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Antidepressants are prescription drugs that are used for treating major depressive disorder and certain other health conditions such as anxiety, insomnia, and chronic pain. These medicines treat depression by changing the levels of certain chemicals in the brain that regulate mood. 

Common side effects of antidepressant medications include nausea, vomiting, diarrhea, drowsiness, sexual problems, and weight gain.

Increased antidepressant exposure in recent years has raised concerns about potential links between antidepressant treatment and the obesity pandemic. 

Types of Antidepressants

The following commonly prescribed antidepressants are approved by the FDA for the treatment of depression and other health conditions.

• Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft). (Check out our blog: “Lexapro & Weight Gain: Is There a Connection?”)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor, Effexor XR), desvenlafaxine (Pristiq), duloxetine (Cymbalta, Irenka, Drizalma), levomilnacipran (Fetzima), and milnacipran (Savella).

• Atypical antidepressant drugs such as bupropion (Wellbutrin), mirtazapine (Remeron), trazodone, nefazodone, vortioxetine (Trintellix), and vilazodone (Viibryd).

• Tricyclic antidepressants (TCAs) such as amitriptyline, nortriptyline (Pamelor), desipramine (Norpramin), imipramine (Tofranil), amoxapine, doxepin, trimipramine, and protriptyline.

• Monoamine oxidase inhibitors (MAOIs) such as phenelzine, selegiline, isocarboxazid, and tranylcypromine.

Mechanisms of Weight Change

Indirect Causes

Many people report gaining weight after starting an antidepressant drug. However, the weight gain is not always a direct result of taking the medication. 

Some people gain weight from overeating and inactivity related to major depression. But they mistakenly blame their weight gain on their antidepressant medication. (Learn more: “Does Stress Cause Weight Gain?”)

In contrast, some people lose weight when they have depression symptoms. After starting treatment with an antidepressant, they experience improved mood, which leads to increased appetite and body weight.

Direct Causes

Antidepressant medications work by increasing the levels of a neurotransmitter called serotonin in the brain. Serotonin is often referred to as the “happy or feel-good” chemical that regulates mood and can also increase appetite as a possible side effect. 

Research suggests that short-term use of antidepressants can help with weight loss by reducing impulsivity and increasing satiety. Improved mood can also support healthy eating and regular exercise. 

However, long-term treatment with antidepressants for more than a year can lead to decreased serotonin activity. This can result in cravings for carbohydrate-rich foods and lead to weight gain. 

Additionally, tricyclic antidepressants are known for their significant anticholinergic properties, which can contribute to weight gain as a side effect. There are reports of cravings for sweets among patients taking nortriptyline, amitriptyline, and imipramine. Besides dry eyes and urinary retention, tricyclic drugs’ anticholinergic activity also causes dry mouth, leading to the consumption of high-calorie beverages, which also contribute to weight gain. 

Learn more: “How Long Does It Take For Depression Medication To Work?”

Which Antidepressants Cause the Most Weight Gain?

Weight gain is a possible side effect of many antidepressants. Certain antidepressants are more likely to cause weight gain than others, for example:

• Amitriptyline, nortriptyline, trimipramine, imipramine, and doxepin (tri-cyclic antidepressants)

• Phenelzine (MAOI)

• Paroxetine and citalopram (SSRIs)

• Mirtazapine (atypical antidepressant)

Which Antidepressants Are Less Likely to Cause Weight Gain?

Generally speaking, newer (second-generation) antidepressants such as SSRIs, SNRIs, and atypical antidepressants are less likely to result in increased weight. Some of the antidepressants that may cause less weight gain than others include:

• Bupropion and nefazodone (atypical antidepressants) 

• Fluoxetine (SSRI)

• Desvenlafaxine (SNRI) 

Do Antidepressants Cause Belly Fat?

Long-term use of antidepressants can cause cravings for sweets and carbohydrates, which can cause belly fat.

Can You Lose Weight on Antidepressants?

Yes, you can lose weight on antidepressants, especially with short-term treatment. Losing weight on antidepressants may occur as a result of less impulsive eating, increased satiety, and overall healthy eating and increased physical activity in association with an improved mood. 

Types of Antidepressants and Their Impact on Weight

Selective Serotonin Reuptake Inhibitors (SSRIs) and Weight Gain

Studies have found that anywhere from 6 to 18% of people taking SSRIs experience significant weight gain. Body weight can increase by 4-7% above baseline during treatment with these drugs. The SSRIs most likely to cause weight gain include paroxetine, citalopram, and fluvoxamine.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) and Changes in Weight

The SNRI venlafaxine ER may result in weight gain in some people. In contrast, desvenlafaxine may not cause significant changes in weight or may cause a small amount of weight loss, especially with short-term treatment.

Tricyclic Antidepressants (TCAs) and Weight Gain

TCAs are an older class of antidepressants that are more likely to cause serious side effects. TCAs can increase hunger, leading to weight gain. Studies have found that about 5% of patients experience weight gain with short-term TCA treatment and about 25% with long-term treatment. 

Low to moderate doses of TCAs such as amitriptyline, nortriptyline, and imipramine can lead to weight gain to the tune of 1.3 to 2.9 pounds (lbs) per month. This weight gain is linear over time. About half of all patients who are prescribed TCAs discontinue these medications due to significant weight gain. Stopping the drug will usually result in loss of the weight gained. You should consult your doctor before stopping any medication.

Monoamine Oxidase Inhibitors (MAOIs) and Weight Gain

The use of MAOIs for treating depression has declined in recent years because of the major risk of drug interactions and the availability of newer, safer antidepressants. Nonetheless, they are still prescribed sometimes. A review of the literature and meta-analysis of studies suggests that the MAOI phenelzine is most likely to cause weight gain, while isocarboxazid and tranylcypromine are less likely to cause this side effect. 

Atypical Antidepressants and Weight Gain

Weight gain is one of the most common side effects of the atypical antidepressant mirtazapine. The majority of weight gain occurs in the first 4 weeks of treatment. The average gain is 3 lbs in the first 8-12 weeks. People taking mirtazapine report increased appetite and cravings for carbohydrates. Notably, mirtazapine is sometimes prescribed off-label by palliative care providers to stimulate appetite in seriously ill patients. Find out: What Are NaSSA Antidepressants?

Factors Influencing Weight Gain on Antidepressants

Each person reacts to antidepressants differently. In other words, not everyone who takes antidepressant drugs gains weight. Some of the factors that can influence weight gain risk include:

• Age: People tend to gain weight as they get older, regardless of the medications they are taking.

• Gender: Studies have found women who are prescribed antidepressants gain significantly more weight than men taking these drugs.

• Initial body mass index (BMI): Weight gain is more likely in people who are in the overweight or obese BMI categories at the start of treatment compared to those with normal BMI at baseline.

• Smoking status: Smokers are more likely to gain weight on antidepressants compared to non-smokers.

• Medical conditions: Health conditions such as diabetes, hypothyroidism (underactive thyroid), polycystic ovary syndrome, and others can be contributing factors to changes in weight.

• Other medications: Certain other medications can also lead to weight gain, such as antiepileptics and antipsychotics. 

Management and Prevention: How to Avoid Weight Gain on Antidepressants?

Many people stop taking their antidepressant medication due to side effects of increased appetite and weight gain. This causes them to experience depression symptoms again. 

Experts at Harvard Medical School recommend the following strategies to help in managing weight gain on common antidepressants. Talk to your healthcare provider about:

• Choosing an antidepressant that is less likely to cause weight gain. 

• Switching to other drugs with a lower weight gain risk (if you have already taken antidepressant treatment and gained weight).

• Taking another medication to suppress appetite and promote weight loss. For example, your doctor may add low-dose bupropion or topiramate to help with weight loss in combination with a reduced-calorie diet and increased exercise. 

Dietary and Lifestyle Modifications

• Be proactive about preventing weight gain on antidepressants by eating a healthy diet and increasing physical activity. 

• Talk to your provider about consulting an expert in clinical nutrition and/or participating in a commercial weight-loss program. 

• Keep a record of your weight every week so that you and your provider are alerted about small weight changes before they become a bigger problem. 

• Maintain a food diary or journal to track your eating behaviors. Practices such as eating slowly and eating smaller, more frequent meals can help in regulating appetite and weight. 

Work With Healthcare Providers

If you have gained weight after starting antidepressant therapy, do not stop treatment without talking to your healthcare provider. It is important to discuss the benefits of your antidepressant versus the risks. Your doctor will tell you how to come off the drug, if needed. Abruptly stopping an antidepressant can cause serious withdrawal symptoms.