People with ADHD plus other mental disorders discontinue treatment more often

Breaking new ground 15. nov 2021 4 min Researcher Isabell Brikell Written by Kristian Sjøgren

Teenagers and young adults with attention-deficit/hyperactivity disorder (ADHD) plus one or more other mental disorders are more likely to discontinue stimulant treatment for ADHD than teenagers and young adults with ADHD alone.

Stimulant medication is effective for most people with ADHD. Nevertheless, many discontinue treatment with stimulant drugs such as methylphenidate.

A recent study shows that especially teenagers and young adults with ADHD plus other mental disorders are at increased risk of discontinuing treatment with stimulant medication or switching to treatment with nonstimulant ADHD medication.

Further, the research shows that children and adolescents with ADHD do not even need to exhibit signs of another mental disorder to be at increased risk of discontinuation. Being genetically predisposed for mood or psychotic disorders was also linked to a slight increase in the risk of discontinuing or switching medication.

“We know that the medication is effective for the vast majority of people with ADHD, but around 10–20% of people with ADHD respond poorly to treatment and as many as 50% discontinue treatment within 2 years. In addition to helping to control the symptoms of ADHD, the medication can improve school performance and reduce the risk of being involved in accidents. Discovering why many people with ADHD discontinue treatment with stimulant medication is therefore important,” explains Isabell Brikell, a researcher at the National Centre for Register-based Research, Aarhus University and Karolinska Institutet, Stockholm, Sweden.

The research has been published in The American Journal of Psychiatry.

9,133 children and adolescents studied

Isabell Brikell and colleagues based their study on the iPSYCH2012 sample, which contains clinical and genetic data on a large cohort of people with a mental disorder and thousands of controls.

The study included 9,133 children and adolescents with a mean age of 12 years when diagnosed with ADHD.

The researchers examined whether various factors were associated with whether the individuals with ADHD in the cohort discontinued the stimulant medication or switched to nonstimulant medication within 2 years of starting treatment.

These factors were:

  • Another mental disorder. 
  • Genetic disposition for ADHD and other mental disorders.
  • Parents’ income and education.
  • Parents’ history of mental disorder.
  • Age when diagnosed with ADHD

More than one disorder often results in discontinuing treatment

The study showed that some of the 9,133 members of the cohort had another mental disorder in addition to ADHD, including depression, anxiety, bipolar disorder, and tics.

The researchers found that people with ADHD plus anxiety, obsessive-compulsive disorder, substance abuse problems or bipolar disorder were less likely to start treatment with stimulant medication.

In addition, when comparing the rates of discontinuing stimulant medication, they found that people with ADHD and tics, anxiety, bipolar disorder or substance abuse were between 10% and 200% more likely to discontinue treatment within 2 years depending on which comorbid disorder they had.

In particular, people with tics were highly likely to discontinue treatment. According to Isabell Brikell, this makes sense since aggravation of tics can be a rare side-effect of stimulant treatment.

“Our findings confirm what we know clinicians focus on in clinical practice. Therefore, it is not surprising that another disorder in addition to ADHD increases the likelihood of not initiating or discontinuing stimulant treatment. This emphasises the importance of monitoring people being treated for ADHD, especially if they have additional disorders or may be at risk of side-effects,” says Isabell Brikell.

Can worsen other disorders

Isabell Brikell explains that people with multiple disorders in addition to ADHD may discontinue treatment more often for many reasons. Examples include the following.

  • Stimulant medication for ADHD may be less well tolerated or less effective among people with multiple disorders. 
  • Stimulant medication is secondary to other treatments for bipolar disorder. In addition, stimulant treatment may exacerbate psychotic or manic episodes in rare cases.
  • Clinicians may hesitate to prescribe ADHD medication for people with substance abuse because they may abuse it.

“These may be some of the reasons why people with ADHD plus other disorders discontinue stimulant medication more often. They or their parents may decide to discontinue treatment, or a healthcare professional may advise them to do so,” explains Isabell Brikell.

Adults discontinue treatment more often than children and adolescents

In addition to the factor of multiple mental disorders, the researchers also found that teenagers and young adults were twice as likely as children to discontinue treatment with stimulant medication.

According to Isabell Brikell, several factors may cause this.

  • Problems can occur in the transition from attending paediatric clinics to attending adult mental health.
  • Teenagers and adults are more likely to manage their own medication (rather than their parents for most children) and may be more unwilling to continue medication or think they do not need it.
  • Finally, adults with ADHD must renew and collect their own prescriptions, and this may be a challenge for people with ADHD, who might struggle with remembering to take and to refill prescriptions etc.

Genetic variants increase the risk of discontinuing treatment

Finally, the researchers also found that a genetic predisposition to mental disorders other than ADHD also increases the likelihood of discontinuing treatment – although only slightly.

The greater the genetic risk of cohort members for depression, bipolar disorder or schizophrenia, the greater the risk of discontinuing treatment or switching to nonstimulant treatment. The risk was present even among individuals who did not have manifestations of these additional mental disorders.

Further, genetic predisposition to ADHD or autism did not increase the likelihood of discontinuing treatment.

“This tells us something about the biological differences that may increase the probability of discontinuing treatment for ADHD and is one of our most novel discoveries,” says Isabell Brikell.

The researchers found no association between the likelihood of discontinuing treatment and parents’ socioeconomic status or history of mental disorder.

Models for optimal individual treatment

The results have various clinical implications.

Isabell Brikell is convinced that healthcare professionals in Denmark are already aware that having more than one mental health disorder can increase the risk of side-effects and poor tolerance among people with ADHD and therefore monitor their treatment more closely.

“The study shows that staying focused on this is important and highlights the problem of people discontinuing treatment, which is still very frequent. More research on the factors that lead to this is required, and our findings show that genetics also plays a role. The more we know about the risk factors for discontinuing treatment, the easier it will become to try and develop models to identify people with ADHD at high risk. This is possible, but the long-term perspective is that this may lead to better opportunities for optimising the treatment of individuals right at the start,” concludes Isabell Brikell.

“Genetic, clinical, and sociodemographic factors associated with stimulant treatment outcomes in ADHD” has been published in the American Journal of Psychiatry. In 2016, the Novo Nordisk Foundation awarded a grant to co-author Søren Dalsgaard for the project Polygenic Risk Scores and Early Social Adversities in Predicting the Developmental Course and Trajectory in Individuals with ADHD.

At the Department of Medical Epidemiology and Biostatistics (MEB) we focus on research and teaching within the fields of epidemiology and biostatistic...

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