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

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Stephen V. Faraone, PhDMethylphenidate (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

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David Giwerc ADHD in Adults 2KdZ7t
ADHD Coaching an Integral Component of Effective Comprehensive Treatment for Adults with ADHD

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.

CBT_treats_Executive_Dysfunction_Free_ADHD_CME_CJkZtu.png.jpgThe 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

Cardiovascular Safety of ADHD Medications - ADHD in Adults

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)

ADHD Success Story #4 – Brendan Montano, MD

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There are so many success stories in treating ADHD in the adult practice of Medicine, and in my office, one of them stands out. I have a patient who was coming in for the first time, 42 years old, a woman who is a single parent and an executive. She came in with a chief complaint of fatigue, anxiety and difficulty sleeping. When we really began to explore what wasBrendan_Montano_AIA_jZJbzO

going on, medically, she had some serious problems. There had been a heart attack. She had had two stents placed in her heart in the past and she was an exceptionally heavy smoker and still smoking.

During the interview, I did a screen to look for ADHD. The screen was time-efficient and it pointed me to think about this as a possible ideology for many of the problems she was having, including the heavy cigarette smoking. We begin to treat her and because of her cardio-vascular disease we treated her with a non-stimulant medication.

It became clear that she was suffering at work, almost to the point where she was going to lose her job. She was put on notice and had to report on a weekly basis with her boss, whether she having progress or not.

Over the course of treatment for her ADHD, her anxiety improved. She was able to sleep well. Her job performance dramatically improved and she got off of cigarettes. So all in all, the continuous stress that was driving her cardio-vascular disease and threatening another heart attack, the continuous stress abated. She was able to keep her job and her health improved dramatically.

ADHD Success Story #3 – Parallel Interviews

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In two separate interviews, a clinician and an ADHD adult describe the two sides of ADHD symptoms and ADHD diagonsis.

Lenard_A_Adler_MD_ADHD_in_Adults
Lenard Adler, MD: I can think of an adult in their forties, a male, who came in after having their seven year old child diagnoses with ADHD, and in fact identify that, as he’s having his symptoms, he coped with them not all that well, was in a managerial position but not functioning optimally, had been passed over for promotions on numerous occasions mainly because he didn’t met his deadlines.

Robert Tudisco, Esq, ADHD Adult: I had to keep track of my time, I had to bill my clients, I had to run an office. It was all of those administrative tasks that were really a problem. At the same time, I thought I was setting a bad example for my son and I was having some difficulty in my marriage. And so, I sought some help, I found out about ADHD.

Lenard Adler, MD: In discussing things with the patient and his wife, she described lots of instances around at home where he didn’t listen to her, to do lists just weren’t completed, things weren’t being done on the weekend and she kind of felt that she was not only taking care of their seven-year-old son but also taking care of the husband. So the diagnosis of ADHD became clear after thorough evaluation and, in fact, this individual went on to treatment with a non-stimulating medicine and actually did quite well.

Robert Tudisco improved family relationships UMPwSv

Robert Tudisco, Esq: There have been so many benefits since I’ve been diagnosed with ADHD. I think I’m a better father. I’m certainly a better husband. My relationship with my wife is much more relaxed because we understand each other a lot better. We also understand that ADHD is not an excuse for what happens and we understand where the behaviors come from so we can kind of work around them in the future. And I really think that a lot of adults would benefit from a diagnosis and it’s just one of the barriers, I think, to a lot of adults getting diagnosed is that there aren’t more clinicians that are diagnosing adults with ADHD.