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

What Is the Naranjo Scale and Why Does It Matter?

When a patient gets sick after taking a new medication, how do you know if the drug caused the problem-or if it was just bad luck? That’s the exact question the Naranjo Scale was built to answer. Developed in 1981 by Dr. Carlos A. Naranjo and his team, this simple 10-question tool helps doctors, pharmacists, and nurses decide whether an adverse reaction is truly caused by a drug, or if something else-like an infection, another medication, or an underlying condition-is to blame.

It’s not fancy. No machines. No blood tests. Just a checklist you can fill out on paper or in an electronic form. But it’s one of the most used tools in the world for drug safety. In fact, 78% of published case reports on adverse drug reactions still rely on it, according to a 2022 analysis. Even though it’s over 40 years old, it’s still the gold standard in hospitals, pharmacies, and regulatory agencies.

How the Naranjo Scale Works: The 10 Questions

The scale asks 10 yes-or-no questions, each worth a certain number of points: +1, +2, 0, or even -1. You add them up, and the total tells you how likely the drug caused the reaction. There are four possible outcomes:

• Definite (9 or higher): Almost certain the drug caused it. The reaction happened after taking the drug, improved when it was stopped, and fits what’s known about that drug.
• Probable (5-8): Very likely, but not 100%. The timing makes sense, and there’s no clear alternative cause.
• Possible (1-4): Could be the drug, but other things might explain it too.
• Doubtful (0 or lower): Probably not the drug. Something else is more likely.

Here’s what the questions actually look like:

1. Have there been previous reports linking this drug to this reaction? (+1 if yes)
2. Did the reaction happen after the drug was started? (+2 if yes, -1 if it happened before)
3. Did the reaction improve when the drug was stopped? (+1 if yes)
4. Did the reaction come back when the drug was restarted? (+2 if yes, -1 if it got worse)
5. Could another condition or drug have caused this? (-1 if yes, +2 if no)
6. Was a placebo given to see if the reaction returned? (-1 if yes, +1 if no)
7. Was the drug level in the blood toxic? (+1 if yes)
8. Did the reaction get worse with a higher dose? (+1 if yes)
9. Has the patient had this same reaction with this drug before? (+1 if yes)
10. Is there objective proof-like lab tests or imaging-that confirms the reaction? (+1 if yes)

Some questions are straightforward. For example, if someone started a new blood pressure pill and got dizzy the next day, that’s a clear +2 for timing. But others? That’s where things get messy.

Where the Naranjo Scale Falls Short

Let’s be real: the Naranjo Scale wasn’t designed for today’s medicine. Most patients on chronic medications take five, six, or even ten drugs at once. The scale can’t handle that. It only looks at one drug at a time. If a 78-year-old on eight medications develops kidney trouble, the scale doesn’t tell you which one caused it-or if it’s a mix.

Another big problem? Question 6: the placebo challenge. It asks if a placebo was given to see if the reaction returned. But in real life, you don’t re-expose someone to a drug that made them seriously ill just to test a theory. That’s unethical. So clinicians usually answer “don’t know,” which lowers the score and makes the reaction seem less likely-even if it clearly was caused by the drug.

And what about new drugs? Immunotherapies, gene therapies, biologics-they work differently than old-school pills. Reactions might show up weeks or months later. The Naranjo Scale doesn’t account for that kind of delayed response. Experts in Nature Reviews Drug Discovery point out it’s not built for modern treatments.

Still, it’s widely used because nothing else has its simplicity and validation. Even the FDA and European Medicines Agency accept it for official reporting.

How Clinicians Actually Use It Today

Most people don’t use the Naranjo Scale alone. They use it as a starting point. Pharmacists in hospitals often run through the 10 questions during daily safety rounds. One pharmacist from Massachusetts General Hospital said it forces them to look at evidence, not just gut feelings.

But they don’t do it by hand anymore. Digital tools are changing the game. A 2023 study showed that using a simple Python app to calculate the score cut assessment time from 11 minutes to just 4.2 minutes. Error rates dropped from 28% to 9%. That’s huge.

Some electronic health records, like Epic, now auto-fill parts of the scale-pulling data from when the drug was prescribed, when symptoms started, and lab results. That cuts down guesswork.

Still, the biggest hurdle isn’t the tool-it’s the training. A 2021 study found that doctors with less than five years of experience took 37% longer to score cases accurately than pharmacovigilance specialists. Why? Because the scale requires deep knowledge of how drugs behave in the body. You can’t just memorize the questions. You need to understand drug mechanisms, disease progression, and what counts as a “reasonable” alternative cause.

What’s Replacing It-and What Isn’t

There are other tools out there. The WHO-UMC system is simpler but less precise. The Liverpool Scale handles multiple drugs better. The PADRAT tool is made for kids. The ALDEN scale is great for antibiotics.

But none of them have the Naranjo Scale’s track record. In a 2022 review of over 1,000 published ADR reports, Naranjo was used in 78% of cases. WHO-UMC? Only 52%. The Liverpool Scale? Just 12%.

Why? Because it’s been tested, validated, and trusted for decades. It’s transparent-you can see exactly how the score was calculated. Other systems use vague categories like “probable” or “unlikely” without showing the math behind them.

Even the International Council for Harmonisation (ICH) is updating the scale in 2024, not replacing it. They’re replacing Question 6 (placebo) with a question about therapeutic drug monitoring-something more practical and ethical.

Is the Naranjo Scale Still Worth Learning?

Yes. Absolutely.

If you work in healthcare-whether you’re a nurse, pharmacist, doctor, or even a student-you need to understand it. It’s not just about filling out a form. It’s about thinking critically about cause and effect. In a world full of new drugs, complex patients, and conflicting information, the Naranjo Scale gives you a clear structure to ask: Is this really the drug?

It’s not perfect. It’s outdated in places. But it’s the best starting point we have. And in pharmacovigilance, where a missed reaction can mean another patient gets hurt, that’s worth a lot.

Try it yourself. Pick a case. Go through the 10 questions. You’ll be surprised how much you learn just by forcing yourself to slow down and look at the evidence.

Where to Find Tools and Training

You don’t need to buy anything to use the Naranjo Scale. Free resources are everywhere:

• The Naranjo Scale Worksheet from Nebraska ASAP has been downloaded over 3,200 times.
• Fiveable offers free interactive case studies used by 15,000+ nursing and pharmacy students.
• GitHub hosts an open-source Naranjo Calculator with over 2,100 stars-updated in 2023.
• The International Society of Pharmacovigilance has a 27-page training manual.

Practice with real cases. Start with simple ones: a patient on one new drug who develops a rash. Then move to complex cases with multiple meds. After 5-10 cases, you’ll start seeing patterns. After 20, you’ll be confident.

Final Thought: A Tool That Won’t Disappear

The Naranjo Scale isn’t going away. AI tools, machine learning models, and automated systems are coming-but they’re built on the same foundation. The scale gives us a common language. Without it, we’d all be guessing.

It’s not the end of causality assessment. It’s the beginning.