The 'Medication Tolerance' Myth in ADHD: What the Evidence Actually Says

For years, a persistent concern has shadowed the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Does the medication eventually stop working? Patients often report that their symptoms seem to return despite consistent use, leading to "dose escalation" or "medication holidays." A new systematic review from Sam Cortese’s team  published in CNS Drugs finally puts these concerns to the test by synthesizing decades of empirical research.

Before diving into the findings, you must understand two often-confused phenomena:

  • Tachyphylaxis (Acute Tolerance): A rapid decrease in response to a drug, often occurring within a single day (24 hours).
  • Tolerance: A gradual reduction in responsiveness over long-term exposure, requiring higher doses to achieve the original effect.

The review analyzed 17 studies covering over 10,000 individuals, and the results provide a much-needed reality check for the clinical community.

The researchers found preliminary evidence that acute tolerance (tachyphylaxis) can occur within a 24-hour window.

  • Subjective Effects: Studies showed that "drug liking" or feelings of euphoria from stimulants often peak and fade faster than the actual drug concentration in the blood.
  • Clinical Impact: This phenomenon is why some older, flat-release formulations were less effective than modern "ascending" delivery systems (like OROS-methylphenidate), which are designed to overcome this daily dip in efficacy.

The most important finding is that tolerance does not commonly develop to the therapeutic effects of ADHD medication in the long term. In one landmark study following children for up to 10 years, only 2.7% of participants lost their response to methylphenidate without a clear external explanation.  Doses, when adjusted for natural body growth, remained remarkably stable over years of treatment.

Consistent with the lack of therapeutic tolerance, the body does not become tolerant to the physical side effects of stimulants.  Increases in heart rate and blood pressure typically persist for as long as the medication is taken.  This underscores why clinicians must continue monitoring cardiovascular health throughout the entire duration of treatment.

If it’s Not Tolerance, What Is It?

If "tolerance" isn't real, why do some patients feel their medication is failing? The review suggests clinicians look at these alternative explanations:

  1. Natural Symptom Fluctuations: ADHD is not a static condition; symptoms naturally wax and wane over time regardless of treatment.
  2. Limited Compliance: Missed doses or inconsistent timing are often the real culprits behind "failing" efficacy.
  3. Life Events & Transitions: New jobs, academic pressures, or stressful life changes can increase the "functional demand" on a patient, making their current dose feel insufficient.
  4. Co-occurring Conditions: The emergence of anxiety, depression, or substance use disorders can mask or mimic a return of ADHD symptoms.

Why This Matters

These results provide clinicians the confidence to tell patients that their medication is unlikely to "wear out" permanently. Rather than immediately increasing a dose when symptoms flare, the first step should be a "clinical deep dive" into the patient's lifestyle, stress levels, and adherence.

For researchers, the review highlights a major gap: most existing studies are small, dated, or of low quality. There is a dire need for robust, longitudinal studies that track both the brain's response and the patient's environment over several years.

For people with ADHD, while your body might get "used to" the initial "buzz" of a stimulant within hours, its ability to help you focus and manage your life remains remarkably durable over the years.

Smith, C., Walker, H., Parlatini, V., & Cortese, S. (2026). Tolerance and tachyphylaxis to medications for attention-deficit/hyperactivity disorder (ADHD): A systematic review of empirical studies. CNS Drugs. . https://doi.org/10.1007/s40263-025-01263-8

Related posts

Unmedicated Adult ADHD Linked to Dementia in Population Study

Background:

Noting that “the association between adult ADHD and dementia risk remains a topic of interest because of inconsistent results,” an Israeli study team tracked 109,218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. 

Israeli law forbids nonprofit HMOs from turning anyone away based on demographic factors,  health conditions, or medication needs, thereby limiting sample selection bias.  

The estimated prevalence of dementia in this HMO, as diagnosed by geriatricians, neurologists, or psychiatrists, is 6.6%. This closely matches estimates in Western Europe (6.9%) and the United States (6.5%). 

Method:

The team considered, and adjusted for, numerous covariates: age, sex, socioeconomic status, smoking, depression, obesity, chronic obstructive pulmonary disease, hypertension, atrial fibrillation, heart failure, ischemic heart disease, cerebrovascular disease, diabetes, Parkinson’s disease, traumatic brain injury, migraine, mild cognitive impairment, psychostimulants. 

With these adjustments, individuals diagnosed with ADHD were almost three times as likely to be subsequently diagnosed with dementia as those without ADHD. Men with ADHD were two and a half times more likely to be diagnosed with dementia, whereas women with ADHD were over three times more likely, than non-ADHD peers. 

More concerning still, persons with ADHD were 5.5 times more likely to be subsequently diagnosed with early onset dementia, as opposed to 2.4 times more likely to be diagnosed with late onset dementia. 

On the other hand, the team found no significant difference in rates of dementia between individuals with ADHD who were being treated with stimulant medications and individuals without ADHD. Those with untreated ADHD had three times the rate of dementia. The team nevertheless cautioned, “Due to the underdiagnosis of dementia as well as bidirectional misdiagnosis, this association requires further study before causal inference is plausible.” 

Conclusions and Relevance:

This study reinforces existing evidence that adult ADHD is associated with an increased risk of dementia. Notably, the increased risk was not observed in individuals receiving psychostimulant medication, however the mechanism behind this association is not clear.

These findings underscore the importance of reliable ADHD assessment and management in adulthood. They also highlight the need for further study into the link between stimulant medications and the decreased risk of dementia.

 

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February 25, 2025

ADHD medication and risk of suicide

ADHD Medication and Risk of Suicide

A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.

The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.

The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.

Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.

The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.

Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.

A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."

The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."

December 13, 2021

Does ADHD Medication Improve the Parenting Skills of Adults with ADHD?

Does ADHD Medication Improve the Parenting Skills of Adults with ADHD?

Raising children is not easy. I should know.

As a clinical psychologist, I've helped parents learn the skills they need to be better parents. And my experience raising three children confirmed my clinical experience.

Parenting is a tough job under the best of circumstances, but it is even harder if the parent has ADHD.

For example, an effective parent establishes rules and enforces them systematically. This requires attention to detail, self-control, and good organizational skills. Given these requirements, it is easy to see how ADHD symptoms interfere with parenting. These observations have led some of my colleagues to test the theory that treating ADHD adults with medication would improve their parenting skills. I know about two studies that tested this idea.

In 2008, Dr. Chronis-Toscano and colleagues published a study using a sustained-release form of methylphenidate for mothers with ADHD. As expected, the medication decreased their symptoms of inattention and hyperactivity/impulsivity. The medication also reduced the mother's use of inconsistent discipline and corporal punishment and improved their monitoring and supervision of their children.

In a 2014 study, Waxmonsky and colleagues observed ADHD adults and their children in a laboratory setting once when the adults were off medication and once when they were on medication. They used the same sustained-release form of amphetamine for all the patients. As expected, the medications reduced ADHD symptoms in the parents. This laboratory study is especially informative because the researchers made objective ratings of parent-child interactions, rather than relying on the parents' reports of those interactions. Twenty parents completed the study. The medication led to less negative talk and commands and more praise by parents. It also reduced negative and inappropriate behaviors in their children.

Both studies suggest that treating ADHD adults with medication will improve their parenting skills. That is good news. But they also found that not all parenting behaviors improved. That makes sense. Parenting is a skill that must be learned. Because ADHD interferes with learning, parents with the disorder need time to learn these skills. Medication can eliminate some of the worst behaviors, but doctors should also provide adjunct behavioral or cognitive-behavioral therapies that could help ADHD parents learn parenting skills and achieve their full potential as parents.

May 7, 2021

The 'Medication Tolerance' Myth in ADHD: What the Evidence Actually Says

For years, a persistent concern has shadowed the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Does the medication eventually stop working? Patients often report that their symptoms seem to return despite consistent use, leading to "dose escalation" or "medication holidays." A new systematic review from Sam Cortese’s team  published in CNS Drugs finally puts these concerns to the test by synthesizing decades of empirical research.

Before diving into the findings, you must understand two often-confused phenomena:

  • Tachyphylaxis (Acute Tolerance): A rapid decrease in response to a drug, often occurring within a single day (24 hours).
  • Tolerance: A gradual reduction in responsiveness over long-term exposure, requiring higher doses to achieve the original effect.

The review analyzed 17 studies covering over 10,000 individuals, and the results provide a much-needed reality check for the clinical community.

The researchers found preliminary evidence that acute tolerance (tachyphylaxis) can occur within a 24-hour window.

  • Subjective Effects: Studies showed that "drug liking" or feelings of euphoria from stimulants often peak and fade faster than the actual drug concentration in the blood.
  • Clinical Impact: This phenomenon is why some older, flat-release formulations were less effective than modern "ascending" delivery systems (like OROS-methylphenidate), which are designed to overcome this daily dip in efficacy.

The most important finding is that tolerance does not commonly develop to the therapeutic effects of ADHD medication in the long term. In one landmark study following children for up to 10 years, only 2.7% of participants lost their response to methylphenidate without a clear external explanation.  Doses, when adjusted for natural body growth, remained remarkably stable over years of treatment.

Consistent with the lack of therapeutic tolerance, the body does not become tolerant to the physical side effects of stimulants.  Increases in heart rate and blood pressure typically persist for as long as the medication is taken.  This underscores why clinicians must continue monitoring cardiovascular health throughout the entire duration of treatment.

If it’s Not Tolerance, What Is It?

If "tolerance" isn't real, why do some patients feel their medication is failing? The review suggests clinicians look at these alternative explanations:

  1. Natural Symptom Fluctuations: ADHD is not a static condition; symptoms naturally wax and wane over time regardless of treatment.
  2. Limited Compliance: Missed doses or inconsistent timing are often the real culprits behind "failing" efficacy.
  3. Life Events & Transitions: New jobs, academic pressures, or stressful life changes can increase the "functional demand" on a patient, making their current dose feel insufficient.
  4. Co-occurring Conditions: The emergence of anxiety, depression, or substance use disorders can mask or mimic a return of ADHD symptoms.

Why This Matters

These results provide clinicians the confidence to tell patients that their medication is unlikely to "wear out" permanently. Rather than immediately increasing a dose when symptoms flare, the first step should be a "clinical deep dive" into the patient's lifestyle, stress levels, and adherence.

For researchers, the review highlights a major gap: most existing studies are small, dated, or of low quality. There is a dire need for robust, longitudinal studies that track both the brain's response and the patient's environment over several years.

For people with ADHD, while your body might get "used to" the initial "buzz" of a stimulant within hours, its ability to help you focus and manage your life remains remarkably durable over the years.

Population Study Finds Association Between Extended Methylphenidate Use By Children and Subsequent Obesity

South Korean Nationwide Population Study Finds Association Between Extended Methylphenidate Use By Children and Subsequent Obesity–Little to No Effect on Adult Height

South Korean Nationwide Population Study Finds Association Between Extended Methylphenidate Use By Children and Subsequent Obesity–Little to No Effect on Adult Height

The Background:

Concerns remain about how ADHD and methylphenidate (MPH) use might affect children's health and growth, and especially how it may affect their adult height. While some studies suggest disrupted growth and a possible biological mechanism, the impact of ADHD prevalence and MPH use is still unclear. Children with ADHD may develop unhealthy habits – irregular eating, low physical activity, and poor sleep – that can contribute to obesity and reduced height. MPH’s appetite-suppressing effect can lead to skipped meals or overeating. Since growth hormone is mainly released during deep sleep, chronic sleep deprivation could plausibly slow growth and impair height development; however, a clear link between ADHD, MPH use, overweight, and shorter stature has never been firmly established. 

The Study:

South Korea has a single payer health insurance system that covers more than 97% of its population. A Korean research team used the National Health Insurance Service database to perform a nationwide population study to explore this topic further. 

The study involved 34,850 children, of whom 12,866 were diagnosed with ADHD. Of these children, 6,816 (53%) had received methylphenidate treatment, while 6,050 (47%) had not. Each patient with ADHD was precisely matched 1:1 by age, sex, and income level to a control participant without ADHD. The sex ratio was comparable in all groups.The team used Body Mass Index (BMI) as an indicator of overweight and obesity. 

The Results: 

The researchers found that being diagnosed with ADHD was associated with 50% greater odds of being overweight or obese as young adults, and over 70% greater odds of severe obesity (BMI > 30) compared to matched non-ADHD controls, regardless of whether or not they were medicated.

Those diagnosed with ADHD, but not on methylphenidate, had 40% greater odds of being overweight or obese, and over 55% greater odds of becoming severely obese, relative to matched non-ADHD controls. 

Methylphenidate users had 60% greater odds of being overweight or obese, and over 85% greater odds of becoming severely obese, relative to matched non-ADHD controls. 

There were signs of a dose-response effect. Less than a year’s exposure to methylphenidate was associated with roughly 75% greater odds of becoming severely obese, whereas exposure over a year or more raised the odds 2.3-fold, relative to matched non-ADHD controls. Using MPH increased the prevalence of overweight from 43.2% to 46.5%, with a greater prevalence among those using MPH for more than one year (50.5%).

It is important to note that most of this effect was from ADHD itself, with methylphenidate only assuming a predominant role in severe obesity among those with longer-term exposure to the medicine. 

As for height, children with ADHD were no more likely to be short of stature than matched non-ADHD controls. Being prescribed methylphenidate was associated with slightly greater odds (7%) of being short of stature, but there was no dose-response relationship. 

Conclusion: 

The team concluded, “patients with ADHD, particularly those treated with MPH, had a higher BMI and shorter height at adulthood than individuals without ADHD. Although the observed height difference was clinically small in both sexes and age groups, the findings suggest that long-term MPH exposure may be associated with growth and body composition, highlighting the need for regular monitoring of growth.” They also point out that “Despite these findings, the clinical relevance should be interpreted with caution. In our cohort, the mean difference in height was less than 1 cm (eg, maximum −0.6 cm in females) below commonly accepted thresholds for clinical significance.”  Likewise, increases in overweight/BMI were small. 

One problem with interpreting the BMI/obesity results is that some of the genetic variants that cause ADHD also cause obesity.  If that genetic load increases with severity of ADHD than the results from this study are confounded because those with more severe ADHD are more likely to be treated than those with less severe ADHD.

Due to these small effects along with the many study limitations noted by the authors, these results should be considered alongside the well-established benefits of methylphenidate treatment.

February 2, 2026

What is An Expert?

What do we mean by expert? In simple terms, an expert possesses in-depth knowledge and specialized training in a particular field. In order to be considered an expert in any field, a person must have both deep knowledge of and competence in their specific area of expertise. Experts have a background that includes education, research, and experience. In the world of mental health and psychology, this typically means formal credentials (a PhD, MD, etc) in addition to years of study, peer-reviewed publications, and/or extensive clinical experience. 

Experts are recognized by their peers (and often by the public) as reliable authorities on a specific topic. Experts usually don’t make big claims without evidence; instead, they cite studies and speak cautiously about what the evidence shows. 

Tip: Those looking for likes and clicks will often speak in absolutes (e.g., “refined sugar makes your ADHD worse, but the Keto Diet will eliminate ADHD symptoms”) while experts will use language that emphasizes evidence (e.g., “research has proven that there is no ‘ADHD Diet’, but some evidence has suggested that certain individuals with ADHD may benefit from such dietary interventions as limiting food coloring or increasing omega fatty acids.”) 

The Double-Edged Sword of Social Media   

Social media has created an incredible opportunity for those with ADHD to gain access to invaluable resources, including the creation of communities by and for those with ADHD. Many people with ADHD report feeling empowered and less alone by connecting with others online. These online social platforms provide a space for those with ADHD to share their own perspectives and their lived experience with the disorder. Both inside and outside of mental health-related communities, social media is a powerful tool for sharing information, reducing stigma, and helping people find community. When someone posts about their own ADHD challenges or tips, it can reassure others that they’re not the only ones facing these issues. This kind of peer support is valuable and affirming.

It is vital for those consuming this media, however, to remember that user-generated content on social media is not vetted or regulated. Short TikTok or Instagram videos are designed to grab attention, not to teach nuance or cite scientific studies. As it turns out, most popular ADHD posts are misleading or overly simplistic, at best. One analysis of ADHD TikTok videos found that over half were found to be “misleading” by professionals. Because social feeds reinforces what we already believe (the “echo chamber” effect, or confirmation bias), we can easily see only content that seems to confirm our own experiences, beliefs, or fears.

Stories aren’t a substitute for expert guidance.

Lived Experience vs. Universal Advice

It’s important to recognize the difference between personal experience and general expertise. Having ADHD makes you an expert on your ADHD, but it does not make you an expert on ADHD for everyone. Personal stories are not scientific facts. Even if someone’s personal journey is true, the same advice or experience may not apply to others. For instance, a strategy that helps one person focus might have no effect– or possibly even a negative effect– on someone else.

Researchers have found that most ADHD content on social media is based on creators’ own experiences, not on systematic research. In one study, almost every TikTok ADHD creator who listed credentials actually just cited their personal story. Worse, about 95% of those videos never noted that their tips might not apply to everyone (journals.plos.org.) In other words, they sound absolute even though they really only reflect one person’s situation. It’s easy to misunderstand the condition if we take those singular experiences as universal facts.

How Real Experts Talk

So how can you tell when someone is speaking from expertise rather than personal experience or hearsay? Experienced professionals usually speak cautiously, rather than in absolutes. They tend to say things like “research suggests,” “some studies show,” or “evidence indicates,” rather than claiming something always or never happens. As one health-communication guide puts it, a sign of a trustworthy source is that they do not speak in absolutes; instead, they use qualifiers like “may,” “might,” or refer to specific studies. For example, an expert might say, “Some people with ADHD may have difficulty with organization,” instead of “ADHD people always lose things.”

Real experts also cite evidence. In science and psychology, experts usually share knowledge through peer-reviewed articles, textbooks, or professional conferences – not just social media posts. Reliable health information is typically backed by references to studies published in reputable journals.

If someone makes a claim online, ask: Do they point to research, or is it just their own testimony? This is why it’s wise to prefer content where the author is a recognized authority (like a doctor or researcher) and where references to scientific studies or official guidelines are provided. In fact, advice from sites ending in “.gov”, “.edu”, or “.org” (government, university, or professional organizations) tends to be more reliable than random blogs. When in doubt, look up who wrote the material and whether it cites peer-reviewed research.

The Take-Away: 

When navigating mental health information online, remember these key points:

  • experts rarely claim absolute truths
  • experts usually have credentials and publications
  • experts speak in precise, cautious language. 

If you see sweeping statements like “This one habit will predict if you have ADHD” or “Eliminating this one food will cure your ADHD symptoms”--- that’s a red flag. Instead, the hallmark of expert advice is a tone of humility (“evidence suggests,” “it appears that,” etc.), clear references to studies or consensus statements, and an acknowledgment that individual differences exist.

At the same time, we need to acknowledge that community voices are incredibly valuable – they help us feel understood and less alone. The goal is not to dismiss personal stories, but to balance them with facts and evidence-based information. Let lived experience spark questions, but verify important advice with credible sources. Follow trusted organizations (for example, the National Institutes of Health, CDC, or ADHD specialist groups) and mental health professionals who communicate carefully. Use the online ADHD community for support and sharing tips, but remember it’s just one piece of the puzzle.

By being a savvy reader (checking credentials, looking for cited evidence, and spotting overgeneralizations), you can make the most of online ADHD content. In doing so, you give yourself both the empathy of community and the accuracy of real expertise. That way, you’ll be well-equipped to separate helpful insights from hype and to keep learning from both personal stories and science-based experts.

January 13, 2026