Drug Holiday? Benefits, Risk to Kids With ADHD

Jennifer Lubell

May 13, 2021

Dr Lily Hechtman

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug "holiday" can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Hechtman, a presenter and moderator of the session, "Unsolved mysteries in the treatment of ADHD with psychostimulants."

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. "So, the longer the child is on medication, the more likely he or she will develop some drug tolerance," said Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren't exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. "Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes" after the holiday, said Hechtman.

The Growth Factor

A drug holiday can also address concerns about growth suppression. "Some studies show that drug holidays help with growth suppression and others do not," said Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, "you could see that the rate of medication use decreased significantly with time" among participants, said Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. "They were pretty close to the controls," said Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. "The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height," summarized Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.

"Negative Things Can Happen"

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. "Negative things can happen during drug holidays," said Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. "Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs," she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. "Their behavior off the medication may be such that it leads to social problems," Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it's a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child's condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.

Do Drug Holidays Matter?

Another session speaker, James Swanson, PhD, who noted that the "emergence of tolerance may limit and eventually undermine initial relative benefit" of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, "most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays," he said in an interview.

"If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me," said Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under "double-blind" conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. "We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit," said Swanson, a coauthor of the MTA study.

Hechtman receives funding from The Canadian Institutes of Health Research. Swanson has two patents: (PIXA4), which uses a "time-of-flight" camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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