Do SSRIs Cause Weight Gain?

Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed type of antidepressant. Considering the prevalence of both depression and overweight, and the link between them, it can be helpful to understand SSRIs in the context of treating patients seeking to manage their weight.

Antidepressants are among the most widely prescribed medications, with about 16% of U.S adults currently taking them. While generally considered safe and well-tolerated, SSRIs can have side effects and adverse events, including weight changes. Some are associated more with weight loss (particularly in the short term), while others are associated with weight gain. Because SSRI selection depends on multiple individual factors, medications associated with weight gain may still be the most appropriate choice for some patients, making it important to recognize and address this potential adverse effect.

Keep in mind, the relationship between obesity and mental health is bidirectional — patients with obesity are at higher risk for depression, and depression can contribute to weight gain. Therefore, a personalized approach is required to find what works best for an individual.

What Are SSRIs and How Do They Work?

First approved in the 1990s, SSRIs work by increasing serotonin activity. Specifically, they inhibit the serotonin transporter at the presynaptic axon terminal. They marked an improvement over the existing tricyclic and MAOI antidepressants, which had significant side effects that included weight gain.

In addition to depression, they can be used to treat anxiety, fibromyalgia, eating disorders, and PTSD, among other conditions.

SSRIs available in the U.S. include:

• Fluoxetine (Prozac or Sarafem)

• Sertraline (Zoloft)

• Paroxetine (Paxil, Paxeva, or Brisdelle)

• Escitalopram (Lexapro)

• Citalopram (Celexa)

• Fluvoxamine (Luvox)

What Is the Relationship Between SSRIs and Weight Gain?

Serotonin affects mood and plays a role in appetite regulation. Patients may experience changes in appetite, cravings (particularly for carbohydrates), and energy expenditure as a result of altered serotonin signaling.

SSRIs have a wide range of potential side effects, and most list weight changes among them, although not always weight gain. Below are details from each medication’s prescribing information:

• Prozac: altered appetite or weight

• Zoloft: decreased appetite and weight loss

• Paxil: weight loss or weight gain, increases in cholesterol levels

• Lexapro: “Patients treated with Lexapro in controlled trials did not differ from placebo-treated patients with regard to clinically important change in body weight.”

• Celexa: decreased weight or increased weight

• Fluvoxamine: (previously sold as Luvox): weight gain and weight loss

Keep in mind, weight gain as a side effect can be difficult to disentangle from weight changes caused by the underlying depression or other mental health condition.

A study published in 2017 followed 40 patients receiving sertraline, escitalopram, fluoxetine, or venlafaxine (the latter of which is an SNRI, brand name Effexor) for eight weeks. There was no change in BMI, but HDL cholesterol levels increased. In patients taking escitalopram, there was an increase in waist circumference. Overall, the researchers concluded that “Treatment did not cause a significant change in the body weight or other body measurement values of the patient group.”

Why Can SSRIs Cause Weight Changes?

The metabolic effects of SSRIs can affect weight in some people. The exact mechanism is not fully understood and may vary by individual and by drug.

Serotonin mediates a range of nervous system functions. Working in the CNS and peripheral nervous system it:

• Regulates behavior

• Suppresses appetite

• Promotes energy expenditure

• Enhances nutrient absorption and storage by upregulating lipid anabolism

• Promotes insulin secretion and de novo lipogenesis

• Mediates non-neuronal processes such as bladder function, respiratory drive, hemostasis, vascular tone, immune function, and intestinal inflammation

SSRIs work by inhibiting the reuptake of serotonin, keeping more of it available in the body. Overall, serotonin tends to inhibit appetite. It has previously been studied as a potential treatment for obesity, for example, in the form of the drug lorcaserin, which is no longer on the market. A selective serotonin 2C receptor agonist, it was associated with significant weight loss and maintenance.

How, then, might SSRIs lead to weight gain? It appears, from a literature review, that weight loss is more common in the short term, while SSRI use exceeding one year is more associated with weight gain. Fluoxetine, paroxetine, and citalopram have all been shown to increase food intake and body weight in the long term.

In addition, SSRIs and other classes of antidepressants have been shown to increase cortisol levels, which is associated with increased insulin resistance. Insulin resistance is always an important factor to monitor in people with overweight or obesity.

Which SSRIs Are Most Likely to Cause Weight Gain?

All SSRIs rely on the same mechanism of action, so side effects are similar, with variation from person to person. Not everyone who uses a certain one will experience the same side effects, including weight changes.

SSRIs vs. Other Antidepressants: How Do They Compare?

SSRIs and their relatives, SNRIs (which inhibit the uptake of both serotonin and norepinephrine), are generally considered to be an improvement over the older tricyclics and MAOIs. The preference is largely due to the reduction in unwanted side effects, including weight gain.

Outside the above categories lies mirtazapine, an atypical tetracyclic antidepressant. Unlike SSRIs, it has strong antihistaminergic properties which can be useful for sleep at lower doses; however, because of this property, it is also associated with an increased risk of weight gain.

By contrast, NDRIs (norepinephrine and dopamine reuptake inhibitors) may offer an alternative when potential weight gain is a concern. This class of drugs includes bupropion, which has a variety of brand names including Wellbutrin, as well as drugs commonly used to treat attention activity and hyperactivity disorder. Though it does not directly act on serotonin neurotransmission, its efficacy is considered equivalent to that of SSRIs.

A physician and patient should always collaborate on the choice of an antidepressant, weighing mental health needs against potential metabolic effects.

Managing Weight Gain in Patients Taking SSRIs

When treating a patient who takes an SSRI, whether they begin at a healthy or unhealthy weight, it can help to follow certain guidelines.

• Counsel patients proactively about the possibility of weight changes before starting treatment, so they are not caught off guard. Monitor weight after initiating or changing SSRI therapy — weight gain or loss may develop gradually and go unnoticed without active tracking.

• Encourage physical activity and mindful eating as part of a comprehensive treatment plan. Acknowledge the emotional and behavioral dimensions of eating and encourage the person to identify connections among stress, emotional eating, and brain-based appetite regulation.

• If weight gain becomes clinically significant, explore other options for depression treatment. If another physician has prescribed the SSRI, confer with them as well as with your patient.

• Discuss the potential use of weight loss medications when clinically appropriate.

Stress and Emotional Eating in SSRI-Related Weight Changes

For many people, SSRI-related weight gain is not purely pharmacological. The psychological and behavioral drivers of eating include stress, emotional eating, and the brain's reward circuitry. Depression itself can lead to over- or under-eating. In turn, weight gain can contribute to depression and related feelings of low self-esteem.

Patients can work with therapists, using cognitive behavioral therapy or other modalities to address emotionally motivated eating. It is important to address the whole person when treating mental health issues.

To further explore this topic, listen to OMA's podcast, Obesity: A Disease, Episode 114. In this episode, Dr. Laurel Mellin discusses Emotional Brain Training — a behavioral approach to rewiring the brain's stress response as a tool for lasting weight management.

SSRIs in Patients Already Diagnosed with Obesity

As the podcast mentioned above and many other sources have illuminated, obesity and depression are closely linked in some people. A literature review published in 2020 observed that:

• Depression is a risk factor for obesity, especially atypical depression and in African-American adolescent males.

• Obesity is a risk factor for depression, especially in women and for recurrent depressive disorder.

• The co-occurrence of obesity and depression is associated with a poorer prognosis and worse clinical outcomes.

If you treat people with obesity, keep in mind their elevated risk for depression. Whether they seek treatment for depression from you or from another practitioner, encourage them to keep you informed of any medications they’re taking, including SSRIs.

A team-based, integrated approach between you and other practitioners can provide more comprehensive support for the patient. If a patient comes to you with concerns about gaining weight on their SSRI, remind them that they should never stop taking a medication without input from the prescriber. Ensure that they have considered other weight management options, such as physical activity, dietary adjustments, and if appropriate, weight loss medications.

The Bottom Line on SSRIs and Weight Gain

SSRIs are effective and widely used treatments for depression, as well as anxiety and other conditions, generally with fewer side effects than older generations of antidepressants. They do carry the risk of metabolic effects, both weight gain and weight loss, which can vary from person to person. Weight gain with long-term use may be a concern for patients already living with overweight or obesity.

The intricate, bidirectional relationship between mental health and weight requires individualized, whole-person care. Discuss any mental health conditions and medication with patients proactively. When necessary, connect with their mental healthcare provider and make team-based decisions about their care.

OMA offers clinical resources, evidence-based tools, and peer networking to support healthcare providers navigating these complex cases.