GLP-1 Medications and Mental Health: Separating Fact from Fiction

Key Points

• GLP-1 medications do not increase risk of depression, anxiety, or suicidality compared to placebo
• These medications modestly improve mental health-related quality of life independent of weight loss
• Emotional eating and food cravings significantly decrease with GLP-1 treatment
• Psychiatrists should proactively prevent weight gain from psychiatric medications, not just accept it as inevitable
• GLP-1s may be particularly useful for antipsychotic-induced weight gain, similar to how we already use metformin
• Side effects are mostly gastrointestinal and manageable with proper dosing and titration

There’s been a lot of noise about GLP-1 medications and mental health. Some of it’s helpful. A lot of it’s confusing or outright wrong.

I’ve heard patients express real fear about these medications based on things they’ve read online. “Don’t they cause depression?” “I heard someone died by suicide while taking one of these.” “My friend said they made her mental health worse.”

I’ve also seen the opposite. Overhyped claims that these medications cure depression or fix all mental health problems. Neither extreme is accurate.

So let’s separate fact from fiction. What does the actual research show about GLP-1 medications and mental health? What are the real risks and benefits? And why do I think these medications should become part of standard psychiatric care, particularly for preventing the weight gain we’ve allowed to happen for too long with medications like antipsychotics?

The Safety Question: Do GLP-1s Cause Psychiatric Problems?

Let’s start with the concern that’s gotten the most attention. Do GLP-1 medications increase risk of depression, suicidality, or other psychiatric problems?

The short answer is no. The data on this is actually quite robust.

A comprehensive meta-analysis published in JAMA Psychiatry in 2025 looked at this question systematically. Researchers pooled data from multiple randomized controlled trials involving thousands of participants taking GLP-1 receptor agonists or placebo. They specifically looked at serious psychiatric adverse events.

The forest plot from this study is striking. Study after study shows no significant difference in psychiatric adverse events between GLP-1 medications and placebo. The confidence intervals cross the line of no effect consistently. This isn’t one or two studies. It’s a pattern across multiple large trials.

The FDA and European Medicines Agency reviewed all available data on suicidality concerns specifically. Their conclusion? No causal link between GLP-1 receptor agonist use and suicidality. They recommend ongoing monitoring as with any medication, but they found no evidence of increased risk.

The STEP trials, which are the major clinical trials of semaglutide for weight management, included detailed psychiatric monitoring. A post-hoc analysis looked specifically at depression and suicidal ideation. Not only did semaglutide not increase these risks, there was actually a small but statistically significant reduction in depressive symptoms compared to placebo.

Now, I need to acknowledge something. There have been case reports of psychiatric symptoms in people taking GLP-1 medications. Depression, anxiety, even suicidal thoughts. These reports exist, and they’re concerning to the individuals who experienced them.

But here’s the context. Case reports show what’s possible, not what’s probable. Any medication used by millions of people will have case reports of various adverse events. The question is whether these events occur more frequently than in people not taking the medication.

The large controlled trials and population-level data show they don’t. Psychiatric adverse events happen at similar or even slightly lower rates in people taking GLP-1 medications compared to placebo.

This doesn’t mean we ignore individual experiences. Some people may have idiosyncratic reactions. We monitor all patients carefully. But the population-level safety data is reassuring.

Real-world pharmacovigilance studies (which track adverse events reported after medications are on the market) show mixed results. Some reports highlight rare psychiatric adverse events. But when you account for the fact that people with obesity have higher baseline rates of depression and anxiety, and when you look at properly controlled comparisons, the signal disappears.

A nationwide case-time-control study specifically examined suicide and suicide attempts in users of GLP-1 receptor agonists. This large study found no increased risk associated with these medications. If anything, there were fewer events than expected.

From a psychiatric safety perspective, the evidence is about as good as you can expect for any medication. These drugs don’t cause psychiatric problems at rates higher than placebo.

The Benefit Side: Improvements in Mental Health

Now let’s talk about potential benefits, because this is where things get really interesting.

Mental health-related quality of life improves. This is one of the most consistent findings across studies. The meta-analysis I mentioned earlier didn’t just look at adverse events. It also examined quality of life outcomes.

Across multiple studies in both diabetes and obesity populations, GLP-1 receptor agonists consistently improved mental health-related quality of life compared to placebo. These improvements were statistically significant and appeared to be independent of the amount of weight lost.

What does this mean practically? People report feeling better emotionally. Less distress. Better mood. Improved wellbeing. These aren’t dramatic transformations, but they’re meaningful improvements that people notice in their daily lives.

The mechanisms probably include multiple factors. Reduced inflammation, which we know affects mood. Improved metabolic health. Decreased weight stigma as weight decreases. Possibly direct effects on brain reward pathways. And the psychological benefit of feeling like you’re finally making progress with something you’ve struggled with for years.

Eating behaviors improve significantly. This is one of the most valuable effects for psychiatric patients. GLP-1 medications reduce emotional eating, decrease food cravings, and help with eating restraint in a healthy way.

People describe it as reducing “food noise.” That constant background chatter about food, what to eat, when to eat, cravings, urges. It quiets down. Food becomes less dominating in thoughts and attention.

For someone using food as their primary coping mechanism for anxiety or depression, this is huge. The medication isn’t just suppressing appetite through willpower or restriction. It’s changing the neurobiological drive to use food for emotional regulation.

A study in the STEP 5 trial looked specifically at eating behaviors over two years. Participants on semaglutide showed significant improvements in control of eating, reduced cravings for both sweet and savory foods, and improvements in eating-related quality of life. These benefits persisted over time.

Another study examining liraglutide combined with behavioral therapy found greater reductions in food cravings and eating disorder psychopathology compared to behavioral therapy alone. The medication enhanced the effectiveness of the psychological intervention.

Mood symptoms may improve modestly. I need to be careful here because I don’t want to overstate this. GLP-1 medications are not antidepressants. They shouldn’t replace established treatments for depression.

But there’s consistent evidence of small improvements in depressive symptoms, even in people without clinical depression at baseline. The STEP trials showed this. Other studies have found similar patterns.

The effects are modest. We’re not talking about remission of major depression. But for someone dealing with both obesity and mild to moderate depressive symptoms, particularly when inflammation appears to be a contributing factor, a GLP-1 medication might provide benefits for both conditions simultaneously.

The anti-inflammatory effects are probably contributing. We know inflammation interferes with neurotransmitter function and contributes to depression. GLP-1 medications reduce inflammatory markers like CRP. That reduction in inflammation likely has direct mood benefits.

Cognitive function may benefit. Some preliminary research suggests GLP-1 medications might have positive effects on cognitive function. This makes sense given that they improve metabolic health, reduce inflammation, and may have direct neuroprotective effects.

For patients with severe mental illness who often experience cognitive impairments, this potential benefit is worth paying attention to. The research here is still early, but it’s promising.

The Antipsychotic Weight Gain Problem We Need to Address

Now I want to talk about something that frustrates me deeply. The way we’ve just accepted weight gain as an inevitable consequence of antipsychotic medications.

Second-generation antipsychotics, particularly olanzapine and clozapine, cause dramatic weight gain in many patients. We’re not talking about 5 or 10 pounds. We’re talking about 30, 40, 50 pounds or more. Some patients gain over 100 pounds.

This weight gain is devastating. It worsens physical health, increasing risk of diabetes, cardiovascular disease, and early death. It destroys self-esteem. It increases depression and anxiety. It leads many patients to stop taking medications that are helping their primary psychiatric condition because the weight gain feels intolerable.

And what have we done about this as a field? Mostly, we’ve shrugged and said it’s an unfortunate side effect. We counsel patients about diet and exercise, knowing that’s usually insufficient against the powerful metabolic effects of these medications. We switch to different antipsychotics when possible, but sometimes the weight-gaining medication is the only one that works for that person’s psychotic symptoms.

We’ve treated the weight gain as an acceptable tradeoff for psychiatric stability. But it shouldn’t be acceptable. We have tools now that we didn’t have before.

Metformin is already part of psychiatric practice. We prescribe it routinely to prevent or treat antipsychotic-induced metabolic dysfunction. It’s in our scope. It’s standard of care in many settings. Nobody questions whether psychiatrists should be prescribing metformin for patients on antipsychotics.

GLP-1 medications should be the same. They’re more effective than metformin for weight management. They address the metabolic dysfunction antipsychotics cause. And as we’ve discussed, they’re safe from a psychiatric perspective.

Emerging evidence specifically supports using GLP-1 medications for antipsychotic-induced weight gain. The research is preliminary, yes. We need larger randomized trials. But the early data is promising, and the biological rationale is strong.

We shouldn’t be waiting for perfect evidence while our patients gain massive amounts of weight that damages their health and quality of life. We should be proactively preventing and treating this weight gain as part of comprehensive psychiatric care.

A Proactive Rather Than Reactive Approach

Here’s what I think should change in psychiatric practice.

Prevention rather than acceptance. When we start someone on an antipsychotic that’s likely to cause weight gain, we shouldn’t just warn them about it and hope for the best. We should be proactively implementing strategies to prevent the weight gain.

This includes intensive lifestyle support, nutritional counseling, exercise programs. But it might also include medications like metformin or low-dose GLP-1 medications, particularly for patients at high risk for significant weight gain or metabolic complications.

The goal is to prevent the 30-50 pound weight gain from happening in the first place, not try to reverse it after the damage is done.

Early intervention when weight gain starts. If someone on an antipsychotic starts gaining significant weight despite lifestyle interventions, we should intervene early and aggressively. Not wait until they’ve gained 50 pounds and developed diabetes.

Adding a GLP-1 medication when someone has gained 15-20 pounds and the trajectory is clearly heading toward severe weight gain makes more sense than waiting until they’ve gained 60 pounds and feel hopeless about ever getting back to a healthy weight.

Choosing psychiatric medications more carefully. We need to think harder about metabolic effects when selecting psychiatric medications. If two medications are similarly effective for someone’s psychiatric condition, but one causes significant weight gain and the other doesn’t, choose the weight-neutral option.

This seems obvious, but it hasn’t been standard practice. Too often, metabolic effects are treated as secondary considerations rather than primary factors in medication selection.

Integrating metabolic care into psychiatric care. Rather than referring patients to endocrinology or primary care for metabolic issues and hoping they follow through, psychiatrists should be equipped to provide this care directly. Check metabolic labs. Monitor weight and metabolic parameters. Prescribe medications that address metabolic dysfunction. This integration improves care and outcomes.

This is already happening with metformin. It should expand to include GLP-1 medications for appropriate patients.

Who Should Consider GLP-1s in Psychiatric Populations?

Given everything we’ve discussed, which psychiatric patients might benefit from GLP-1 medications?

Patients on antipsychotics with significant weight gain. This is the clearest indication. If someone is on an antipsychotic that’s working for their psychiatric condition but causing substantial weight gain despite lifestyle interventions, a GLP-1 medication makes sense.

We’re not talking about cosmetic concerns. We’re talking about preventing serious metabolic complications and addressing weight gain that’s affecting quality of life and potentially adherence to necessary psychiatric medications.

Patients starting antipsychotics with high risk of weight gain. For someone starting olanzapine or clozapine, particularly if they have risk factors for metabolic complications, considering preventive strategies including possibly a low-dose GLP-1 makes sense.

This is proactive care. Preventing the problem rather than treating it after it’s severe.

Patients with binge eating disorder. The effects on eating behaviors make GLP-1s potentially valuable for binge eating disorder. Combined with therapy addressing the psychological aspects of binge eating, even low doses can make a significant difference.

Patients with both obesity and treatment-resistant depression. When inflammation appears to be contributing to depression that’s not responding well to standard treatments, a GLP-1’s anti-inflammatory effects might help. It’s addressing a different mechanism than traditional antidepressants.

Patients with substance use disorders and obesity. We’ll discuss this more in upcoming articles, but the emerging evidence for GLP-1s in substance use disorders, particularly alcohol use disorder, is compelling. For patients dealing with both addiction and obesity, these medications might address both concerns.

My Approach: Part of a Comprehensive Functional Medicine Framework

I want to be clear about how GLP-1 medications fit into my practice, because context matters.

Many of my patients deal with both psychiatric and metabolic concerns. Not all, but a significant portion. For these patients, I’ve developed an approach that integrates functional medicine principles with psychiatric care.

What does that actually look like? It means I’m thinking about nutrition, not just as general “eat healthy” advice, but as a therapeutic intervention. Anti-inflammatory diets. Blood sugar stabilization. Gut health. Nutrient deficiencies that affect mood and cognition. Food sensitivities. The role of the microbiome.

It means comprehensive metabolic assessment. Not just standard labs, but looking at inflammatory markers, detailed metabolic panels, sometimes testing for nutrient deficiencies, assessing insulin resistance. Understanding the full metabolic picture.

It means addressing lifestyle factors systematically. Sleep optimization. Stress reduction. Movement and exercise. Social connection. Environmental factors that affect both metabolic and mental health.

And yes, it includes medications when appropriate. Sometimes psychiatric medications chosen carefully to minimize metabolic effects. Sometimes metabolic medications including metformin or GLP-1s. But medications are one component of a comprehensive approach, not the entire treatment.

GLP-1 medications as one tool among many. In this framework, a low-dose GLP-1 isn’t a standalone treatment. It’s supporting the nutritional work. It’s making the lifestyle changes more achievable. It’s reducing the inflammation while we address other inflammatory triggers. It’s quieting the food noise while we work on the psychological relationship with food.

The medication makes everything else work better. But everything else is still essential.

I’ve had patients achieve remarkable results with this integrated approach. Not just weight loss, though that often happens. But genuine metabolic healing. Inflammatory markers normalizing. Mood stabilizing. Energy returning. A sense of taking control of their health.

Could they achieve this with nutrition and lifestyle alone, without medication? Maybe some could, eventually. But the GLP-1 medication accelerates progress. It removes some of the biological barriers that make the lifestyle work feel impossible. It creates momentum that supports continued effort.

This requires time and expertise. I’m not running a medication mill where I see someone for 15 minutes and write prescriptions. I’m spending time understanding their complete health picture. I’m providing or coordinating nutritional guidance. I’m monitoring multiple systems. I’m adjusting the approach based on what we’re learning.

Not every psychiatrist practices this way, and that’s fine. Different practice models serve different patients. But for patients dealing with complex metabolic-psychiatric interactions, this comprehensive functional medicine approach works really well.

The Training Pathway: Obesity Medicine Board Certification

Here’s something important that addresses scope of practice concerns directly. Psychiatrists are eligible to become board certified in obesity medicine.

The American Board of Obesity Medicine offers certification that’s open to physicians from any specialty, including psychiatry. The requirements include completing appropriate education and training in obesity medicine, then passing a comprehensive examination.

More psychiatrists are pursuing this pathway now, and I think it’s valuable, particularly for those of us who work extensively with patients dealing with both metabolic and psychiatric issues.

What this training involves:

Comprehensive education in obesity science. The biology of weight regulation, metabolic physiology, endocrinology relevant to obesity, and nutrition. Understanding obesity as a chronic disease with multiple contributing factors, not a simple matter of willpower.

Training in obesity medications including GLP-1 receptor agonists. Their mechanisms of action, appropriate prescribing, monitoring requirements, management of side effects. This goes well beyond what most of us learned in residency.

Knowledge about behavioral interventions for weight management. How to integrate psychological and medical approaches. Understanding when different interventions are indicated.

Skills in metabolic monitoring. Interpreting relevant lab work, recognizing and managing metabolic complications, knowing when to refer for specialized care.

Why this matters:

When psychiatrists have formal obesity medicine training and board certification, the question of whether it’s appropriate for us to prescribe GLP-1 medications becomes less contentious. We’re not expanding scope inappropriately. We’re practicing within an area where we have specific expertise and certification.

It addresses the legitimate concern that psychiatrists might prescribe these medications without adequate knowledge. Board certification demonstrates you have that knowledge.

It provides a framework for the kind of comprehensive care I’ve been describing. You’re not just prescribing medications. You’re approaching obesity as a complex chronic disease requiring multifaceted treatment.

My own path:

I’ve pursued extensive training in functional medicine, metabolic health, and obesity medicine specifically because my patient population needed it. Trying to treat psychiatric symptoms while ignoring the metabolic dysfunction that was contributing to them was producing incomplete results.

Getting this additional training changed how I practice. It gave me the knowledge and confidence to prescribe and monitor metabolic medications including GLP-1s within a comprehensive treatment framework. It helped me understand the biology in ways that make me more effective for my patients.

I’m not suggesting every psychiatrist needs obesity medicine certification. But for those of us whose practices include significant numbers of patients with both metabolic and psychiatric concerns, it’s a logical path that improves the care we can provide.

The Practical Side: Using GLP-1s in Psychiatric Patients

If we’re going to use GLP-1 medications in psychiatric populations, how do we do it well?

Collaboration is important. Even when psychiatrists prescribe these medications, working with primary care, endocrinology, or functional medicine practitioners is valuable. These patients often have complex medical needs. Communication and coordination improve outcomes.

That said, psychiatrists with appropriate training should be equipped to prescribe and monitor these medications directly. We shouldn’t create unnecessary barriers by requiring every patient to see multiple specialists.

Start low, go slow, combine with comprehensive support. My approach of using lower doses combined with nutritional support, lifestyle interventions, and psychological work is particularly important in psychiatric populations. These patients often need extra support. They may have difficulty with standard lifestyle interventions due to their psychiatric symptoms.

Lower doses minimize side effects while still providing benefit. The comprehensive support addresses the multiple factors contributing to both psychiatric symptoms and metabolic dysfunction. The medication supports the work, but it’s not the whole treatment.

The cost and access question. I need to address something that comes up constantly. Brand-name GLP-1 medications cost $900-$1,400 per month without insurance. Many insurance plans don’t cover them, or coverage requires extensive prior authorization that often gets denied.

This leaves patients who could genuinely benefit without access. It’s a real ethical problem.

Compounded semaglutide and tirzepatide are available from compounding pharmacies at significantly lower cost, often $200-$400 per month. For patients who can’t afford or access brand-name versions, compounded medications may be the only feasible option.

I want to be honest about this. Many physicians, including psychiatrists practicing metabolic medicine, do prescribe compounded GLP-1 medications. But we need to be clear about the considerations.

Compounded medications are not FDA-approved in the same way as brand-name drugs. Quality and consistency can vary between compounding pharmacies. The active ingredient should be the same, but formulation may differ. Dosing requires more steps and careful attention.

If I prescribe compounded versions, I only work with compounding pharmacies I’ve carefully vetted. I need to know they’re following proper standards, testing their products, and maintaining quality control. I provide very clear instructions on reconstitution and dosing. I monitor just as carefully, actually maybe more carefully, than with brand-name medications.

I’m transparent with patients about the differences. They need to understand they’re making a choice based on access and cost, and that there are some additional considerations with compounded medications.

If brand-name medication is accessible and affordable, that’s generally preferable. But while we advocate for better insurance coverage and more reasonable pricing, patients need treatment now. Carefully prescribed compounded GLP-1s may be a pragmatic solution for some.

Monitor carefully. All psychiatric patients on GLP-1 medications should have ongoing monitoring for mood changes, eating behaviors, substance use, and overall psychiatric status. We don’t assume the medications will only have positive effects. We watch for problems and address them early.

This includes metabolic monitoring too. Labs, weight, blood pressure, symptoms. Within the functional medicine framework, I’m often tracking additional markers like inflammatory indicators, nutrient levels, and other parameters that give insight into overall metabolic health.

Individualized risk-benefit assessment. Not every psychiatric patient needs or would benefit from a GLP-1 medication. The decision should be individualized, considering severity of weight concern, presence of metabolic complications, patient preference, cost and access, other treatment options.

For some patients within a comprehensive functional medicine approach, it’s clearly indicated. For others, it’s not appropriate. The assessment should be thoughtful and collaborative.

Side Effects: Being Realistic

I’ve emphasized that GLP-1 medications are safe from a psychiatric perspective. But they do have side effects, and we need to be honest about them.

Gastrointestinal symptoms are common. Nausea is the most frequent side effect. Some people also experience vomiting, diarrhea, or constipation. These symptoms are usually worse when starting the medication or increasing the dose.

With the low-dose approach I use and slow titration, these symptoms are much less severe. Most patients have minimal nausea. But some people are more sensitive, and GI symptoms can be bothersome.

The good news is that these symptoms usually improve over time. Many people who have nausea initially find it resolves after a few weeks. The body adjusts.

From a functional medicine perspective, supporting gut health through probiotics, digestive enzymes, or other interventions can sometimes help with these side effects.

Rare but serious side effects exist. Pancreatitis, though rare, can occur. Gallbladder problems are possible. There’s a black box warning about thyroid C-cell tumors based on rodent studies, though this hasn’t been observed in humans.

These risks need to be part of informed consent. They’re reasons to monitor appropriately and maintain good communication about any concerning symptoms.

Hypoglycemia is possible in diabetes patients. For patients with diabetes, particularly if they’re on insulin or sulfonylureas, there’s risk of low blood sugar when adding a GLP-1. Careful monitoring and possibly adjusting other diabetes medications is necessary.

Some people just don’t tolerate them. Despite best efforts with dosing and titration, some people can’t tolerate GLP-1 medications. The nausea is too severe, or they have other bothersome side effects. That’s okay. These medications aren’t right for everyone.

We try, we monitor, and if it’s not working, we discontinue and focus on the other elements of the comprehensive approach. There are always other options.

Who Should Avoid GLP-1 Medications?

Certain patients shouldn’t take GLP-1 medications, or should only do so with extreme caution.

Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 is a contraindication based on the black box warning.

History of pancreatitis generally means we don’t use these medications, or we’re extremely cautious if we do.

Severe gastroparesis is problematic because GLP-1s slow gastric emptying.

Pregnancy or planning pregnancy means we don’t use them. They should be discontinued if someone becomes pregnant.

Severe eating disorders with extreme restriction aren’t appropriate candidates. For someone with anorexia nervosa or very restrictive eating, medications that decrease appetite further could be harmful. We need to treat the eating disorder first.

Active suicidality requires stabilization before starting any new medication. While GLP-1s don’t increase suicide risk, introducing new medications during a crisis needs careful consideration.

The Bigger Picture: Changing How We Practice

I think GLP-1 medications represent a broader shift in how psychiatry needs to practice. We can no longer separate mental health from metabolic health. They’re interconnected systems, and treating them separately produces incomplete results.

Metformin has already shown us that psychiatrists can and should be managing metabolic medications for our patients when appropriate. The addition of GLP-1 medications is a natural extension, particularly for those of us who’ve pursued additional training in obesity medicine or functional medicine.

More importantly, we need to stop accepting weight gain from psychiatric medications as inevitable. We have tools now. We should be using them proactively to prevent the metabolic harm that our treatments sometimes cause.

This isn’t about psychiatrists trying to expand our scope inappropriately. It’s about providing comprehensive, integrated care for patients whose mental and metabolic health are inseparable. When you add obesity medicine training and certification, and when you’re working within a functional medicine framework that addresses nutrition, lifestyle, and metabolic health comprehensively, prescribing GLP-1s makes complete sense.

The patients I work with appreciate this approach. They’re tired of being bounced between providers who don’t communicate. They want someone who understands how everything connects and addresses their health holistically.

That’s what this kind of integrated practice looks like. And GLP-1 medications, used thoughtfully as part of comprehensive care, are one valuable tool in that approach.

In the next article, we’ll look specifically at GLP-1 medications for binge eating disorder. What does the research show? How do these medications work for the psychological aspects of binge eating, not just the physical appetite suppression? This is an area where the evidence is still emerging but really interesting.

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