COMMENTARY

Obesity Treatment in Mental Illness: Is Semaglutide a Game Changer?

Dinah Miller, MD

Disclosures

July 28, 2021

It's probably fair to say that most people would like to be thinner. More than 42% of Americans have obesity and another 30% are classified as being overweight, according to the latest statistics from the CDC.

Excess body weight is associated with many illnesses and plays a role in mental health; being heavy can take a toll on self-esteem. Many people worry that carrying excess weight makes them less attractive to potential romantic partners, and both physicians and employers treat those with obesity differently. Furthermore, in psychiatry, many of the medications we prescribe lead to weight gain.

In my clinical practice, I have listened as patients blamed themselves for their body habitus; many won't consider biological treatments as they feel that would be "cheating" or taking an easy way out. They often point to periods in their life when they did lose weight and believe that they should be able to do it again, even if the weight loss took tremendous effort, was not sustained, and occurred decades ago.

That said, we psychiatrists often find ourselves in the position of managing obesity in our patients. I have been known to give patients who gain weight on antipsychotics either stimulants or metformin, or to add naltrexone to their Wellbutrin (bupropion) to effectively mimic a weight loss medicine called Contrave. I do think psychiatrists sometimes have an important role in obesity care, an often overlooked aspect of our profession.

Obesity a Treatable Medical Condition

It wasn't until 2013 that the American Medical Association recognized obesity as a medical condition.

In a New Yorker article that same year, "Diet Drugs Work: Why Won't Doctors Prescribe Them?" Suzanne Koven wrote, "…Several obesity experts told me they've encountered doctors who confide that they just didn't like fat people and don't enjoy taking care of them. Even doctors who treat obese patients feel stigmatized: 'diet doctor' is not a flattering term."

Eat less, exercise more — with a blame-the-patient attitude — is still what people see as the "right" way to lose weight.

On June 4, 2021, the FDA approved semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, previously used for the treatment of diabetes, for use as a weight loss agent for patients with obesity, or for those with a body mass index over 27 if they also have a weight-related comorbidity.

Semaglutide has three trade names, all manufactured by Novo Nordisk. The pill version is called Rybelsus and comes in 7 mg and 14 mg tablets. Ozempic is available in 0.5 mg and 1.0 mg doses and is administered weekly by subcutaneous injection for diabetes. The new, higher-dose preparation for weight loss, Wegovy, 2.4 mg, also comes as a weekly subcutaneous dose and is now available for the hefty price of $1400 per month.

In STEP 1 trials, the higher-dose Wegovy was associated with an average 14.9% weight loss (15.3 kg) over 68 weeks, more than any other single-agent weight loss medication on the market.

GLP-1 receptor agonists work in the brain to decrease appetite, slow gastric emptying, increase insulin secretion, and stimulate brown adipose tissue thermogenesis.

Psych Drugs Lead to Weight Gain

Elaine Weiner, MD, is the medical director in the Outpatient Research Program of the Maryland Psychiatric Research Center, where she treats patients with schizophrenia.

"Nearly all of our patients gain 20 pounds or more on the combinations of medications we use, mostly atypical antipsychotics," she said. "Weight management is difficult for people who don't have problems with motivation, but in our patients, lack of motivation is a core part of their illness, so asking them to adhere to diet and exercise regimens is of limited utility.

"Then, add to that the fact that they sometimes don't have primary care doctors, and these issues of weight gain and metabolic syndrome come back to the psychiatrist. It is a really bad problem and we need more treatments."

Fatima Cody Stanford, MD, MPH, MPA,  is a fellowship-trained obesity medicine physician-scientist at the Massachusetts General Hospital Weight Center and Harvard Medical School. She has treated thousands of patients with obesity, speaks internationally on the topic of weight loss medicine, and has published over 100 peer-reviewed articles on obesity.

We spoke at length about recent changes in the field of obesity medicine and the introduction of the new GLP-1 receptor agonists.

"We as physicians have learned so little," Stanford said. "This mantra of 'calories in, calories out' is not working; this is inaccurate and our focus on this has led to a rise in obesity. All calories are not created the same, and I think we are finally starting to see obesity medicine take off."

Stanford is quick to note that obesity is a complex problem. Several different hormones are involved in regulating both appetite and satiety, processed foods promote weight gain, sleep is crucial to weight loss, and exercise helps maintain weight loss but is not usually effective in promoting it. "There are many contributors to energy storage," she said.

The stimulant phentermine was approved in 1959. Addiction was a concern, and then in the 1990s, it was used in combination with fenfluramine to promote weight loss, a combination known as phen-fen. Fenfluramine was pulled from the market in 1997 when it was found to be associated with pulmonary hypertension and then heart valve abnormalities.

"This frightened quite a few physicians," Stanford noted. Phentermine is still used for weight loss, either alone or together with topiramate, as a combination medication called Qsymia, nicknamed phen-top.

"Phen-top is the next best thing we have to semaglutide, and there is an average weight loss of 8%-9% of body weight. Semaglutide is going to be really significant for those people who are responders, and this has been quite well tolerated, the most common side effect being nausea," she said.

However, she is quick to note that not everyone responds to every medication. "I use each patient's clinical profile to determine what strategies and which medications to use."

Cardiologists Getting in the Game

Michael Miller, MD, is a cardiologist at the University of Maryland in Baltimore and author of Heal Your Heart (Rodale, 2014). He is very enthusiastic about the approval of semaglutide.

"We are so excited because you finally can use these medicines without having to be diabetic," Miller said. "We're waiting on the results of the SELECT [Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity] trials looking at people who are not diabetic or who are prediabetic, to see the 5-year outcomes with regard to cardiac events.

"Usually endocrinologists prescribe these medications, but cardiologists have started to get into the game since GLP-1 receptor agonists reduce cardiovascular events." Miller is hopeful that this medication may neutralize the weight gain caused by psychotropic medications.

Wegovy is administered via weekly injection and, like insulin, is a subcutaneous medication that patients self-administer. Will patients be amenable to injecting a medication for weight-loss? Stanford said that roughly 20%-30% of her patients are hesitant when she suggests that they use liraglutide, another GLP-1 receptor agonist that is approved for weight loss, and some are very fearful of needles.

However, she also notes that during the COVID-19 pandemic, many more patients have sought treatment from obesity medicine physicians because of the association between obesity and mortality from COVID-19. Patients have been willing to consider treatments that they were not previously open to pursuing.

So if people are willing to take Wegovy and doctors are willing to prescribe it, will insurers pay for it?

These medications are not covered by Medicare or Medicaid, and Stanford, who is well versed as to exactly which private insurers in Massachusetts will and will not reimburse specific medications, said her patients with insurance coverage have been known to delay retirement so that they can remain on the more expensive medications.

"For the past 8 years," she said, "the Treat and Reduce Obesity Act has had bipartisan support in Congress but has not passed. We are still hopeful that insurers will be required to cover medical and behavioral treatments for obesity."

As our society struggles to destigmatize so many disorders, obesity remains a highly stigmatized condition, one that our patients cannot hide and one that leads to so many other comorbid illnesses. As new treatments are approved, there will be more for physicians to offer. Semaglutide, if it becomes available to those who need it most, could be a game changer. For patients who have not had success with traditional weight loss methods, it's encouraging to have another option available, one that may be reasonable to try before resorting to bariatric surgery.

For decades, psychiatrists have been comfortable prescribing treatments that lead to weight gain. Now, maybe it's time they also prescribe those that prevent it.

Dinah Miller is coauthor of Committed: The Battle Over Involuntary Psychiatric Care (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

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