Tuesday, November 28, 2023
Although this article has "drug holiday" in its title, the following is really a summary of the case for and against 7-day, every-day dosing of stimulant medication in treating attention deficit hyperactivity disorder (ADHD). These comments are directed toward stimulant medications, because nonstimulants are not necessarily conducive to start-stop dosing.
What do we mean by "drug holiday?" Also called a structured treatment interruption in the medical literature, a drug holiday is the conscious, deliberate suspension of medication, usually for a short time. Drug holidays may include weekend, weeklong, monthly (such as school vacations), or any combination of these. Holidays are used to: (1) demonstrate the clinical need for medication; (2) temporarily remove side effects to medication (such as sleep delay, appetite suppression, and perceived or real tolerance to treatment); and (3) satisfy the notions of caregivers that medicine should not be used if it can be avoided.
To suspend medication to assess its need can be a useful exercise. Stimulant medications typically enhance a child's ability to meet demands. They prolong time on task (sustain attention) and inhibit automatic motor and attention shifts (inhibit distractibility) when novel stimulus events occur in the immediate environment. Sustaining attention and inhibiting off-task responsivity are problems in demand situations, which makes ADHD a disorder. In demand situations, children and adults avoid adverse consequences by remaining task-oriented. A child completes spelling homework to avoid getting a bad grade on the spelling test; an adult completes tax filings to avoid legal and financial penalties for not doing so. Subsequently, managing symptoms of ADHD becomes more important when demand is high and less important when demand is low. When a child is playing outside with friends or watching television, the need to sustain or inhibit attention on demand is lessened. Even a very distractible child may not experience impairment when doing something he or she enjoys. This seeming inconsistency can be confusing. For example, when a child of divorced parents spends weekdays with 1 parent (the school parent) and weekends with the other parent (the recreational parent), symptoms will be problematic in the setting of high demand (school) but not in the setting of low demand. One parent may then claim that medicine is needed while the other claims it is not. In such a case, suspending medication can confirm the difference pharmacotherapy makes to impaired individuals in demand situations. Other situations in which suspending medication can solve problems include teenagers claiming they don't need medicine anymore because "I can do it myself"; parents of children who have been on medicine for long periods wondering whether pharmacotherapy is still necessary; and washout periods before starting a new medicine.
The second reason for suspending pharmacotherapy for ADHD is to help manage tolerable side effects to medicine. The benefit of medicine often outweighs the presence of mild side effects, and tolerable side effects can often be managed. (If side effects are intolerable, treatment would be stopped, of course.) The most common dose-related side effects of stimulants are appetite suppression (anorexia) and sleep delay (insomnia). Both may be managed through various strategies, one of which may be a drug holiday. A child whose caloric intake is low enough that parents fear the possibility of growth suppression may not be treated on weekends or during prolonged vacations from school to ensure that calorie intake is acceptable. Sleep delay may be managed similarly. Teenagers who complain that medication produces an overfocused effect and suppresses "natural exuberance" may suspend medication on weekends for greater freedom in self-expression within a peer group.
The third reason for conducting medication holidays is that parents request it. Often parents fear they are drugging their child and are concerned about an unknown or imagined adverse consequence to treatment. Many parents who fear medicine because they have heard critiques by pseudo-experts will often be so focused on the possibility of harm that they fail to see the benefit derived from pharmacotherapy. Although medication suspension is often implemented at parent initiative (often without physician knowledge), it usually serves little purpose. Parents fearful of side effects will often hold this opinion even though a "holiday" results in a deterioration of functioning.
What does the clinical evidence on drug holidays indicate? The most frequently cited study was conducted by Martins and colleagues.[1] This study of 40 children showed that weekend holidays from methylphenidate treatment tended to reduce insomnia and appetite suppression, and did not significantly increase ADHD symptoms on weekends (as reported by parents) and on the Monday in school following the drug holiday (reported by teachers). In contrast to this evidence, anecdotal reports of physicians who routinely use weekend drug holidays indicate that some patients have difficulty adjusting to re-dosing for 1 to 3 days after the holiday; patients experience mild side effects, inconsistent response effectiveness, and varied duration of action.
Physicians may opt to (1) recommend medication suspension as a general rule, (2) forego medication suspension and treat every day; or (3) use selective suspension to apply medicine when it is needed and withhold medicine when it is not needed (such as when demand is low). Little evidence supports the first option. The notion that stimulant medicine should be applied as little as possible is usually the assumption driving this strategy. Evidence from epidemiologic and controlled research supports the second option. Indeed, a growing body of evidence from multiple investigators using different methods substantiates that ADHD is a chronic disorder and should be treated as such. Individuals with ADHD have more traffic mishaps, fewer sustained social relationships, greater employment difficulties, and overall substandard quality of life. Suspending the treatment that improves these conditions is not in a patient's best interest.
Using selective holidays to treat the times and settings of dysfunction may be reasonable, but it is limited in its evidence base. Selectivity may be appropriate for the socially active, inattentive child who shows academic impairment but no impairment when demand is low (that is, on weekends or school breaks). It is critical to appreciate, however, that impairment is not static. For example, an 8-year-old child may not show dysfunction on weekends, but an adolescent might, and driving a car is not something an 8-year-old child does, but it is something most 17 year olds do. The following 2 examples illustrate the need to look more closely at the specific elements of individual situations before making treatment decisions.
Marti was an 11-year-old girl in 5th grade diagnosed with ADHD, predominantly inattentive type. She was generally a quiet, mild-mannered child with or without stimulant medicine; however, her schoolwork, productivity, and ability to complete chores, manage routines, and participate with friends dramatically improved with stimulant treatment. Marti's parents were divorced, and she spent alternate weekends with her father. Although she completed household chores, schoolwork, and managed routines in a timely way with pharmacologic intervention on school days with her mother, her father argued vehemently that Marti "doesn't need that stuff (medicine) since she's just fine without it." Marti's father typically filled Marti's weekends with fun activities. He seldom told Marti to finish a task by a certain time or required adherence to a rigorous schedule. When Marti returned home on Sunday evening, her homework was seldom completed, and it took her 2 days to adjust to a routine and the demands of getting ready for school and going to bed on time. Also, she was beginning to say, "my Mom thinks there's something wrong with me," because her mother administered medicine and the father did not. In Marti's case, a drug holiday was not justified and was imposed for the wrong reasons. Eliminating structured treatment interruption was in the best interests of this child.
Josh is an example of a patient who benefited by strategically interrupted treatment. A very bright 17-year-old high school junior, he was diagnosed at age 13 years with ADHD combined type. He was a careful automobile driver, was socially adept, had a number of friends and acquaintances, and had gained a reputation in his social network for being witty and quick with a comeback. Although Josh reported frequent restless, he kept himself active in year-round sports and various school activities, and showed no obvious clinically dysfunctional hyperactivity. His difficulty in school was associated with an inability to manage sustained attention in classes and on homework. This loss of attention resulted in consistent work incompletion, poor test performance, and gradually declining grades starting in middle school.
In Josh's sophomore year, he was successfully treated with a stimulant. His ability to sustain attention improved notably in the second week of treatment when the dose was titrated up to a moderate level. Although his ability to attend improved significantly, he complained of mild appetite suppression and said he felt "like a blob," and that his friends complained that he was not "as much fun anymore." Given that he did not show dysfunction at home or with his peers on weekends and school vacations, and coupled with psychosocial intervention in which he used a study buddy to complete work on weekends and a structured study hall on Fridays, his parents and physician recommended a structured treatment interruption on weekends and holidays. This handled Josh's complaint regarding his social participation, and it allayed his parents' concerns about suppressed appetite because he increased his weekly calorie intake noticeably during the medication holiday.
Nothing replaces sound clinical judgment. The vicissitudes of clinical practice usually preclude algorithmic solutions. Is there, then, a definitive conclusion regarding medication holidays? Not at present. Given the evidence to date, the most conservative strategy, ie, every-day treatment, is likely to yield the best outcomes.
