Are There Adverse Effects to Long-Term Treatment of ADHD with Methylphenidate?

Stephen V. Faraone, PhD on October 17, 2019

Methylphenidate (MPH) is one of the most widely-prescribed medications for children. Given that ADHD frequently persists over a large part of an individual’s lifespan, any side effects of medication initiated during childhood may well be compounded over time. With funding from the European Union, a recently released review of the evidence looked for possible adverse neurological and psychiatric outcomes.

From the outset, the international team recognized a challenge: “ADHD severity may be an important potential confounder as it may be associated with both the need for long-term MPH therapy and high levels of underlying neuropsychiatric comorbidity.” Their searches found a highly heterogeneous evidence base, which made meta-analysis inadvisable. For example, only 25 of 39 group studies reported the presence or absence of comorbid psychiatric conditions, and even among those, only one excluded participants with comorbidities. Moreover, in only 24 of 67 studies was the type of MPH used (immediate or extended-release) specified. The team, therefore, focused on laying out an “evidence map” to help determine priorities for further research.

The team found the following breakdown for specific types of adverse events:

  • Low mood/depression. All three noncomparative studies found MPH safe. Two large cohort studies, one with over 2,300 participants, the other with 142,000, favored MPH over the non-stimulant atomoxetine. But many other studies, including a randomized controlled trial (RCT), had unclear results. Conclusion: “the evidence base regarding mood outcomes from long-term MPH treatment is relatively strong, includes two well-powered comparative studies, and tends to favor MPH.”
  • Anxiety. Here again, all three noncomparative studies found MPH safe. But only two of seven comparative studies favored MPH, with the other five having unclear results. Conclusion: “while the evidence with regard to anxiety as an outcome of long-term MPH treatment tends to favor MPH, the evidence base is relatively weak.”
  • Irritability/emotional reactivity. A large cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: “the evidence base … is limited, although it includes one well-powered study that found in favor of MPH over atomoxetine.”
    Suicidal behavior/ideation. There were no noncomparative studies, but all five comparative studies favored MPH. That included three large cohort studies, with a combined total of over a hundred thousand participants, that favored MPH over atomoxetine. Conclusion: “the evidence base … is relatively strong, and tends to favor MPH.”
  • Bipolar disorder. A very large cohort study, with well over a quarter-million participants, favored MPH over atomoxetine. A much smaller cohort study comparing MPH with atomoxetine, with less than a tenth the number of participants, pointed toward caution. Conclusion: “the evidence base … is limited and unclear, although it includes two well-powered studies.”
  • Psychosis/psychotic-like symptoms. By far the largest study, with over 145,000 participants, compared MPH with no treatment and pointed toward caution. A cohort study with over 2,300 participants favored MPH over atomoxetine. Conclusion: “These findings indicate that more research is needed into the relationship between ADHD and psychosis, and into whether MPH moderates that risk, as well as research into individual risk-factors for MPH-related psychosis in young people with ADHD.”
  • Substance use disorders. A cohort study with over 20,000 participants favored MPH over anti-depressants, anti-psychotics, and no medication. Other studies looking at dosages and durations of treatment, age at treatment initiation, or comparing with no treatment or “alternative” treatment, all favored MPH with the exception of a single study with unclear results. Conclusion: “the evidence base … is relatively strong, includes one well-powered study that compared MPH with antipsychotic and antidepressant treatment, and tends to favor MPH.”
  • Tics and other dyskinesias. Of four noncomparative studies, three favored MPH, the other, with the smallest sample size, urged caution. In studies comparing with dexamphetamine, pemoline, Adderall, or no active treatment, three had unclear results and two pointed towards caution. Conclusion: “more research is needed regarding the safety and management of long-term MPH in those with comorbid tics or tic disorder.”
  • Seizures or EEG abnormalities. With one exception, the studies had small sample sizes. The largest, with over 2,300 participants, compared MPH with atomoxetine, with inconclusive results. Two small studies found MPH safe, one had unclear results, and two others pointed towards caution. Conclusion: “While the evidence is limited and unclear, the studies do not indicate evidence for seizures as an AE of MPH treatment in children with no prior history … more research is needed into the safety of long-term MPH in children and young people at risk of seizures.”
  • Sleep Disorders. All three noncomparative studies found MPH safe, but the largest cohort study, with over 2,300 participants, clearly favored atomoxetine. Conclusion: “more research is needed into the relationship between ADHD, sleep, and long-term MPH treatment.”
  • Other notable psychiatric outcomes. Two noncomparative studies, with 118 and 289 participants, found MPH safe. A cohort study with over 700 participants compared with atomoxetine, with inconclusive results. Conclusion: “there is limited evidence regarding long-term MPH treatment and other neuropsychiatric outcomes and that further research may be needed into the relationship between long-term MPH treatment and aggression/hostility.”

Although this landmark review points to several gaps in the evidence base, it mainly supports prior conclusions of the US Food and Drug Administration (FDA) and other regulatory agencies (based on short-term randomized controlled trials) that MPH is safe for the treatment of ADHD in children and adults. Give that MPH has been used for ADHD for over fifty years and that FDA monitors the emergence of rare adverse events, patients, parents, and prescribers can feel confident that the medication is safe when used as prescribed.

REFERENCES:
Helga Krinzinger, Charlotte L Hall, Madeleine J Groom, Mohammed T Ansari, Tobias Banaschewski, Jan K Buitelaar, Sara Carucci, David Coghill, Marina Danckaerts, Ralf W Dittmann, Bruno Falissard, Peter Garas, Sarah K Inglis, Hanna Kovshoff, Puja Kochhar, Suzanne McCarthy, Peter Nagy, Antje Neubert, Samantha Roberts, Kapil Sayal, Edmund Sonuga-Barke , Ian C K Wong , Jun Xia, Alexander Zuddas, Chris Hollis, Kerstin Konrad, Elizabeth B Liddle and the ADDUCE Consortium, “Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence,” Neuroscience and Biobehavioral Reviews (2019) DOI: https://doi.org/10.1016/j.neubiorev.2019.09.023

ADHD Coaching an Integral Component of Effective Comprehensive Treatment for Adults with ADHD

David Giwerc, MCAC, MCC on July 14, 2016

Research clearly indicates psychopharmacology’s prominent role as an ADHD intervention.

Even if the primary care physician is comfortable with treating an ADHD adult, the typical office visit does not allow sufficient time to address every issue that confronts the newly diagnosed adult ADHD patient. The patient may leave with an appropriate ADHD medication regimen, but many other critical problems related to the diagnosis may remain unaddressed.

Medications can significantly improve focus while reducing other symptoms of ADHD. However, ADHD medications alone cannot teach the patient how to compensate for life skills that were never learned due to the years of executive function impairment.

ADHD coaching builds a bridge between biology and behavior and narrows the gap between ability and performance. Patients and physicians are beginning to realize the importance of including an ADHD coach as part of the treatment team. Just as an athletic coach motivates an athlete, ADHD coaches are very adept at motivating their clients who have ADHD, while partnering with them to develop and practice newly learned personal, social, and professional skills. For some patients, these skills may not have been developed due to lack of ADHD education, proper diagnosis, and treatment.

The stigma surrounding ADHD as nothing more than an “unruly child syndrome,” coupled with the popularity of incorrectly self-diagnosing an ADHD impairment, means too many patients are conditioned not to speak up and not to seek support, especially in the workplace. Adult ADHD coaching clients have often stated that an ADHD coach was the first person to not only understand the frustration of their invisible challenges, but also to sincerely believe all of their ADHD stories.

Physicians can rarely provide the level of attention and encouragement an adult patient needs within the restrictions of the typical office visit. The coach, therefore, can reinforce their patients’ natural talents and successes. The PAAC* or ICF**-certified ADHD coach can create an environment that encourages open communication (necessary for behavioral changes to occur) and forms a foundation of unconditional acceptance. Coupled with science-based instruction about ADHD, the coach focuses on identifying the patient’s natural talents and successes and develops a plan to convert that into daily strengths.

ADHD coaches help the client develop coping strategies, a valuable adjunct to medication management. They are highly specialized professionals, well-versed in ADHD-specific coaching competencies. The coach provides psycho-educational support, improves self-awareness of how symptoms of ADHD, and helps translate that into improved short and long-term performance.

While coaching cannot replace stimulant medications or therapy as a treatment, a coach can provide customized strategies and education that work alongside medication. The ADHD coach may suggest lifestyle changes such as proper sleep, nutrition, physical activity, and breathing exercises. In addition, ADHD coaching is accessible, with most coaching being conducted via phone/Skype, eliminating the need for geographical proximity or disruption to the work day.

*PAAC: Professional Association of ADHD Coaches, (PAAC)

**ICF: International Coach Federation

 

Resources:

Lidia Zylowska, The Mindfulness Prescription for Adult ADHD (Boston, Trumpeter, 2012)

Thomas E. Brown, A New Understanding of ADHD in Children and Adults, Executive Function Impairments (New York, Rutledge, 2013)

David Giwerc, Permission to Proceed: The Keys to Creating a Life of Passion, Purpose and Possibility (Albany New York, ADD Coach Academy Press, 2011)

John Ratey, Spark Revolutionary New Science of Exercise & the Brain (New York, Little, Brown & Co. 2008)

African American Adults with ADHD – Cultural Barriers and Reduced Access to Care

Anthony L. Rostain, MD MA on March 24, 2016

Clin Psychiatry. 2015; 76(3):279-283.
“Cultural Background and Barriers to Mental Health Care for African American Adults”
Rostain, A.L., Ramsay, J.R., Waite, R.

This article delineates key patient and provider cultural biases that interfere with access to care for African American Adults with ADHD. It provides an important framework for understanding how these biases come about and what clinicians can do to address them. A brief review of the relationship between psychiatry and African Americans points out that beginning with slavery and continuing through the Tuskegee experiment, there is a legacy of racism in American medicine that influences the way patients view health care providers (and vice versa).

For instance, drapetomania was a clinical diagnosis given to slaves who demonstrated resistance to the institution by running away, refusing to follow rules, destroying property and fighting the plantation slave owners. In this fashion, psychiatry played an important role in supporting racism and racist beliefs. Similar analogies can be made to the ways that psychiatry classified homosexuality as a mental illness.

 

The point of this historical review is to underscore the longstanding mistrust that exists within the African American community toward medicine in general and psychiatry in particular. Add to this, the stigma associated with mental illness and substance abuse, it becomes easier to understand why many African American adults fail to seek treatment for disorders like ADHD.

The article goes on to discuss barriers to obtaining mental health treatment including patient factors (e.g. low income, lack of health insurance, fear and other negative attitudes) and health care system factors (e.g. limited access to culturally and technically competent providers and provider biases). Without question, higher rates of poverty and of lack of insurance among the minority population leads to markedly reduced access to care. The article points out that whereas rates of adequate mental health treatment among whites is 33%, the figure drops to 12% for African Americans. Moreover. white 
children are twice as likely to receive ADHD medication as African American children. Cultural biases among providers may lead them to be insufficiently attuned to the presence of ADHD in adult patients, ascribing the symptoms of ADHD, such as inattention, restlessness and disorganization either to personal failing (e.g. lack of self-discipline) or to environmental factors (e.g. low SES, lack of education) rather than to the influence of ADHD.

The paper concludes with practical recommendations for clinicians to address these barriers including providing accurate science based information, listening and being sensitive to stigmatizing experiences that African American patients may have encountered, and recognizing the deleterious effects of conscious and unconscious biases among well-meaning providers.

ADHD Success Story #6 – ADHD and College Students

Anthony L. Rostain, MD MA on March 27, 2014

Let me tell you about a success story of mine, a college student who I’ll call Carrie. Carrie is about to finish her sophomore year in college after a very, very rocky start to her college career. She was a bright, enthusiastic and vivacious high school student who managed to get by through her intelligence, her energy, and being able, at the last minute, to get her work done. She also had very supportive teachers who gave her the benefit of the doubt if she did turn in assignments late.

 

Now, Carrie thought she might have ADHD but she never went for help. She actually was kind of skeptical about it and thought she just needed to try harder. So she was active in the high school drama club and actually went off to college hoping to become a playwright someday. So, after arriving at college, Carrie became very active in one of the drama clubs on her campus. She began to stage-manage and she started hanging out with all of the drama club students and was enjoying a great deal, and contributing great deal, to the activities of that organization. She also used the same studies, strategies that she had used in high school. So she talked a lot in class but never really read all of the assignments and she’d waited until the last minute to do the reading or to turn in the papers. She found herself cramming for the exams. It turned out that she ended up spending too much time with her extracurriculars and not enough time studying.

 

So after failing two classes in her spring semester, Carrie was asked to take an academic leave of absence from her college. She came back home and was evaluated in our program and we did in fact diagnose her with ADHD. We explained to her exactly how it was that she had managed to do fine until college and that she had managed to get by until she was in this unstructured learning environment. We spent a lot of time teaching her about adult ADHD, we started her on an ADHD medication, and she began coming for weekly cognitive behavioral trainings sessions.

 

Over the course of the next few months, she began to get more and more comfortable with the diagnosis and with figuring out what she needed to do to get difficult tasks done. She managed to get a job in selling tickets in local theater company and eventually she decided to take some courses in community college. She did extremely well and she really figured that she was now ready to go back to college.

 

She went back this past year and has done exceptionally well, getting most As and a few Bs, keeping herself very organized and able to balance the lifestyle that she wants. She’s able to get the studying done that she wants, she’s able to participate in the drama club and guess what, she’s pursuing her dream of becoming a playwright and is now a full-fledged English major in good standing.

 

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