Adderall and Ritalin are common ADHD drugs with very different impacts on the brain. A new paper in the New England Journal of Medicine reports that for some patients, in particular, Adderall has a very dark side. The authors of that paper believe Adderall has strong ties to a persistent psychological disorder that causes delusions or a detachment from reality, while Ritalin does not.

Using the insurance records of nearly 221,846 ADHD patients, Dr. Lauren V. Moran, a psychiatrist and assistant professor at Harvard Medical School, showed that patients who were prescribed amphetamine-based ADHD drugs like Adderall developed more cases of psychosis, a group of symptoms that includes delusions, hallucinations, and a loss of touch with reality. In the study, one in every 486 patients on amphetamine-based drugs developed psychosis, whereas only one in 1,146 on methylphenidate-based drugs like Ritalin had the same outcome.

"That lead me to think, maybe the Adderall-like drugs are more likely to cause psychosis than the Ritalin-like drugs."

It’s important to note that in this study, overall rates of psychosis were rare: Only 0.1 percent of all the patients analyzed developed it. Still, Moran tells Inverse she’s already seen more than one patient come in with a psychosis case at Harvard’s McLean Hospital after using (and abusing) drugs like Adderall or Ritalin.

“At McLean, we see people who were prescribed the medication developing psychosis, but we also see people who are abusing it getting psychosis as well,” she says. “There are so many college students around here, and we’ve been seeing patients come in who are developing a first episode of psychosis in the context of stimulant use — more often, amphetamines.”

Adderall and Ritalin are both sometimes used as a study drug, but this study found that Adderall is more strongly tied to psychosis than its competitor, Ritalin. Pixabay

To be clear, Moran’s study looked at people with new onset psychosis cases, so people who have spent years on Adderall and not seen these effects are probably fine. But for someone who is already at risk for psychosis — due to family history, drug abuse, or, controversially, marijuana use — it might be worth opting for one type of drug over the other, just in case.

Adderall vs. Ritalin

Moran says her paper demonstrates a connection between amphetamines and psychosis that fits well with other psychosis research. It all comes back to dopamine — a neurotransmitter that is abundant in patients with psychotic disorders like schizophrenia. Dopamine isn’t the only neurotransmitter associated with psychosis, but it is a major one.

“There’s been a lot of work done looking at psychosis in patients,” she explains. “What we see is that there seems to be more release of dopamine in patients with psychosis, whether it’s patients with schizophrenia or patients at risk for psychosis.”

Adderall is a prescription drug for ADHD. Wikimedia / Guinnog

The crucial point Moran makes is that Adderall and Ritalin are both stimulants that affect levels of dopamine in the brain, but they do it in very different ways. She calls Adderall a “releaser” because it causes the brain to release dopamine. Ritalin, on the other hand, is a “blocker” — it stops the dopamine that’s already been released from being reabsorbed by neurons.

"The patterns that we see with amphetamines more closely parallel what the studies of people with psychosis show."

“The patterns that we see with amphetamines more closely parallel what the studies of people with psychosis show,” she says. “And so that led me to think, maybe the Adderall-like drugs are more likely to cause psychosis than the Ritalin-like drugs.”

Because Moran used insurance data, she can’t be sure exactly what was happening in the brains of the people who developed psychosis. But a release of dopamine caused by amphetamine-based “releaser” drugs is her best guess for now.

“That’s What Makes It Concerning”

What really concerns Moran is that ADHD prescriptions have been increasing on their own, which the CDC noted in January 2018. Between 2003 and 2015, the rates of women who filled prescriptions for ADHD medications (including both Ritalin and Adderall) increased by 344 percent, the CDC reported. Moran notes the amphetamine prescriptions themselves have also increased.

“One of the things that was surprising to me is that the rates of amphetamine use, particularly in this age group, is going up dramatically,” she says. “I guess that’s what’s kind of concerning, even though it’s a rare side effect.”

Though psychosis is not a common side effect, Moran is clear that it can be a devastating one. It may not be on the forefront of a prescriber’s mind, let alone a college student desperately seeking a study drug, but it might give both of them a reason to think again before they reach for the amphetamines.

Abstract:

Background: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit–hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied.

Methods: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases.

Results: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09).

Conclusions: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.)