Methylphenidate in the Treatment of ADHD

Introduction and Background 

Methylphenidate belongs to a class of drugs known as stimulants. It acts as a stimulant to the central nervous system stimulant commonly manage the symptoms of Attention-Deficit/ Hyperactivity Disorder (ADHD) (Myer et al., 2018). The drug is also marketed under other brand names such as Concerta, Biphenti, or Ritalin. It is used together with other treatment options (behavioral, cognitive, educational, and psychological therapy) to improve developmentally inappropriate signs associated with ADHD. These signs include short attention span, emotional liability, impulsivity, and distractibility. Methylphenidate is widely used for ADHD treatment and is considered the first-line option for children, teenagers, and adults following recommendations by the Canadian ADHD Resource Alliance (CADDRA) (Myer et al., 2018). This paper examines the causes and symptoms of ADHD, optional treatments and medications, and the use of Methylphenidate for the treatment of ADHD. 

Symptoms, Causes, and Various Types of ADHD 

ADHD is a cognitive disorder that makes it challenging for an individual to pay attention or control their impulses. A patient who has ADHD may be continuously active or continuously restless. ADHD is not only a childhood disorder ( Kemper et al., 2018) . Although the disorder begins during childhood, the symptoms can spill over into adolescence to adulthood. Hyperactivity typically tends to improve as an individual gets into adolescence. However, inattention, poor control of impulses, and disorganization often continue into adulthood. People with ADHD may also experience low self-esteem, poor academic performance, and troubled relationships. Although ADHD symptoms decline with age, some people never outgrow them completely though they can adapt coping strategies to maintain a productive lifestyle. 

Symptoms 

The main symptoms of ADHD are hyperactivity and inattention. These symptoms often start before the age of 12 years, but they are noticeable as early as three years in some children ( Danielson et al., 2018) . The symptoms range from mild, to moderate, to severe and may sometimes prolong into adulthood. ADHD is more common in males than it is in females, and behaviors vary between the two sexes ( Danielson et al., 2018) . For example, girls tend to be more inattentive, while boys tend to be more hyperactive. 

Types of ADHD 

ADHD occurs in three forms namely, predominantly inattentive, predominantly hyperactive, and combined. A predominantly inattentive person is unable to pay attention to essential activities (Kemper et al., 2018) . Predominantly hyperactive, one is unable to control their impulses and exhibits hyperactive behaviors. A person with combined ADHD has a mix of both inattention and hyperactivity. 

Causes of ADHD 

Currently, there is no definitive cause for ADHD, but research continues to put efforts into determining the exact causes. However, factors such as genetics, environmental stimulants, and disorders of the central nervous system are said to be the leading causes of ADHD ( Danielson et al., 2018) . Some of the risk factors for the disorder include genetic affiliation, environmental triggers such as lead, use of cigarettes, alcohol, or drugs during pregnancy, and premature birth ( Danielson et al. 2018) . Sugar is also said to cause hyperactivity, but there is no credible proof that this is the case. 

Treatment Options 

ADHD is not curable, but proper treatment and therapy can help control the various symptoms and enable one to lead a healthy life. Treatment typically involves the administration of certain medications, but a more comprehensive approach includes a combination of drugs, education, and behavioral therapy ( Coeytaux et al., 2018) . Medicines for ADHD works by increasing the amounts of norepinephrine and dopamine in the brain. The most common drugs prescribed for ADHD are stimulants that are available in the form of capsules, liquids, pills, or skin patches. Some of the most common stimulants include Adderall, Focalin, Daytrana, Dexedrine, and Vyvanse ( Coeytaux et al., 2018) . Although the FDA disapproves of it, sometimes physicians prescribe the use of antidepressants alone or with other stimulants to control the condition. Antidepressants include Tofranil, Wellbutrin, Norpramin, and Aventyl ( Coeytaux et al., 2018) . Apart from medication, other non-pharmacological treatments can be used to manage ADHD. These include the following 

Parent-led Behavioral Therapy 

This therapy works by treating the primary symptoms of ADHD and non-compliant behaviors associated with it ( Danielson et al., 2018) . The model combines behavior management strategies with therapeutic elements basing on the cognitive and social development models. 

Classroom-led Behavioral Therapy 

This type of therapy provides real-life training on the acceptable and expected behavior within specific contexts (Kemper et al., 2018) . The interventions can be applied by immediate teachers who will adhere to the appropriate methods of training and combine cognitive-behavioral modification and behavior modification techniques. 

Cognitive Behavioral Therapy (CBT) 

This type of therapy involves self-instructional training applied to an individual or a group. The treatment helps patients to develop a more reflective and planned approach to behaving, thinking, and social interactions. It also allows patients to adopt a more systematic, goal-oriented, and reflective approach to daily activities, tasks, academics, and problem-solving ( Danielson et al., 2018) . Regular application of CBT has been found to effectively control ADHD symptoms in children, teenagers, and adults. 

Neurofeedback 

Neurofeedback involves computer-programmed exercises, which offer feedback about attention levels to facilitate behavioral training. The brain activities of patients are measured using an electroencephalogram during a task (Kemper et al., 2018) . The task is usually a computer game where participants receive points when the activities in their brains exhibit positive changes. Patients are then trained on how to monitor the patterns of their brainwaves and how to change them. 

Dietary Techniques 

The diet for patients who have ADHD involves eliminating wheat, sugar, eggs, milk, food additives, and food colorings. Patients should cut down on their sugar intake and things such as soda and candy ( Coeytaux et al., 2018) . Including herbal, mineral, and vitamin supplements into the diet is also an effective technique to control the symptoms of ADHD. Fatty acids from Omega-3 may also help to treat the symptoms. 

Pharmacological Aspects of Methylphenidate 

Class and Indication 

Methylphenidate is used to control and manage the symptoms of Attention Deficit Hyperactivity Disorder. It acts by altering the amounts of specific natural elements in the brain (Myer, Boland, & Faraone, 2018). The drug belongs to a drug class known as stimulants, which help to increase attention spans and control behavioral problems (Myer, Boland, & Faraone, 2018). Methylphenidate is available in different brand names such as Ritalin, Concerta, Metadate, Methylin, Daytrana, and Aptensio XR (Myer, Boland, & Faraone, 2018). 

Mechanism of Action 

Methylphenidate acts as a dopamine and norepinephrine inhibitor. It means that it increases the presence of the two neurotransmitters in the brain, thus extending their action. Methylphenidate has a dose-related effect on receptor stimulation. High doses increase norepinephrine and dopamine efflux in the brain, thus resulting in impaired cognition (Myer et al., 2019). 

On the contrary, low doses selectively activate the two neurotransmitters within the prefrontal cortex, thus improving its clinical efficacy and reducing the adverse effects of the drug. Unlike the higher doses, lower doses do not activate locomotion, but instead, they reduce impulsivity, movement, and enhance attention and memory. The beneficial effects of Methylphenidate in improving concentration are also associated with the alpha-1 adrenergic receptor activity. 

Absorption 

Methylphenidate is readily absorbed in the body. After oral intake of Methylphenidate, plasma methylphenidate concentrations reach the maximum at an hour. They further ascend gradually over the next 5 hours (Myer, Boland, & Faraone, 2018). Mean peak times to achieve maximum concentrations of Methylphenidate occur between 5 to 10 hours. Depending on the provided doses, Cmax is found to be 6.0-15.0ng/mL, Tmax 8.1-9.4h, and AUC 50.4-121.5 ng·h/mL in children (Myer, Boland, & Faraone, 2018). 

Metabolism 

Methylphenidate metabolizes hepatically. It is extensively and rapidly metabolized by carboxylesterase CES1A1. Through this carboxylesterase CES1A1, the drug goes through de-esterification. In this process, it produces ritalinic acid, which hardly has any pharmacologic activity (Myer et al., 2019) . 

Elimination Route 

Following oral administration of a release methylphenidate formulation, about 98% of the drug is excreted through the urine, while 1% is excreted through the feces as metabolites within a maximum of 96 hours. Only about 1% of unchanged Ritalin is found in the urine (Myer et al., 2019) . About 60 to 86% of the drug is excreted in the urine in the form of ritalinic acid; the remaining amount is accounted for by minor metabolites (Myer et al., 2019) . 

Side Effects 

Insomnia and nervousness are the most common side effects of Methylphenidate, but they are typically managed by lowering the dose and stopping the drug in the evenings and afternoons (Myer, Boland, & Faraone, 2018) . Methylphenidate also has other reported adverse effects. These include: 

Hypersensitivity 

Anorexia 

Dizziness 

Nausea 

Headache 

Palpitations 

Drowsiness 

Dyskinesia 

Pulse changes 

Blood pressure 

Cardiac arrhythmia 

Angina 

Weight loss and abdominal pain. 

There have been rare cases where patients have experienced Tourette's and toxic psychosis (Myer, Boland, & Faraone, 2018) . Although there is no established causal relationship, patients on Methylphenidate also experience the following effects: 

Cases of cerebral arteritis, occlusion, hepatic coma, abnormal functioning of the liver, depression, and hair loss. 

Toxicity 

In case of an overdose, patients have been found to experience: 

Agitation 

Vomiting 

Hyperreflexia 

Tremors 

Convulsion 

Muscle twitching 

Confusion 

Euphoria 

Delirium 

Hallucinations 

Headache 

Tachycardia 

Hyperpyrexia 

Flushing 

Hypertension 

Dry mucous membranes 

Mydriasis 

Cardiac arrhythmia (Myer et al., 2019) . 

Contraindications 

Methylphenidate is contraindicated in patients with agitation, anxiety, and tension. The drug seems to aggravate the symptoms. It is also contraindicated in patients who are hypersensitive to Ritalin or other elements of the drug (Myer et al., 2019) . Patients with glaucoma are also warned against taking Methylphenidate. Methylphenidate is also contraindicated in patients experiencing motor tics or patients diagnosed with the Tourette's syndrome. The drug is also contraindicated during the administration of monoamine oxidase inhibitors and also less than 14 days following intake of monoamine oxidase inhibitors. Administration of Methylphenidate may result in a critical case of hypertension (Myer et al., 2019) . Lastly, Methylphenidate is contraindicated in patients with angina pectoris, hypertension, heart failure, cardiac arrhythmia, myocardial infarction, thyrotoxicosis, and hyperthyroidism. 

Conclusion 

Methylphenidate belongs to a class of drugs known as stimulants and is used in the treatment of ADHD. ADHD is a cognitive disorder that makes it challenging for individuals to pay attention or control their impulses. A patient who has ADHD may always be active or continuously restless. Its symptoms include hyperactivity and inattention and may range from mild to moderate to severe and may sometimes prolong into adulthood. Factors such as genetics, environmental stimulants, and disorders of the central nervous system are said to be the leading causes of ADHD. ADHD risk factors include genetic affiliation, environmental triggers such as lead, use of cigarettes, alcohol, or drugs during pregnancy, and premature birth. 

Treatment of ADHD includes the administration of medications such as Adderall, Focalin, Daytrana, Dexedrine, and Vyvanse. It may also include a range of non-pharmacological therapies such as CBT, parent-led behavioral therapy, and dietary changes. Methylphenidate is the most effective medication for managing the symptoms of ADHD . It increases the presence of the dopamine and norepinephrine neurotransmitters in the brain, thus extending their action. Despite its benefits in the treatment of ADHD, Methylphenidate should be taken with caution since it can have adverse effects such as Insomnia, nervousness, hypersensitivity, anorexia, dizziness, nausea, headache, palpitations, drowsiness, dyskinesia, pulse changes, blood pressure, cardiac arrhythmia, angina, weight loss, and abdominal pain, among others. 

References 

Coeytaux, R. R., Maslow, G. R., Davis, N., Goode, A. P., Namdari, B., Lapointe, N. M. A., & Befus, D. (2018). Nonpharmacologic Treatments for Attention-Deficit/Hyperactivity Disorder: A Systematic Review. Pediatrics , 141(6). doi: 10.1542/peds.2018-0094. 

Danielson, M. L., Visser, S. N., Chronis-Tuscano, A., & DuPaul, G. J. (2018). A national description of treatment among United States children and adolescents with attention-deficit/hyperactivity disorder.  The Journal of pediatrics ,  192 , 240-246. 

Kemper, A. R., Maslow, G. R., Hill, S., Namdari, B., LaPointe, N. M. A., Goode, A. P & McBroom, A. J. (2018). Attention deficit hyperactivity disorder: Diagnosis and treatment in children and adolescents. AHRQ Comparative Effectiveness Reviews, 203. DOI: https://doi.org/ 10.23970/AHRQEPCCER203 . 

Myer, N. M., Boland, J. R., & Faraone, S. V. (2018). Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD.  Molecular psychiatry ,  23 (9), 1929-1936. 

Myer, N., Boland, J., Faraone, S., & Krause, D. (2019). Pharmacogenetics Predictors of Methylphenidate Efficacy Response in Childhood ADHD.  European Neuropsychopharmacology ,  29 , S957-S958.