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.
Most healthy women, who live long enough, will eventually become unhealthy.
So it should not at all come as a surprise to anyone, that the vast majority of women with “healthy” obesity (a misnomer, as in my view, the medical term “obesity” should only apply to people who already have health problems attributable to abnormal or excess body fat), eventually end up with “unhealthy” obesity.
This, essentially, is the gist of a paper by Nathalie Eckel and colleagues, published in The Lancet.
In their study of 90,257 participants of the Nurses Health Study, who were followed-up from 1980 to 2010 for incident cardiovascular disease (representing over 2 million person-years of follow-up), they found that around 80% of metabolically healthy women with obesity converted to metabolically unhealthy obesity over the course of follow-up.
But one might say that this was only marginally higher that the 70% of metabolically healthy “normal weight” women, who also converted to metabolically unhealthy over the 20 years of observation. In fact, the population-attributable risk of the latter group was much higher, as it consisted of almost 10 times the number of women than in the former.
While the risk of cardiovascular disease was statistically elevated (by about 40%) in the metabolically healthy women with obesity, this risk was 243% higher in metabolically unhealthy women with normal weight, 260% higher in metabolically unhealthy women with overweight and 315% higher in metabolically unhealthy women with obesity, all compared to metabolically healthy women with normal weight.
So, yes, women with metabolically “healthy obesity” have a high risk of becoming metabolically unhealty and developing cardiovascular disease, so are metabolically healthy normal-weight women.
Overall, I believe it is safe to say that the vast majority of metabolically healthy women (regardless of body weight) will eventually become metabolically unhealthy, at which time their risk for cardiovascular disease increases.
Bottom line, everyone (not just women with obesity) will benefit from efforts to stay as metabolically healthy as possible for as long as possible – fortunately, we know that healthy diets and regular physical activity (while not necessarily preventing weight gain) can help maintain metabolic health, irrespective of current body weight.
Clearly, living as healthy as possible is not just good advice for women with obesity – who would have guessed?
p.s. although this was a study in women, I have no doubt whatsoever that the findings also apply to men – most metabolically healthy men will eventually become metabolically unhealthy over the course of their lifetime.
Anyone familiar with the issue, would readily agree that the actual surgery involved in bariatric surgery is only a small (but undeniably important) technical piece in what is a rather complex treatment for a rather complex chronic disease.
Clearly, this is not exactly how all bariatric surgeons approach or treat their bariatric patients.
Since 2012, the US has a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program that designates bariatric surgery centers as Centres of Excellence if they meet specified requirements in 7 core standards that include case volume, commitment to quality, appropriate use of equipment and instruments, critical care support, continuum of care, data collection, and continuous quality improvement.
However, as a recent paper by Andrew Ibrahim and colleagues, published in JAMA Surgery, elaborates, despite these quality criteria, there remains a substantial variability in outcomes across designated Bariatric Centres of Excellence.
Based on their retrospective analysis of claims data from 145 527 patients who underwent bariatric procedures, there was a 17-fold variation (ranging from 0.6% to 10.3%) in rates of serious 30-day complications across accredited bariatric centers nationally and up to 9.5-fold variation across individual states.
As the authors note,
“this finding suggests that participation alone in the Center of Excellence Program did not ensure uniform high-quality care….Given that most bariatric procedures are now performed at accredited centers, wide variation among these centers suggests that accreditation alone does not discriminate enough to guide patients to the best centers for care.”
Moreover, they found that poor performing centres were often located close to better performing centres (regression to the mean?). Interestingly, in contrast to what one may suspect, outcomes overall were not related to case volume (perhaps because in order to be a designated Centre of Excellence, all centres needed to have a minimum number of cases per year).
Rather, the authors discuss that poorer outcomes may be largely attributable to varying technical skills of the surgeons as well as inconsistent adherence to accepted bariatric care pathways.
Finally, the authors argue that there is need to make performance data available to the public, as simply trusting in the “Centre of Excellence” designation by no means guarantees excellent outcomes.
As important as these data may be, it is also important to note that this paper only looked at complications within a 30-day time period following surgery.
As anyone dealing with bariatric patients is well aware, successful outcomes of bariatric surgery(as well as its complications) should be measured in years (if not decades). This is where much of bariatric surgery falls down, as one of the key criteria mentioned above, i.e. “continuum of care” seldom extends beyond the rather brief period of post-surgical discharge. Indeed, in most cases, bariatric patients continue to be prematurely discharged into “the wild” with little ongoing support from health professionals competent in looking after the psychological and medical needs of this population.
None of this takes away from the fact that bariatric surgery is still the most effective long-term treatment for severe obesity – however, clearly there remains substantial room for improvement.
Liraglutide Effects on Upper Gastrointestinal Investigations: Implications Prior to Bariatric Surgery
With the considerable waits that patients in Canada often face prior to bariatric surgery, we generally recommend that patients, who have access to them, try anti-obesity medications while waiting. This not only prevents further wait gain, but also often helps them shed a significant amount of weight prior to surgery.
The GLP-1 analogue liraglutide is now approved for long-term obesity treatment and is generally well tolerated. Nevertheless, we now present a series of patients in Obesity Surgery, who were treated with liraglutide 3.0 mg whilst waiting for bariatric surgery, and showed significant upper GI dismotility that was reversible on discontinuation of liraglutide.
Although, investigations of upper GI motility are by no means part of routine assessment for bariatric surgery, tests may be ordered in patients who present with unclear upper GI symptoms, as the findings may guide the choice of surgical intervention.
In this paper, we present six cases in which patients treated with liraglutie 3.0 mg presented with varying degrees of esophageal and/or gastric dysmotility demonstrated using a variety of investigative procedures including formal gastric emptying scintiography as well as less specific esophageal manometry, and upper endoscopy.
In all cases normal motility was restored on discontinuation of liraglutide and all patients subsequently underwent or are continuing to wait for bariatric surgery.
Based on our observations we discuss that,
“Liraglutide is associated with decreased esophageal peristalsis and gastric emptying. These effects can result in abnormal upper GI investigations, leading to delays, increased testing, and questions of patient candidacy for surgery. If patients on liraglutide are noted to have abnormal esophageal manometry or gastric emptying studies, medication should be discontinued, with repeat studies done to look for reversibility. If this abnormal result is due to drug effect, this should not preclude patients from having bariatric surgery.”
Just how long liraglutide needs to be stopped prior to performing upper GI investigations remains unclear. Furthermore, as the dysmotility often appears to be symptomless and well-tolerated, we do not recommend routine ordering of motility tests in patients treated with liraglutide.
Disclaimer: I have served as a consultant and speaker for Novo Nordisk, the makers of liraglutide.
Obesity medicine, which I define as the medical care of someone living with obesity, should approach patients holistically with the aim of improving their overall health and well-being. Advice to lose weight may or may not be part of obesity management – much can be gained for someone living with obesity by promoting their health behaviours, getting them to feel better about themselves, improving their mental health, and helping them better managing their health issues. Much of this can be achieved with no or very little weight loss.
Thus, we must consider the question of when weight loss would specifically need to be part of the treatment objectives.
In my own practice, I approach this problem by considering the following three questions:
- Is this a problem unrelated to abnormal or excess body weight?
- Is this a problem aggravated by abnormal or excess body weight?
- Is this a problem caused by abnormal or excess body weight?
From what I hear from my patients, the most common mistakes in medical practice fall into the first group – trying to address unrelated issues with weight loss recommendations. There are endless stories of patients going to see their health provider with problems clearly unrelated to their body fat (e.g. a broken arm, a sore throat, the flu, depression, migraines, etc.), who simply get told to lose weight. Indeed, there is evidence to suggest that patients with obesity are less likely to undergo diagnostic testing, most likely based on the assumption that their problems are simply related to their excess weight. This is not only where grave medical errors can be made (late or misdiagnosis), but also where the advice to lose weight is clearly wrong. If the presenting problem has nothing to do with excess weight, then no amount of weight loss will fix it.
The second category deals with issues that are not causally related to abnormal or excess body fat but where the underlying problem either causes more symptoms or is more difficult to treat because of the patient’s size or fat distribution. There are countless medical problems that fall into this category. For e.g. a heart or respiratory problem entirely unrelated to excess weight (e.g. a valvular defect or asthma) can become worse, cause more symptoms, or be much more difficult to treat simply because of the patient’s size. This group also includes issues like neck or joint pain from a trauma (e.g. a motor vehicle or skiing accident), reflux disease (e.g. from a hiatal hernia), urinary incontinence (from multiple child births), etc., etc., etc. – the list is long. Here, although obesity has nothing to do with the underlying problem, weight loss may alleviate the symptoms or at least make them more manageable (they are however unlikely to be fully resolved). These patients present with what may be described as a relative or “secondary” indication for weight loss. Of course, if there are viable treatments options for the primary problem, then this is where the emphasis should be. Weight loss can best be considered as “second-line” treatment. It would be completely unethical to withhold effective treatment for the underlying problem just because of the patient’s size (as in, “no treatment for you until you lose X lbs!”)
Finally, we have the third category of health issues that are directly causally linked to the excess weight – in most cases, the problem did not exist prior to weight gain and losing weight is often likely to completely resolve the problem (unless the patient has already sustained irreversible organ damage). This group of health issues not only includes the vast majority of cases of type 2 diabetes, hypertension, obstructive sleep apnea, fatty liver disease, infertility, etc. but also all of the functional limitations that people may experience simply because of their excess body fat. This is the only category of patients who would be deemed to have a “primary” indication for weight loss. Losing the weight literally solves their problem. Indeed, trying to manage the problem without weight loss is nothing less than “palliative” care. This is not to say that weight loss will always guarantee success even if the underlying problem is directly related to excess weight. For e.g. although there is ample evidence that excess weight is a prime risk factor for gall bladder disease, (rapid) weight loss may actually promote formation of gall stones. Similarly, although intertrigo (skin fold infections) can occur as a direct consequence of excess weight (e.g. chaffing), losing weight may actually make the problem worse by deepening the skin folds. Thus, even in this category, one needs to carefully consider risk-benefit ratios.
Of course, any recommendation to lose weight must take into account the complex nature of obesity in the first place and the fact that long-term weight-loss maintenance will require an approach (behavioural, medical, or even surgical) that takes into account the chronic relapsing nature of this disorder. Simply telling people with obesity to “eat less and move more” is about as medically sound and effective, as simply telling people with depression to “cheer up”.
Both, to avoid grave medical errors and to not insult their patients, I strongly recommend that medical practitioners first approach all their patients with obesity based on the assumption (that their presenting health issues are unrelated to their excess weight) before considering possibilities two (unrelated but aggravated) and three (causal). Advise to lose weight has no role in situation 1, can be considered in situation 2, and is clearly the best course of action for situation 3.