Literature Review of Clinical Use of Caffeine for Treatment of ADHDSamuel Lee
Introduction/Background to Caffeine and ADHD
ADHD is one of the most prevalent psychiatric disorder in children which can continue through adolescence and adulthood with symptoms of hyperactivity, inattention, and impulsivity. Currently methylphenidate is the most common drug used to treat ADHD. Methylphenidate serves as a blocker of monoamine reuptake, specifically dopamine transporters. By blocking the dopamine transporters, higher concentrations build up in the synaptic cleft which leads to increased neurotransmission of dopamine. However, methylphenidate often comes with side effects, such as insomnia, weight loss, and reduced appetite. In order to avoid these side effects, new treatment regimens need to be proposed. Adenosine neuromodulation controls dopamine which can simulate the effects of methylphenidate. Since caffeine is an adenosine antagonist, there is interest in manipulation of the adenosine modulation system to see its potential in alleviating the symptoms of ADHD. Caffeine and its therapeutic effects on people with ADHD needs to be further explored and researched.
Caffeine has been around since the Stone Age as humans found out that chewing on leaves of certain plants stimulated awareness, eased fatigue, and elevated mood. We now know caffeine is a central nervous system and metabolic stimulant. As a stimulant, caffeine acts as an A1 and A2A receptor antagonist, meaning it inhibits the adenosine receptors due to its similar structure to adenosine. Through adenosine antagonism, caffeine affects dopaminergic, noradrenergic, and glutaminergic neurotransmitter systems. Dysregulation of dopaminergic and noradrenergic systems has been associated with the pathophysiology of ADHD. Since both adenosine and dopamine modulation systems are tightly intertwined, it is logical to question the possible therapeutic effects of caffeine.
History of Caffeine in Use with ADHD
According to Konstantinos Ioannidis et. al in their study, “Ostracising Caffeine from the Pharmacological Arsenal for Attention-deficit Hyperactivity Disorder – Was This a Correct Decision? A Literature Review,” caffeine was first proposed to be in relation with ADHD in a study by Schnackenberg in 1973. In his study he used 11 hyperactive children who had been previously treated with mehylphenidate and then developed side effects. He found that all the children showed improved symptoms after treatment of coffee. In addition he found there to be no side effects associated with coffee which sparked the idea of caffeine in its clinical use for ADHD. Attempting to replicate this new study, many studies arrived at different results. Some studies did find similar findings, but the replicability of Schnackenberg’s findings was limited. Therefore caffeine was thought to be inferior to the first line of stimulants. Less research was done after this until a meta-analysis was done that showed that caffeine was less efficacious than methylphenidate, but was more effective than no treatment or a placebo.
Caffeine has proved to be beneficial in cognitive skills as seen in “Effects of Diurnal Variation and Caffeine Consumption on Test of Variables of Attention (TOVA) Performance in Healthy Young Adults.” The TOVA, a test commonly used as a clinical assessment tool for ADHD, tests attention, impulsivity and processing speed. Those who are diagnosed with ADHD generally show lower TOVA scores since they usually show a slower processing speed, inattention and impulsivity. Mellisa G. Hunt et. al looked at the effects of caffeine on the TOVA scores with those who had a lower average consumption of caffeine and those with a higher average consumption of caffeine. Those with a lower average consumption of caffeine scored much higher on the TOVA than the placebo group, demonstrating the cognitive enhancing effects of caffeine on attention, impulsivity, and processing speed which are often associated with ADHD.
There have been promising results from some animal studies that use rat models in their experiments. In the animal study, “Caffeine Improves Attention Deficit in Neonatal 6-OHDA Lesioned Rats, an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD),” there were improvements in attention deficit in 6-OHDA lesioned rats, an animal model used for ADHD. Seven days after birth, Miguel Caballero et. al made a lesion at the left striatum. The lesion in the brain causes the rats to have similar symptoms of ADHD. After performing surgery on their brains, Miguel Caballero et. al measured their spatial recognition and motor skills by using the Olton maze. Then they started to provide caffeine in the drinking water of the rats and again measured their spatial recognition and motor skills with the Olton maze. Interestingly they found that caffeine consumption improved spatial attention, but not motor skills, leading us to believe that caffeine may help with attention deficit during the prepubertal period. Another animal model study, “Chronic Caffeine Treatment during Prepubertal Period Confers Long-term Cognitive Benefits in Adult Spontaneously Hypertensive Rats (SHR), an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD),” was done with the SHR (spontaneously hypertensive rat) which is an animal model often used to study ADHD. Vanessa A. Pires treated the SHR rats with caffeine and methylphenidate which improved object-recognition deficits, but not their motor activity, strengthening the idea presented in the previous study that caffeine does not have an effect on motor skills. The results from both animal model studies support the use of caffeine as a therapeutic agent to treat ADHD. Although both animal studies point to caffeine as a possible treatment, one should be cautious in thinking that this will work with humans based solely off animal studies.
A caffeine dosing regimen needs to be considered, for caffeine to one day to actually be used. One of the only available meta-analysis study suggests that the optimal dose of caffeine may be 150 mg/day. Higher dosages can actually induce an increase instead of a decrease of adenosine receptors, causing unwanted side effects, so low to moderate dosages of caffeine are most likely optimal. Furthermore, methylphenidate usually works well in treating ADHD, but discontinuing the use of the drug in the middle of its treatment plan warrants the introduction of second line drugs. Further research needs to be done in order to see whether caffeine is as effective as these second line drugs and the possibility of using caffeine alone or in combination with other drugs. In addition there is a high correlation between people who have ADHD and caffeine consumption which suggests there is a possibility that people self-medicate themselves with caffeine. Caffeine is readily available in all kinds of forms such as tea, coffee, chocolate and soft drinks which grants people easy access to caffeine. According to one survey, “75: Adolescent Caffeine Use and Its Association with ADHD and Cigarette Smoking,” people with ADHD were almost twice as likely to consume more caffeine than people without ADHD. Overconsumption can lead to a condition called “caffeinism” which can cause anxiety, restlessness, and nervousness. In order to avoid over consumption, it would be worthwhile to consider developing a pharmacologically sound caffeine regime for people diagnosed with ADHD. If a caffeine treatment plan were to be made, a “drug holiday,” a day of no caffeine should be considered, for habitual caffeine consumption can cause tolerance. In addition as the previous study, “Effects of Diurnal Variation and Caffeine Consumption on Test of Variables of Attention (TOVA) Performance in Healthy Young Adults,” suggests, those who have a lower average caffeine consumption displayed greater cognitive improvements. As we can see many questions regarding the dosing regimen of caffeine still need to be answered.
Many of the clinical studies have been done with small sample sizes so there is still some research to be done. Furthermore, we struggle to see demographically what works for children, adolescents and adults. Some studies with children have shown that caffeine produces therapeutic effects, but to a lesser degree than methylphenidate. Not enough data has been collected on adolescents and adults to conclude any effects of caffeine on these age groups even though 65% of the time ADHD progresses to adolescence and adulthood. Therefore, it is essential to research more on the therapeutic effects on caffeine of varying age groups and demographics. Due to the dearth of research done demographically and lack of data, it would be worthwhile to conduct more research on caffeine and its beneficial effects on people diagnosed with ADHD.
Caballero, Miguel, Fabiana Núñez, Siobhán Ahern, Maria L. Cuffí, Lourdes Carbonell, Silvia Sánchez, Víctor Fernández-Dueñas, and Francisco Ciruela. “Caffeine Improves Attention Deficit in Neonatal 6-OHDA Lesioned Rats, an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD).” Neuroscience Letters 494.1 (2011): 44-48. Web of Science. Web. 2 Sept. 2014.
Hunt, Melissa G., Ani J. Momjian, and Keri K. Wong. “Effects of Diurnal Variation and Caffeine Consumption on Test of Variables of Attention (TOVA) Performance in Healthy Young Adults.” Psychological Assessment 23.1 (2011): 226-33. Web.
Ioannidis, Konstantinos, Samuel R. Chamberlain, and Ulrich Muller. “Ostracising Caffeine from the Pharmacological Arsenal for Attention-deficit Hyperactivity Disorder – Was This a Correct Decision? A Literature Review.” Sage Journals 28.9 (2014): 830-36. Web of Science. Web. 3 Sept. 2014.
Liu, Kezhi, Xuemei Liang, and Weihong Kuang. “Tea Consumption Maybe an Effective Active Treatment for Adult Attention Deficit Hyperactivity Disorder (ADHD).” Medical Hypotheses 76.4 (2011): 461-63. Web of Science. Web. 2 Sept. 2014.
Pires, Vanessa A., Fabrício A. Pamplona, Pablo Pandolfo, Rui D.s. Prediger, and Reinaldo N. Takahashi. “Chronic Caffeine Treatment during Prepubertal Period Confers Long-term Cognitive Benefits in Adult Spontaneously Hypertensive Rats (SHR), an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD).” Behavioural Brain Research 215.1 (2010): 39-44. Web of Science. Web. 2 Sept. 2014.
Walker, Leslie R., Kwame Ofori, Lauren Wine, Anisha Abraham, and Kenneth P. Tercyak. “75: Adolescent Caffeine Use and Its Association with ADHD and Cigarette Smoking.” Journal of Adolescent Health 40.2 (2007): S51-52. Web of Science. Web. 3 Sept. 2014.