The U.S. FDA has just approved a new ADHD medication called centanafadine (Simtriyo) for adults and children aged 6 and older. It is being described as a new type of ADHD medication because it works on three neurotransmitter systems — dopamine, norepinephrine and serotonin.
But whenever a new medication is approved, we tend to see headlines saying things like:
“Clinical trials show statistically significant improvements.”
That sounds impressive.
But what does statistically significant actually mean? And does it mean that most people taking the medication suddenly got dramatically better?
No. And this is where the numbers become really interesting.
When researchers conduct a clinical trial, they aren't simply asking: “Did people taking the medication improve?” They're asking something much more specific: “Did they improve more than people taking a placebo, and is that difference unlikely to have happened just by chance?”
This is where the p-value comes in.
A p-value below 0.05 is generally considered statistically significant.
For example, one of the adult centanafadine trials produced a p-value of 0.002 for the 200 mg dose. In simple terms, if centanafadine actually had no effect compared with placebo, there would be roughly a 0.2% chance of seeing a difference this large simply through random chance.
That's why researchers consider the result statistically significant.
But here's the important part: statistically significant does not mean “massively effective.”
It simply means that the researchers have strong evidence that the difference they observed wasn't just random noise.
This is where I think we need to look beyond the headline.
In the adult Phase 3 trials, researchers measured ADHD symptoms using the Adult ADHD Investigator Symptom Rating Scale, or AISRS:
The results were statistically significant, with p-values ranging from 0.001 to 0.039, depending on the dose and study.
So yes, centanafadine performed better than placebo. But we're talking about an average difference of a few points on an ADHD symptom scale.
That brings us to another important concept:
Effect size tells us something different from statistical significance. Instead of asking: “Is there a difference?” it asks: “How big is that difference?”
The adult centanafadine trials produced effect sizes of approximately 0.24 to 0.40:
So the results sit somewhere between small and moderate.
And I think that's actually a much more useful way of looking at the research. Centanafadine clearly appears to work. But the clinical trials don't suggest that everyone taking it is going to experience a dramatic transformation.
One of the Phase 3 trials included 459 adolescents between 13 and 17 years old.
After six weeks, the higher dose produced an average reduction in ADHD symptoms of:
That's a difference of approximately 4.35 points.
The p-value was 0.0006.
A p-value of 0.0006 means that, assuming there really was no difference between the medication and placebo, there would be only about a 0.06% probability of getting a difference this large by chance alone.
That's very strong statistical evidence. But again, the medication group only improved by around 4 points more than the placebo group.
This is why I think it's so important not to confuse statistical significance with clinical significance.
This is another really interesting part of ADHD research.
People receiving placebo often improve too.
In one of the adult studies, ADHD symptom scores improved by approximately 17.7% in the placebo group, compared with approximately 25.5% in the centanafadine 200 mg group.
So why would someone taking a placebo improve?
Because a clinical trial isn't just a pill. Participants are being monitored regularly. They're talking to researchers. They're paying more attention to their symptoms. They may have expectations that they're going to improve.
All of these things can influence how someone experiences and reports their symptoms.
This is one of the reasons placebo-controlled trials are so important. We don't just want to know: “Did people get better?” We want to know: “Did they get better because of the medication?”
One of the most interesting comparisons is between centanafadine and atomoxetine (Strattera).
Atomoxetine has been used for ADHD for many years and is a non-stimulant medication. It works primarily by blocking the reuptake of norepinephrine, increasing its availability in the brain.
Centanafadine works differently. It inhibits the reuptake of norepinephrine, dopamine and serotonin, making it the first approved medication in this particular NDSRI class.
So, could centanafadine be better than atomoxetine?
We don't know yet.
There hasn't been a clinical trial where patients were randomly assigned to either centanafadine or atomoxetine and the two drugs were directly compared.
Researchers have instead used a statistical method called a matching-adjusted indirect comparison (MAIC). Basically, they take data from separate clinical trials and adjust the patient groups so that they are as comparable as possible.
And the results are interesting.
In one comparison, there was no statistically significant difference in ADHD symptom improvement between centanafadine and atomoxetine. In other words, based on the available data, researchers couldn't confidently say that one was more effective than the other.
The longer-term analysis found something similar: after matching the patient populations, there was a 1.60-point difference in ADHD symptom scores between the medications, but this was not statistically significant (p = 0.21).
A p-value of 0.21 means the evidence isn't strong enough to conclude that this difference represents a genuine difference in effectiveness rather than random variation.
This is where centanafadine gets more interesting.
In the indirect comparison, centanafadine was associated with lower rates of several side effects than atomoxetine, including:
For example, the reported difference in nausea was 18.64 percentage points, favouring centanafadine.
But there's an important caveat: these weren't direct comparisons. They came from different clinical trials, and the analysis was conducted by researchers including employees of Otsuka, the company developing centanafadine. That doesn't invalidate the findings, but it does mean we should be cautious about treating them as definitive proof that centanafadine is safer than atomoxetine.
At the moment, I'd say neither has clearly won the argument.
Atomoxetine has something centanafadine doesn't have yet: years of real-world clinical experience.
Centanafadine has something atomoxetine doesn't: a completely different mechanism involving dopamine, norepinephrine and serotonin.
There is also an important distinction that people should understand: Strattera is a non-stimulant. Centanafadine is classified by the FDA as a CNS stimulant, despite its novel mechanism. Centanafadine also carries warnings relating to abuse, misuse and addiction, while its U.S. controlled-substance schedule is still being determined.
So I wouldn't describe centanafadine simply as “the new non-stimulant version of Strattera.” It isn't.
It's a new class of ADHD medication that gives clinicians another option.
Based on the clinical trial evidence, yes.
The Phase 3 programme showed statistically significant improvements in ADHD symptoms compared with placebo across adults, adolescents and children at the effective doses studied. Some studies also found that the medication began separating from placebo as early as the first week.
But here's where I think we need to be realistic: Centanafadine isn't a miracle drug.
The evidence suggests that it produces a genuine benefit, but the average effect seen in the adult trials was relatively modest.
And averages can be misleading when we're talking about individuals:
That's true of ADHD medication generally.
This is probably the question many South African readers will be asking.
The short answer is: we don't know yet.
Centanafadine was approved by the FDA in the United States in July 2026. However, FDA approval does not automatically mean that a medication becomes available in South Africa.
For centanafadine to be routinely prescribed and sold here, the manufacturer would need to go through the South African regulatory process with SAHPRA — the South African Health Products Regulatory Authority.
At present, there is no confirmed South African launch date that I can point to. If the manufacturer submits the medication to SAHPRA and it is subsequently registered and scheduled, South African availability could follow, but the timing is impossible to predict with confidence.
So if you're in South Africa and you're wondering whether you'll be able to walk into a pharmacy and ask for centanafadine later this year, I wouldn't assume that.
A future South African launch is certainly possible, but until there is a formal regulatory announcement, any specific date would be speculation.
When you hear:
“Centanafadine produced statistically significant results in clinical trials,”
don't automatically interpret that as: “This medication dramatically improved ADHD.”
A better interpretation would be:
“The clinical trials provide strong evidence that centanafadine produces a genuine improvement in ADHD symptoms compared with placebo, although the average additional improvement was relatively modest.”
And honestly, that's still pretty significant.
Because ADHD treatment isn't about finding one magic medication that works for everybody. It's about having more options.
Some people respond extremely well to existing stimulant medications. Others don't. Some experience side effects. Some don't get enough benefit. And some people may eventually find that a medication like centanafadine provides the balance they've been looking for.
We just don't know yet who those people will be.
As with any prescription medication, centanafadine should only be started, stopped or changed in consultation with a qualified healthcare professional.
Let’s get you back on track!