Stimulants are highly popular medications, used primarily to control the symptoms of Attention Deficit Hyperactivity Disorder (ADHD).  The two main drugs in the category of stimulants are amphetamine and methylphenidate.  Amphetamine is a familiar chemical in the public, where it is commonly called speed.

Both amphetamine and methylphenidate appear to work through their impact on the neurotransmitter dopamine.  Amphetamine boosts the release of dopamine in the brain.  Methylphenidate slows its clearance once it is released.  Curiously, many psychotic conditions are associated with increased release of dopamine.

Types and Brands of Stimulants Sold in the United States

Amphetamine in the US is sold under two brand names: Adderall and Vyvanse.  Vyvanse is simply a molecule of amphetamine attached to an amino acid.  This renders the medication ineffective until it is swallowed and the digestive system removes the amino acid, transforming Vyvanse into Adderall.

Methylphenidate in the US is sold under at least 7 brand names:  Ritalin, Concerta, Methylin, Metadate, Daytrana the patch form), Quillivant (the liquid form), and Focalin.  Focalin is the right-handed version of methylphenidate.  Most biologic chemicals have handedness.  A most familiar example is glucose.  Like our hands, the molecule has two 3D forms that look exactly identical except they are mirror images of each other.  The right handed form of glucose is called dextrose.  Well, all methylphenidates are half left-handed, half right-handed.  So Focalin simply takes only the right-handed version and only that is in its pills.

The Popularity of Stimulants

The popularity of stimulants in the United States can be summarized in one word: Wow!  The use in all age groups is zooming, dramatically.

In September of 2016, an article published tallied how many of us take stimulants.

Here are the trends:

• From the period 1994-1997  to the period 2006-2009, the use of stimulants in the US went up 7-fold
• In 2014, the following number of children and adults were taking stimulants:
  • 0-9 year olds:  3.1%
  • 10-19 year olds:  7.2%
  • 20-39 year olds:  3.6%
  • 40-64 year olds:  1.5%
• For children, ages 0-19 year olds, 7% of boys and 3.5% of girls were taking stimulants

Across the world, methylphenidate is now the most commonly prescribed drug in many countries.

The Study

In a March 21, 2019 article in The New England of Medicine, authors from a number of medical institutions affiliated with the Harvard Medical School, published a detailed analysis of the use of stimulants and the association of those using these drugs with the onset of a serious psychosis.

Psychosis is a very severe condition in which the ability of a person’s mind to are so impaired that they can no longer relate, understand, or operate in reality effectively.

The study examined the use of stimulants in databases of people numbering over 185 million people ages 13 to 25 years old.

An episode of psychosis was defined as severe enough to require the prescription of an anti-psychotic drug, so these were not incidents of someone losing their ability to think effectively for a brief moment.  Rather, these were episodes of a very severe loss of mental function.

People with a wide variety of conditions that themselves could cause psychosis, such as schizophrenia, were not included in the analysis.  Nor were people taking a variety of other drugs besides stimulants, to make sure they were not counting psychoses caused be other drugs.

Findings on Use of Stimulants

In the period from 2005 to 2014, the number of people ages 13-25 years old prescribed an amphetamine went up 3.8 fold, and a methylphenidate up 1.6 fold.

About a third of people had their stimulant prescribed by a family medicine or internal medicine doctors, about a third by a pediatrician, and about a fifth by a psychiatrist.   About 18% of those prescribed suffered from depression as well as ADHD, about 13% had anxiety or PTSD as well as ADHD.

Psychosis in those Using Stimulants

The total number of people studied totaled 221,846 people, and of those, 343 episodes of psychosis occurred.   That comes to a total of 1 in 647 people ages 13-25 years old taking stimulants suffered a serious bout of psychosis, serious and sustained enough to require being placed on medication to treat psychosis.

There was a difference in the occurrence of psychosis in those taking amphetamines and methylphenidates.  For the 110,923 people taking methylphenidates, 106 people suffered psychosis.  For the 110,923 people taking amphetamine, 237 people suffered psychosis.  So taking amphetamine carried over twice the risk of psychosis that methylphenidate does.

A serious psychosis occurred typically an average of 128 days after the medication was started, so it often took many months of treatment before the psychosis erupted.

This was not a randomized controlled trial, so it does not prove that taking a stimulant causes psychosis, but it strongly raises that possibility.

BOTTOM LINES

1. A major study by The New England Journal of Medicine published on March 21, 2019, establishes the very real possibility that taking stimulants for ADHD may cause about in 1 in 647 adolescents and young adults to suffer a bout of psychosis severe enough to require medication to treat.
2. This finding is important.   Many, many millions of our children are now taking drugs in the category of stimulants.  The fact that they may cause psychosis to occur should give each of us pause.  Certainly all doctors prescribing these medications should be informing families this can happen.  And all families should now be aware of this risk before deciding to have their children take stimulants.
3. This study is important because the use of stimulants is rising and rapidly.  More and more people are taking them, across all ages groups for 0-9 through age 64.  In many countries stimulants are prescribed more than any other drug.
4. At Advanced Pediatrics we remain committed to this standard when considering the prescription of a stimulant:
   1. The symptoms of ADHD can be explained by a wide variety of causes that include, but are not limited to ADHD.  Like fever, there are many causes for a symptom, and it is important for all concerned to be fully aware of what may be causing your child’s particular ADHD symptoms.  Knowing the actual cause of a symptom is the key to effective treatments.
   2. For many children who have symptoms of ADHD, finding other causes for their symptoms of inattention, impulsivity, and/or hyperactivity opens paths to treatments that are more effective and clearly more safe than the use of stimulants.
   3. Given the profile of possible side effects from stimulants:  loss of appetite, loss of sleep, headaches, stomach aches, loss of height growth, tics, concerns about long-term impact on heart function, and now, psychosis, we approach the use of stimulants with great caution.
5. The stance of Advanced Pediatrics to any intervention, including stimulants, is not to be in favor or in opposition to their use.  We don’t take sides.  Rather we think of our decision making as putting all the facts into a balance, and then as objectively as possible, seeing how the balance looks.  Does the intervention provide more benefit or harm, in what situations is the benefit or the harm greater?  There are situations in which the benefits of stimulants outweigh their potential harms.  As with any other intervention, we do think it prudent to take the known harms into consideration before recommending use.

Stimulants are one of the major categories of drugs prescribed and their use continues to increase dramatically.  We now know that their use may cause an adolescent or young adult to experience a psychosis serious enough to require medical treatment, at a rate of roughly on in 647.

Once again, we are reminded that the use of powerful medications must be measured, with clear awareness of the risks.

To your health,
Dr. Arthur Lavin