TCPR: What’s missing in how we treat ADHD?

Dr. Brown: Even with stimulant treatment, patients can still have a lot of executive dysfunction. Many have comorbid conditions like dyslexia or processing disorders that stimulants do not treat.

TCPR: How do you screen for those problems?

Dr. Brown: Neuropsychological testing is not necessary for diagnosing ADHD, but it can identify these co-occurring problems. If the patient can’t afford testing, I’ll refer them to a university with a good psychology program to get it done by a trainee. The biggest problems I see on these test results are dyslexia, slow processing speed (visual, verbal, or both), and decreased working memory.

TCPR: What do those problems look like in everyday life?

Dr. Brown: When patients ask what working memory is, I say, “Your brain has a ‘clipboard’ much like your computer does. It keeps important things in active play while you’re working on solving a problem. People with ADHD have a harder time holding things in their clipboard.” For simple information like numbers, most adults can hold five to nine items in their working memory, but that range goes down as the information gets more complicated.

TCPR: How does dyslexia present in ADHD?

Dr. Brown: People with dyslexia have difficulty reading or processing what they hear. Their mind reverses letters and numbers as they read (visual dyslexia) or doesn’t accurately process sounds (verbal dyslexia). About one in three people with ADHD have dyslexia, and the rate is higher if we count all learning disorders like slow processing speed (Handler SM et al, Pediatrics 2011;127(3):e818–e856). To screen, I’ll ask: “Do you have trouble reading or taking notes in class?” “Do you do better if you hear the material or see it?”

TCPR: Do medications help dyslexia?

Dr. Brown: In dyslexia, there is more evidence for complementary treatments than there is for medications, starting with piracetam. This is a synthetic compound that was discovered by a Belgian chemist in the 1950s, and it’s considered the first “nootropic,” which means “to learn better.” In the 1980s, piracetam improved reading ability in students with dyslexia. I rarely use it, though, because it comes as a huge pill or bulky powder that’s hard to swallow (dose 4.8 mg/day; Wilsher CR, J Psychopharmacol 1987;1(2):95–100). I’ve had success with similar “racetam” drugs that are descended from piracetam and are easier for patients to take. The two I use most often are aniracetam (800 mg BID) and pramiracetam (600 mg BID). They are affordable and well tolerated, and they don’t carry any serious risks. Both are classified as pyrrolidinones and work via the NMDA and acetylcholine systems. At higher doses they have anticonvulsant activity, and they are structurally related to the anticonvulsant levetiracetam (Keppra).

TCPR: Do the racetams treat any other psychiatric conditions?

Dr. Brown: We have a few small, controlled trials for racetams in other disorders. In childhood autism, piracetam improved behavioral symptoms (800 mg/day), and in schizophrenia it improved positive and negative symptoms as well as tardive dyskinesia (3.2–4.8 g/day; Akhondzadeh S et al, Child Psychiatry Hum Dev 2008;39(3):237–245; Libov I et al, J Clin Psychiatry 2007;68(7):1031–1037).

TCPR: Do you have a preferred brand for these nootropics?

Dr. Brown: Currently I recommend Pure Nootropics, but let me clarify: I don’t receive any funding from the industry or from any brands I recommend. My recommendations may change with time, especially as we see more shifts in manufacturing from Europe to less regulated countries in the East. Also, all of the therapies I’ll discuss today can be safely combined with stimulants.

TCPR: Is there anything that improves working memory in ADHD?

Dr. Brown: The alpha-agonists have data there: clonidine and guanfacine. I think the benefit is real, but I have not been wowed by it in clinical practice. Both clonidine and guanfacine are FDA approved in ADHD, and they have more steady effects throughout the day than the stimulants do, so I’ve found them helpful to augment stimulants when patients have problems with their stimulant wearing off too early in the day. Some patients have that “crash,” and they get irritable or have trouble going to bed at the end of the day, and these alpha-agonists have the benefit of improving sleep. Sedation is also their main drawback, though. On the complementary side, I’ve found American ginseng helpful for working memory.

TCPR: What is the evidence for American ginseng?

Dr. Brown: There are several types of ginseng: Korean (Panax ginseng), Chinese (Panax notoginseng), and American (Panax quinquefolius). All of them contain ginsenosides, which modulate acetylcholine and glutamate and have anti-inflammatory and neuroprotective effects in the CNS. They all have evidence to improve memory in various populations, and I’ve seen the best effect with American ginseng. It improved working memory in several controlled trials, and the benefits are measurable after just a few hours, but they also held up in studies lasting several months (Ossoukhova A et al, Hum Psychopharmacol 2015;30(2):108–122). Most of these studies were conducted in healthy adults, but ginseng also improved inattentive and hyperactive symptoms of ADHD in two placebo-controlled trials in children (Lee J and Lee SI, J Atten Disord 2021;25(14):1977–1987; Ko HJ et al, J Child Adolesc Psychopharmacol 2014;24(9):501–508).

TCPR: How do you dose American ginseng?

Dr. Brown: A typical dose is 500–1000 mg BID of ginseng with 10% ginsenosides. I use the Hsu’s American Gin-Max brand of American ginseng (Editor’s note: Cost is 50 cents per 500 mg tablet on Amazon). People feel it working right away, whereas other brands have a slower onset. They solve problems more quickly. They process things a little bit better. One of my patients who switched said, “It’s like I went from an old-fashioned TV to high definition.” I’ve not seen many side effects with ginseng, but it can cause insomnia, anxiety, and headaches (Editor’s note: Ginseng doesn’t have major medical risks but may increase bleeding time—exercise caution with patients who are undergoing surgery or taking anticoagulants).

TCPR: You’ve talked about working memory and dyslexia. Do you also use complementary therapies for core symptoms of ADHD?

Dr. Brown: There are a lot of options out there with positive controlled trials, like B vitamins, omega-3 fatty acids, and zinc. What I do is try these out in practice and stick with the ones that are affordable, tolerable, and effective for my patients. I prescribe a lot of stimulants, and I recommend them first line, but sometimes patients have had problems with stimulants or want to start with natural things. Others get better on stimulants but not all the way, in which case I may augment with a complementary therapy.

TCPR: Which treatments do you find most helpful?

Dr. Brown: One overlooked treatment that I’ve found useful is pycnogenol, which is an extract of the French maritime pine bark tree. Pycnogenol is patented, which is a good thing in terms of ensuring quality, but you can find it in various brands because the company franchises the extract.

TCPR: What does pycnogenol do in the brain?

Dr. Brown: Pycnogenol is a polyphenol with neuroprotective properties, which puts it in the class of nutrients that have cognitive benefits, like those found in ginkgo, green tea, blueberries, and dark chocolate. Pycnogenol also seems to correct the low ratio of zinc to copper that we tend to see in people with ADHD.

TCPR: How good is the evidence?

Dr. Brown: Pycnogenol has two small, randomized, placebo-controlled trials in ADHD. One was positive, involving children at a dose of 0.5 mg/lb/day. The other was negative, involving adults at about twice the pediatric dose (1 mg/lb/day). The negative study is not very informative, though. It’s a “failed” study because the active treatment arm—which was methylphenidate 45 mg/day—did not separate from placebo either. So the evidence is not definitive, but a larger trial is underway (Trebatická J et al, Eur Child Adolesc Psychiatry 2006;15(6):329–335).

TCPR: Saffron is getting a lot of media attention in ADHD.

Dr. Brown: Yes, saffron has potential. Unfortunately, it has only one controlled trial in ADHD, but it did improve cognition in trials with other populations. In the ADHD trial—which was small, involving 54 children—saffron 30 mg/day worked as well as methylphenidate 30 mg/day (a lower dose, 20 mg/day for each drug, was used for children under 65 lbs). Although the result is encouraging, the study lacked a placebo arm, so we don’t know if the improvements in both treatments were due to a robust placebo effect (Baziar S et al, J Child Adolesc Psychopharmacol 2019;29(3):205–212). In my experience, I’ve found saffron helpful for ADHD, depression, premenstrual dysphoric disorder, anxiety, and dementia (Editor’s note: Saffron has positive controlled trials in each of those conditions, as monotherapy and augmentation, at a dose of 30–60 mg/day, although most of the trials come from a single academic center; see Hausenblas HA et al, J Integr Med 2015;13(4):231–240).

TCPR: What else do you find helpful in ADHD?

Dr. Brown: I am seeing good results with Rhodiola rosea. It affects dopamine, as well as norepinephrine and serotonin, and it has a few small, positive controlled trials in depression (Gao L et al, J Affect Disord 2020;265:99–103). Rhodiola rosea is an herbal adaptogen—in other words, it helps people respond better to stress. Although it has not been studied in ADHD specifically, it did improve cognition and attention in controlled trials of other populations, like healthy adults who were under stress and people with nonspecific cognitive difficulties, including astronauts in spaceflight and men with brain injuries due to gunshot wounds (Lewis JE et al, J Clin Transl Res 2021;7(4):575–620). In my own practice, I have seen some turnarounds with it in ADHD.

TCPR: You also mentioned B vitamins, omega-3 fatty acids, and zinc, and I’ve seen positive trials involving vitamin D and l-carnosine in ADHD. Are any of those worth trying?

Dr. Brown: L-carnosine is often used to reduce inflammation in diabetes and improve exercise tolerance, and there are a few positive reports in autism and ADHD, but my experience with it was overwhelmingly unimpressive, so I stopped using it a few years ago. Vitamin D has largely been a “D” for disappointment. It may just be a marker for other factors that influence health, like how much time you spend outdoors. B vitamins, omega-3 fatty acids, and zinc have controlled trials in ADHD, but the effects are small—I don’t see much difference in practice with them.

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