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

What Exactly Is the Naranjo Scale?

The Naranjo Scale is a standardized, 10-question tool used by healthcare professionals to determine whether an adverse drug reaction (ADR) was likely caused by a specific medication. It was first published in 1981 by Dr. Carlos A. Naranjo and his team in Clinical Pharmacology and Therapeutics. Before this, doctors often guessed whether a side effect was due to a drug or something else-like an infection, another medication, or the patient’s underlying condition. The Naranjo Scale changed that by turning guesswork into a clear, repeatable process.

It’s not a fancy algorithm or a high-tech device. It’s a simple checklist you can use on paper, in an electronic form, or even in your head. But don’t let its simplicity fool you. This tool is used in hospitals, pharmacies, and regulatory agencies around the world to decide if a patient’s bad reaction to a drug was actually caused by the drug.

How the Naranjo Scale Scores Your ADR

The scale has 10 yes-or-no questions. Each answer gets a score: +2, +1, 0, or -1. You add them up, and the total tells you how likely it is the drug caused the reaction.

• Score of 9 or higher = Definite ADR. The timing fits, the reaction improved when the drug was stopped, and there’s no better explanation.
• Score of 5 to 8 = Probable ADR. The evidence is strong, but maybe you couldn’t rechallenge the patient (which we’ll get to), or there’s a small chance something else was involved.
• Score of 1 to 4 = Possible ADR. The drug could be the culprit, but other factors like an infection or another medication make it unclear.
• Score of 0 or lower = Doubtful ADR. The reaction likely came from something else-maybe the disease itself, a different drug, or even coincidence.

Each question targets a different kind of evidence. For example:

• Question 2: Did the reaction happen after the drug was given? (+2 if yes, -1 if it happened before)
• Question 3: Did the reaction get better when the drug was stopped? (+1 if yes)
• Question 5: Could something else have caused it? (-1 if yes, +2 if no)
• Question 4: Did the reaction come back when the drug was given again? (+2 if yes, -1 if it got worse)

Some of these are straightforward. Others? Not so much.

Why the Naranjo Scale Still Matters Today

Even in 2026, with AI and machine learning tools popping up everywhere, the Naranjo Scale is still the most-used tool for ADR assessment in published case reports. A 2022 study found it was used in 78% of ADR case studies in medical journals-far more than any other method.

Why? Because it’s transparent. Every score has a reason. If you’re a pharmacist documenting a reaction for the FDA or the European Medicines Agency, you need to show your work. The Naranjo Scale gives you that paper trail.

Regulators like the FDA and EMA explicitly mention the Naranjo Scale in their guidelines. It’s not optional-it’s the baseline. If you’re reporting a serious side effect, you’re expected to use it. Even if you use a newer tool, you’ll still need to justify your conclusion using the same logic the Naranjo Scale teaches.

Where the Naranjo Scale Falls Short

It’s not perfect. In fact, it was designed in the 1980s for simple, single-drug reactions. Today, most patients take five, six, or even ten medications. That’s where the Naranjo Scale starts to struggle.

Take Question 4: Did the reaction return when the drug was restarted? In real life, you almost never do this. If a patient had a life-threatening rash or liver failure from a drug, no doctor is going to give it back to them just to see if it happens again. So you answer “don’t know.” That knocks your score down, and suddenly a definite reaction becomes probable.

Then there’s Question 6: Did the reaction improve with a placebo? That’s a red flag. Giving a placebo to someone who had a bad reaction? That’s unethical now. Most clinicians skip this question entirely or mark it “don’t know.”

And what about biologics, immunotherapies, or gene therapies? These drugs can cause reactions months after stopping. The Naranjo Scale assumes reactions happen quickly. It doesn’t account for delayed immune responses. Experts say it’s not built for modern medicine.

How Real Clinicians Use It

On Reddit’s r/Pharmacology, a 2023 thread with over 40 comments showed that 68% of pharmacists and clinical pharmacologists use the Naranjo Scale daily. But they don’t use it the way the textbook says.

One pharmacist from Massachusetts General Hospital said: “We use it to force ourselves to think systematically. Without it, we’d just say, ‘Yeah, that looks like a drug reaction,’ and move on.”

But they adapt. They skip the rechallenge question. They ignore the placebo one. They treat Question 5 (alternative causes) as the most important-because in a 78-year-old on eight meds, figuring out what else could be causing the problem is the real challenge.

Many hospitals now use digital versions. A 2023 study found that when clinicians used a Python-based calculator, they finished assessments in 4.2 minutes instead of 11.3. Errors dropped from 28% to 9%. That’s huge.

Still, the biggest barrier isn’t tech-it’s training. A 2021 study showed that doctors with less than five years of experience took 37% longer to score the scale accurately than pharmacovigilance specialists. Why? Because they don’t know the drug’s typical side effect profile. You can’t answer Question 9 (Has this reaction happened before with this drug?) if you don’t know what reactions this drug usually causes.

What’s Replacing It? Not Much.

There are alternatives. The WHO-UMC system is simpler but less precise. The Liverpool Scale handles multiple drugs better. The PADRAT is designed for kids. But none of them are used as widely.

Why? Because the Naranjo Scale is the only one with decades of validation. Thousands of studies have tested it. It’s been used in clinical trials, regulatory filings, and court cases. You can’t just replace that overnight.

Instead of replacing it, the field is layering on tools. Some hospitals now use the Naranjo Scale as a first pass, then cross-check with the ALDEN algorithm for complex cases. Others use AI tools to predict likelihoods, but still ask a human to score the Naranjo questions to stay compliant.

Even the International Council for Harmonisation (ICH) is considering updates. In 2024, they proposed replacing the placebo question with one about therapeutic drug monitoring-something more realistic and ethical.

How to Learn It

You don’t need a PhD. Most people get comfortable after 3-5 practice cases. There are free resources: Fiveable has 12 interactive case studies used by over 15,000 students. The Nebraska ASAP group offers a downloadable worksheet. GitHub has open-source calculators.

Start with one real case. Pick a patient who had a reaction. Ask the 10 questions. Don’t guess. Look at the chart. When did the drug start? When did the reaction appear? Was it stopped? Did it improve? What else could explain it?

After five tries, you’ll start seeing patterns. You’ll notice that certain drugs almost always cause certain reactions. You’ll learn that a rash after starting a new antibiotic is almost always probable. A sudden drop in blood pressure after a new beta-blocker? That’s often definite.

It’s not about memorizing scores. It’s about thinking like a detective.

Final Thought: A Tool, Not a Rule

The Naranjo Scale doesn’t tell you what happened. It tells you how likely the drug caused it. That’s different. A score of 7 means “probable,” but maybe you have other evidence-a lab test, a biopsy, a known drug interaction-that makes it certain. Don’t let the score override your clinical judgment.

It’s a tool to reduce bias, not replace it. Used right, it helps you catch dangerous reactions you might have missed. Used wrong, it gives you false confidence.

It’s not the future of pharmacovigilance. But for now, it’s still the foundation. And if you work with drugs and patients, you need to know how to use it.

Next Steps: What to Do If You Suspect an ADR

If you’re a clinician and think a drug caused a reaction:

1. Stop the drug if it’s safe to do so.
2. Document the reaction: timing, symptoms, severity.
3. Review all medications-new and old.
4. Run through the 10 Naranjo questions. Be honest. Don’t guess.
5. Use a digital calculator if available to avoid scoring errors.
6. Report it to your institution’s pharmacovigilance team or national database (like FAERS in the U.S.).

Don’t wait for the perfect tool. Use what’s proven. The Naranjo Scale isn’t flashy, but it’s reliable. And in drug safety, reliability beats innovation every time.