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Do Anti-Depressants Promote Weight Gain?

There is no doubt that some people gain weight when started on anti-depressant medications. However, it is also true that the increased appetite and listlessness that accompanies “atypical” depression can contribute to weight gain. Finally, there is evidence that weight-gain in turn may decrease mood, which in turn may further exacerbate weight gain.

Trying to cut through all of this is a study by Rafael Gafoor and colleagues from King’s College London, in a paper published in BMJ.

They examined data from the  UK Clinical Practice Research Datalink, 2004-14, which included data on 136,762 men and 157,957 women with three or more records for body mass index (BMI).

In the year of study entry, 17,803 (13.0%) men and 35,307 (22.4%) women with a mean age of 51.5 years were prescribed anti-depressants.

While during 1, 836,452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed anti-depressants was 8.1 per 100 person years, it was slightly higher at 11.2 per 100 person years in those prescribed an anti-depressant.

In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27.

Thus, there appears to be a slight but discernible increased risk of weight gain associated with the prescription of anti-depressants, which may persist over time and appears highest during the second and third year of treatment.

However, as the authors caution, these associations may not be causal, and residual confounding might contribute to overestimation of associations.

Nevertheless, the notion that there may be a distinct weight-promoting pharmacological effect of some anti-depressants is supported by the finding that certain anti-depressants (e.g. mirtazapine) carry a far greater risk of weight gain than others (e.g. paroxetine).

Given the frequency with which anti-depressants are prescribed, it could be argued that the contribution of anti-depressants to the overall obesity  epidemic (particularly in adults) may be greater than previously appreciated.

If nothing else, patients prescribed anti-depressants should be carefully monitored for weight gain and preventive measures may need to be instituted early if weight gain becomes noticeable.

@DrSharma
Edmonton, AB

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The Three Clinical Faces of Obesity

In my experience, patients presenting with obesity tend to fall into three categories, each of which requires a distinct management approach.

They are 1) Active Gainers, 2) Weight Stable, and 3) Post-Weight Loss.

Active Gainers are patients currently at their lifetime maximum and continuing to gain significant amounts of weight – i.e. more than the usual 0.5 to 1 lb/year. Patients in this category require immediate attention – if nothing happens, their weight will most likely just continue to increase. The good news is that in almost every patient in this category, there is an identifiable reason for the ongoing weight gain – this can be psychosocial (e.g. depression, binge-eating disorder, etc.), due to a medical comorbidity (arthritis, chronic pain, etc.) or medications (e.g. atypical antipsychotics, hypoglycemic agents, etc.). From a management perspective, the sooner we identify and address the underlying problem, the sooner we can slow or even halt the rate of weight gain – in this patient – gaining less weight than before is the first sign of success. There is really no point trying to embark on losing weight as long as the underlying problem driving the weight gain has not been addressed, as this is likely to make sustained weight loss even more unlikely that it already is..

Weight Stable patients are those that present with excess weight but are relatively weight stable. Even though they may be at their lifetime maximum, they have been pretty much the same weight (perhaps a few lbs up or down but nothing drastic) for several years (sometimes even decades). By definition, a patient who is weight stable is in caloric balance, and thus, by definition is not eating too much. In fact, these patients are eating the exact number of calories needed to sustain their bodies, which is why they are weight stable. (Remember, even if you are weight-stable eating 4000 Cal a day, you are technically not “overeating”.)  These patients of course have experienced significant weight gain in the past (historical weight gain), but whatever it was that caused them to gain weight is no longer an active problem (e.g. pregnancy, past depression, etc) – and therefore, probably doesn’t need to addressed (although, I always find it of interest to find out what caused the weight gain in the first place). With these patients, we can determine whether or not their weight is affecting their health, and if it is, we can jump right into discussing treatment options (behavioural, medical and/or surgical).

The third group of patients, Post-Weight Loss, are those who are not at their lifetime maximum, or in other words, have already lost weight (by whatever means). These patients generally present either because they want to lose even more weight (Doctor, my diet has stopped working! = “weight-loss plateau“), or are experiencing weight regain (Active Regainers).  In case of the patients experiencing a “weight-loss plateau”, one needs to determine if there is in fact any medical indication for further weight loss – many of these patients may already be at their “Best Weight”. If there is indeed a medical indication for further weight loss, it generally means adding therapeutic options that may include anti-obesity medications and/or surgery. (In my experience, patients who have been maintaining a significant amount of weight loss on their own, generally leave little room for further behavioural intervention). On the other hand, there are the post-weight loss patients who are actively regaining weight. These tend to fall into two groups – the first one are those, who have lost a significant amount of weight with a strategy that is in fact unsustainable (e.g. a very low-calorie diet, an excessive exercise program, or whatever else desperate patients will try just to drop their weight). As the strategy they were on is not one that they can sustain (for good reasons), some weight regain is inevitable and the best we can do is to offer a weight management strategy that is sustainable in the long run (and may include medication or surgery) . The other group of Active Regainers, are those that were on a more-or-less sustainable management plan (behavioural, medical or surgical) and have for some reason “fallen off”. Here one needs to determine what exactly they have stopped doing (e.g. no longer keeping their food journal, stopped their anti-obesity medications, etc.) or what additional weight-gain promoting change has occurred that has thrown them off (again, reasons can be psychosocial or medical). Here one needs to determine if the patient can in fact go back to doing what was “working”, which may require addressing the new problem that has arisen or add additional therapeutic options (e.g. medications or surgery).

Thus, as each type of patient needs a somewhat different assessment and management strategy, I find this approach to thinking about each patient most helpful.

Comments are very much appreciated.

@DrSharma
Edmonton, AB

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What Smoking Cessation Does To Your Metabolism

sharma-obesity-smoking-cigarette1One of the most pervasive problems with quitting cigarettes, is the accompanying weight gain – in fact, post-cessation weight gain is reportedly the number one reason why smokers, especially women, fail to stop smoking or relapse after stopping.

But what exactly happens when you stop smoking?

This is the topic of a comprehensive review article by Kindred Harris and colleagues published in Nature Reviews Endocrinology.

The paper begins by examining the magnitude of weight gain generally experienced after smoking cessation – an amount that can vary considerably between individuals.

As for mechanisms, the authors note that,

“Several theories have been proposed to explain increased food intake after smoking cessation. One theory is that the ability of nicotine to suppress appetite is reversed. Substitution reinforcement, which replaces the rewards of food with the rewards of cigarettes could occur. Nicotine absence increases the rewarding value of food. Reward circuitries in the brain, similar to those activated by smoking, are activated by increased intake of food high in sugar and fat. Furthermore, nicotine withdrawal leads to an elevated reward threshold, which might cause individuals to eat more snacks that are high in carbohydrates and sugars.”

There are also known effects of smoking on impulsive overeating and individuals with binge eating disorder are at risk of even greater weight gain with cessation.

Smoking cessation also has metabolic effects including a drop in metabolic rate that may promote weight gain and new evidence shows that smoking cessation can even change your gut microbiota.

The authors provide evidence that behavioural interventions can prevent much of the cessation weight gain and argue that such programs should be offered with cessation programs.

Finally, it is important to always remember that the health benefits of smoking cessation by far outweigh any health risks from weight gain, which is why fear of weight gain should never stop anyone from quitting.

@Drsharma
Edmonton, AB

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In-Bred Obesity Resistance Can Be Cancelled Out By Perinatal High-Fat Diet

sharma-obesity-running-mouseThe periods of early development both in utero and shortly after birth appear to be critical periods for epigenetic programming of lifelong obesity risk.

This is once again demonstrated in a fascinating series of experiments by Stefano Guidotti and colleagues from the University of Groningen, The Netherlands, in a paper published in Physiology and Behaviour.

The researchers performed their experiments in mice that were selectively bred over 50 generations to voluntarily spend hours in running wheels. Interestingly, the female “runner” mice remain resistant to becoming obese as adults when exposed to a high-fat diet even when they don’t have access to a running wheel.

Thus, these mice are resistant to developing obesity whether they run or just sit around.

What the researchers now show is that this “resistance” to gaining excess weight (bred over generations) can be fully cancelled out simply by exposing the mice to a high-fat diet for a couple of days shortly after birth.

With this exposure, these mice (and even their offspring) are suddenly no longer resistant to weight gain later in life and in fact gain as much weight on high-calories diets as normal mice.

Even more interestingly, the short term perinatal exposure to the high-energy diet does not cancel out their love for running. When given a wheel, they continue running just as much as before but even this no longer prevents them from gaining weight.

Thus it appears that exposure to a high-energy diet during the perinatal period can have profound effects on the risk of developing adult obesity even in animals bred to be obesity resistant – and, the love for running, does not appear to protect against weight gain.

Or, as the authors put it,

“..resistance to high-energy diet-induce obesity in adult female mice from lines selectively bred over ~ 50 generations for increased wheel running behavior was blocked by additional perinatal high-energy diet exposure in only one cycle of breeding. An explanation for this effect is that potential allelic variants underlying the trait of diet-induced obesity proneness were not eliminated but rather silenced by the selection protocol, and switched on again by perinatal high-energy diet exposure by epigenetic mechanisms”

Moreover, this effect of perinatal high-energy diet exposure and its “reversal effect” on obesity resistance can be passed on to the next generation.

Reason enough to wonder just how much the rather dramatic changes in perinatal feeding of infants over the last few decades may be contributing to the obesity epidemic.

@DrSharma
Edmonton, AB

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Cold Exposure Promotes Gut Microbes That Stimulate Brown Fat

Graphical_Abstract_Chevalier_StojanovicIt seems that there is no end to how intimately gut microbes are linked to metabolic function.

Thus, a study by Claire Chevalier and colleagues from Geneva, Switzerland, published in CELL, not only shows that cold exposure (of mice) changes their gut microbes but also that, when transplanted into sterile mice, these “cold” microbes stimulate the formation of thermogenic brown fat.

All of this makes evolutionary sense, as the increase in heat-generating (and calorie-burning) brown fat with cold exposure would protect the organism against cold exposure – however, that gut bacteria would be involved in this process is indeed rather surprising.

Unfortunately, at least for those thinking that “cold bacteria” may be the panacea for stimulating brown fat and thus weight loss are likely to be disappointed.

The researchers also show that with prolonged exposure to cold, these “cold bacteria” induce changes to the structure and function of the gut that enable more glucose to be absorbed.

While in the short-term, this extra fuel can be used by the brown fat to generate heat, in the long-term, some of these extra calories probably go towards building more white fat and thus weight gain.

Again, this makes evolutionary sense. After all, it is ecologically a far better strategy to insulate the house than to waste extra calories heating it.

This is why, the naive notion that simply lowering ambient temperature as a means to generate more brown fat and thus, burn more calories, may not be all that effective.

Indeed, these experiments suggest rather that chronic cold exposure would ultimately stimulate extra insulation, i.e. more subcutaneous fat and weight gain.

Funnily enough, these findings turn the hypothesis that reducing room temperature would promote weight loss into exactly the opposite. Perhaps it is the excessive use of air-conditioning to generate freezing indoor temperatures (as any European visitor to the US will readily attest to), is part of the problem.

Fascinating stuff for sure.

@DrSharma
Gurgaon, Haryana

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