Causality Assessment for Adverse Drug Reactions: How the Naranjo Scale Works in Real Clinical 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 the patient had a virus. Maybe their condition worsened on its own. Or maybe the drug triggered a rare reaction. Without a clear way to tell, doctors and pharmacists risk missing serious side effects-or blaming drugs for problems they didn’t cause. That’s where the Naranjo Scale comes in.

What Is the Naranjo Scale?

The Naranjo Scale is a simple, 10-question tool used by healthcare professionals to decide if a drug caused an adverse reaction. It was created in 1981 by Dr. Carlos A. Naranjo and a team of researchers in response to the thalidomide disaster, when thousands of babies were born with severe birth defects after their mothers took the drug during pregnancy. Back then, there was no standard way to link drugs to side effects. The Naranjo Scale fixed that.

It’s not fancy. No machines. No blood tests. Just a checklist you fill out based on what you know about the patient, the drug, and what happened after they took it. Each question gives you points-positive, negative, or zero. Add them up, and you get a score that tells you how likely the drug caused the reaction.

How the Scoring Works

The scale has 10 questions. Here’s what they look like, simplified:

1. Have other reports linked this drug to this reaction before? (+1 if yes)
2. Did the reaction happen after the drug was given? (+2 if timing fits, -1 if it happened before)
3. Did symptoms get better after stopping the drug? (+1 if yes)
4. Did the reaction come back when the drug was given again? (+2 if yes, -1 if it got worse)
5. Could something else have caused it? (-1 if yes, +2 if no)
6. Did giving a placebo cause the same reaction? (-1 if yes, +1 if no)
7. Was the drug at toxic levels in the blood? (+1 if yes)
8. Did the reaction get worse when the dose went up? (+1 if yes)
9. Has the patient had this reaction to the same drug before? (+1 if yes)
10. Is there objective proof, like lab results or imaging, confirming the reaction? (+1 if yes)

You don’t answer ‘maybe.’ You pick Yes, No, or Don’t Know. Each choice adds or subtracts points. The total score tells you the likelihood:

• 9 or higher = Definite reaction
• 5 to 8 = Probable reaction
• 1 to 4 = Possible reaction
• 0 or lower = Doubtful reaction

That’s it. No guesswork. No gut feeling. Just numbers.

Why It’s Still Used Today

You might think a 40-year-old tool would be outdated. But it’s not. In 2023, a study in Cureus found that the Naranjo Scale was still used in 78% of published drug safety case reports-more than any other tool. Why?

Because it works. Hospitals, pharmacies, and regulatory agencies use it to decide whether to report a side effect to the FDA or EMA. It’s built into electronic health records like Epic. Pharmacists in Massachusetts General Hospital use it daily to document reactions. It forces you to ask the right questions instead of jumping to conclusions.

One pharmacist told a Reddit thread: “We use it every day. It stops us from blaming drugs for everything. And it stops us from ignoring real reactions.”

Where It Falls Short

The Naranjo Scale isn’t perfect. It was designed for single drugs and simple reactions. Today, patients often take five, six, even ten medications at once. That’s a problem.

Imagine an 80-year-old with heart disease, diabetes, and arthritis. They start a new blood pressure pill and get dizzy. Was it the new drug? Or the statin they’ve been on for 10 years? Or the interaction between all of them? The Naranjo Scale can’t handle that. It only looks at one drug at a time.

Another issue: Question 6 asks about placebo rechallenge. That means giving the patient a sugar pill to see if they still react. But in modern medicine, that’s unethical. You don’t give someone a placebo if they had a dangerous reaction before. So most clinicians answer “Don’t Know,” which lowers their score-even if the reaction is real.

And what about new drugs? Immunotherapies, gene therapies, biologics-these can cause side effects months after stopping. The Naranjo Scale doesn’t account for delayed reactions like that. A 2024 analysis in Nature Reviews Drug Discovery pointed out that the scale’s framework just doesn’t fit these modern treatments.

What’s Replacing It?

There are newer tools. The Liverpool ADR Probability Scale can handle multiple drugs. The PADRAT is designed for kids. The WHO-UMC system is simpler but less precise. The ALDEN scale is better for antibiotics.

But here’s the thing: none of them have the same global reach. The Naranjo Scale is in 78 of the 152 countries in the WHO’s drug safety program. It’s the default in North America and Europe. Regulatory agencies like the FDA and EMA still reference it in their guidelines.

Instead of replacing it, people are upgrading it. A 2023 study built a Python app that auto-fills the scale using electronic health data. It cuts assessment time from 11 minutes to 4.2 minutes and cuts errors from 28% to 9%. Hospitals are starting to use it.

How to Use It Right

If you’re a nurse, pharmacist, or doctor trying to use the Naranjo Scale, here’s what you need to know:

• Don’t skip the “Don’t Know” answers. They’re not a cop-out. They’re honest.
• Question 5 (“Could something else cause this?”) is the trickiest. Talk to a clinical pharmacist if you’re unsure.
• Don’t force a “definite” score just because you think the drug is guilty. Stick to the facts.
• Use digital tools if you can. They reduce mistakes and save time.
• Training takes 2-4 hours. Practice with 5-10 real cases before using it alone.

There’s a free worksheet from Nebraska ASAP and a 27-page training manual from the International Society of Pharmacovigilance. Use them.

What Happens After You Score It?

If you score a reaction as “probable” or “definite,” you report it. In the U.S., that means filing a report to the FDA’s FAERS system. In Europe, it goes to EudraVigilance. These reports help regulators spot dangerous drugs before they hurt more people.

But reporting isn’t just about compliance. It’s about safety. One case report using the Naranjo Scale helped identify a new interaction between a common antibiotic and a blood thinner. That led to updated prescribing guidelines-and saved lives.

Final Thoughts

The Naranjo Scale isn’t magic. It doesn’t replace clinical judgment. But it gives you structure. It turns guesswork into evidence. In a world full of complex drugs and confusing symptoms, that’s powerful.

It’s not going away anytime soon. Even as AI and new tools emerge, the Naranjo Scale will stick around-not because it’s perfect, but because it’s simple, transparent, and proven. For now, it’s still the best starting point for figuring out if a drug really caused a reaction.