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Weight gain affects the efficacy of antidepressants, new study finds

Weight gain is a side effect of antidepressants, adding another layer of problems.

A woman helps an overweight person on April 12, 2016 in Berck-sur-Mer, northern France.

Photo: Philippe Huguen/AFP via Getty Images
  • A comprehensive scoping review of 12 studies found that being overweight negatively affects the efficacy of antidepressants.
  • McGill University researchers investigated SSRIs, SNRIs, tricyclic antidepressants, and tetracyclic antidepressants.
  • A double-edged sword: Obesity impacts antidepressants, yet a side effect of these drugs is weight gain.

The initial European trials for gaboxadol produced positive results. Merck and Lundbeck were convinced they had a blockbuster drug on their hands. Researchers considered it a major improvement over Ambien, which sometimes left users feeling groggy the next day. Gaboxadol also didn't produce negative effects when mixed with alcohol, making it a rare sleeping pill. Then the U.S. trials began.

The drug bombed. In 2007, the pharmaceutical giants canceled development of the drug; Lundbeck sold the rights to it in 2015. While no specific reason for its failure has been stated, pharmacology professor Richard J Miller writes that the protein molecule that carries gaboxadol also transports amino acids, such as tryptophan, across the blood-brain barrier. Since Americans consume 20 percent more daily calories from meat than Europeans, gaboxadol likely failed because it was competing with extra tryptophan.

Drugs are complex. A one-size-fits-all approach to drug development often doesn't work. If gaboxadol works for vegetarians, should it be reconsidered? Perhaps in a research field focused on individualized medicine, but that's not the system we live in. Gaboxadol is now being studied for use in treatments of Fragile X syndrome and Angelman syndrome.

There are many reasons a drug might work for you and not me. This is true of antibiotics and vaccines, though these classes of drugs have a solid track record. When considering more controversial treatments, such as antidepressants, the story changes.

Antidepressants Make it Harder to Empathize, Harder to Climax, and Harder to Cry. | Julie Holland

Add to this tale a new study, published in Journal of Affective Disorders, investigating the efficacy of antidepressants in overweight users. A team at McGill University reviewed 12 studies that focused on SSRIs, SNRIs, tricyclic antidepressants, and tetracyclic antidepressants conducted between 2004-2019. Eleven of them found that weight class or body mass index (BMI) negatively affects the efficacy of these antidepressants.

This comprehensive scoping review from the McGill team is troubling for two reasons. First, obesity is already a predictor for depression. Second, weight gain is also a side effect of antidepressants, implying that their efficacy could dwindle with long-term usage. Recent evidence confirms that extended usage of antidepressants results in withdrawal symptoms that persist for over a year, obesity included in that list.

According to the study, over 300 million people suffer from depression around the world. The WHO reports that depression is the leading cause of disability worldwide. Pharmaceutical intervention is problematic with roughly half of prescription users. While the reasons for this are not well understood, obese and overweight patients suffer from treatment-resistant depression at higher rates than those with normal weight.

man sitting in a chair holding his head

Photo by Nik Shuliahin on Unsplash

The researchers offer a few possibilities for why being overweight could negatively affect antidepressants.

  • Antidepressants might not dissolve as effectively in increased body fat.
  • Variations in plasma concentrations are caused by extra adipose tissue.
  • Obese patients are more likely to be on other drugs, any of which could effect the efficacy of antidepressants.
  • Obesity is a state of systemic low grade inflammation that impacts how drugs act in the body.
  • Excess adipose tissue secretes more adipokines, suppressing neurotransmitter systems.
  • Levels of leptin, the hormone that signals hunger, are compromised as weight gain increases.
  • Genetic factors, such as neurotransmitter receptors and drug metabolizing enzymes, could play a role.
  • Comorbid medical conditions—sleep apnea, asthma, metabolic syndrome—can contribute to depression as well as dampen the response to medications.

This wide range of potential factors shows the complexity of drug interactions within the human body. One thing is clear from the McGill team's review: being overweight reduces the efficacy of the world's most popular antidepressants. This trend reiterates the need for better mental treatments, such as psychotherapy and psychedelic therapy. The time for an overhaul of the psychiatry industry and its reliance on this class of drugs has come.

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Stay in touch with Derek on Twitter, Facebook and Substack. His next book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."

The “new normal” paradox: What COVID-19 has revealed about higher education

Higher education faces challenges that are unlike any other industry. What path will ASU, and universities like ASU, take in a post-COVID world?

Photo: Luis Robayo/AFP via Getty Images
Sponsored by Charles Koch Foundation
  • Everywhere you turn, the idea that coronavirus has brought on a "new normal" is present and true. But for higher education, COVID-19 exposes a long list of pernicious old problems more than it presents new problems.
  • It was widely known, yet ignored, that digital instruction must be embraced. When combined with traditional, in-person teaching, it can enhance student learning outcomes at scale.
  • COVID-19 has forced institutions to understand that far too many higher education outcomes are determined by a student's family income, and in the context of COVID-19 this means that lower-income students, first-generation students and students of color will be disproportionately afflicted.
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Climate change melts Mount Everest's ice, exposing dead bodies of past climbers

Melting ice is turning up bodies on Mt. Everest. This isn't as shocking as you'd think.

Image source: Wikimedia commons
Surprising Science
  • Mt. Everest is the final resting place of about 200 climbers who never made it down.
  • Recent glacial melting, caused by climate change, has made many of the bodies previously hidden by ice and snow visible again.
  • While many bodies are quite visible and well known, others are renowned for being lost for decades.
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Creativity: The science behind the madness

Human brains evolved for creativity. We just have to learn how to access it.

Creativity: The science behind the madness | Rainn Wilson, David Eagleman, Scott ...
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  • An all-star cast of Big Thinkers—actors Rainn Wilson and Ethan Hawke; composer Anthony Brandt; neuroscientists David Eagleman, Wendy Suzuki, and Beau Lotto; and psychologist Scott Barry Kaufman—share how they define creativity and explain how our brains uniquely evolved for the phenomenon.
  • According to Eagleman, during evolution there was an increase in space between our brain's input and output that allows information more time to percolate. We also grew a larger prefrontal cortex which "allows us to simulate what ifs, to separate ourselves from our location in space and time and think about possibilities."
  • Scott Barry Kaufman details 3 brain networks involved in creative thinking, and Wendy Suzuki busts the famous left-brain, right-brain myth.

Dinosaur bone? Meteorite? These men's wedding bands are a real break from boredom.

Manly Bands wanted to improve on mens' wedding bands. Mission accomplished.

Sex & Relationships
  • Manly Bands was founded in 2016 to provide better options and customer service in men's wedding bands.
  • Unique materials include antler, dinosaur bones, meteorite, tungsten, and whiskey barrels.
  • The company donates a portion of profits to charity every month.
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Politics & Current Affairs

How #Unity2020 plans to end the two-party system, bring back Andrew Yang

The proposal calls for the American public to draft two candidates to lead the executive branch: one from the center-left, the other from the center-right.

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