Weight gain affects the efficacy of antidepressants, new study finds
Weight gain is a side effect of antidepressants, adding another layer of problems.
- 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.
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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Join Radiolab's Latif Nasser at 1pm ET on Monday as he chats with Malcolm Gladwell live on Big Think.
University of Utah research finds that men are especially well suited for fisticuffs.
- With males having more upper-body mass than women, a study looks to find the reason.
- The study is based on the assumption that men have been fighters for so long that evolution has selected those best-equipped for the task.
- If men fought other men, winners would have survived and reproduced, losers not so much.
Built for mayhem<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjY2NDIyMy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMzk4NTQ2OX0.my6nML12F3fEQu3H4G0BScdqgaMZkRQHxgyj-Cmjmzk/img.jpg?width=980" id="906fc" class="rm-shortcode" data-rm-shortcode-id="dd77af7a881631355ed8972437846394" data-rm-shortcode-name="rebelmouse-image" />
Image source: Ollyy/Shutterstock<p>The researchers are, of course, talking averages here, not stating a rule: There are plenty of accomplished female pugilists, as well as lots of males who have no idea how to throw a punch.</p><p>Even so, says co-author <a href="https://www.wofford.edu/academics/majors-and-programs/biology/faculty-and-staff" target="_blank">Jeremy Morris</a> says, "The general approach to understanding why sexual dimorphism evolves is to measure the actual differences in the muscles or the skeletons of males and females of a given species, and then look at the behaviors that might be driving those differences."</p><p>Carrier has been interested in the idea that millennia of male fighting has shaped certain structures in male bodies. Previous research has reinforced his hunch:</p> <ul> <li><a href="https://jeb.biologists.org/content/216/2/236" target="_blank">When a hand is formed into a fist, its structure is self-protective</a>.</li> <li><a href="https://unews.utah.edu/flat-footed-fighters/" target="_blank">Heels planted firmly on the ground augment upper-body power</a>.</li> <li><a href="https://www.ncbi.nlm.nih.gov/pubmed/24909544" target="_blank">A study examined facial bone structure as being especially well-suited for taking a punch</a>.</li> </ul> <p>(That last one is our favorite. Do you know the German word "<a href="https://www.urbandictionary.com/define.php?term=Backpfeifengesicht" target="_blank">backpfeifengesicht</a>?" It's an adjective describing "a face that badly needs a punching.")</p><p>"One of the predictions that comes out of those," asserts Carrier, "is if we are specialized for punching, you might expect males to be particularly strong in the muscles that are associated with throwing a punch."</p>
Testing the theory<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjY2NDIzMy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNzMxMTE2MH0.UXJICMy57UPYUWskhK98alctOrPidJL9yxMkz3HDQrM/img.jpg?width=980" id="98718" class="rm-shortcode" data-rm-shortcode-id="b12287684ac3e740b70392e6433a6b8f" data-rm-shortcode-name="rebelmouse-image" />
Image source: Ollyy/Shutterstock<p>The researchers measured the punching — and spear-throwing — force of 20 men and 19 women. The assumption was that early humans were punchers <em>and</em> spear-throwers.</p><p>Prior to testing, each participant had filled out an activity questionnaire so that "we weren't getting couch potatoes, we were getting people that were very fit and active," says Morris.</p><p>For punching, participants operated a hand crank that required movement similar to throwing a haymaker. The purpose of the hand crank was to spare participants any damage that might be inflicted on their fists by throwing actual punches. Subjects were also measured pulling a line forward over their heads to assess their strength at throwing a spear.</p><p>Even though all of the participants, male and female, were routinely fit, the average power of males was assessed as being 162% greater than females. There were no gender differences in throwing strength recorded. Other untested, though presumably likely, hand-to-hand combat activities come to mind including tackling, clubbing, running, kicking, scratching, and biting.</p><p>Carrier's takeaway: "This is a dramatic example of sexual dimorphism that's consistent with males becoming more specialized for fighting, and males fighting in a particular way, which is throwing punches."</p>
Boys will be boys<p>It, er, strikes us as odd that, even in science fiction — hi-tech weaponry notwithstanding — the hero <em>is</em> going to wind up duking it out with some bad guy, or alien, in the climactic battle. What is it about men punching, anyway? Are they more sexually attractive? The study suggests so:</p><p style="margin-left: 20px;"><em>The results of this study add to a set of recently identified characters indicating that sexual selection on male aggressive performance has played a role in the evolution of the human musculoskeletal system and the evolution of sexual dimorphism in hominins.</em></p><p>It's tough to contribute to the gene pool after being killed in battle.</p><p>Also, while the authors aren't <em>quite</em> saying that males' historical fighting role is mandated by biology and not by social expectations, neither are they quite <em>not</em> saying it.</p><p>As Carrier explain to <a href="https://attheu.utah.edu/facultystaff/carrier-punch/" target="_blank">theU</a>: "Human nature is also characterized by avoiding violence and finding ways to be cooperative and work together, to have empathy, to care for each other, right? There are two sides to who we are as a species. If our goal is to minimize all forms of violence in the future, then understanding our tendencies and what our nature really is, is going to help."</p>
Innovators don't ignore risk; they are just better able to analyze it in uncertain situations.
The Labour Economics study suggests two potential reasons for the increase: corruption and increased capacity.
Cool hand rebuke<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyMTIyNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjY1NTYyOH0.0MCPKN3If94mYCNf3mMNrnTvJXjXN_bKLhgk9203EXk/img.jpg?width=917&coordinates=0%2C0%2C0%2C0&height=453" id="1627b" class="rm-shortcode" data-rm-shortcode-id="6d76421ba1ea0de4b09956b97e80c384" data-rm-shortcode-name="rebelmouse-image" />
A chart showing prison population rates (per 100,000 people) in 2018. The United States has the highest rate of incarceration in the world.