"The groundwork of all happiness is health." - Leigh Hunt

Be cautious when using stimulants off-label with other medications

May 2, 2023 – Lizzy P., a 77-year-old retired nurse from Delaware, has been taking Adderall for about 10 years.

“The doctor prescribed it for me for a lot of reasons,” she said. “I get tired easily – it's a stimulant, so he thought it would help me stay awake as I was driving long distances at the time. I also suffer from severe depression and he thought it might help with that too.”

Lizzy takes five other medications. Two of them are for “physical” problems: She takes Synthroid (levothyroxine) to extend thyroid hormones and Norvasc (amlodipine) for her hypertension.

“The rest is emotional and psychological issues,” she said. “I take Lexapro [escitalopram]an antidepressant that I have been taking for decades; I take Valium [diazepam] for anxiety or when I have trouble sleeping; and I take an opioid, Vicodin [hydrocodone]against arthritis pain.”

Lizzy does not want her full name used in this article. “I live in a retirement community where some people may be nosy, and I don't want them to know all my health problems and gossip,” she says. “And it's embarrassing because I find it confusing sometimes taking so many pills. Often it's difficult to maintain track – what I'm taking and once I'm speculated to take it.”

“High potential for abuse”

Lizzy is typical of an increasingly common trend: adults in the United States who take a stimulant along with other drugs that affect the central nervous system, such as antidepressants, opioids and anti-anxiety drugs – according to a new Study published in the journal BMJ open.

The drugs are “the old amphetamines and methylphenidate [Ritalin]”, which are Schedule II controlled substances, said the lead study author Thomas J. Moore, faculty member of epidemiology at the Johns Hopkins Bloomberg School of Public Health and Johns Hopkins Medicine in Baltimoree. These drugs have been around and used for 85 years.

According to the U.S. Drug Enforcement AdministrationAmphetamine and methylphenidate are considered “dangerous” due to their high potential for abuse. They also have a high potential for physical or psychological dependence.

The FDA has approved these stimulants to treat attention deficit/hyperactivity disorder in children and adults, but they are also used to treat nasal congestion, narcolepsy, binge eating, depression and senile behavior, as well as appetite suppressants, the authors said. And they are increasingly being used “off-label” — that is, to treat conditions for which they are not approved, Moore said.

Moore and colleagues had previously examined prescribing trends for stimulants and found that use of these drugs had increased by 79% between 2013 and 2018. The researchers wanted to examine how these stimulants were being used, and in particular, they wanted to know what types of other medications were being taken at the same time.

Use the lowest dose for the shortest period of time

Moore and his team examined prescription drug claims for over 9.1 million adults (ages 19–64) from 2019 to 2020 from a large commercial insurance claims database.

They found that 3% of people in the database (276,223 people) had taken a Schedule II stimulant in 2020. Of these, 45.5% also took a central nervous system medication. Almost a quarter (24.3%) took two or more of these medications simultaneously.

The most commonly co-prescribed medications were antidepressants, anti-anxiety medications, and opioids. Nearly half (47.6%) of stimulant users also took an antidepressant, while nearly one-third (30.8%) filled prescriptions for anti-anxiety meditation/sedatives/hypnosis and one-fifth (19.6%) received opioid prescriptions.

Other medications included antiepileptics, sometimes used to stabilize mood (14%), antipsychotics (8%), and other stimulants (2%).

Most patients taking these medications become “long-term users” after starting treatment, with three-quarters of patients continuing to take them during the one-year study period.

There is not much research on such combinations, so the “advantages and extra risks” of taking these drugs together are “unknown,” Moore said.

He warned that amphetamine stimulants in adults “ought to be used at the bottom dose that produces an effect for the shortest possible time and that use ought to be closely monitored by the prescribing physician.”

Complex prescription regimens

These new findings “require further research to enhance our understanding of the clinical relationships underlying these complex prescribing regimens, in addition to their effectiveness and safety,” said Mark Olfson, MD, MPH, professor of psychiatry, medicine and law, and professor of epidemiology at Columbia University Irving Medical Center in New York City.

Lizzy agrees. “Sometimes it appears like the doctors have just been 'throwing darts at a goal' and hoping something will hit the precise goal. Unfortunately, I still suffer from depression and anxiety though I'm on this complicated cocktail of medicines,” she said.

In the meantime, Lizzy plans to see her psychiatrist and ask him to review the treatment plans. “Maybe we are able to try to miss a number of medications and see if I really want them. That would simplify things and might even alleviate my symptoms.”