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 the problem? It’s not always obvious. The patient might have had an underlying condition. Maybe they took something else. Or it could just be bad timing. That’s where the Naranjo Scale comes in. It’s not magic. It’s not a fancy machine. It’s a simple, 10-question checklist used by doctors, pharmacists, and researchers around the world to figure out if a drug really caused an unexpected side effect.

What Is the Naranjo Scale, Really?

The Naranjo Scale was created in 1981 by a team of researchers led by Dr. Carlos A. Naranjo. It came out of a growing need after the thalidomide disaster - when a drug meant to help pregnant women caused severe birth defects - showed how badly we needed a way to prove which drugs were dangerous. Before this, doctors often guessed. Now, they answer 10 specific questions. Each answer gives you points: +2, +1, 0, or even -1. Add them up, and you get a score that tells you how likely the drug caused the reaction.

It’s not perfect. But it’s the most used tool of its kind. A 2022 study found it was used in 78% of published drug reaction reports - more than any other method. Hospitals, pharmacies, and drug companies rely on it to report side effects to regulators like the FDA and the European Medicines Agency. You won’t find it in your GP’s office every day, but if you’re in a hospital pharmacy or a clinical trial, you’ll see it in use.

How the 10 Questions Work

Here’s how it breaks down. Each question is designed to test a different clue that helps link the drug to the reaction.

• Question 1: Has this reaction been reported before with this drug? (+1 if yes)
• Question 2: Did the reaction start after the drug was given? (+2 if timing fits, -1 if it didn’t)
• Question 3: Did symptoms get better when the drug was stopped? (+1 if yes)
• Question 4: Did the reaction come back when the drug was given again? (+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 - but this one’s controversial)
• Question 7: Were drug levels in the blood toxic? (+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 proof - like lab results or imaging - that confirms the reaction? (+1 if yes)

That’s it. Ten questions. No blood tests needed. No scans. Just answers based on medical records, patient history, and clinical judgment.

What the Score Means

Your total score tells you the likelihood:

• 9 or higher: Definite - the drug almost certainly caused it. You’ve got timing, improvement after stopping, and no better explanation.
• 5 to 8: Probable - likely the drug, but maybe not 100% sure. Maybe rechallenge wasn’t possible, or evidence is thin.
• 1 to 4: Possible - it could be the drug, but other factors (like infection or another medication) might be involved.
• 0 or lower: Doubtful - the reaction probably wasn’t caused by the drug at all.

For example: A 72-year-old woman starts taking a new blood pressure pill. Three days later, she develops a rash and swelling. Her doctor stops the pill. The rash fades in two days. She’s never had this reaction before. No other drugs changed. No infection. Score? +2 (timing), +1 (improvement), +1 (no alternative cause), +1 (objective evidence - the rash), +1 (previous similar reaction? no). Total: 5. That’s probable. The team reports it. That’s how drug safety systems learn.

Why It’s Still Used - Even in 2026

It’s old. It’s simple. And it’s still the gold standard. Why? Because it forces you to think systematically. Without it, people rely on gut feelings. One doctor might say, “That looks like a side effect.” Another says, “She’s just getting older.” The Naranjo Scale removes the guesswork. It makes sure everyone’s asking the same questions.

It’s also free. No software license. No subscription. You can print it out. Fill it in by hand. That’s why it’s still used in clinics across Africa, Asia, and rural hospitals where high-tech tools aren’t available. Even in fancy hospitals, it’s the starting point.

And it’s built into major reporting systems. The FDA’s FAERS database and the WHO’s global drug safety program both accept Naranjo scores as part of their official reports. If you’re a pharmacist filing a side effect report, you’ll be asked to score it.

Where It Falls Short

But here’s the problem: modern medicine isn’t what it was in 1981.

First, most patients take five or six medications. The Naranjo Scale only looks at one drug at a time. If a patient is on warfarin, metformin, lisinopril, and a new antibiotic - and they get liver damage - which one caused it? The scale doesn’t help. That’s why tools like the Liverpool ADR Scale were created - they handle multiple drugs.

Second, some questions are outdated. Question 6 asks if a placebo was used to test the reaction. In 2026, giving someone a placebo to see if they get sick again? That’s unethical. Most clinicians mark “don’t know.” That skews the score. Experts now suggest replacing it with a question about therapeutic drug monitoring - like, “Was the drug level in the blood checked?”

Third, it doesn’t work well for new types of drugs. Immunotherapies for cancer can cause side effects months after stopping. Gene therapies can have irreversible effects. The Naranjo Scale assumes reactions happen quickly and go away when you stop the drug. That’s not always true anymore.

And then there’s the human factor. One study found that 35% of doctors disagreed on whether an alternative cause was “sufficient.” What counts as a “reasonable” explanation? A cold? Stress? Age? That’s where training matters.

How It’s Being Updated - and Used Today

People aren’t just using paper forms anymore. In 2023, a team in India built a Python program that auto-calculates the Naranjo score. Nurses type in answers, and it spits out the result in seconds. Error rates dropped from 28% to 9%. Time saved: from 11 minutes to 4.

Some electronic health records - like Epic - now auto-fill four of the ten questions. Did the patient take the drug? When? Was it stopped? Did symptoms improve? The system pulls that from the chart. That leaves only the tricky ones: alternative causes, rechallenge, objective evidence.

Medical schools and pharmacy programs now teach it with interactive case studies. Fiveable, a popular learning platform, has 15,000 students using its free Naranjo Scale module. Most master it after 3 to 5 practice cases.

And while AI tools like the FDA’s Sentinel Initiative are starting to predict drug risks using machine learning, they still use Naranjo scores to train their models. It’s the foundation.

Who Uses It - and When

You won’t see it in a quick clinic visit. But you’ll find it in:

• Hospital pharmacovigilance units
• Pharmaceutical safety departments
• Clinical trial monitoring teams
• Regulatory agencies reviewing drug safety data

It’s used when someone reports a serious side effect - like liver failure, severe rash, or heart rhythm problems. That’s when the formal assessment kicks in. A pharmacist reviews the chart. Answers the 10 questions. Scores it. Files it. That data goes into national and global databases. And over time, patterns emerge. A drug once thought safe gets flagged. A warning gets added. Someone else avoids the reaction.

It’s slow. It’s manual. But it’s the backbone of drug safety.

What Comes Next

Will the Naranjo Scale be replaced? Probably not soon. It’s too simple, too proven, too widely accepted. But it’s evolving. Digital tools are making it faster. New guidelines are replacing outdated questions. And in complex cases, it’s being used alongside newer tools like ALDEN or the Liverpool Scale.

Its future isn’t about being the only tool. It’s about being the first tool. The starting point. The common language. Even in a world of AI and gene therapy, if you can’t agree on whether a drug caused a reaction, you can’t fix the problem. The Naranjo Scale gives you that agreement.

It’s not glamorous. But it saves lives.