Is Wegovy or Zepbound Right for Antidepressant-Related Weight Gain?
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Since the U.S. Food and Drug Administration (FDA) approved it in June of 2021, Wegovy (semaglutide) has taken weight management by storm. And it’s no wonder that it did.
A large randomized controlled trial showed that those who took Wegovy lost 14.9 percent of their body weight (compared with just 2.4 percent in those who took the placebo), making Wegovy one of the most effective weight loss medications on the market.
And the options for weight loss medications are expanding. Recently, the FDA approved another medication, Zepbound (tirzepatide).
Similar to semaglutide (Wegovy and Ozempic), tirzepatide (Zepbound and Mounjaro) mimics a hormone called glucagon-like-peptide (GLP-1), which helps regulate appetite and feelings of fullness. This medication appears to be just as — if not more — effective (for weight loss and blood glucose level control) than semaglutide, according to research on people diagnosed with type 2 diabetes.
With weight gain and diabetes being such a common side effect of psychiatric medications, it is also no wonder that psychiatrists are increasingly considering if these weight loss medications are right for their patients’ psychiatric-medication–related weight gain.
Why wouldn’t it be right for these patients? As a psychiatrist who treats individuals with a range of mental health conditions, prescribing the new weight loss drugs for psychotropic-related weight gain (“psychotropic” is the term for psychiatric medications) gives me pause. That doesn’t mean these drugs should not be prescribed to individuals with mental illnesses, but there are a few important things to keep in mind — for both patients and clinicians — to determine if they are appropriate.
The first is that many mental health issues were exclusion criteria in the studies that led to the FDA’s approval of Wegovy and Zepbound. For example, a history of major depressive disorder within two years of the study, diagnosis of any other severe psychiatric disorder, such as schizophrenia and bipolar disorder, and any history of suicide attempts or recent suicidal behavior were all listed as exclusion criteria for Wegovy’s and Zepbound’s largest trials.
So we don’t know how these medications interact with these diseases, both in terms of the efficacy of the medication in this population and any adverse impact it might have on psychiatric symptoms.
As a psychiatrist, it pains me that many clinical trials use psychiatric illnesses as exclusion criteria when selecting study participants. This practice further marginalizes those with mental illness and could contribute to the already wide health gap that exists between those with mental illness and those without.
There is a large body of research that shows those with mental illnesses are more likely to struggle with weight and die prematurely from weight-related cardiometabolic illnesses, like heart disease and stroke, than the general population. If tools like Wegovy and other prescription weight loss drugs could help prevent some of these morbidities, the lack of data showing their safety and effectiveness in this population (which is what gives me confidence as a provider in prescribing that drug) is a missed opportunity.
People with mental illness deserve to have all the tools at their disposal that others have to prevent these outcomes.
4 Questions to Discuss With Your Doctor
That being said, because of the absence of studies involving Wegovy or Zepbound and people with mental illnesses, there are a number of questions patients should discuss with their doctor to determine if these medications are an appropriate tool to manage their psychiatric medication–related weight gain.
1. What Does the Evidence Show and How Does It Apply to Me?
Not only have Wegovy and Zepbound not been studied in those with serious mental illness, they also have not been studied specifically for psychotropic-related weight gain. This is very important for two big reasons.
The first is that we cannot be as certain of these medications’ efficacies. We don’t understand all the mechanisms, but we know from research that psychiatric medications can impact metabolism and weight in various ways. Although a few case studies seem to suggest Wegovy, and GLP-1 receptor agonists in general — are still somewhat effective at counteracting these mechanisms, we don’t know if they will be as effective in this setting.
The second is that we also cannot be as certain of Wegovy’s and Zepbound’s side effects. More specifically, we don’t know what impact these medications could have on existing psychiatric symptoms.
Additionally, although none of the Wegovy clinical trials demonstrated an increase in suicidal thoughts, the link is now being researched further as a number of reports of suicidal thoughts from people taking Wegovy have emerged. And, importantly, although rare, with only 5 events among the 2,539 adults in the study, there were cases of major depressive disorder or suicidal ideation reported in one of the Zepbound trials.
This means the risk-benefit discussion regarding Wegovy and Zepbound is more difficult when it comes to someone with psychiatric-medication-related weight gain because there are more unknowns. This does not mean the medication cannot be used, but, as a patient, you should be informed of these unknowns.
You should also be in close communication with your provider to determine if the medication is benefiting you and so they stay informed of side effects you are experiencing.
2. What Diet and Exercise Behaviors Will I Need to Change?
It is important to note that the FDA approved both Wegovy and Zepbound in combination with diet change and exercise. Lifestyle change plays a significant role in weight management, even when alone it is not enough.
Research already shows that people with mental illnesses are less likely to receive lifestyle counseling, to their detriment.
If your doctor is talking to you about weight loss medications, make sure they are also giving you information and counseling on lifestyle changes that can help support you in your health goals. As previously said, those with mental illness deserve to have all the tools others have in preventing disease — and that includes lifestyle counseling.
3. How Will I Get Appropriate Follow-Up Care?
Psychiatrists have been prescribing metformin, another medication, for medication-related weight gain for a number of years. Nevertheless, psychiatrists are not endocrinologists, and this is not our specialty.
Wegovy and Zepbound are much newer medications, and there are a number of important side effects to consider, including the potential risk of certain types of thyroid tumors, pancreatitis, gallstones, and eye issues. It is essential that a person be counseled on all these side effects and that there’s follow-up to ensure they are not developing them.
Ideally, a psychiatrist would refer their patient to a specialist for Wegovy or Zepbound. But this is not always realistic. In this case, it is important that the psychiatrist is in close communication with an endocrinologist, obesity medicine doctor, or other specialist in this area, and if possible, that the patient is also followed by that specialist, even if they see their psychiatrist more often.
This may mean that there are more appropriate clinical settings for these medications to be prescribed to someone for psychiatric medication-related weight gain than others. For example, it may be best to see a psychiatrist in person and in a clinic or office that is associated with other medical specialties, rather than in a siloed telehealth private practice setting in which physical examination and follow-up is more challenging
4. How Much Is the Drug Going to Cost Me?
There have already been issues obtaining Wegovy, which has been out longer than recently approved Zepbound, because of supply issues, according to Novo Nordisk, the pharmaceutical company that makes the drug.
Both medications are expensive, and it’s unclear if insurance companies will cover what may be considered “off-label” uses (they might consider use of the drug to mitigate psychotropic-related weight gain such a use).
This has already led to the creation of compounded versions Wegovy, which the FDA has warned against because of safety and efficacy concerns.
To make sure patients are not tempted by these less-safe and less-effective options, doctors should ensure patients have access to these medications before prescribing them. Patients should also have a clear understanding of how much it will cost them and of any availability issues. If cost or availability make it an unrealistic choice, alternatives should be offered in the interim.
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