In the landscape of mental health treatment, antidepressant medications play a crucial role in managing conditions like Depression. However, patients and clinicians often express concern about potential side effects, with weight gain frequently cited as a significant worry. A recent study has shed new light on how various commonly prescribed antidepressants affect weight over time, providing valuable information for treatment decisions.
Understanding the Scope of Antidepressant Use
Antidepressants rank among the most commonly prescribed medications in the United States.
Data show that approximately 14% of U.S. adults reported using an antidepressant in 2017-2018, demonstrating a significant increase from 11% in 2009-2010. This widespread use makes understanding all effects of these medications particularly important.
Weight gain associated with antidepressant use presents multiple concerns for patients. Beyond the immediate impact on body image and self-esteem, sustained weight gain can affect long-term metabolic health—especially considering how challenging weight loss can be to achieve and maintain. Furthermore, weight-related side effects may lead to decreased medication adherence, potentially resulting in poor clinical outcomes including increased risk of Depression relapse and hospitalization.
Comparing Weight Changes Across Medications
While previous research has suggested that antidepressants in general tend to cause weight gain, specific medications within this broad category may affect weight differently. For example,
Selective Serotonin Reuptake Inhibitors (SSRIs) have generally been associated with weight gain, while bupropion has been linked to modest weight loss. However, prior studies examining these effects have had limitations, including:
- Focusing on established medication users rather than new users
- Examining entire medication classes (e.g., SSRIs) rather than individual drugs (e.g., sertraline)
- Having sample sizes too small to detect subtle but meaningful differences
To address these gaps, Petimar et al. conducted a large cohort study, examining prescription data from 8 health systems participating in PCORnet (The National Patient-Centered Clinical Research Network) which resulted in an impressive analytical sample of 183,118 patients. The researchers sought to “provide important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants.”
Study Design and Methods
Weight changes were compared across 8 commonly prescribed first-line antidepressants:
- Sertraline (Zoloft)
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Fluoxetine (Prozac)
- Paroxetine (Paxil)
- Bupropion (Wellbutrin)
- Duloxetine (Cymbalta)
- Venlafaxine (Effexor)
Using sertraline—the most commonly prescribed antidepressant in the dataset—as the reference point, the researchers measured weight changes at 6, 12, and 24 months after medication initiation. The analysis primarily estimated the effects of initiating each treatment by measuring patients’ 6-month weight changes. Secondary analyses examined the impact of both initiating and adhering to each medication regimen as measured by 12- and 24-month weight changes, as well as the probability of gaining at least 5% of baseline weight at each of the 3 time points.
Short-Term Key Findings
Petimar et al.’s study revealed notable differences in weight changes associated with various antidepressants at the 6-month mark:
Compared to sertraline, patients taking escitalopram gained an average of 0.41 kg (0.9 lbs) more, while paroxetine users gained 0.37 kg (0.8 lbs) more. Duloxetine was associated with 0.34 kg (0.75 lbs) additional weight gain, venlafaxine with 0.17 kg (0.37 lbs) more, and citalopram with 0.12 kg (0.26 lbs) more.
Fluoxetine showed similar weight patterns to sertraline, with no statistically significant difference. Most notably, bupropion stood out as the only medication associated with less weight gain than sertraline, with patients gaining 0.22 kg (0.49 lbs) less on average. When looking at the probability of gaining at least 5% of baseline weight over the first 6 months—a threshold often considered clinically significant—the patterns remained consistent. Bupropion users had a 15% reduced risk of significant weight gain compared to sertraline users. Conversely, escitalopram users had a 15% increased risk, while paroxetine users had a 14% higher risk and duloxetine users had a 10% higher risk compared to sertraline users.
Longer-Term Weight Effects
The study also examined weight changes at 12 and 24 months, though these findings were limited by declining medication adherence over time. Across all medications, adherence ranged from 28% to 41% at 6 months, dropped to 16-21% at 12 months, and fell to just 4-5% by 24 months.
Despite these limitations, some interesting patterns emerged in the longer-term data:
- Bupropion continued to show the least weight gain at both 12 and 24 months (0.71 kg and 0.91 kg less than sertraline, respectively).
- Escitalopram was associated with greater weight gain than sertraline at 12 months (0.41 kg more) but showed no significant difference at 24 months.
- Duloxetine and venlafaxine—both Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)—showed less weight gain than sertraline at 24 months (0.69 kg and 0.59 kg less, respectively). This appears to be due to weight gain plateauing for SNRIs around 12-18 months, while SSRIs (such as sertraline) showed continued weight increases.
Differences Within and Between Medication Classes
One of the study’s most valuable contributions is highlighting differences both within and between antidepressant subclasses:
As EurekAlert! points out, “results showed a large percentage of patients were taking a medication that led to greater weight gain than alternatives that are commonly available in the same class.” An example of this can be seen from the fact that many patients were prescribed escitalopram and paroxetine, even though both of these SSRIs were associated with an approximately 15% higher risk of gaining a clinically significant amount of weight in the first 6 months than the SSRI sertraline. This information could be particularly important for clinicians to consider when treating patients concerned about weight-related side effects.
As mentioned above, SNRIs (duloxetine and venlafaxine) showed greater 6-month weight gain than the SSRI sertraline but demonstrated a different long-term pattern with weight gain eventually plateauing around 12-18 months.
The weight effects of bupropion were even more pronounced among patients with documented baseline Depression or anxiety, with these patients showing 0.25 kg less weight gain than the
overall bupropion group. This difference may be because the analysis removed patients taking bupropion primarily for smoking cessation, who might be more prone to weight gain.
Clinical Implications and Considerations
The study conducted by Petimar et al. provides valuable data that can be used to guide clinical practice. For patients particularly concerned about weight gain, bupropion might be considered as a first-line option when appropriate for their specific mental health condition. Conversely, clinicians might exercise caution with escitalopram, paroxetine, and duloxetine in patients at
higher risk for weight-related complications or in those where weight gain might compromise treatment adherence. As the research paper’s lead author Petimar told MedPage Today, “a lot of patients might be reluctant to adhere to their medication if they start taking it, and they notice that they’re gaining weight.”
However, it’s also worth noting that weight changes are just one consideration in antidepressant selection. Treatment decisions should continue to be guided by each medication’s effectiveness for the specific condition being treated, the patient’s prior response to medications, potential drug interactions, and other individual factors.
Looking Beyond Medication: Advanced Treatment Options
For patients concerned about medication side effects or those who have not responded adequately to antidepressants, Mid City TMS offers two innovative treatment alternatives: Transcranial Magnetic Stimulation (TMS) and Spravato (esketamine). TMS is an FDA-approved, non-invasive therapy that uses magnetic pulses to stimulate brain regions involved in mood regulation. Unlike medications, TMS does not cause weight gain or other systemic side effects, making it an attractive option for many patients. Spravato, a nasal spray formulation of esketamine, is also FDA-approved and represents a groundbreaking approach for treatment-resistant Depression. This novel medication works differently than traditional antidepressants, targeting the glutamate system rather than serotonin or norepinephrine. Spravato can provide rapid relief of depressive symptoms—often within hours or days—compared to the weeks required for conventional antidepressants. Importantly, Spravato also does not typically cause the weight gain associated with many traditional antidepressants.
Mid City TMS specializes in both TMS and Spravato treatment, providing patients with medication alternatives that have shown remarkable success rates, even for treatment-resistant Depression. If you’ve been concerned about antidepressant-related weight gain or haven’t found relief with traditional treatments, we encourage you to reach out to our clinic for a consultation. Our experienced team can help determine which advanced treatment option might be right for you, potentially offering a path to recovery without weight-related side effects. Your journey toward mental wellness doesn’t have to include unwanted weight changes—contact us today to learn more about TMS and Spravato treatment options.
Sources:
- George, C. (2024, March 12). Antidepressant use tied to modest weight gain. MedPage Today. https://www.medpagetoday.com/psychiatry/depression/110914
- Stanborough, R. J. (2023, August 30). Why do people gain weight after quitting smoking? Healthline. https://www.healthline.com/health/diet-weight-loss/weight-gain-after-quitting-smoking#causation
- Aubin, H. J., Farley, A., Lycett, D., Lahmek, P., & Aveyard, P. (2012). Weight gain in smokers after quitting cigarettes: Meta-analysis. Obesity Reviews, 13(9), 746–765. https://doi.org/10.1111/obr.12934
- Filozof, C., Fernández Pinilla, M. C., & Fernández-Cruz, A. (2004). Smoking cessation and weight gain. Obesity Reviews, 5(2), 95–103. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629701/
- Roque, C., Salvo, V., Repetto, C., & Foguet, Q. (2016). Weight gain and psychiatric treatment: Is there a link? Journal of Affective Disorders, 202, 89–96. https://doi.org/10.1016/j.jad.2015.11.044
- Endocrine Society. (2024, February 15). Antidepressant use linked to modest weight gain in large study. EurekAlert!. https://www.eurekalert.org/news-releases/1049472
- Sharma, A., Madaan, V., & Petty, F. D. (2006). Antidepressant-induced weight gain: A review of the literature. Menopause International, 12(3), 88–94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819980/