develops to the memory and thinking effects. Rarely it causes agitation or rage instead of calm, and it can worsen depression. There have been deaths in people with severe lung disease shortly after starting alprazolam.

Dependence and withdrawal

Alprazolam acts fast and wears off fast, which makes it effective for panic and also habit-forming. People can feel anxiety return in the early morning or between doses, which the label calls interdose symptoms, and take more to relieve it.

Since September 2020 the boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary has said that continued use can lead to clinically significant physical dependenceDrug dependenceThe body's adaptation to a drug taken regularly, so that stopping it suddenly causes withdrawal symptoms. It is not the same as addiction.More in the glossary, and that stopping abruptly or cutting the dose quickly can cause acute withdrawal that can be life-threatening. The label says there is some risk of dependence even after fairly short use at up to 4 mg a day, and that the risk and severity appear greater above 4 mg a day and beyond 12 weeks.

Among 641 people with panic disorder who came off alprazolam, 29.5% had insomnia, 19.2% anxiety, 17.3% abnormal involuntary movements, 17% headache and 16.5% nausea or vomiting. More severe reactions include seizures, delirium and psychosis. A protracted withdrawal syndrome, with anxiety, poor concentration, insomnia, tingling and tinnitus, can last from weeks to more than 12 months.

The label advises reducing by no more than 0.5 mg every 3 days, and slower if needed. None of this should be done without the prescriber.

The deadly combinations

The boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary puts its first paragraph on opioids. Benzodiazepines and opioids each suppress breathing, and together they can cause profound sedation, coma and death. A national study of US deaths from 2000 to 2019 found 118,208 overdose deaths involving benzodiazepines, and 84% also involved an opioid. NIDA reports that in 2021 nearly 14% of US overdose deaths involving opioids also involved a benzodiazepine.

Combined with	Risk
Opioids (oxycodone, hydrocodone, codeine, tramadol, fentanyl)	Slowed or stopped breathing, death
Alcohol	Extra sedation, blackouts, overdose
Sleeping pills, sedating antihistamines, gabapentin, pregabalin	Extra sedation and breathing risk
Ketoconazole, itraconazole	Alprazolam levels rise about 4-fold and 2.7-fold (contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary)
Ritonavir	Start alprazolam at half the dose; back to target after 10 to 14 days
Fluvoxamine, nefazodone, cimetidine and other CYP3ACYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary inhibitors	Higher levels, more sedation; a lower dose may be needed

In an overdose, the antidote flumazenil can itself trigger seizures in people who are dependent, so it is used with care. Call Poison Help on 1-800-222-1222 in the US, NHS 111 in the UK, or emergency services if someone is hard to wake or breathing slowly.

Counterfeit Xanax

Illegal "Xanax bars" are a separate and larger danger. Many are pressed in illicit labs and contain fentanyl or designer benzodiazepines. In a CDC review of overdose deaths among 10- to 19-year-olds from mid-2019 to 2021, nearly a quarter (24.5%) had evidence of counterfeit pills, which often looked like oxycodone or alprazolam, and 84% involved illicit fentanyl. The DEA placed bromazolam, a designer benzodiazepine often pressed to look like alprazolam, in Schedule I by temporary order on 16 March 2026. Tablets from anywhere other than a pharmacy should be treated as unknown drugs.

Doses

Use	Start (US label)	Maximum
Generalised anxiety	0.25 to 0.5 mg three times a day	4 mg a day
Panic disorder	0.5 mg three times a day, up by no more than 1 mg a day every 3 to 4 days	Trials used 1 to 10 mg a day (average 5 to 6 mg)
Older adults, liver disease	0.25 mg two or three times a day	Increased slowly if tolerated

Most guidelines advise using benzodiazepines for anxiety for no more than 2 to 4 weeks. For long-term anxiety and panic, antidepressants such as sertraline and talking therapies are first-line treatments.

Who should be careful

Talk to your doctor or pharmacist before taking alprazolam if you take an opioid or drink regularly, have had a substance use problem, are over 65, have sleep apnoea or lung disease, have depression, or drive or operate machinery for work. In late pregnancy it can leave a newborn sedated, floppy or in withdrawal, although studies have not shown a clear link to major birth defects. Store it securely, because tablets are often taken from family medicine cabinets.

How we scored it

Track record (90) is the only strong factor. Dependence (15), regulatory warnings (20) and interactions (25) are in the lowest band because of the 2020 boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary on addiction and withdrawal, the risk with opioids and alcohol, and its reliance on the CYP3ACYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary enzyme. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (40) is better than for opioids because alprazolam alone rarely kills.