Kids and Anti-Obesity Medications: Real-World Challenges

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.