By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Psychiatric medications and weight gain: the treatment works, but the scale goes up
Psychiatric medications and weight gain often create a painful dilemma. The medication stabilizes mood, eases anxiety and prevents mania or psychosis. The person gets their life back. At the same time, though, their weight starts to climb, sometimes sharply.
This is not a minor side issue. Some of these drugs act directly on the brain’s hunger and satiety centers and on its reward system. They also affect insulin sensitivity and metabolism. As a result, the patient feels much hungrier, thinks about food constantly and struggles to feel full. They gain weight even without having “decided to eat more.”
Here is the important good news: today, you don’t have to choose between mental health and metabolic health. Sometimes it is possible to pick a medication with a milder metabolic effect. In other cases, the right move is to keep an effective, stable treatment and treat the obesity itself, for example with medications from the GLP-1 family.
Which psychiatric medications cause the most weight gain?
The standout group is the antipsychotics. However, the risk varies widely from one drug to another.
- Especially high risk: olanzapine (Zyprexa) and clozapine (Clozaril). Olanzapine stands out again and again in studies for its strong metabolic effect.
- Moderate risk: quetiapine (Seroquel), risperidone (Risperdal) and paliperidone (Invega). These can also raise weight, but on average less than olanzapine and clozapine.
- Usually a favorable profile: aripiprazole (Abilify), lurasidone (Latuda) and ziprasidone. “Favorable” does not mean zero risk, and individual responses vary a great deal.
Antidepressants: small but consistent differences
Mirtazapine is known for increasing appetite and weight. Paroxetine also tends in that direction.
A large 2024 study followed 183,118 patients who started one of eight antidepressants. The researchers compared each drug with sertraline. After six months, weight gain with escitalopram was 0.41 kg higher. With paroxetine the gap was 0.37 kg, and with duloxetine 0.34 kg. These three drugs raised the risk of gaining at least 5% of body weight by 10%–15%. In contrast, bupropion (Wellbutrin) lowered that risk by 15%.
In other words, the average differences are small, but for a given person they can add up. Even so, bupropion is not an automatic “substitute.” The choice depends on the diagnosis, coexisting anxiety, bipolar disorder, sleep, seizure history and other medications.
Mood stabilizers: differences here, too
Valproate can cause weight gain. Lithium is also sometimes linked to weight gain, although the data on it are complex. On the other hand, lamotrigine (Lamictal) is usually weight-neutral. Topiramate even lowers weight in some patients. Still, each drug has its own indications and side effects, so there is no automatic swap here.
Why do psychiatric medications cause weight gain?
The reason is not just “appetite.” The drugs with the biggest impact act on several systems in the brain and body at once.
First, blocking histamine H1 receptors increases appetite and drowsiness. Second, blocking serotonin 5-HT2C receptors weakens an important satiety pathway in the hypothalamus. When that signal fades, the brain “asks” for more food. This is one of the main explanations for weight gain with olanzapine and clozapine.
In addition, these drugs affect dopamine, the reward system and leptin. Some of them impair insulin sensitivity and change blood lipids, sometimes even before major weight gain. Finally, fatigue reduces movement and NEAT, the energy the body burns walking, standing and moving through the day. That is why the advice to “just eat less” falls short.
Where does prolactin fit in?
Dopamine naturally restrains the release of prolactin from the pituitary gland. Drugs that block dopamine D2 receptors remove this brake, so prolactin levels rise. Risperidone, paliperidone and amisulpride are especially notable for this effect.
High prolactin causes menstrual irregularities, breast milk discharge (galactorrhea), lower libido and sexual dysfunction. The link to weight, however, is complex. Hyperprolactinemia lowers estrogen or testosterone, and that may change body composition and insulin sensitivity. Yet not all the weight gain can be blamed on prolactin, because the same drug works through several pathways. So, when weight gain comes together with menstrual or sexual problems, it is worth checking prolactin.
Weight gain on psychiatric medications: should you switch?
Sometimes, yes. If there is a suitable drug with lower metabolic risk and the patient is stable, the psychiatrist may consider a carefully supervised switch.
But one principle matters far more: we don’t sacrifice good mental stability just because of the number on the scale. A patient who finally stabilized after years of severe depression, psychosis or bipolar instability is not an automatic candidate for a switch. Often the right question is not “Which drug do we stop?” but rather “How do we treat the obesity at the same time?” This is crucial: never stop psychiatric treatment on your own. Any change should be made gradually, together with your psychiatrist.
Metformin: an older, familiar option
Metformin is one of the most studied drugs for antipsychotic-related weight gain. Its effect on weight is modest. In a 2026 network meta-analysis of 95 studies, metformin lowered weight by an average of 3.86 kg compared with placebo. Topiramate lowered it by 3.95 kg. That makes metformin especially suitable when there is also prediabetes or insulin resistance.
Semaglutide for weight gain from psychiatric medications: what the studies show
Semaglutide, the active ingredient in Wegovy, activates the GLP-1 receptor. It boosts satiety, reduces hunger and slows stomach emptying. It also improves blood sugar control.
An early study with liraglutide already included patients with schizophrenia taking clozapine or olanzapine. After 16 weeks, weight fell by 5.3 kg compared with placebo. Moreover, 63.8% of patients reached normal glucose tolerance, versus 16.0% on placebo.
Today the data with semaglutide are much stronger. The HISTORI trial enrolled 154 patients with schizophrenia, prediabetes and overweight or obesity. They received semaglutide up to 1 mg a week or placebo for 30 weeks. The difference in weight reached 9.21 kg. In addition, 81% of patients on semaglutide reached a normal HbA1c, compared with 19% on placebo. Psychotic symptoms did not worsen.
Another study in JAMA Psychiatry included 73 patients who had started clozapine or olanzapine within the past five years. After 26 weeks, weight dropped by 9.2 kg compared with placebo. Waist circumference also fell by 7.0 cm and fat mass by 6.1 kg. Here, too, there was no difference in psychiatric symptoms. In the 2026 network meta-analysis, semaglutide came out on top with an average loss of 10.98 kg. Another review of 55 studies also ranked it first.
What about Mounjaro?
Mounjaro, or tirzepatide, works through two pathways: GIP and GLP-1. In the general population it produces substantial weight loss and improves insulin resistance. So it makes a lot of sense to use it in psychiatric patients who meet the criteria for obesity treatment, too.
But we need to be precise. As of October 2026, the direct evidence in people with serious mental illness concerns mainly semaglutide and liraglutide. Controlled trials of tirzepatide in this population are still lacking. Therefore, we can’t simply copy the results over. Even so, in a suitable patient, tirzepatide may be considered as part of a shared, monitored plan. I compare the two drugs in my article on Mounjaro vs. Wegovy.
Do Wegovy or Mounjaro disrupt mental stability?
Current data are reassuring. On January 13, 2026, the FDA requested removal of the warning about suicidal thoughts. The request applies to Wegovy, Saxenda and Zepbound, the obesity version of tirzepatide. The reason: a comprehensive review found no increased risk. Beyond that, in the schizophrenia trials, semaglutide did not worsen mental health compared with placebo. You can read more in my article on GLP-1 medications and mental health.
In short, a psychiatric disorder is not a reason to rule out obesity treatment. Monitoring, however, remains important. With active severe depression, uncontrolled bipolar disorder, active psychosis or an eating disorder, close coordination with the psychiatrist is essential. I expand on this in my article on mental health monitoring during treatment.
Treating psychiatric medication weight gain with injections: everyday tips
GLP-1 drugs don’t “counteract” psychiatric medications. However, they sometimes cause nausea, vomiting, constipation and a sharp drop in food intake. So it is important to make sure the patient keeps taking their medications as prescribed. They also need to drink enough and eat adequate protein to prevent malnutrition and dehydration. My nutrition guide for weight loss injections explains how.
In addition, GLP-1 slightly slows stomach emptying. For drugs with a narrow therapeutic window, or when there is an unexpected clinical change, we review the whole treatment. We don’t assume that every new symptom is “psychiatric.”
A two-track plan
I suggest not thinking in terms of “the medication or the weight.” Instead, we build a plan with two tracks running in parallel.
On the first track, we protect mental stability. Together with the psychiatrist, we check whether the drug is essential, whether the dose is the lowest effective one, and whether there is a good metabolic alternative. On the second track, we treat obesity as a disease in its own right. We monitor weight, waist circumference, blood pressure, fasting glucose, HbA1c, blood lipids and liver function. When needed, we also check prolactin and TSH.
Right from the start of a treatment with high metabolic risk, it is worth adopting a diet rich in protein and fiber. It also helps to cut back on ultra-processed foods and sugary drinks, add strength training and protect your sleep. Early action beats waiting. Once obesity is already present, metformin, semaglutide and sometimes tirzepatide can be considered. I also explain the link between mood and weight in my article on obesity and depression.
Bottom line: psychiatric medications, weight gain and metabolic health
Weight gain from psychiatric medications is a real biological side effect. It is not a sign of weak willpower. Nor is it a reason to stop, on your own, a treatment that protects your mental health. On the other hand, obesity, diabetes or high lipids should not be accepted as “the price you have to pay.”
Medicine today lets us think differently. We keep the medication that works, choose a metabolically friendlier alternative when possible, and actively treat the obesity. The semaglutide studies in schizophrenia show a broad principle: we can treat the mind and the body at the same time.
The information in this article is general and does not replace personal medical advice.
