Which medication is most likely to cause weight gain?

Studies show that about 20% of U.S. adults take at least one medication that can cause weight gain [1.3.1]. When considering which medication is most likely to cause weight gain, certain antipsychotics like clozapine and olanzapine often top the list [1.4.3, 1.4.5].

Quick Summary

An overview of common medications known to cause significant weight gain, including antipsychotics, antidepressants, corticosteroids, and diabetes drugs. The mechanisms and effective management strategies are also explored.

Key Points

• Highest Risk Medications: Atypical antipsychotics, particularly clozapine and olanzapine, are most strongly associated with significant weight gain [1.4.5].

• Common Culprits: Other major classes include certain antidepressants (like paroxetine), corticosteroids (like prednisone), and some diabetes medications (like insulin) [1.2.1, 1.8.1, 1.9.2].

• Primary Mechanisms: Medications can cause weight gain by increasing appetite, slowing metabolism, causing fluid retention, or altering how the body stores fat and sugar [1.5.1, 1.5.3].

• Management is Key: Strategies to manage weight gain include discussing medication alternatives with a doctor, adopting a healthy diet, increasing physical activity, and prioritizing sleep [1.6.5].

• Do Not Stop Medication: It is critical to consult a healthcare provider before stopping or changing any medication, as this can have serious health consequences [1.6.4].

• Weight-Neutral Options Exist: For many conditions, there are alternative medications that are weight-neutral or may even promote weight loss, such as the antidepressant bupropion or the diabetes drug metformin [1.7.4, 1.9.3].

• Long-Term vs. Short-Term: The risk of weight gain is often higher with long-term use and at higher doses for many medications, such as corticosteroids and some SSRIs [1.8.2, 1.7.4].

The Unwanted Side Effect: Understanding Medication-Induced Weight Gain

Weight gain is a common and often distressing side effect of many widely prescribed medications. This phenomenon, sometimes called iatrogenic obesity, occurs when a drug alters the body's natural processes, leading to an increase in pounds [1.11.1]. Research indicates that approximately 1 in 5 U.S. adults uses a medication associated with weight gain [1.3.5]. The effects can range from a few pounds to a significant increase of 10% or more of a person's body weight [1.11.1]. While many drugs can contribute to this issue, some have a much higher propensity for causing weight gain than others. Understanding which medications are the primary culprits, the mechanisms behind the gain, and how to manage it is crucial for patient health and medication adherence [1.5.2].

Why Do Medications Cause Weight Gain?

The reasons behind drug-induced weight gain are complex and vary depending on the medication class [1.5.2].

Several core mechanisms are often involved:

• Increased Appetite: Many medications are orexigenic, meaning they stimulate appetite [1.2.1]. They can interfere with brain chemicals and hormones that control hunger and satiety, causing you to eat more without feeling full [1.2.3].
• Slowed Metabolism: Some drugs can slow down your basal metabolic rate. This means your body burns fewer calories at rest, making it easier to gain weight even if your eating habits haven't changed [1.5.3]. Beta-blockers, for instance, are thought to cause weight gain partially through this mechanism [1.9.3].
• Fluid Retention: Certain medications, notably corticosteroids, can alter the body's electrolyte and water balance, causing it to hold onto more sodium and water. This leads to swelling and an increase on the scale, often referred to as "water weight" [1.8.4].
• Changes in Fat Storage and Nutrient Absorption: Some drugs affect how the body processes and stores fats and sugars. Corticosteroids can cause fat to redistribute to the abdomen, face, and neck [1.8.3]. Meanwhile, certain diabetes medications like insulin improve glucose absorption into cells; if calorie intake isn't adjusted, this excess glucose is converted to fat [1.9.2].

High-Risk Medication Classes

While weight gain can occur with many drugs, some classes are more notorious than others. Among the most significant are antipsychotics, with certain drugs in this class causing the largest increases in weight [1.3.4].

Antipsychotics and Mood Stabilizers

This class of medication is strongly associated with significant weight gain [1.2.2].

• High Risk: Clozapine (Clozaril) and olanzapine (Zyprexa) are consistently identified as having the highest risk, with patients sometimes gaining a significant amount of weight over the course of treatment [1.2.2, 1.4.3, 1.4.5]. On average, patients on clozapine can gain between 4.5 and 16.2 kg, while those on olanzapine can gain between 3.6 and 10.2 kg [1.2.2].
• Moderate Risk: Risperidone (Risperdal) and quetiapine (Seroquel) carry a moderate risk [1.4.3].
• Low Risk: Aripiprazole (Abilify), ziprasidone (Geodon), and lurasidone (Latuda) are associated with the least amount of weight gain in this class [1.2.2]. Lithium, a common mood stabilizer for bipolar disorder, is also associated with notable weight gain [1.2.2].

Antidepressants

Tricyclic antidepressants (TCAs) like amitriptyline are most likely to cause weight gain [1.7.4]. Among the more commonly prescribed SSRIs, paroxetine (Paxil) is most strongly linked to both short-term and long-term weight gain, while others like sertraline (Zoloft) and escitalopram (Lexapro) are more associated with weight gain during long-term use [1.7.4]. Bupropion (Wellbutrin) is an exception in this class and is often associated with weight neutrality or even weight loss [1.7.4].

Corticosteroids

Oral steroids like prednisone are well-known for causing weight gain, especially with long-term use [1.8.1]. About 70% of people who take steroids long-term experience this side effect [1.8.2]. This is primarily due to increased appetite, fluid retention, and a change in how the body stores fat, often leading to a "moon face" and fat deposits in the abdomen and neck [1.8.2, 1.8.3].

Diabetes Medications

Ironically, some medications used to treat type 2 diabetes can cause weight gain. Insulin therapy is a primary example; as it allows cells to absorb more glucose, excess calories can be stored as fat [1.9.2]. Sulfonylureas (e.g., glyburide, glipizide) and thiazolidinediones (e.g., pioglitazone) also promote weight gain [1.9.4]. In contrast, other diabetes drugs like metformin are weight-neutral, and classes like GLP-1 agonists (e.g., semaglutide) and SGLT2 inhibitors are associated with weight loss [1.9.3].

Other Notable Medications

• Antihistamines: Chronic use of some antihistamines, such as cetirizine (Zyrtec) and fexofenadine (Allegra), has been linked to weight gain. They can block histamine receptors in the brain that help regulate appetite [1.10.4].
• Beta-Blockers: Used for high blood pressure, drugs like metoprolol and atenolol can cause modest weight gain, possibly by reducing metabolic rate and causing fatigue [1.9.3].
• Anti-epileptic Drugs: Medications like valproic acid (Depakote) and gabapentin (Neurontin) are also associated with an increased risk of weight gain [1.5.3].

Comparison of Common Medications and Weight Gain Risk

Medication Class	High Risk for Weight Gain	Moderate Risk for Weight Gain	Low/Neutral Risk for Weight Gain
Antipsychotics	Clozapine, Olanzapine [1.4.3]	Risperidone, Quetiapine [1.4.3]	Ziprasidone, Lurasidone [1.2.2]
Antidepressants	Amitriptyline, Mirtazapine, Paroxetine [1.7.4]	Citalopram, Sertraline (long-term) [1.7.4]	Bupropion, Fluoxetine (short-term) [1.7.4]
Corticosteroids	Prednisone, Cortisone (long-term) [1.8.3]	(Dose and duration dependent) [1.8.2]	Inhaled/topical steroids (lower risk) [1.2.4]
Diabetes Drugs	Insulin, Sulfonylureas, Pioglitazone [1.9.4]	Repaglinide [1.9.4]	Metformin, GLP-1 Agonists, SGLT2 Inhibitors [1.9.3]

Strategies for Managing Medication-Induced Weight Gain

If you suspect your medication is causing weight gain, it is crucial not to stop taking it abruptly. Always consult your healthcare provider first [1.6.4]. They can help determine if the medication is the cause and discuss the best course of action.

Management strategies include:

1. Medication Adjustment: Your doctor might be able to switch you to an alternative medication with a lower risk of weight gain, if one is available and appropriate for your condition [1.6.5]. Sometimes, adjusting the dose can also help [1.6.3].
2. Dietary Changes: Focus on a balanced diet rich in fruits, vegetables, lean proteins, and whole grains [1.6.3]. Limiting processed foods, sugary drinks, and excess sodium can help control calorie intake and reduce fluid retention [1.6.1, 1.6.2]. Eating smaller, more frequent meals may also help manage an increased appetite [1.8.3].
3. Regular Physical Activity: Incorporating regular exercise helps burn extra calories, boost metabolism, and manage weight [1.6.1].
4. Prioritize Sleep: Lack of sleep can increase cravings for high-calorie foods. Ensuring adequate rest can help regulate appetite [1.6.2].
5. Stay Hydrated: Drinking plenty of water can help you feel full and can also help your body flush out excess sodium, reducing water retention [1.6.2].

Conclusion

While many medications can lead to weight gain, antipsychotics like olanzapine and clozapine carry one of the highest risks. However, antidepressants, corticosteroids, and certain diabetes medications are also significant contributors. The weight gain is caused by a variety of factors, including increased appetite and metabolic changes [1.5.1]. Managing this side effect requires a collaborative approach with a healthcare provider to explore alternative medications or implement targeted lifestyle adjustments involving diet and exercise. Never stop a prescribed medication without medical advice [1.6.4].

For more information from an authoritative source, you can visit: The Mayo Clinic on Antidepressants and Weight Gain

Frequently Asked Questions

Which specific drug is known to cause the most weight gain?

Among commonly prescribed medications, the atypical antipsychotics olanzapine (Zyprexa) and clozapine (Clozaril) are consistently cited as causing the most significant weight gain [1.2.2, 1.4.5].

Why do steroids like prednisone make you gain weight?

Steroids like prednisone cause weight gain primarily by increasing appetite, causing fluid retention, and changing how the body stores fat, often leading to deposits in the face, neck, and abdomen [1.8.1, 1.8.3].

Which antidepressants are least likely to cause weight gain?

Bupropion (Wellbutrin) is the antidepressant least likely to cause weight gain and is sometimes associated with weight loss. Other options with a lower risk include fluoxetine (Prozac) for short-term use and vilazodone (Viibryd) [1.7.4].

Can I stop taking my medication if I notice weight gain?

No, you should never stop taking a prescribed medication without first consulting your healthcare provider. Abruptly stopping can lead to a return of symptoms or other serious health risks [1.6.4].

How can I manage weight gain caused by my medication?

Talk to your doctor about potentially switching to a different medication. You can also manage the weight gain through lifestyle changes such as a healthy diet, regular exercise, limiting sodium, and ensuring you get enough sleep [1.6.5].

Do all diabetes medications cause weight gain?

No. While insulin, sulfonylureas, and thiazolidinediones can cause weight gain, other diabetes medications are weight-neutral (like metformin) or promote weight loss (like GLP-1 agonists and SGLT2 inhibitors) [1.9.3].

Do over-the-counter allergy medicines cause weight gain?

Yes, chronic use of some over-the-counter antihistamines like cetirizine (Zyrtec) and fexofenadine (Allegra) has been linked to weight gain. This may be because they can increase appetite [1.10.4].