James M. Lewis M.D.

The Complexity of ADHD


When ADHD Medication Fails

Part 2: Successful ADHD treatment depends on overcoming these four pitfalls.

Posted Apr 23, 2019

Because stimulants are not a cure for ADHD, but can be the key that opens the doors to effective behavioral and educational therapies, the reasons for treatment failures need to be found and fixed. The problems related to the medication itself have been discussed in an earlier post leaving the following three areas:

  1. adverse side effects
  2. co-existing conditions inside the child
  3. circumstances outside the child

Problems Caused by Severe Side Effects

There are a number of key side effects which when present cause medication failure by discontinuation.

Weight loss 

Stimulants will almost always decrease appetite when the level peaks around lunchtime. Even though mothers try to improve unappetizing school cafeteria fare by packing their favorite food with encouraging notes attached to tempting snacks, most children will lose weight during the first months of treatment. It is reassuring to document that during this time the height is rarely affected. Both height and weight should be routinely measured at least every 3 months and a complete medical evaluation should be performed in any child that shows any evidence of delayed growth.      

If stimulant medication actually caused permanent weight loss, the current obesity epidemic in children, adolescents and adults could be quickly ended. Over time child resumes a normal intake of calories by eating a late dinner, adding a bedtime snack and taking breakfast at home. The medication should not be prescribed if the parent cannot guarantee that the child eats a high calorie, protein-rich breakfast every morning at home. Breakfast at school is unreliable because the medicine may dull the appetite early on, the food is unattractive and the friends distracting. Around six months of treatment, the weight stabilizes at the same percentile of the height and tends to remain at that level. In all too many cases, the excessive weight gain returns resulting in obesity and associated health problems.

Headaches and stomachaches  

If the child eats a good breakfast at home every day, not only will the weight stabilize but headaches and stomachaches will rarely occur.  If the child skips breakfast both at home and school and does not eat lunch because of the medication effect, their blood sugar levels can drop after this extended period without food. This relative reactive hypoglycemia is the most common cause of afternoon headaches, stomachaches or feelings of jitteriness, lightheadedness, rapid pulse or irritability. 


Although stimulants can affect sleep, in most cases the medication will be long gone from their system before bedtime. A morning coffee (also a stimulant) that helps someone start the day off does not cause sleeplessness at night. ADHD itself is the most common cause for sleep onset difficulties because when the medication wears off the symptoms of mental hyperactivity and restless physical and emotional energy return. Although not caused by the medication, insomnia will result in treatment failure because of the inattention and irritability caused by persistent fatigue and drowsiness during the day. 


Like sleep disturbances, irritability is often already present in children with ADHD due to their emotional impulsivity. Occasionally the stimulant medications may trigger irritable reactions especially during the initial months of treatment. The key is managing the behavior is determining the time it most frequently occurs. There may be difficulties in the morning at home before the medicine kicks in, but more commonly the behavior is seen in the afternoon when the medicine is leaving their system. Parents can almost set heir watch by the regularity of the episodes which happen daily around 3 to 4:30 every afternoon. This problem usually improves over time or when larger doses of medicine are given. An afternoon dose of short-acting stimulant may make a difference while families learn to work around the emotional outburst.


Sudden facial twitches, grimaces or unpredictable but repeated noises, grunts or sniffs are common in children with ADHD. Often there is a positive family history. Although previously believed to triggered by the medications, more recent research has shown that stimulant treatment can decrease the frequency or severity of tics by decreasing stress. Tics will often change, come and go for unknown reasons and usually resolve as the child ages. Guanfacine ER can be helpful in persistent cases.

Problems Caused by Complicating Conditions

The third reason why medication may fail is the complicating presence of five additional co-existing conditions: anxiety, learning disabilities, oppositional defiant disorder, demoralization and autism spectrum disorder.

Anxiety disorders  

Generalized anxiety, separation anxiety, panic attacks, school phobia and obsessive-compulsive disorder with rituals and tics may occur in up to 50% of children with ADHD.  Early symptoms of separation anxiety can later transform into specific fears and phobias such as storms, bees or burglars. Devastating social anxiety may eventually develop in teenagers. A strong family history of anxiety or depression is often present. Unfortunately, the most common but destructive defense mechanisms of denial and avoidance often firmly in place. Anxiety clouds the decision for a trial of medication and can exaggerate the presence of side effects for both child and parent. Although a little anxiety can counterbalance the impulsivity of ADHD, too much often limits the reaction of the child to most basic responses of freeze, flee or fight. Family disintegration, few friends, falling grades, mountains of homework and missed assignments can so intensify the anxiety that stimulant medication may show little or no effect.  

Oppositional defiant disorder

A personality that can be best described as “sensitive but stubborn” is also present in up to 50 percent of children with ADHD. Although this may be an admirable trait in some situations, defiance, and refusal at home or school is never a good thing. Behavioral modification based on rules, rewards, and consequences works better when the medicine prolongs the response time of the child. Taking the time to think can considerably improve the odds of making a good decision.  Children with difficult temperaments may still insist on their path even after considering the options. An effective and consistent school and home behavioral plan with specific goals and appropriate rewards can work wonders that medication by itself cannot achieve.

Learning disabilities

The presence of specific learning difficulties in reading, writing, math, and organization can also limit the effect of medication. Stimulant therapy often improves handwriting legibility and decreases careless mistakes and messy work. Similarly, ability in subjects that are progressive like math may jump ahead. Division can magically become possible once the missing multiplication skills are mastered. Specific disabilities in reading and executive function, however, will almost always require academic and achievement testing and the implementation of appropriate educational modifications. Frequent re-evaluation and adjustment of the accommodations is critical for successful medication management. Teaching strategies for children with intellectual disabilities and autism spectrum disorder are essential.


Children and adolescents with ADHD may eventually just give up, stop trying, and simply refuse to do the work. Hundreds of “stop that, sit down, no talking, get busy and finish your work, keep your hands to yourself, don’t argue, figure it out for yourself, no recess, what is the matter with you?” eventually take a toll in even the most resilient student. When these children with ADHD drop out because of discouragement depression and more, it is impossible for any amount of medication to get them back.

Autism spectrum disorder   

Recent research has proven that children with ADHD can also have features of autism without an official diagnosis of Autism Spectrum Disorder. The shared characteristics are problems with communication, difficulties in communication and unusual restricted and repetitive interests or activities. Although medication cannot change the thought disorder of ASD, it can work to improve attention span, decrease hyperactivity and slow impulsive behaviors providing at least an opportunity for better relationships and learning. When these spectrums collide special care must be given in the use of stimulants.

  1.  increases should be made no more than monthly rather than weekly
  2.  long-acting preparations should always be used to reduce irritability, anorexia, and insomnia
  3.  side effects should be expected to persist over a longer time
  4. expectations of improvement should be lowered

Problems Caused by External Circumstances

The role of the world around the child in reducing the effectiveness of medication is more describing by a recent patient encounter:

Matthew is a 13-year-old who started middle school about two months ago. He is receiving special education through an Individualized Educational Plan based on academic on achievement testing.  He is accompanied by his great-grandmother who babysits him frequently and is a retired school teacher. He is sitting quietly on the examination table playing with his phone and does not stop or even look up when I enter the room. His face is expressionless as he answers all my questions about school, the medicine and life at home with a monotone delivery of “I don’t know.” When his grandmother supplies some information about his grades and classes he snaps sharp answers back to her saying “That is not true!”

I am uncertain of what I can do because his medications are already at fairly high levels. In the past both his ADHD and anxiety disorder well controlled with the treatment regimen. In reviewing his chart, I note that he has also previously failed multiple medications given at appropriate doses and duration of treatment. His physical examination, blood pressure, and pulse are normal and he is tracking on the 50th percentile for both weight and height growth. He does admit that he skips breakfast frequently both at home and school. He has no trouble falling asleep but wakes frequently through the night. Neither he nor his great-grandmother can confirm that he regularly takes his afternoon dose of the stimulant because of his mother has recently been ill. 

She now explains that his mother has rheumatoid arthritis that has suddenly flared up. She is very proud of how Matthew has stepped up to care for her while she if sometimes been unable to get out of bed. She missed his appointment today because her job is in jeopardy due to multiple absences. As I look to Matthew to ask if his worrying about his mother has affected his sleep, he slowly nods his head and his eyes tear up. Now his great-grandmother almost nonchalantly reminds him that the whole household has also been upset since his 21-year-old uncle has moved in with his girlfriend after he recently lost his job. She implies that the problem is related to the opioid crisis currently raging in our Appalachian city.

Instead of changing or increasing his medications, we decide to meet with his teachers as a team to evaluate their effectiveness, duration of effect and possible adverse reactions. This will also provide the opportunity to explain his family stresses and discuss possible adjustments to his IEP due to the new academic and social challenges of Middle School.  We agree to work on establishing a regular sleep schedule and routine breakfast at home. When Matthew steps out of the room to go to the bathroom, great-grandmother leans over to me and whispers “I am really worried because his mother had a huge fight with his grandmother that I think is causing most of his problems.” When she states that his mother is seeing a counselor we agree that Matthew should be included in a family therapy approach.

In conclusion, the decision for a trial of medication should be made carefully and can be life-changing for the child and the family. Success will depend on monitoring the administration, managing side effects, dealing with co-existing conditions and understanding the circumstance around the child.