Mental sickness could cause or worsen weight problems, and weight problems could cause or worsen psychological sickness. As an endocrinologist (Jody) and a psychiatrist (Karen), we all know this connection higher than most individuals, so we’ve lengthy checked in with one another to assist our mutual sufferers. Till just lately, a fast curbside chat would do, asking, “Can I add bupropion if this affected person is taking one other antidepressant?” or, “What ought to I exploit subsequent, if metformin just isn’t serving to with weight reduction in a affected person taking an atypical antipsychotic?”
With the rise of GLP-1s, our menu of therapy choices elevated, however so have questions on whether or not these medicines may help sufferers’ psychological well being or harm it. Sufferers now ask Jody: “Will Wegovy make my melancholy worse?” They usually ask Karen: “Can I take Wegovy now that I’ve gained 50 kilos on the antipsychotic?”
Whereas we anticipate extra information to make clear the connection between GLP-1s and psychological well being, it’s essential for endocrinologists — who prescribe most of those medicine — and psychiatrists to work collectively to handle the tangled connections between physique weight and psychological well being. An endocrinologist wants a psychiatrist’s experience from the highest down, and a psychiatrist wants an endocrinologist’s experience from the physique up.
The most effective-known of the GLP-1s are semaglutide (Wegovy and Ozempic), liraglutide (Saxenda and Victoza), and dulaglutide (Trulicity). Tirzepatide (Zepbound and Mounjaro) is a more recent molecule in the identical household. These medicines will be each extremely efficient and extremely polarizing when taken for weight reduction: They’re FDA-approved for the long-term therapy of weight problems, but there are some who — wrongly — decide their use as “dishonest” within the quest to drop extra pounds.
Their impact on psychological well being stays unclear. Prescribing tips for a number of GLP-1s warn about danger of suicidal ideas and self-injury, and the FDA Hostile Occasion Reporting System (FAERS) recognized a “sign” that linked the GLP-1s and suicidality. Nonetheless, a sign doesn’t denote trigger and impact, however reasonably requires additional investigation of the affiliation between the remedy and the reported facet impact. The FDA has thus far not recognized a causal hyperlink between GLP-1s and suicidal ideas or actions, and after evaluating all adversarial occasions reported to FAERS for GLP-1s, a Canadian group concluded in an October 2023 paper that no causal hyperlink between GLP-1s and suicidality exists.
Determining whether or not the adversarial impact is attributable to the drug or by the underlying sickness the drug is prescribed to deal with will be thorny. Weight problems itself can result in melancholy and anxiousness, which might typically result in suicidal ideas and actions. We additionally know that, regardless of their confirmed effectiveness total, some individuals are non-responders to a number of GLP-1s. Expectations are all the time excessive firstly of therapy, so when disappointment and discouragement are piled on high of melancholy, the subsequent step will be despair.
Yet one more twist that you just may not anticipate: We now have noticed that some tremendous responders are usually not fairly positive find out how to dwell of their physique after dropping, say, 100 kilos; an individual with PTSD who has felt protected in opposition to hurt from others by excessive physique weight could really feel weak with out that layer of safety. With out extra weight, some individuals really feel uncovered as by no means earlier than.
Wanting on the weight problems/psychological well being connection from the opposite path, the commonest problems, together with melancholy, anxiousness, and PTSD, can all have an effect on consuming behaviors, and lots of the lifesaving medicines to deal with these problems trigger important weight achieve. People who find themselves already stigmatized on account of psychological well being diagnoses face double jeopardy when additionally they have weight problems: Social isolation could worsen on account of poor vanity and disgrace associated to their weight. Simply as utilizing substances of abuse generally is a manner of self-medicating the signs of psychological sickness, so can also overeating, as the 2 share a few of the similar mind biology. As a common grownup psychiatrist, Karen hears from her sufferers that bingeing has a dissociative side — numbing or distracting from painful emotions, ideas, reminiscences, and signs. The phrase “swallowing one’s emotions” involves thoughts.
There’s nonetheless a lot we don’t know concerning the psychiatric results of GLP-1s. Regardless of experiences of suicidality to the FAERS, a really massive cross-sectional examine carried out by the Nationwide Institutes of Well being and Case Western Reserve, revealed in January 2023, confirmed a lower risk for suicidal ideation in these taking semaglutide in contrast with non-GLP-1 pharmacotherapy for weight problems or diabetes. In truth, there may be now rising information that GLP-1s could also be neuroprotective by a wide range of mechanisms, particularly with respect to depression, substance use disorders, and cognitive function.
Further observational information and interventional research will assist us perceive the complicated relationship between GLP-1s and psychological well being. Within the meantime, conversations and shut collaborations between medical doctors who deal with the physique and medical doctors who deal with the thoughts will assist sufferers. It’s powerful for busy internists to focus in on their sufferers’ psychiatric challenges, however physicians who specialize within the bodily side of medical weight administration want to know what it takes to deal with the thoughts: Sufferers with melancholy, anxiousness, schizophrenia, bipolar dysfunction, and/or PTSD can’t cease or change their weight-promoting psychiatric medicines with out sickness recurrence. Psychiatrists could attempt to deal with their sufferers with weight-neutral medicines, however typically those that change into only trigger a profound and difficult-to-treat improve in physique weight. Psychiatrists then battle to deal with psychological sickness with out inflicting or worsening medical sickness.
Antipsychotics have the best capability to trigger weight achieve, adopted by many antidepressants and temper stabilizers. And a few sufferers have to take all three sorts for symptom aid. Individuals with psychological sickness die a median of 10 years younger than individuals with out it — way more typically from medical causes than from suicide. Antipsychotic medicines particularly could cause metabolic syndrome (the 5 indicators of that are extra stomach weight, hypertriglyceridemia, low HDL ldl cholesterol, elevated blood sugar, and hypertension), which will increase an individual’s danger for cardiac illness, stroke, and sort 2 diabetes. There are new data indicating that the GLP-1s lower the chance of coronary heart assault and stroke in individuals with coronary heart illness who’ve chubby or weight problems.
Psychiatrists are studying that the GLP-1s are sometimes the one actually efficient medicines for weight problems in sufferers with psychological well being problems. With steering from their endocrinologist colleagues, some psychiatrists are beginning to prescribe the GLP-1s to their sufferers. With weight reduction comes a notable brightening of temper and lifting of tension. As individuals invariably begin to really feel higher about themselves, we watch them get promoted at work, improve socialization, and enhance relationships. High quality of life dramatically improves in some ways. These psychological results, in addition to their direct results on the mind, could nicely account for the lower in suicidality proven within the massive examine of GLP-1s.
The underside line is that as GLP-1s produce weight reduction, they concurrently deal with the depressive signs, disgrace, and low vanity that come from having been discriminated in opposition to. Although we could not but have clear solutions concerning the particular results of GLP-1s on psychological well being, we all know from the sufferers we share that the arrows connecting weight problems and psychological sickness level in each instructions. Given the excessive acuity and time constraints of our practices, it’s straightforward to miss these double arrows, however our sufferers, doubly stigmatized, want our mixed areas of experience to find out one of the best path ahead.
Jody Dushay, M.D., MMSc, is an endocrinologist on the Beth Israel Deaconess Medical Middle and assistant professor of drugs at Harvard Medical College. She can also be the founder and director of Wellpowered, a complete wellness and weight administration program. Karen S. Greenberg, M.D., is a psychiatrist affiliated with the Beth Israel Deaconess Medical Middle and teacher, part-time, at Harvard Medical College. She can also be an alumna of the Harvard Medical College Middle for Bioethics fellowship.
For those who or somebody you recognize could also be contemplating suicide, contact the 988 Suicide & Disaster Lifeline: name or textual content 988 or chat 988lifeline.org. For TTY customers: Use your most well-liked relay service or dial 711 then 988.
