It may be dispensed by a barista and not a pharmacist, and the unit sizes may be small, medium and large, but caffeine is a chemical and also a drug, just as much as methylphenidate (Ritalin) is. Caffeine is even sold as a drug — alone and in combination with other products. But I regularly speak with consumers who are instinctively resistant to what they perceive as drug therapy — they want “natural” options. Caffeinehas been touted as a viable alternative to prescription drugs for ADHD. But is caffeine a science-based treatment option? This question is a good one to illustrate the process of applying science-based thinking to an individual patient question.
I’ve already described my personal fondness of caffeine, particularly when it’s in the form of freshly-roasted coffee. I’m not alone in my love. Caffeine is the most widely consumed drug in the world — more than alcohol, and more than tobacco: 90% of adults worldwide consume it daily. The average American consumption is 280mg per day — about two cups of coffee. The main source is coffee, but tea consumption is growing. And caffeinated soft drinks and energy drinks are a growing source of caffeine for children. Why do we love it so much?
Caffeine is quickly absorbed once consumed — and it immediately gets to work stimulating neurotransmitter release. Besides psychiatric effects, it has effects on alertness (positive), headache (also effective, except in withdrawal situations), athletic performance (another win), the cardiovascular system (my fingers are crossed), and the endocrine system, where it may improve diabetic control. It’s also being studied for effects on the gastrointestinal system, as well as its impact on cancer risk. In adults, caffeine consumption is associated with a negative relationship with all-cause mortality, largely due to a reduction of cardiovascular effects. Causation hasn’t been established though. Most of you are very familiar with the side effects of caffeine: agitation, tremors, insomnia, headache. Overall, despite documented cases of dependence and withdrawal, caffeine consumption has a generally attractive safety profile with a wide therapeutic range.
The symptoms of Attention Deficit Hyperactivity Disorder (inattention, impulsiveness and hyperactivity) have been identified for at least 100 years. But once the diagnosis appeared in the DSM-IV, its standardized criteria became commonly used, and the prevalence is now estimated at about 3-7% of children. The term Attention Deficit Hyperactivity Disorder is somewhat of a misnomer, as the dysfunction appears related to an inability to regulate attention — not a deficit. Magnetic resonance studies suggest ADHD may manifest as a weakening of inhibitory signalling in the frontal cortex.The cause appears most likely to be genetic, with environmental influences.
The two main interventions for ADHD are behavioural treatments and drug therapies. The traditional therapies are the stimulant drugs, including amphetamine (Adderall), methylphenidate (Ritalin), and dextroamphetaime (Dexedrine). Some have been in use since the 1960’s. Over time, a wide array of dosage forms including controlled-release versions have emerged, driven by the desire to stabilize blood levels. The basic drugs themselves are short-acting, leading to a fluctuation of effects and the need for mid-day treatments — not ideal for school-age children. Non-stimulant drug therapies (e.g., antidepressants) have more recently emerged as treatment options and may be combined with stimulants, as additional therapies where symptom control isn’t reached with stimulants.
The treatment goals with ADHD are symptom based, so dosing is dependent on the effects observed. Treatment goals usually include reductions in disruptive behaviours, improvements in relationships (with peers, siblings, teachers, and parents), or specific academic parameters. Ideally, treatment goals should be objective and measurable, and agreed-up by parents, teachers, physicians, and children.
The stimulant medications have an impressive safety record and are generally well tolerated. There’s a long history of use. Are they effective? There’s reasonably good data to suggest they are, although comparative data are lacking. [PDF] Response rates to ADHD treatments appears high — 60-80%, and side effects are generally mild and manageable.
So that brings us back to the original question — I developed a focused clinical question using the PICO framework:
- Patient: Who are what are we treating? In this case, children.
- Intervention: What are we treating with? Caffeine
- Comparison: Compared to what? Let’s assume stimulants.
- Outcome: The effect we want to measure. In this case, symptomatic control.
So the question may be summarized as: In children, how does caffeine compare to stimulants for symptomatic control of ADHD?
It’s helpful to start with pharmacology to consider plausibility before we look at clinical trials. Caffeine, or more properly, 1,3,7-trimethylxanthine, has central nervous system effects, mainly thought to be due to blocking adenosine receptors in the brain. Given we don’t know the specific mechanism of action of the ADHD drugs, I’ll accept caffeine as a plausible treatment: it crosses into the brain, and it has CNS stimulant effects.
So let’s look at the data. I started with a tertiary reference: the Natural Medicines Comprehensive Database rates caffeine as “possibly ineffective”. Then I went to PubMed, and ran my own search. Are there placebo-controlled, or head-to-head trials? Yes, and they’re disappointing:
The data are limited by small trials, mostly conducted in the 1970s. There doesn’t appear to be many trials exploring the dose-response relationship, and trials don’t seem to titrate doses — so it’s not clear if we’re evaluating comparable doses. While there don’t appear to be any systematic reviews, there are trials comparing caffeine to other drugs. In one comparison, 20mg of methylphenidate was found to be superior to 160mg of caffeine. In another trial, seventeen children who had positively responded to stimulant drugs were trialed on placebo, or two different doses of caffeine. Caffeine didn’t have any statistically significant effects on behavioural measures. In a trial comparing amphetamines to 600mg caffeine daily, plus amphetamines, caffeine was reported to provide incremental benefit, but side effects were noted. That’s not surprising: 600mg is the caffeine in two Starbucks Grande-sized coffees. A double-blind crossover examination of caffeine, methylphenidate, and dextroamphetamine in 29 children concluded that while the two stimulants had meaningful effects, caffeine was indistinguishable from placebo. Overall — no strong signals of efficacy in the evidence.
Caffeine is a questionable treatment option for ADHD. There is mixed to negative efficacy data, and no long-term safety information in children. Depending on the form given, there’s challenge of ensuring standard doses (especially when using coffee) and maintaining stable blood levels. In comparison, prescription stimulant medications offer a variety of drug choices that have more convincing efficacy data, and are accompanied by a long history of use. There’s also a wide array of product types, making it easier to customize a treatment regimen. So while I can understand the hesitation to medicate and to “go natural” instead, it’s not a trade off that’s attractive. “Go science” instead — look to the data, and make treatment decisions based on the best evidence.