New research published in Current Medical Research and Opinions studied the impact of symptoms and the adverse effects of medication on adults receiving treatment for ADHD.
The results of this study suggest that adults who are diagnosed with ADHD and taking medication often experience side effects and symptoms that substantially reduce their quality of life. For example, the researchers found evidence of reduced well-being, increased unemployment, mood issues, and insomnia.
It appears that the study was produced by employees and consultants for the pharmaceutical company Otsuka, which is currently developing and promoting its own drug for ADHD, Centanafadine. As such, the company may benefit from research that shines a light on the failures and adverse effects of current treatments for ADHD.
The authors from Otsuka frame the study this way:
“[Previous] studies illustrate that emotional symptoms can hurt the quality of life in adults with ADHD. The current study extends these findings by evaluating the impact of the most common symptoms associated with ADHD/treatment-related adverse side effects on the daily living of adults with ADHD and quantifying the burden exerted by these symptoms. Considering that all symptoms in this study were captured over the month prior to data collection, the impact of symptoms described herein may represent only the tip of the iceberg in regard to the real burden experienced by patients over their ADHD journey, which often lasts for several years or even over the entire lifespan for some.”
While pharmacological treatments, especially stimulants, are the primary treatment for adults with ADHD in the United States, the side effects of these treatments have also been documented in the scientific literature. The most common side effects are sleeping problems or insomnia, restlessness, loss of appetite, weight loss, dry mouth, depressed mood, and emotional dysregulation.
Due to the similarities between ADHD symptoms and the side effects of the medication used to treat it, researchers often have difficulties identifying whether the patients’ experiences are caused by ADHD, by the treatment, or by a combination of both. For this reason, the researchers of this study focused on studying ADHD/treatment-related adverse events rather than identifying them as different phenomena.
Most research on ADHD has focused on the effects symptoms and treatments might have on children and adolescents. Many studies have identified how pharmacological treatments for ADHD lead to symptom reduction but often miss how these treatments might influence other areas of the child’s life and well-being. For example, a recent study found children diagnosed with ADHD had poorer quality of life and were more likely to engage in self-harm than kids who shared the same symptoms but were not diagnosed.
Other studies also suggest that these treatments influence children’s growth and brain development. One research study published this year found that kids diagnosed with ADHD who were under pharmacological treatment were more likely to finish in-class activities and experience behavioral changes in the classroom but did not see an improvement in learning when compared to kids with ADHD that were not on medication. Despite these complicated findings, ADHD continues to be overdiagnosed in children.
Because of the limited research on ADHD in the adult population and the limited research on the effects of pharmacological treatments on quality of life, the researchers developed a survey study to identify ADHD/treatment-related adverse effects in this group. Participants in this online survey were adults living with ADHD in the United States.
The survey was composed of four parts. First, they were screened for eligibility and signed their consent to participate. Second, the researchers asked participants about individual characteristics and general outcomes of treatment. Third, they asked about sleep disturbances, including but not limited to insomnia. Finally, they asked about their emotional impulsivity.
Among the 585 adults living with ADHD who participated in the survey, 58.5% identified as female, 40.5% identified as male, and 1% identified as non-binary. Regarding race, 74.4% identified as White, 14.2% identified as African American or Black, 11.1% identified as Hispanic or Latino, 4.4% identified as Asian or Pacific Islander, 3.6% identified as Native American or Alaskan Native, 0.7% identified as Other, and 0.2% preferred not to answer. In addition, 60.9% had been diagnosed with ADHD before 18, many experienced comorbidities, and all were under pharmacological treatment.
The results show that 95.2% of the participants experienced at least 1 symptom of ADHD/treatment-related adverse effect during the last month, with the average being about 6 symptoms per participant. The most common adverse effects were insomnia and other sleep disturbances, anxiety and panic attacks, depressed mood, and emotional impulsivity or mood liability. These were experienced by slightly less than half of the participants.
People who experienced sleep disturbances and emotional impulsivity often presented more symptoms than those who did not, reporting about eight symptoms of ADHD/treatment-related adverse effects.
Other reported ill effects were feeling jittery and restless, headaches and migraines, fatigue and drowsiness, excess energy, dry mouth, decreased appetite, weight loss, sweats or hot flashes, constipation, painful menstrual cramps, involuntary movements or tremors, diarrhea, abdominal pain, nausea or vomiting, substance abuse, skin rash, problems with urination, problems with erection, and being in an accident.
Upon further analysis, the researchers found a negative relationship between adverse side effects and quality of life, meaning the quality of life worsened with every adverse effect. They also found a significant relationship between these effects and their employment probability. The more reported symptoms of ADHD, the higher the odds of unemployment. Those who experienced sleep disturbances and emotional impulsivity were also less likely to be employed than those who did not.
As expected, they also found that the more adverse effects experienced, the worse their activity impairment. This was also significantly worse among those who had trouble sleeping and emotional impulsivity than those who did not experience these symptoms.
The authors name some of the main limitations of their study. Among them were the sampling method, the comorbidities present in the sample, their need to recollect past events to provide accurate information, and the difficulty in distinguishing between ADHD symptoms and the adverse effects of pharmacotherapy.
This research also assumes symptoms of ADHD are the result of either a mental illness, the effects of medication, or a combination, while there is a large body of research that suggests there is a relationship between ADHD symptoms and exposure to environmental problems and socioeconomic deprivation.
This research adds to the growing literature on the negative impact of ADHD diagnoses and treatments on well-being and quality of life. It is novel in its focus on the adult population. While there is significant research on the ill effects of diagnosis and psychopharmacological treatments of ADHD in children, this study might serve in the development of future research questions that could provide more accurate information about the possible side effects of these treatments, beyond simple treatment reduction (or not), in adults.
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Declaration of funding
Financial support for this research was provided by Otsuka Pharmaceutical Development & Commercialization, Inc. The study sponsor was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication.
Declaration of financial/other relationships
JS is an employee of Otsuka Pharmaceutical Development & Commercialization, Inc. AC received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the U.S. Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, Tulex Pharma, and Lumos Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. MC, MGL, RB, and AG are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Otsuka Pharmaceutical Development & Commercialization, Inc. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
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Schein, J., Cloutier, M., Gauthier-Loiselle, M., Bungay, R., Guerin A. & Childress, A. (2022). Symptoms associated with ADHD/treatment-related adverse side effects and their impact on quality of life and work productivity in adults with ADHD. Current Medical Research and Opinion, DOI: 10.1080/03007995.2022.2122228 (Link)
Neuroimaging
Modern brain imaging techniques have critically contributed to elucidating the etiology of ADHD. While MRI provides detailed insights into the brain microstructure, such as for example gray matter volume, density, cortical thickness, or white matter integrity, fMRI allows insights into brain functions through activation and connectivity measures with high–spatial resolution.
Delayed Maturation and Persistent Alterations in the Brain Microstructure in ADHD The brain undergoes pronounced developmental alterations in childhood and adolescence. Gray matter volume and cortical thickness show nonlinear inverted U -shaped trajectories of maturation with a prepubertal increase followed by a subsequent decrease until adulthood while white matter volume progressively increases throughout adolescence and early adulthood in a rather linear way. 162 163 164 165 Large variations of the maturational curves in different brain regions and subregions suggest that phylogenetically older cortical areas mature earlier than the newer cortical regions. Moreover, brain areas associated with more basic motor or sensory functions mature earlier than areas associated with more complex functions including cognitive control or attention. 163 164 Altered maturation of the cortex for ADHD has been reported for multiple areas and cortical dimensions, 166 167 mainly in the form of delayed developmental trajectories in ADHD but recently also as persistent reductions, particularly in the frontal cortex. 168 Such findings speak for delayed maturation in specific areas rather than a global developmental delay of cortical maturation in ADHD. Microstructural alterations in ADHD have been associated with a decreased intracranial volume 169 and total brain size reduction of around 3 to 5%. 100 168 170 In accordance, increasing ADHD symptoms in the general population correlated negatively with the total brain size. 171 A meta-analysis (Frodl et al) and a recent cross-sectional mega- and meta-analysis (Hoogman et al) indicate that such reductions in brain volume may be due to decreased gray matter volumes in several subcortical structures, such as the accumbens, amygdala, caudate, hippocampus, and putamen but also cortical areas (prefrontal, the parietotemporal cortex) and the cerebellum. 170 172 173 174 175 176 177 Effects sizes of subcortical alterations were highest in children with ADHD and the subcortical structures showed a delayed maturation. 169 Moreover, higher levels of hyperactivity/impulsivity in children were associated with a slower rate of cortical thinning in prefrontal and cingulate regions. 167 178 Differences in brain microstructure have also been reported in a meta-analysis for white matter integrity as measured with diffusion tensor imaging in tracts subserving the frontostriatal-cerebellar circuits. 179 To summarize, diverse neuroanatomical alterations in total brain volume and multiple cortical and subcortical dimensions characterize ADHD. These alterations are most pronounced in childhood and suggest a delayed maturation of specific cortical and subcortical areas along with some persistent reductions in frontal areas in a subgroup of ADHD patients with enduring symptoms into adulthood.
Neuropediatrics. 2020 Oct; 51(5): 315–335
We are just beginning to understand ADHD. Interviewing adults with untreated ADHD as children, who can articulate the profound changes medication generates within them is a worthy, long overdue story. Here, I am not referring to famous successful individuals with an ADHD label. Slight changes in prescription lenses that improve one’s vision from 20/25 to 20/20 are not worth discussing. ADHD which causes the equivalent of legal blindness corrected to 20/20, that is the idea.
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And yet adults diagnosed with “ADHD” report on the average lower quality of life. Which means for every success story, there is someone made at least that much worse. Decades of research show no improvements in long-term outcome for ADHD kids treated with stimulants over those who are not. So whether it has a “biological etiology” or not, stimulant treatment by itself does nothing to make life better on the average for those so treated.
I do rejoice for your personal success, and hope it continues to go well for you. But the idea that we are “nearing an understanding” of “ADHD” is not supported by the literature. In fact, the BEST “treatment” for ADHD seems to be to put kids in a non-traditional classroom where they get more control of their activities. No “medications” needed. On the average, of course.
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There’s a reason that studies run or funded by pharmaceutical companies are not given much weight.
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None of the studies I referred to were funded by pharmaceutical companies. Government studies, especially when longitudinal, are generally more reliable.
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We’ve spent zillions of dollars on neuroimaging studies of ADHD, and not one patient in the world has benefited.
We’ve spent zillions of dollars on genome-wide association studies of ADHD, and not one patient in the world has benefited.
There is no abnormality of brain structure that can be used to diagnose ADHD.
There is no abnormality of brain function that can be used to diagnose ADHD.
There is no gene for ADHD.
And how could there be? There are literally hundreds of reasons why a child or an adult might have problems with inattention or hyperactivity. Far better to identify the cause of a person’s distress and address that, than to attribute that person’s problems to some mythical disease entity, the existence of which has never been demonstrated.
There is also no evience of any long-term benefit of drugging kids for something called “ADHD.”
The MTA study was far and away the largest and far and away the longest randomized controlled trial of the effects of stimulant drugs on children. And the only long-term effect the researchers were able to document — the ONLY one — was that the drugs stunted the kids’ growth. Ad they didn’t “catch up.” By the time of the sixteen-year-follow-up, the drugged kids were an average of TWO INCHES shorter than the undrugged ones.
I don’t like to say “I told you so,” but…
https://www.amazon.com/gp/product/B09Z7LLCKP/ref=dbs_a_def_rwt_hsch_vapi_tkin_p1_i1
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Outcomes from 351 studies were grouped into 9 major categories: academic, antisocial behavior, driving, non-medicinal drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. The following broad trends emerged: (1) without treatment, people with ADHD had poorer long-term outcomes in all categories compared with people without ADHD, and (2) treatment for ADHD improved long-term outcomes compared with untreated ADHD
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Why do you reference a book you wrote to back up what you contend to be true right here?
There are many, “many” established differences between ADHD brains and non-ADHD brains. And we stand at the threshold of finding fantastic breakthroughs. This is just the beginning.
Until recently, within the past decade or so, we just discovered that 90% of our universe does not consist of “normal” matter, that is, matter composed of atoms–electrons, protons, neutrons. Astrophysicists are confounded. Stunned. Incredulous.
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Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is the most common behavioral disorder of childhood. Twin, adoption, segregation, association, and linkage studies have confirmed that genetics plays a major role in conferring susceptibility to ADHD. We applied model-based and model-free linkage analyses, as well as the pedigree disequil…
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A common variant of the Latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication
February 2010Molecular Psychiatry 15(11):1053-1066
DOI:10.1038/mp.2010.6
SourcePubMed
Authors:
Mauricio Arcos-Burgos
University of Antioquia
Mahim Jain
Baylor College of Medicine
Maria Teresa Acosta
Children’s National Medical Center
Sharon B Shively
Uniformed Services University of the Health Sciences, Henry M. Jackson Foundation
… LPHN3 was associated with ADHD in a large sample of children and adults, and subsequently replicated in an independent adult form of ADHD sample. The function of this gene, which encodes a G-proteincoupled receptor, is still not well understood (Martinez, Muenke, & Arcos-Burgos, 2011;Arcos-Burgos et al., 2010). In addition, studies of rare genetic variants have identified probable causative mutations for adult form of attention deficit/hyperactivity disorder. …
Reference: The Effectiveness of intervention programs in the case of pupils with… quick summaries
Polymorphisms in the neural nicotinic acetylcholine receptor α4 subunit (CHRNA4) are associated with ADHD in a genetic isolate
Citing article
May 2009PubMed
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More, recent, similar research:
“The neural nicotinic acetylcholine receptor α4 subunit (CHRNA4), at 20q13.2-q13.3, is an important candidate gene for conferring susceptibility to attention deficit/hyperactivity disorder (ADHD). Several studies have already looked for association/linkage between ADHD and CHRNA4 in different populations. We used the Pedigree Disequilibrium Test to search for evidence of association between ADHD and six SNP marker loci in families from the isolated Paisa population. We found that the T allele of SNP rs6090384 exhibits a deficit of transmission in unaffected individuals (OR = 5.43, IC 1.54-19.13) (global P value = 0.014). We also found significant association and linkage to extended haplotypes rs2273502-rs6090384 (combination of variants C-T, respectively) (P = 0.02) and rs6090384-rs6090387 (P = 0.04) (combination of variants T-G, respectively). SNP rs6090384, variant T, has also been reported to be associated with inattention in a previous study. This makes ours the ninth study to examine the association of CHRNA4 with ADHD and the seventh one to find evidence for association in a population with a different ethnicity.”
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“Candidate gene…” “association/linkage…” These are speculative ideas, probabilities, not causal factors. A causal factor will be present when the situation is occurring and absent when it is not. In these GWAS tests, the “candidate gene” is present in the unaffected population in large numbers, just somewhat larger numbers in the “test” population. It doesn’t really explain anything at all.
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“In conclusion, our findings replicate previous studies that show LPHN3 confers ADHD susceptibility, and moderates response to MPH treatment in children and adolescents with ADHD.”
This was an amazing study. Inch by inch, step by step we are zeroing in on this monster.
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Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD’s high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD’s heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD’s heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.
Mol Psychiatry. 2019; 24(4): 562–575. Published online 2018 Jun 11. doi: 10.1038/s41380-018-0070-0
PMCID: PMC6477889NIHMSID: NIHMS1022091PMID: 29892054
Genetics of attention deficit hyperactivity disorder
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“…may eventually have implications…” Hope springs eternal!
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“There are many, “many” established differences between ADHD brains and non-ADHD brains.”
In fact there are none. There is no abnormality of brain structure that can be used to diagnose ADHD. There is no abnormality of brain function that can be used to diagnose ADHD. And this is after more than eighty years of brain-imaging studies, going all the way back to Charles Bradley’s experiments on children at the Bradley Home.
Psychiatric genetics is a gigantic multibillion-dollar fraud.
The fundamental assumption of family studies — that familial equals genetic — is false.
The fundamental assumption of twin studies — the equal environment assumption — is false.
The fundamental assumption of adoption studies — that adoption randomizes environmental variation — is false.
Linkage studies and candidate-gene studies have failed to find a single gene for any of those condition called “mental illnesses.”
Genome-wide-association studies are pseudoscientific nonsense. You screen the entire genome looking for single-nucleotide polymorphisms (not actual genes) correlated with the index condition, and if you don’t find a correlation you just keep increasing the sample size until you do. Although it never seems to work the other way around — you never hear these guys saying “Well maybe uf we looked at another population this correlation would disappear.” It’s like you and I betting on the outcome of a coin toss, with this stipulation — heads I win, tails we keep on flipping until it comes up heads.
And the legacy media (which is heavily dependent on drug company advertising to stay afloat) never mentions how absurdly tiny these claimed “effect sizes” are — one in a hundred, on in five hundred, one in two thousand. How can a gene correlated with a one in a hundred chance of developing a condition serve as a target for drug development?
There is no gene for ADHD. And how could there be? There are literally hundreds of reasons why any given child might have problems with inattention and hyperactivity. How could there be a common neural substrate, or a common genetic substrate, underlying all these disparate problems?
Billions of dollars spent on neuroimaging studies and genome-wide association studies of “mental illness” and not one patient in a clinic anywhere in the world has benefited. You don’t have to take my word for that. That’s what Thomas Insel said when he stepped down as head of the NIMH in 2017. It’s time we stopped throwing money down this particular balck hole and started talking about real-world solutions to real-world problems.
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ADHD ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD.
CONCLUSION
We demonstrate the necessity to carefully differentiate between ADHD and ADHD ODD/CD since we found similarities (reduced volume of the total GM and SA) but also differences in brain morphology between the disorders (increase in rostral middle frontal thickness for ADHD ODD/CD). The increased rostral middle frontal thickness hints at a specific developmental brain alteration in ADHD ODD/CD, probably related to a delayed cortical thinning. Implications for treatment could be to specifically focus on the (adolescent) boys with a “double burden” of ADHD and ODD or CD that seem to be even more affected than boys with ADHD-only.
And, from a different study, “How does ADHD affect the frontal lobe?
Children with ADHD have a frontal lobe that is developing slower than their peers’. This impacts much of their day-to-day life and includes even more than what’s mentioned above. It’s also instrumental in understanding cause-and-effect, changing habits, long-term memory, and reading social cues.”
Differences exist and we are just beginning to plumb the depths of all of them. The human brain. What an absolutely incredible 3 pounds of jello-like flesh and blood, the seat of our thinking, our emotions, our sense of self, our capacity to hate and to love, to sing, to play the piano, to assemble a 50 megaton thermonuclear device, to develop string theory and find Higgs-Boson.
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Keeping people out of prison is hip. Preventing crime is cool. Improving self esteem ain’t bad. Helping the disabled to function better is priceless. Setting free the child without hope cannot be measured. Helping people to read, to do math, behave appropriately, to be able to use one’s brain, there are no words or price tags.
We will uncover the scattered pieces of this puzzle and fit them in where they belong or increase the functionality of the surrounding cast. We’ve already come a long way. As a child, I was confined to hell. Soon, perhaps before I graduate to the next dimension, no child will be left out.
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TOM INSEL,
{Even after running clinical trials of new drugs and observing dramatic responses to medications in my patients, I was reluctant to use psychiatric medication in my own family. When my son showed every sign of ADHD, my wife and I reached for therapy, a special school, and parent training before we considered a stimulant drug. Our whole grain, no sugar, eight-year old on a psychotropic drug? No way, until a child psychiatrist friend recommended a pilot trial of methylphenidate (sold under the trade name Ritalin). Unlike antidepressants and antipsychotics, stimulants have rapid effects. Within a few hours we watched our whirling dervish slow down, put away his toys, and begin to listen for the first time. We were stunned. But our son was unimpressed. We asked him about the medication a week later. His response remains one of the most convincing statements I have ever heard about psychopharmacology. “Doesn’t do much for me, Dad, but it makes everybody else a lot nicer.”}
HE BEGAN TO LISTEN FOR THE FIRST TIME
The breakthrough moment when everything changed and after decades of unrelenting pain, there it was! The answer that we dreamed might come one day, that never did. Here it was.
When Anne Bancroft used one hand to pump the well and formed the letters for “water” inside Helen’s hand with other as water spilled over both. “w a t e r”. “Wa wa.” YES!
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But at Sami Timimi’s clinics this is a standard outcome with no drugs and no diagnosis. If Sami is not lying your argument does not stand.
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Psychiatric Times yesterday published a piece stating that Adult ADHD cannot be substantiated!!!!!!!! Now, that’s a first.
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Wow, that’s kind of stunning! Do you have a link to the articles?
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Hi Steve, It looks like Google is burying it. Found it.https://www.psychiatrictimes.com/view/adult-adhd-a-scientifically-invalid-disorder
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Thanks!
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