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Side Effects A-Z: Avoiding Weight Gain (Hyperphagia)

Posted Aug 27 2009 11:38pm

One of the most alarming and universally unacceptable of medication side effects is that of permanent weight gain, and it is not an uncommon one. This article focuses on weight gain as a side effect of psychotropic medication, which falls under the area of my expertise, but the general principles are applicable to weight gain from any medication or substance--including, for example, the recreational drug marijuana.


Weight changes due to the routine ingestion of a chemical compound, be it a prescription medication, an over-the-counter preparation, or some other substance, could be due to three primary mechanisms.


1. Water retention or loss. The composition of normal body tissues is largely aqueous; at least 70% of our body weight is attributable to the weight of water. Water weight is not, however, what people worry about when they think about weight change due to medication. Although the bathroom scale can register sometimes rather impressive shifts due to this mechanism, and bloating due to water retention can feel uncomfortable and make your clothes fit more snugly about the waist, this is a relatively modest effect that is seen mostly with prescription hormone therapies. It waxes and wanes depending on the dosing schedule and is not the kind of weight gain that involves an increase in the actual size of fat cells. Similarly, but in the opposite direction, diuretics which are used to lower blood pressure may also result in a rapid and pronounced weight change according to the scale, but no actual permanent change occurs with regard to a person's girth.


2. A change in metabolism. A few commonly prescribed medications directly impact a person's metabolic rate, increasing it (medications that significantly lower a person's metabolism, such as those used in anesthesia, are administered in highly controlled settings for brief periods of time and are not generally prescribed to outpatients). Thyroid hormone, for example, stimulates the metabolism and is prescribed in hypothyroid conditions and also as an adjunct in treating medication-resistant major depression. Drugs that increase sympathetic arousal--that is, stimulants--increase metabolism by virtue of the fact that they increase the activity of the central nervous system and stimulate the heart rate, both of which consume extra energy.


But, again, medication-induced weight change is not typically accomplished by this particular mechanism. Patients taking stimulants lose weight because those medications strongly suppress the appetite, not because the autonomic nervous system is activated, and certainly weight gain due to a medication or substance is never the result of a metabolism that has ground to a halt. Other, more serious and life-threatening problems would result! No, although many patients are not typically aware of it at first and will honestly deny that they have changed their eating habits, virtually all weight change that occurs due to medications and other substances is due to:


3. A change in appetite. By far, the weight gain seen as a side effect of psychotropic and other medications is due to this process: a change in the drive to eat. That is, a change in eating behavior. Understanding this is key to preventing and foregoing continued weight gain.


Just as the anorexia that is induced by stimulant medications is responsible for the vast majority of the weight loss that is seen with those medications (even though they also slightly increase metabolism), the weight gain that is seen with many antidepressant and antimanic and antipsychotic medications is due to overeating, including binge eating. The medical term for this side effect is hyperphagia.


As stated, it is not uncommon for people to swear that they are not eating any differently or any more than usual, leading them to believe that their metabolism has somehow shifted dramatically because of the medication, but in such cases individuals are simply not noticing that they are, in fact, snacking more than usual, or that they have, indeed, increased their portion size or else have shifted their dietary preferences in favor of sweets and starches (see below).


So…what to do?


Be mindful. The simplest, though not often the easiest, thing to do is to guard your eating habits closely and look for behaviors such as increased snacking or the tendency to go back for seconds. Because weight gain--even relatively rapid weight gain--occurs over time, there will be ample opportunity to curb it, and then reverse it, if you notice it in time. Often patients who are not cautioned about the potential for weight gain will be oblivious to it until they have put on an extra 10 or 20 pounds, seemingly overnight. So, simply put: be cautioned. If it is a major concern for you, and since it is relatively common, always ask about the potential for weight gain, especially with psychotropic medications. Some medications are notorious for it. In psychiatry, these include SSRIs (especially Paxil and Lexapro), mood stabilizers (especially lithium and Depakote), and the newer, so-called atypical antipsychotic agents (especially Zyprexa and Clozaril), among others.


Remember that, although the weight gain may seem to occur overnight, it doesn't, quite. That is to say, it takes many days to weeks to gain more than a couple of pounds (real pounds of fat, not water), so the first thing to do is to be aware of the possibility and to pay attention. That said, the other thing to know is that the urge to eat more (and that's more than your typical urge to overeat, which almost all of us already experience to some degree or another at our baselines) may not be able to be overcome with sheer willpower. In other words, merely paying attention may not help you regain the control over your eating that the medication takes away from you, particularly if you already struggle with this issue, but at least it will keep you from gaining an unacceptable amount of weight before you are even aware of what is going on, early enough to discuss switching medications with your doctor, if necessary.


Beware carbohydrates. Hyperphagia as a medication side effect is not indiscriminant. Instead, it is rather specific to sweets and starchy foods like bread and pasta. You are not going to suddenly begin craving steak under the influence of a medication; rather, you will crave potatoes. Likewise, you don't feel like munching on green leafy vegetables under the influence of marijuana; instead, you develop an acute hankering for ice cream, cookies and chips! In fact, one way to distinguish substance-induced hyperphagia from an increase in appetite due to other factors (such as a depressed mood, for example) is that substance-induced cravings are specifically carbohydrate cravings. Unfortunately, as many of us already know, we naturally tend to crave carbs whenever we crave anything to begin with, so it is not unusual to develop a sweet tooth for other reasons (such as mood or stress) and therefore it is not always obvious from this alone that it is a given medicine that is making us overeat.


Another clue is the intensity of the craving. Carb cravings due to a substance or medication are intense, and if you pay attention, you will notice not only an increase in craving cakes, cookies, ice cream and candy, but a sharply increased pleasure in their consumption. Certain foods taste better when the brain is amenable to them. When this effect is due to marijuana intoxication it is colloquially called "the munchies," and is essentially the same phenomenon as the overeating that is due to treatment with certain antidepressants (albeit as a result of different molecular mechanisms).


Of course, many patients do notice the increase in their appetites. In fact, many will report feeling "hungry all the time." But hunger per se is not increased in hyperphagia. It is good to keep this fact in mind, because it may help you to resist unplanned meals. Weight gain occurs precisely because you are eating when your body does not require it. Just because you are eating more--even when it's because your brain is telling you to eat more--doesn't mean you are actually feeling hunger. Hunger is the discomfort felt by your brain when your stomach is empty and your blood sugar level is falling. Medication that causes you to gain weight will signal to your brain that it's a good idea to eat, even when your stomach is not empty and your blood sugar level is fine, but it's a different signal. It's not a hungry, you're-getting-low-on-fuel signal; it's a gee-that-looks-good, "Let's eat!" signal. The medication is not making you hungrier, in the strict sense of the word, but you may actually have to remind yourself of that.


Avoid temptation. The drive to overeat may be irresistible while on a medication, and so if you don't want to change the medication, another strategy is not to place yourself in situations that will tempt you. The only way to overcome a temptation that you cannot resist is to avoid it altogether, and this is doable: because you are not actually hungry all of the time, you will not necessarily seek out food that isn't there, the way you might if your stomach were actually rumbling and you were overdue for a meal. But, if the snack is in front of you already, and your appetite is in overdrive because of a medication, you will likely succumb to the temptation to "taste just a little." But even if you are only sampling a little here and there, the cumulative effect is one of certain weight gain over time. This is one of the ways in which people don't necessarily notice a major change in their eating habits despite putting on a lot of weight: they are constantly "grazing" and the pounds add up.


Don't enable yourself. This is just another way to say: avoid temptation. The problem is that we keep snack food handy--at our desks, on the coffee table in front of the TV, on our nightstands, in the car, etc. Food is usually within sight and often within reach, which enables the compulsive snacking that is seen with certain medications. When you are prone to overeating for whatever reason, hanging out in the kitchen is an example of risky behavior. So is opening the refrigerator just to see what's in there. Under any circumstances, if you wander into the kitchen because you're bored and you aimlessly open the fridge, you are much more likely to eat something as a reward for your curiosity. On the other hand, if you are already prone to overeating or if you are under the influence of a medication that compels you to overeat, then to do so is practically to ensure that you will have a meal you don't need.


So, the rule to follow when you are susceptible to binge eating is to stay away from temptation if you can't resist it, whether the inability to resist is relative or absolute, and whether this is due to a medication, bulimia nervosa, or some other neurological condition. Take your cue from alcoholics, who know to stay out of bars. Of course, you can't (and shouldn't) avoid three square meals a day, so you will still have to watch meal choices and portion size at other times for as long as you remain affected by hyperphagia.


Will you develop tolerance to medication-induced hyperphagia, the way tolerance is usually developed toward other unwanted medication side effects? It is certainly reasonable to surmise that, over time, the brain might lose some or all of its sensitivity to the appetite-stimulating effect of a given medication. Clinically, I have certainly seen this with medications that suppress the appetite: over time, individuals become insensitive to the anorexigenic effect of stimulant medications and their appetites return to normal, so it is plausible that the same thing happens with medications that stimulate the appetite. This has been difficult for me to confirm in my practice, however, because by the time such a tolerance were developed (weeks or months into treatment, at the least), a patient has either already gained a significant amount of weight, or else in many cases has asked to be switched to something different to avoid further weight gain. And while it is true that an individual does not go on gaining weight indefinitely and at some point a person's weight will plateau, it is difficult to say whether this represents having developed resistance to the appetite-stimulating effect of the drug, or whether the new weight merely represents a new steady state for the hyperphagic individual.


Switch medications. When all else fails, a medication change may be in order. Unfortunately, dosage adjustments are typically ineffective. While many side effects occur when a medication dose reaches a certain threshold level and will wax and wane in intensity depending upon the corresponding dosage, in the long run weight gain (which, remember, occurs over time) tends to be an "all or nothing" phenomenon, such that an individual either will or will not tend to gain weight on a particular medication, regardless of the actual dose s/he is exposed to. At the end of the day, lowering the dose rarely if ever corrects the appetite; at best it may slightly decrease the total amount of weight gained, or else delay the maximum weight reached by a few weeks or months, but you get there regardless. Switching to a different medication in the same class is the best first option. The sooner you identify a problem and the sooner you and your doctor change course, the less you will ever gain and have to worry about losing later.


An ounce of prevention… What can also be said is that discontinuing the medication will not necessarily result in weight loss all by itself. While returning to one's normal weight will be much easier off the medication (indeed, losing weight can be impossible on certain medications), even after one's appetite normalizes, weight loss is typically a purpose-driven, labor-intensive undertaking that can be quite a challenge.


Weight gain will occur over time, so catching it early and either modifying your eating habits accordingly or else discontinuing the medication (check with your doctor) will prevent any long-term gain. For this reason you should not rule out trying a medication that is likely to help you, based upon the risk of weight gain alone. There's always the possibility that you may not be affected, or else that you will be successful being mindful and/or compensating with exercise, and you wouldn't want to miss out on a life-saving antidepressant or mood stabilizer that you truly need.

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