TCPR: In our first interview, you said stimulants are helpful for nontraditional ADHD, but I imagine the benefits are limited.
Dr. Gualtieri: Time-limited, yes. They can be quite helpful for a while, but stimulants don’t have reliable, long-term benefits on memory, attention, executive function, creativity, or test scores (Advokat C, Neurosci Biobehav Rev 2010;34(8):1256–1266). Some artists will tell you that stimulants enhance their creativity, but I don’t believe that. Artists and poets have said that about cannabis, cocaine, opium, and alcohol. Stimulants don’t improve cognitive flexibility; rather, they confine one’s perspective. They can make people hyperfocused, stubborn, and robotic—like a zombie. These effects tend to be dose-dependent, but there’s one group who is especially vulnerable.

TCPR: What group is that?
Dr. Gualtieri: Anxious and compulsive patients. These are patients who are constantly doubting themselves, to the point that they start to think they have ADD. They’ll tell you, “My high school GPA was 5.5, but I always had to work so hard.” What they’re saying is true, but it’s not the ADD that’s making them work hard; it’s obsessive anxiety. Perfectionism. People with this trait do well on cognitive tests, but it takes them longer because they have to use a lot of mental energy to overcome the internal negative biases that distract them.

TCPR: Do the stimulants make them more anxious?
Dr. Gualtieri: You would think so, but anxious patients often respond favorably. Anxious patients have slower mental processing speed, and stimulants increase processing speed. Maybe stimulants give them a boost of mental energy to control anxiety. The problem is that stimulants are “on-off” drugs. You experience their effects when they are working, and you can feel when they wear off. Patients who are anxious or compulsive already have problems with self-absorption. They are obsessive about their mental state. When we give them stimulants, we are conditioning them to monitor their mental state, which is not necessarily a good thing. When the stimulant wears off at the end of the day, their mental state changes, and their anxiety ramps up: “Wait, I’m fatigued, I’m distracted.” They obsess about being on just the right dose and how long that dose lasts. It never lasts long enough or works well enough. To be clear, I’m talking here about people with anxiety and obsessive-compulsive personality traits, not OCD. About a third of people have such traits—as does virtually everyone who gets into medical school.

“It’s important to remember a patient doesn’t have ADHD just because they say they do. While attention problems are real, they don’t automatically mean ADHD. Instead, they should prompt a careful differential diagnosis to determine the actual cause.”

C. Thomas Gualtieri, MD 

TCPR: A few years ago, there was a trial that randomized professional chess players to methylphenidate or placebo. The ones who got the stimulant performed worse because they kept second-guessing their moves (Franke AG et al, Eur Neuropsychopharmacol 2017;27(3):248–260).
Dr. Gualtieri: Yes. And it’s why a dose of amphetamine won’t help you on the SATs. Stimulants are cognitive enhancers in patients with ADD and many brain injury patients, but not in people who are cognitively normal. Stimulants just give them a bit more energy and confidence. Even in ADD, the cognitive effects of stimulants are mixed. When we give patients a dose of a stimulant in the clinic and test them an hour later, they usually improve on tests of attention and mental processing speed, but they get worse on the Stroop test, a measure of cognitive flexibility.

TCPR: What about people who just have too much on their plate?
Dr. Gualtieri: Overload can make one inattentive. So can fatigue, sleep deprivation, stress, and a physically deconditioned state. But overwork is something that often brings patients to our clinic. Some people take on too much work because they are compulsive. For others, it’s out of necessity. They are working two jobs, or managing kids while working virtually from home. They are sleep deprived. Often they’ll take a friend’s stimulant, or one of their children’s, and experience a pleasing burst of energy. So, they decide they must have ADD. They visit a doctor, check the right boxes on a short questionnaire, and presto! They have ADD. Stimulants may help in such circumstances. They do help with mental energy, and there is evidence that they stimulate mitochondrial activity. But they don’t help multitasking as such. They just give patients a bit more energy to get stuff done.

TCPR: What are the risks of giving stimulants to normal, overworked people?
Dr. Gualtieri: If you’re dealing with a responsible individual, it’s not a major risk to prescribe them a low dose of a stimulant to take occasionally, by which I mean like once a week or once a month. Where we can run into trouble is when a patient has a psychotic illness, bipolar disorder, a substance use disorder, or cardiovascular risk factors. Some people get a transient blood pressure spike when they take stimulants intermittently, and this can pose a problem, particularly in elderly patients.

TCPR: How do you handle stimulants in patients with major psychiatric disorders?
Dr. Gualtieri: Practically all major psychiatric disorders compromise attention and executive function. But the risk of psychosis is high when people with bipolar disorder or schizophrenia take a stimulant. I will use them occasionally in bipolar disorder if the patient is conscientious about treatment and has had a stable mood for a long time. But otherwise, it’s not a good idea (Moran LV et al, Am J Psychiatry 2024;181(10):901–909).

TCPR: Some people don’t have a lot on their plate, but they complain of mental fatigue. They may be older, have long COVID or other medical problems, or are burned out on their job.
Dr. Gualtieri: Or they have “brain fog” from cancer chemotherapy or menopause, chronic fatigue syndrome, or fibromyalgia. Sometimes stimulants are effective there, sometimes not. There are, of course, nonstimulant alternatives, but they don’t always work. These people are experiencing real suffering, and it’s frustrating when no drug helps.

TCPR: Do stimulants help age-related cognitive decline?
Dr. Gualtieri: Low doses of methylphenidate, like 5–20 mg a day in long-acting form, help cognition, mood, and energy in older adults with various medical problems (Sassi KLM et al, Curr Neuropharmacol 2020;18(2):126–135). It’s not unreasonable to try a stimulant for conscientious older patients who won’t overuse it and don’t have cardiovascular disease. However, cholinesterase inhibitors (eg, donepezil, galantamine, rivastigmine) and some antidepressants (eg, bupropion, vortioxetine) are better cognitive enhancers for older people (Lenze EJ et al, Am J Psychiatry 2020;177(6):548–555).

TCPR: How do you counsel patients who aren’t so conscientious and don’t have classic ADHD? 
Dr. Gualtieri: The problem is that some people misuse stimulants. During past amphetamine epidemics in countries like Japan and Sweden, up to 10% of the adult population was using these drugs. In the US, we’re approaching similar numbers—though now it’s largely through prescriptions under what’s considered medical supervision. But how careful is that supervision, especially with the rise of telemedicine? It’s important to remember a patient doesn’t have ADHD just because they say they do. While attention problems are real, they don’t automatically mean ADHD. Instead, they should prompt a careful differential diagnosis to determine the actual cause (see the table below).

TCPR: What about people who overuse stimulants?
Dr. Gualtieri: Some of them have stimulant use disorder. Others don’t meet the criteria for that, but stimulants have become part of their way of life, as coffee is for other people. They may smoke cannabis to go to sleep and take stimulants to wake up. It’s not a great idea, to say the least, but is it substance use disorder? In some colleges, 25% of students seem to be doing just that (McCabe SE et al, JAMA Netw Open 2023;6(4):e238707). 

TCPR: And sometimes their clinician will oblige them and raise the dose.
Dr. Gualtieri: You and I are not that kind of clinician, nor the majority of our colleagues. When encountering such patients, I explain that stimulants have an inverted U-shaped curve in their cognitive effects: Low doses improve cognition, but higher doses impair cognition. Those high doses can also cause a cardiac arrhythmia. They listen politely and go find another prescriber. If I can get them to stay, I lower the dose by about 10 mg a month. They complain that they can’t function without more, but on testing their cognition usually improves.

TCPR: Thank you for your time, Dr. Gualtieri.