Study Reveals Varying Weight Gain Risks With Different Antidepressants

A recent study revealed that some antidepressant meds can cause you to gain more pounds than others. To manage depression without experiencing side effects, try these natural alternatives.

STORY AT-A-GLANCE

• Depression affects about 29% of American adults. Antidepressants are commonly prescribed but can cause side effects like weight gain, as highlighted by a 2024 Harvard study comparing eight first-line medications

• Results showed escitalopram, paroxetine and duloxetine users were 10% to 15% more likely to gain at least 5% of their baseline weight compared to sertraline users

• Bupropion users were 15% less likely to experience significant weight gain compared to those on sertraline. Fluoxetine showed slightly less weight gain than sertraline

• Nondrug strategies for managing depression include exercise, nutritional interventions (especially omega-3s, B vitamins and vitamin D), probiotics and Emotional Freedom Techniques (EFT)

• Other helpful approaches include limiting EMF exposure, improving sleep hygiene, optimizing gut health, spending time outdoors and considering supplements like St. John's Wort and SAMe

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Depression, also known as depressive disorder, is one of the most common mood disorders in the U.S., affecting about 29% of American adults at some point in their lives, with 17.8% still undergoing treatment in 2023, as reported by a Gallup survey.¹

It can negatively affect your ability to carry out everyday activities and impact all aspects of life, from relationships with family and friends to community involvement and job performance. To mitigate the impact of depression, patients are typically put on antidepressant medications, which have been linked to various health problems.

One of the most common side effects of antidepressant drugs is weight gain. Case in point, a July 2024 study² led by researchers from Harvard Medical School revealed that common brands of first-line antidepressants can cause varying degrees of weight gain in users, which can affect their long-term metabolic health and lead to poor health outcomes.

Some Antidepressants Cause More Weight Gain Than Others

The study,³ published in the Annals of Internal Medicine, compared weight changes associated with eight commonly prescribed first-line antidepressants over a 24-month period. The authors examined electronic health records of 183,118 patients across eight U.S. health systems between 2010 and 2018. The medications evaluated were sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine and venlafaxine.

Their findings showed that at six months, users of escitalopram (Lexapro), paroxetine (Paxil) and duloxetine (Cymbalta) were 10% to 15% more likely to gain at least 5% of their baseline weight compared to those using sertraline (Zoloft). On the other hand, bupropion (Wellbutrin) users were 15% less likely to experience weight gain than those on sertraline. Patients taking fluoxetine (Prozac) also gained slightly less weight than those using sertraline.

The researchers described the difference between the weight changes as small but suggested it could be significant in helping patients make informed decisions. Joshua Petimar, the study lead author and a Harvard Medical School assistant professor of population medicine at the Harvard Pilgrim Health Care Institute, said in a news release:⁴

"Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants. Clinicians and patients can use this information, among other factors, to help decide on the right choice for them."

More Reasons Why Antidepressants May Not Be the Best Option

While the featured study⁵ aims to aid patients and physicians in choosing antidepressants, I advise against relying on these drugs as a primary treatment option in the first place. The real issue isn't which drug causes slightly less weight gain — it's that all these medications come with significant risks. Even the antidepressants associated with less weight gain have been linked to troubling side effects.

For instance, a January 2024 study⁶ showed that Prozac, which belongs to a class of medication called selective serotonin reuptake inhibitors (SSRIs), causes hallmark signs of symptoms of chronic fatigue syndrome (CFS) in mice that were given this medication for four weeks, albeit at dosages that are two to five times higher than what is used in clinical practice for depressive patients. SSRIs, in general, have also been linked to a long list of other side effects, including:⁷

• Feeling anxious or agitated

• Sleep disturbances

• Loss of libido

• Indigestion

• Loss of appetite

• Difficulty achieving orgasm

• Constipation or diarrhea

• Blurred vision

• Erectile dysfunction

Moreover, research⁸ published in the journal PLoS ONE showed that depressive individuals who took antidepressants did not exhibit significant improvement in their condition compared to those who were not on medications. "The real-world effect of using antidepressant medications does not continue to improve patients' HRQoL [health-related quality of life] over time," the authors noted.

In fact, with all the side effects of these drugs, it can even be argued that SSRIs may lower quality of life. Research⁹ also found that up to 75% of the effectiveness of antidepressants may be attributed to placebo effects. This raises the question — Is it worth risking your health to the potential side effects of antidepressants when its purported benefits might largely be attributed to the power of suggestion?

GABA Is a Better Choice Than Antidepressants

Depression is routinely treated with SSRIs under the belief that it's caused by a deficiency in serotonin, often mistakenly referred to as the "happiness hormone." The problem is, low serotonin level is not responsible for depression; rather, it's excessive serotonin levels that may be the issue. I discuss this in detail in my article "Media Twists Findings of Study Linking High Serotonin to Dementia."

Having excessive serotonin levels is the last thing you want, as it destroys empathy, love and wisdom. Elevated serotonin also impairs thyroid function, reduces your metabolism and contributes to premature aging by increasing reductive stress. A far more common problem in depression is gamma-aminobutyric acid (GABA) deficiency.

Increasing your GABA levels is a more effective solution for conditions typically treated with SSRIs, without the adverse effects associated with elevated serotonin. In our previous interview, Dr. Scott Sherr,¹⁰ director of integrative hyperbaric medicine and health optimization at Hyperbaric Medical Solutions and an expert on neurotransmitter balancers like GABA, explained:

"GABA deficiencies are associated with anxiety, with fear, with depression, with a short temper, phobias, impulsiveness, disorganization, addictions. It's even associated with schizophrenia and OCD [obsessive-compulsive disorder].

You can also have things like IBS [irritable bowel syndrome] and diarrhea, hypertension, tinnitus, chronic pain, migraines, allergies, frequent urination, flushing, sweating, salt cravings, muscle tension. These are all things that could be signs of GABA deficiency. Many have been prescribed an SSRI for some of these symptoms, but … we know that depression is not related to serotonin deficiency."

In my view, GABA is one of the most effective solutions for depression, anxiety, and insomnia, whether used alone or with progesterone. I recommend a daily GABA dose of 500 milligrams to 2,000 milligrams (2 grams). This range has been shown to help relieve anxiety and insomnia in individuals already taking SSRI drugs.

According to Sherr, even as little as 100 milligrams of GABA can significantly lower anxiety and depression assessment scores. The effects can be further enhanced by combining it with L-theanine, a natural GABA agonist (i.e., GABA promoter). Just be careful of using GABA products that contain magnesium. While magnesium is beneficial, taking high doses of GABA can lead to excessive magnesium levels, which can cause a laxative effect.

Interestingly, if you take too much GABA, some of it will be deaminated and converted into succinic acid, an intermediate of the Krebs cycle. This means that at high doses, GABA also helps boost mitochondrial function, making it a very safe option from a toxicity perspective.

Holistic Strategies to Help Manage Depression

If you're at all interested in following science-based recommendations, you'd place antidepressants at the very bottom of your list of treatment candidates. Instead of choosing the lesser-evil antidepressant medication, I recommend adopting effective nondrug strategies for managing depression, including:

• Exercise — Studies¹¹ ¹² have shown that exercise is an effective treatment for depression. It helps create new GABA-producing neurons,¹³ which help induce a natural state of calm, as well as boosts dopamine and norepinephrine, which helps buffer the effects of stress.¹⁴

  Research has shown a strong correlation between improved mood and aerobic capacity,¹⁵ but even gentle forms of exercise can be effective. Yoga, for example, has received particular attention in several studies.¹⁶ ¹⁷ ¹⁸

  A 2021 study¹⁹ published in the British Journal of Sports Medicine showed that doing yoga helped reduce depressive symptoms more than just waiting without treatment, getting regular treatment or getting a fake treatment. The researchers also found that the more often people did yoga each week, the better their depression symptoms got.

  I also recommend doing moderate exercises such as walking, as they cannot be overdone. To learn more, check out "Meta-Analysis Confirms the Therapeutic Potential of Exercise for Depression."

• Nutritional intervention — Keeping inflammation in check is an important part of any effective treatment plan. If you're gluten-sensitive, you will need to remove all gluten from your diet.

  A food sensitivity test can help ascertain this. Reducing lectins and linoleic acid from seed oils is also a good idea. As a general guideline, eating a whole-food diet can go a long way toward lowering your inflammation level. Certain nutritional deficiencies are also notorious contributors to depression, especially:

  • Omega-3 fats — Omega-3 fats have been shown to improve major depressive disorder,²⁰ so make sure you're getting just enough omega-3s from marine-based sources like sardines and anchovies. However, be careful about consuming too much fatty fish, as omega-3 fats are still considered polyunsaturated fats, which can be problematic when consumed in excess.

  • B vitamins (including B1, B2, B3, B6, B8 and B12) — Vitamin B deficiency has been found to increase the risk for depression.²¹ One study²² published in the Journal of Affective Disorders found increased dietary B vitamins helped lower the prevalence of not only depression but also anxiety and stress.

• Vitamin D — Studies²³ ²⁴ ²⁵ ²⁶ have shown vitamin D deficiency can predispose you to depression and that depression can respond favorably to optimizing your vitamin D stores, ideally by getting sensible sun exposure. In one such study,²⁷ people with a vitamin D deficiency were found to be 75% more likely to develop depression compared to those with adequate levels.

  A double-blind randomized trial²⁸ published in 2022 concluded that supplementing with vitamin D "resulted in a significant increase in serum 25(OH)D concentrations of adult subjects with mild to moderate depression, which was accompanied with amelioration for their depression severity."

  Research²⁹ also claims that low vitamin D levels appear to be associated with suicide attempts. For optimal health, make sure your vitamin D level is between 60 ng/mL and 80 ng/mL (150-200 nmol/L). year-round. Ideally, get a vitamin D test at least twice a year to monitor your level.

  The most efficient way to increase your vitamin D levels is through sensible sun exposure. I recommend exposing as much skin as you can to the sun for at least an hour daily, ideally around solar noon, which is from 12:30 to 1:30 PM for those on Daylight Saving Time. Timing your walk during this time allows you to get additional benefits of UVB and near-infrared solar radiation.

• Probiotics — Keeping your gut microbiome healthy also has a significant effect on your moods, emotions and brain.

• Emotional Freedom Techniques (EFT) — EFT is a form of psychological acupressure that has been shown to be quite effective for depression and anxiety.³⁰ ³¹ For serious or complex issues, seek out a qualified health care professional that is trained in EFT to guide you through the process.

  That said, for most of you with depression symptoms, this is a technique you can learn to do effectively on your own. In the video below, EFT practitioner Julie Schiffman shows you how.

• Get more tips from one of my favorite books — When my mom passed away unexpectedly, I was very grateful she did not have cancer or struggle with any abuses from the conventional health system that many of our readers do. However, losing my mother was a major challenge in grief management for me.

  I realize grief is not depression, but the book "Letting Go: The Pathway of Surrender"³² by Dr. David Hawkins, was one of the best books I have read, and it helped teach me the useful tool of how to free yourself of painful emotions. I have read many of Hawkins' previous books, but this was his last one as he also has since passed.

Other Helpful Ways to Safeguard Your Mental Health

Here are several additional strategies to help you maintain optimal mental well-being:³³

• Limit microwave exposure from wireless technologies — Studies have linked excessive exposure to electromagnetic fields (EMFs) to an increased risk of both depression and suicide.³⁴ Addiction to or "high engagement" with mobile devices can also trigger depression and anxiety.³⁵ Research³⁶ by Martin Pall, Ph.D., helps explain why these technologies can have such a potent impact on your mental health.

  Embedded in your cell membranes are voltage-gated calcium channels (VGCCs), which are activated by microwaves. When that happens, about 1 million calcium ions per second are released, which triggers a biochemical cascade that results in mitochondrial dysfunction.

  Your brain, along with the pacemaker in your heart, has the highest density of VGCCs of the organs in your body, which is why Alzheimer's, autism, anxiety and depression appear to be strongly linked to excessive EMF exposure.

  So, if you struggle with anxiety or depression, be sure to limit your exposure to wireless technology. Simple measures include turning your Wi-Fi off at night, not carrying your cellphone on your body unless it's in airlplane mode or in a faraday bag, and not keeping portable phones, cellphones and other electric devices in your bedroom.

• Clean up your sleep hygiene — Make sure you're getting enough high-quality sleep, as sleep is essential for optimal mood and mental health. A fitness tracker that tracks your sleep can be a useful tool. The inability to fall asleep and stay asleep can be due to elevated cortisol levels, so if you have trouble sleeping, you may want to get your saliva cortisol level tested with an Adrenal Stress Index test.

  If you're already taking hormones, you can try applying a small amount of progesterone mixed with natural vitamin E to your gums when you awaken during the night and can't fall back to sleep. Another alternative is to take adaptogens, herbal products that help lower cortisol and adjust your body to stress. There are also other excellent herbs and amino acids that help you to fall asleep and stay asleep. Meditation can also help.

• Optimize your gut health — Several studies³⁷ ³⁸ have confirmed gastrointestinal inflammation can play a critical role in the development of depression. Optimizing your gut microbiome will also help regulate a number of neurotransmitters and mood-related hormones,³⁹ ⁴⁰ ⁴¹ including GABA and corticosterone, resulting in reduced anxiety and depression-related behavior.

  To nourish your gut microbiome, be sure to eat plenty of fresh vegetables and traditionally fermented foods. Healthy choices include fermented vegetables, lassi, kefir and natto. If you do not eat fermented foods on a regular basis, taking a high-quality probiotic supplement is recommended.

• Visualization — Visualization and guided imagery have been in medical settings used to help relieve stress and anxiety in patients⁴² ⁴³ — all to achieve better results through convincing your mind you have already achieved successful results. Similar success has been found in people with depression.⁴⁴ ⁴⁵

• Cognitive Behavioral Therapy (CBT) — CBT has been used successfully to manage depression.⁴⁶ ⁴⁷ This therapy assumes mood is related to the pattern of thought. CBT attempts to change mood and reverse depression by directing your thought patterns.

• Spend more time outdoors — Spending time in nature has been shown to lower stress, improve mood and reduce symptoms of depression.⁴⁸ Outdoor activities could be just about anything, from walking a nature trail to gardening, or simply taking your exercise outdoors. Soothing images and sounds of nature can also help improve your mood and well-being.⁴⁹

• Make sure your cholesterol levels aren't too low for optimal mental health — Low cholesterol is linked to dramatically increased rates of suicide, as well as aggression toward others. This heightened tendency for self-harm and violence may result from reduced membrane cholesterol, which in turn decreases the number of serotonin receptors in the brain.⁵⁰

  While elevated serotonin levels can be harmful, chronic serotonin deficiency can be just as bad, as it has been linked to impulsive aggression. This underscores the importance of maintaining a balanced serotonin level for mental and emotional well-being.⁵¹

• Helpful supplements — Several herbs and supplements can be used in place of drugs to help reduce symptoms of anxiety and depression. These include:

  • St. John's Wort (Hypericum perforatum) — This medicinal plant has a long historical use for depression, and is thought to work similarly to antidepressants, optimizing brain chemicals associated with mood.⁵²

  • S-Adenosylmethionine (SAMe) — SAMe is an amino acid derivative that occurs naturally in all cells. It plays a role in many biological reactions by transferring its methyl group to DNA, proteins, phospholipids and biogenic amines. Several scientific studies indicate that SAMe may be useful in the treatment of depression.

  • XingPiJieYu — This Chinese herb, available from doctors of traditional Chinese medicine (TCM), has been found to reduce the effects of "chronic and unpredictable stress," thereby lowering your risk of depression.⁵³

Guidelines for Safe Drug Withdrawal

If you're currently on an antidepressant and want to get off it, ideally you'll want to have the cooperation of your prescribing physician. It would also be wise to do some homework on how to best proceed. Dr. Joseph Glenmullen from Harvard has written a helpful book on how to withdraw called "The Antidepressant Solution: A Step-by-Step Guide to Safely Overcoming Antidepressant Withdrawal, Dependence, and Addiction."⁵⁴

You can also turn to an organization with a referral list of doctors who practice more biologically or naturally, such as the American College for Advancement in Medicine at www.ACAM.org. A holistic psychiatrist will have a number of treatment options in their toolbox that conventional doctors do not, and will typically be familiar with nutritional supplementation.

Once you have the cooperation of your prescribing physician, start lowering the dosage of the medication you're taking. There are protocols for gradually reducing the dose that your doctor should be well aware of. At the same time, it may be wise to add in a multivitamin and/or other nutritional supplements or herbs. Again, your best bet would be to work with a holistic psychiatrist who is well-versed in the use of nutritional support.

If you have a friend or family member who struggles with depression, perhaps one of the most helpful things you can do is to help guide them toward healthier eating and lifestyle habits, as making changes can be particularly difficult when you're feeling blue — or worse, suicidal.

Encourage them to unplug and meet you outside for walks. Don't underestimate the power of human connection, and the power of connection with nature. Both, I believe, are essential for mental health and emotional stability.

If you are feeling desperate or have any thoughts of suicide, please call the National Suicide Prevention Lifeline, a toll-free number: 1-800-273-TALK (8255), or call 911, or simply go to your nearest hospital emergency department. You cannot make long-term plans for lifestyle changes when you are in the middle of a crisis.

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The information on this website is not intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice. It is intended as a sharing of knowledge and information from the research and experience of Dr. Mercola and his community. Dr. Mercola encourages you to make your own health care decisions based upon your research and in partnership with a qualified health care professional. The subscription fee being requested is for access to the articles and information posted on this site, and is not being paid for any individual medical advice.

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