Causality Assessment for Adverse Drug Reactions: How the Naranjo Scale Works in Real-World Practice

When a patient gets sick after taking a new medication, how do you know if the drug actually caused it? It’s not always obvious. Maybe it was the flu. Maybe it was stress. Or maybe it was the antibiotic they just started. This is where the Naranjo Scale comes in. It’s not fancy. It doesn’t need a computer. But it’s one of the most trusted tools doctors and pharmacists use to figure out if a bad reaction was really caused by a drug.

What Is the Naranjo Scale?

The Naranjo Scale is a simple 10-question checklist developed in 1981 by a team of researchers led by Dr. Carlos A. Naranjo. It was created because, after the thalidomide disaster in the 1960s, the world realized drug safety needed better rules. Before this, doctors guessed. Now, they score. Each question adds or subtracts points based on simple yes/no answers. The total score tells you how likely it is that the drug caused the reaction.

The scale doesn’t care if you’re a nurse, pharmacist, or resident. You just need to know the patient’s history and what happened after they took the medicine. It turns a hunch into a number. And that number matters - it’s used in hospitals, drug companies, and even by regulators like the FDA to decide if a reaction should be reported.

How the Scoring Works

Here’s how it breaks down. Each of the 10 questions gives you a score: -1, 0, +1, or +2. You add them up. That’s it.

• Question 1: Have other reports linked this drug to this reaction before? (+1 if yes)
• Question 2: Did the reaction happen after the drug was started? (+2 if yes, -1 if it happened before)
• Question 3: Did symptoms get better after stopping the drug? (+1 if yes)
• Question 4: Did the reaction come back when the drug was restarted? (+2 if yes, -1 if it got worse)
• Question 5: Could something else have caused it? (-1 if yes, +2 if no)
• Question 6: Was a placebo used to test the reaction? (-1 if yes, +1 if no - though this is rarely done today)
• Question 7: Was the drug at toxic levels in the blood? (+1 if yes)
• Question 8: Did higher doses make the reaction worse? (+1 if yes)
• Question 9: Has the patient had this reaction to the same drug before? (+1 if yes)
• Question 10: Is there objective evidence confirming the reaction? (+1 if yes - like lab results or imaging)

After adding everything up, the score tells you the likelihood:

• 9 or higher: Definite - the drug almost certainly caused it
• 5 to 8: Probable - very likely, but not 100%
• 1 to 4: Possible - could be the drug, but other factors might explain it
• 0 or lower: Doubtful - probably not the drug

Why It’s Still Used Today

You’d think a 40-year-old tool would be outdated. But it’s not. In 2023, a study in Cureus showed that over 78% of published ADR case reports still used the Naranjo Scale. Why? Because it works.

It’s objective. It forces you to think through every angle. A nurse in Boston told a Reddit thread: “We use it daily. It stops us from blaming the patient’s age or other meds when it might actually be the new blood pressure pill.”

It’s also built into major systems. The FDA’s Adverse Event Reporting System (FAERS) and the European Medicines Agency’s guidelines both list it as an acceptable method. In North America, 92% of pharmacovigilance teams use it. In hospitals with dedicated drug safety teams, it’s standard procedure.

Where It Falls Short

The Naranjo Scale isn’t perfect. And that’s important to know.

First, it doesn’t handle multiple drugs well. Most older patients take five or six medications. If someone gets a rash after starting three new pills, the scale can’t tell you which one did it. That’s why tools like the Liverpool Scale were developed - they’re better for complex cases.

Second, some questions are outdated. Question 6 asks if a placebo was used to test the reaction. But in modern medicine, giving someone a placebo to see if they get sick again? That’s unethical. Most clinicians just mark “don’t know,” which lowers their score and makes the reaction seem less certain than it might be.

Third, it doesn’t account for new kinds of drugs. Biologics, immunotherapies, gene therapies - these can cause reactions months later or have effects that never go away. The Naranjo Scale was built for antibiotics and statins. It wasn’t designed for cancer drugs that trigger immune storms.

And then there’s the human factor. One study found that 35% of doctors disagreed on what counts as a “reasonable alternative cause.” One doctor thinks a UTI explains the fever. Another says no, it’s the new antibiotic. That inconsistency is real.

How People Use It in Practice

In hospitals, the Naranjo Scale is often filled out by pharmacists during daily safety rounds. They review patient charts, talk to nurses, check lab results, and score each suspected reaction. The results go into a database. If five patients on the same drug get the same reaction and all score “probable,” the hospital might issue a warning.

Some places have digitized it. A Python-based calculator released in 2023 lets users answer questions on a screen. It auto-scores, flags inconsistencies, and cuts assessment time from 11 minutes to 4.2 minutes. Error rates dropped from 28% to 9%. That’s huge.

Medical students learn it in pharmacology classes. On Fiveable, a free learning platform, nursing and pharmacy students spend hours practicing on case studies. Most say they get it after 3-5 examples. But it’s not just about memorizing the questions - it’s about understanding drug mechanisms. A new grad might miss that a headache after starting a beta-blocker is a known side effect. A seasoned pharmacist knows it right away.

What’s Next for the Naranjo Scale?

It’s not going away. But it’s changing.

In 2024, the International Council for Harmonisation proposed replacing Question 6 (placebo challenge) with a question about therapeutic drug monitoring - checking if drug levels in the blood match known toxic ranges. That’s a smart update.

AI is also stepping in. The FDA’s Sentinel Initiative uses machine learning to spot patterns across millions of patient records. It doesn’t need a 10-question form - it finds signals automatically. But it still uses the Naranjo Scale as a benchmark to train its models.

Experts agree: the Naranjo Scale won’t be replaced. It’ll be augmented. Think of it like a flashlight in a dark room. AI is the spotlight. But the flashlight? Still useful when you need to check one corner.

Bottom Line

The Naranjo Scale isn’t magic. It’s not perfect. But it’s reliable, simple, and grounded in real-world evidence. For most cases - especially when one drug is involved - it’s still the best starting point. It turns guesswork into structure. And in drug safety, structure saves lives.

If you’re a healthcare worker, learn it. Practice it. Use it. If you’re a patient, understand that when your doctor says, “This reaction is probable,” they didn’t just guess. They scored it. And that score matters.