Ritalin for ADHD Treatment

Ritalin is a medication that, since the 1950s, doctors in the United States, Europe, and elsewhere have prescribed to treat individuals with a variety of psychiatric symptoms, including depression, fatigue, and difficulties with attention and impulsivity. Chemist Leandro Panizzon first synthesized the drug in 1944 under the scientific name methylphenidate while working at the pharmaceutical company CIBA in Basel, Switzerland. CIBA patented the drug in 1950 and marketed it as Ritalin. The US Food and Drug Administration, or FDA, approved Ritalin for use in children in 1961 and by the 1970s doctors were prescribing the drug to children who had received a medical diagnosis of hyperactivity. The American Psychiatric Association, or APA, replaced the diagnosis of hyperactivity with attention deficit disorder, or ADD, in 1980, and with attention-deficit/hyperactivity disorder, or ADHD, in 1987. Over that time, and since, Ritalin has remained a first-choice drug for physicians treating hyperactivity and attention deficits in both adults and children, while also generating discussion and debate about potential overuse, especially in children.

1. Early Development of Ritalin
2. Transition of Ritalin to a Hyperactivity Treatment
3. Mechanism of Action of Ritalin
4. Potential Side Effects
5. Social Impact

Early Development of Ritalin

According to Professor Klaus Lange of the Department of Biological and Abnormal Psychology of the University of Regensburg in Regensburg, Germany, Panizzon was the first recorded researcher to synthesize the compound methylphenidate in 1944. As a chemist for the Switzerland-based CIBA pharmaceutical company, Panizzon reportedly designed the compound to help his wife Marguerite, nicknamed Rita, be more active on the tennis court. After it improved her tennis aptitude by making her more energized, he named the compound Ritaline after his wife.

CIBA filed the first patent for preparation of methylphenidate in 1950, and in 1954, filed a patent specifically for the use of methylphenidate to treat psychiatric disorders. That was for the immediate release, or IR, oral tablet, which is a medication that dissolves quickly into the user’s system. In the 1950s, CIBA manufactured Ritalin within Sweden but distributed it internationally, although they did not distribute it in the United States until 1961. According to Nathan Moon, a public policy researcher at Georgia Institute of Technology in Atlanta, Georgia, after CIBA released Ritalin, physicians and researchers during the 1960s had full autonomy in how they prescribed the drug, with no limitations on what disorders and doses they could administer to patients.

According to Matthew Smith, a professor of health history at the University of Strathclyde in Glasglow, Scotland, in a 2019 article in the journal Clinical Psychology Forum, physicians in the 1950s Europe first used Ritalin to treat patients within psychiatric asylums. Moon claims that physicians prescribed Ritalin in conjunction with electrotherapy treatments to treat what physicians perceived as depression and to improve the patient’s mood. According to Moon, clinicians located in Europe and the United States in the 1950s broadly prescribed Ritalin for many disorders and conditions, such as obesity, and continued to find new uses for the medication. The FDA approved Ritalin in 1955 for the treatment of a variety of psychiatric conditions, including depression and fatigue, in adults.

Transition of Ritalin to a Hyperactivity Treatment

Although doctors initially prescribed Ritalin primarily to adults, that would change due to research into the effects of stimulants on treating child behavioral problems in the 1950s and 1960s. On the basis of prior observational studies, the FDA approved Ritalin in 1961 for use in children with behavioral issues like hyperactivity. Among the first clinical trials of Ritalin in children was one conducted by, Keith Connors and Leon Eisenberg, researchers at Johns Hopkins University in Baltimore, Maryland. According to Alan Schwarz, a former Pulitzer-Prize-nominated investigative journalist for The New York Times, they decided to reinvestigate and reproduce Charles Bradley’s 1930s experiments with stimulants on children with behavioral problems. 

In 1963, Connors and Eisenberg published the results of a study in which they recruited eighty-one children from a foster home and psychiatric treatment center to be part of their experiment. They placed the children into three different intelligence groups groups—low, middle, and high—with half of each IQ group receiving a placebo and the other half receiving Ritalin. According to Connors and Eisenberg, the children treated with Ritalin in all intelligence groups were calmer and better-behaved than their placebo counterparts. Their research demonstrated to physicians that Ritalin was effective in treating children with behavioral issues. Smith claims that Connor’s and Eisenberg’s work established clinical evidence that methylphenidate was effective in treating hyperactive children. However, physicians did not immediately recognize and adopt Ritalin in their practice until the early 1970s. According to Moon, physicians were skeptical that Ritalin, a drug which excites the central nervous system, could work to calm hyperactive children. The American Psychiatric Association, or APA, which publishes the Diagnostic and Statistical Manual of Mental Disorders, first included hyperactivity as a diagnosis in 1968, under the technical term hyperkinetic reaction of childhood.

Shifting expectations during the Cold War of how children should behave may have contributed to Ritalin’s rise in popularity. According to historian Matthew Smith, Americans, fueled by fears of losing the intellectual arms-race with Russia during the Cold War, emphasized the importance of academic excellence for all students. Guidance counselors suggested that parents refer struggling students to physicians who linked their disorderly classroom behavior to a medical diagnosis of hyperkinetic impulse disorder. According to Smith, the political climate of the Cold War, combined with an increase in parents seeking medication for their children’s behavior, led to the popularization of Ritalin as a treatment for hyperactive children during the 1970s. Ritalin rose as a solution to what appeared to be the growing emergence of hyperactive children.

The APA changed the diagnosis of hyperkinetic reaction of childhood to attention deficit disorder, or ADD, with or without hyperactivity, in 1980, and to attention-deficit/hyperactivity disorder, or ADHD, in 1987.

Mechanism of Action of Ritalin

Methylphenidate, which is the scientific name of Ritalin, is a stimulant, or drug that excites the body’s central nervous system. The scientific formula of methylphenidate is C₁₄H₁₉NO₂. The molecule works to help the neurotransmitters norepinephrine and dopamine stay and accumulate in the brain longer by blocking the recycling and transportation of those chemical messengers. Within the context of methylphenidate’s medical uses, dopamine regulates feelings of pleasure and attention, and norepinephrine regulates concentration and alertness. The increased levels of norepinephrine and dopamine then work to stimulate the prefrontal cortex, the front part of the brain which handles decision-making with concentration and organization tasks.

Historically, physicians wrote of methylphenidate calming hyperactive individuals as paradoxical, since the medication excites the central nervous system yet seemingly calms hyperactive individuals. However, according to neurobiology researcher Amy F.T. Arnsten of Yale University School of Medicine in New Haven, Connecticut, the assumption that methylphenidate affects hyperactive individuals differently is wrong: stimulants improve both hyperactive and non-hyperactive individuals’ ability to focus when administered in low doses by aiding processes that work to increase prefrontal cortex activity.

Because CIBA’s patent on the generic version of Ritalin, methylphenidate, expired in the 1960s, many generic versions of Ritalin have been produced. Before the 1980s, Ritalin was available only as IR tablets. In the 1980s, the sustained-release tablet version of Ritalin became available to consumers in the US. In 1996, CIBA became Novartis after it merged with Sandoz, another Swiss pharmaceutical company. In 2002, the FDA approved an extended-release capsule version of Ritalin, which Novartis branded as Ritalin LA. In 2006, the transdermal patch version of Ritalin, also approved by the FDA, was available to consumers.

Potential Side Effects

Ritalin may be addictive when used improperly, even when prescribed to individuals as indicted. According to Stefania Ciappini, a professor of psychiatry at the Saint Camillus International University of Health Sciences in Rome, Italy, Ritalin increases dopamine and norepinephrine concentration within the brain. The increase in dopamine levels activates dopaminergic pathways involved in reward and motivation, producing a strong, rewarding feeling for the individual every time they take a dose, increasing the risk of misuse. The risk of addiction also varies by formulation. Ciappini explains that IR formulations, by design, produce stronger, more rapid results for the patient, but due to the mechanisms mentioned above, they can increase the risk of misuse and addiction. In contrast, ER formulations are theoretically less addictive, as Novartis designed them to have slower results, spread over a longer period, allowing the patient to feel less potent effects. However, according to researcher and physician Stephen V. Faraone, substance use disorders often co-occur with ADHD, suggesting that increased risks of substance abuse in individuals taking Ritalin may be due to individuals with ADHD being more prone to drug addiction. The FDA classifies products containing methylphenidate, including Ritalin LA, as Schedule II controlled substances.

Some research indicates that Ritalin may be associated with growth suppression, meaning shorter stature, in children. However, the mechanisms behind that relationship are complex, with researchers speculating that it could be due to reduced calorie intake and methylphenidate adversely impacting dopamine pathways concerning growth. According to physician Ran D. Goldman, a research gap exists on the mechanisms behind stimulant medications, including methylphenidate, and growth suppression due to the lack of longitudinal follow-ups documenting the final heights of patients. Goldman, in a 2010 article, states that there are three possible mechanisms at play. First, stimulants may suppress the appetite of the child, leading to the child eating less, and thus, growing at a slower rate. Second, the increased levels of dopamine may inhibit the release of hormones that can trigger growth in children. Third, stimulants medications can hamper bone growth by interfering with the development of the tissue within growth plates. When stimulants alter processes related to dopamine, they prevent hormones that dopamine normally helps to regulate, such as growth hormones, from being properly activated, leading to slower development of the child’s growth plates. However, researcher Richard Ahlberg and his colleagues in Sweden found that individuals diagnosed with ADHD tend to be shorter than their peers even in studies conducted prior to the existence of ADHD medications. Ahlberg observes that past studies studying the correlation between methylphenidate and height suppression did not adequately consider a child’s socioeconomic status or genetic background, which can affect height. The past studies also did not consider the association between the disorder and shorter height overall.

Researchers continue to explore how methylphenidate produces increases in blood pressure within its users, and how it might lead to cardiovascular events, such as heart attacks. In their 2016 article “Cardiovascular Safety of Methylphenidate among Children and Young People with Attention-Deficit/Hyperactivity Disorder (ADHD): Nationwide Self-Controlled Case Series Study,” researcher Ju‑Young Shin and his colleagues detail that previous studies on methylphenidate have reported a significant, although small, increase in blood pressure in children taking the medication. Physician A. Sinha of Saint Luke’s University Health Network in Bethlehem, Pennsylvania, and his colleagues claim that, as of 2016, how stimulants, and by what mechanism, may impact the cardiovascular system is unknown. They propose that stimulants may raise the individual’s blood pressure and heart rate, trigger tightening of their blood vessels, and increase the concentration of inflammatory molecules in their bloodstream, although those mechanisms are hypothetical.

Social Impact

Throughout the 1970s to the 1980s, public debates emerged as to whether schools were pressuring parents to give their children Ritalin to control disruptive behavior. In 1970, reporter Robert Maynard of the Washington Post penned an article alleging schools were pressuring parents to medicate their children with Ritalin as a means of improving classroom behavior. According to Rick Mayes, an associate professor of public policy at the University of Richmond in Richmond, Virginia, and Adam Rafavolick, an associate professor of sociology at the Pacific University Oregon in Forest Grove, Oregon, Maynard’s 1970 article generated what they called a negative media blitz, resulting in a congressional hearing on the stimulant use in school age children. In September 1970, New Jersey Congressman and Representative Cornelius E. Gallanger held a congressional hearing on the ethics of hyperactivity research. Testimonies from the hearing reported that there were anecdotal cases of schools pressuring parents into giving their children Ritalin, although there is no record of lawsuits or changes in legislation occurring because of the hearing. According to historian Smith, Ritalin prescriptions for ADHD continued to grow during the 1970s despite emerging concerns because of Ritalin’s rapid and observable results in its intended clinical use, which was treating children with ADHD.

The Church of Scientology launched an anti-psychiatry campaign against Ritalin from the 1980s to the 1990s. Stephen A. Kent of the University of Alberta in Edmonton, Alberta, defines the Church of Scientology as a complex religious ideology whose core tenets depict medical, especially mental health, professionals as devils. According to Leslie Iversen, who was a professor of pharmacology at King’s College London in London, the United Kingdom in the 2000s, the Church of Scientology, through their nonprofit Citizens Commission on Human Rights, led a public campaign against the use of Ritalin in treating children.

In a 1990 Los Angeles Times article titled “The Scientology Story,” reporters Joel Sappell and Robert W. Welkos describe how the Church of Scientology launched a campaign to discredit psychiatry as a profession. They claim that the Church was motivated in part by psychiatrists’ criticism of the Church’s use of spiritual techniques for medical problems and by their founder’s own denunciation of psychiatrists as so-called “psychotic criminals.” Sappell and Welkos allege that the Church, in internal documents, stated that the purpose of their anti-Ritalin campaign was to disparage the reputation of psychiatry, rather than the drug itself. In 1987, the Church engaged in public protests against the use of pharmaceuticals outside of psychiatric conferences. According to Sappell and Welkos, the Church of Scientology shifted public conversations about ethical concerns regarding Ritalin towards a broader critique of all psychiatric medications. Schwarz details that the Church was effective in damaging the reputation of Ritalin among parents in the US, with Ritalin prescription rates for ADHD decreasing in the early 1990s. Simultaneously, the Church helped parents to pursue litigation against psychiatrists who prescribed their children Ritalin.

In the late 1980s, parents of school-aged children filed lawsuits against CIBA, the APA, physicians who diagnosed ADD, and school districts. The Citizens Commission on Human Rights often supported those parents by publicizing their lawsuits. Debra Cassens Moss, a lawyer and reporter for the American Bar Association Journal, described in a 1988 article how parents had filed sixteen lawsuits in 1988 alone, many alleging that schools had required students to take Ritalin under threat of expulsion. However, many judges dismissed those lawsuits due to insufficient evidence. According to Adam Schwarz, an investigative journalist and author of the 2016 book ADHD Nation: Children, Doctors, Big Pharma, and the Making of an American Epidemic, schools denied the claims that they had pressured parents into taking Ritalin. Additionally, the Church of Scientology undermined the credibility of those lawsuits, as the Church participated in threatening physicians.

In the early twenty-first century, Ritalin became entangled in debates surrounding neurodiversity and the ethics of medicating neurodiverse individuals. According to Thomas Armstrong, author of the 2010 book The Power of Neurodiversity: Discovering the Extraordinary Gifts of Autism, ADHD, Dyslexia, and Other Brain Differences, the neurodiversity perspective rejects the idea that an individual’s deviation from what cultures deem as appropriate ways of thinking or behaving is a sign of illness. Moreover, it asserts that one’s differences may be a source of advantages in certain contexts. In a 2020 article entitled, “The Right to Dignity or Disorder? The Case for Attention Deficit Hyperactivity Diversity,” psychology researcher Kate Carr-Fanning of the University College Dublin, in Dublin, Ireland, also defines neurodiversity as a framework that argues against labeling individuals diagnosed with ADHD as medically abnormal. Under that paradigm, Carr-Fanning explains that society should not push individuals labeled with ADHD towards treatment such as Ritalin.

Beginning as a stimulant for depression and other conditions in adults in the 1950s, Ritalin grew into a first-choice drug for physicians to treat ADHD in both children and adults. While not without critics, Ritalin offered what historian Matthew Smith described as hope to individuals struggling with hyperactivity, and later, ADHD.

References

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