TCPR: Dr. Yohanan, as an internist specializing in geriatric medicine, you see many patients with “metabolic syndrome.” But there is a great deal of confusion out there as to what metabolic syndrome actually is, and whether that term remains useful.
Dr. Yohanan: Yes, the definition of metabolic syndrome has evolved over several years. Traditionally the components are large waist circumference, hyperlipidemia, low HDL, high blood pressure, and an elevated fasting glucose. People thought these symptoms might be unified by some sort of insulin resistance, but this does not seem to be the case. It has gradually become clear that the notion of a metabolic syndrome doesn’t provide any meaning above and beyond its constituent components.
TCPR: Before we review each of these components, what is your bottom line recommendation for how psychiatrists should monitor for these conditions after starting patients on atypicals?
Dr. Yohanan: There are some screening labs that everybody should get before starting any of these medicines. You should get a fasting blood sugar, a hemogobin A1C (a measure of long term glucose levels), LFTs, BUN and creatinine, and a fasting lipid panel. You should weigh the patient and either check blood pressure yourself or have the PCP do it. But I wouldn’t necessarily order an EKG in all of these patients. If a patient had a risk factor for cardiac disease, like being overweight or having high cholesterol, that would be the patient for whom I would think about ordering a baseline EKG.
TCPR: Are there any downsides to getting a baseline EKG?
Dr. Yohanan: Absolutely there are. It’s easy to say “Oh, it’s just a $35 EKG, why not order it?” But you risk opening a can of worms, since there are false positive abnormalities, and when you get a result you are obligated to follow it up, and this can involve a range of expensive and invasive tests that carry their own potential adverse events.
TCPR: After these baseline labs, how frequently should we monitor?
Dr. Yohanan: After the patient starts taking the medication, you should repeat these labs in three months, because that is about the time period when a potential metabolic problem will declare itself. If there are abnormalities, you should refer these patients to their PCPs for treatment. If the labs are normal, you can repeat them every six months to a year.
TCPR: How do you diagnose hyperlipidemia?
Dr. Yohanan: We diagnose hyperlipidemia in a couple of ways. As a general goal we want people to have a total cholesterol of less than 200. I focus on the big three: the LDL (the bad cholesterol), the HDL (the good cholesterol), and the triglycerides. We want LDL to be no more than 160, but the threshold of concern varies depending on whether the patient has other cardiac risk factors.
TCPR: And what are these risk factors?
Dr. Yohanan: Older age (45 or older in men and 55 or older in women), family history of premature coronary artery disease, smoking, hypertension, type 2 diabetes, and low HDL. If people have fewer than two risk factors, we want the LDL to be less than 160. If they have two or more, we want an LDL of less than 130. If people have a known history of cardiac disease, we want an LDL that is less than 100. LDL is the measure that we really follow the most. When it comes to HDL (the “good cholesterol”), a high HDL lowers the risk of a cardiac event. Finally, we like to see triglyceride levels less than 200.
TCPR: And how do most internists approach the management of hyperlipidemia? Do you start by recommending improved diet and exercise, and then move on to medication?
Dr. Yohanan: Unfortunately, the most recent studies have shown that the cardiovascular benefit of exercise is rather modest. You begin to see some benefit in patients who can sustain moderate to vigorous exercise on the order of four to five hours a week. So it is not 30 minutes on the treadmill three or four times a week, as some people have heard. There are other reasons to exercise, such as weight loss, but exercise is not going to really affect lipid levels or yield much in terms of cardiovascular health. The bottom line is that diets low in fats and high in complex carbohydrates (such as the South Beach diet and the Dean Ornish diet) tend to help people lower their LDL modestly, but only if they really follow the diets religiously. In terms of weight loss, there was a study in JAMA this past year that compared several diets, and found that it didn’t much matter if the diet was low carb, low fat, Weight Watchers, whatever—as long as the dieter stuck to it. One important factor in the metabolic syndrome is high fructose corn syrup, which is found in many processed foods. It is difficult for the body to digest, and probably has some correlation with the increased prevalence of hyperlipidemia. So if someone comes into the office and has a high cholesterol level I think it’s helpful to have a sense of how much processed food they’re eating. As to what instruction to give, rather than prescribing a specific diet plan, I like what Michael Pollan says in The Omnivore’s Dilemma: eat food, mostly plants, not too much. The corollary to that, also from Pollan is: don’t eat food that doesn’t rot. In any case, I tend to give a person three to six months to try lifestyle changes, and if they don’t reach their LDL goal, I start a statin.
TCPR: Can you give us a little primer on which statins are typically used?
Dr. Yohanan: Statins work by reducing the body’s production of cholesterol, and the ones that have been around the longest are Lipitor (atorvastatin) and Zocor (simvastatin). In terms of which to choose, it is a coin flip. Generic Zocor is now available, and so it is a bit cheaper than Lipitor, but Lipitor will soon go off patent as well. There are some newer statins, such as Crestor (rosuvastatin), but in general I am more in favor of medicines that have been around for a while, because you become familiar with the dosing and the side effects. Of course, many psychiatrists will be more comfortable referring patients to their primary care doctors to manage hyperlipidemia. In that case, be sure to ask your patients if they’re taking the medicine as prescribed.
TCPR: Are statins safe?
Dr. Yohanan: Yes, they are pretty safe. The big side effects you worry about with a statin are liver dysfunction [primarily elevations in alanine aminotransferate (ALT)] and rhabdomyolysis (a breakdown of muscle tissue, in which there is an elevation in the enzyme creatine phosphokinase, or CPK). If you are starting statin therapy you should get baseline liver function tests and a CPK.
TCPR: Is there anything that psychiatrists should be particularly watchful of in patients taking statins?
Dr. Yohanan: Since hypothyroidism can predispose patients to the myopathy caused by statins, you want to be particularly vigilant about monitoring thyroid stimulating hormone (TSH) if you have a patient on both lithium and statins.
TCPR: So let’s say you start a patient on statins. How frequently do you monitor their lipid levels?
Dr. Yohanan: You would check an LDL level about six weeks after you started the statin, then 12 weeks after that. Once you are at the goal LDL level you can check it every four to six months.
TCPR: Let’s move on to obesity. In psychiatry, we confront this issue especially when we prescribe some of the atypical antipsychotics. How should we monitor and treat this problem?
Dr. Yohanan: At a minimum, every psychiatrist who prescribes atypicals should have a scale in their office. You may want to have a tape measure to monitor waist circumference as well.
TCPR: What extra information does waist circumference give you beyond what you would learn from a patient’s weight?
Dr. Yohanan: Waist circumference has traditionally been one of the criteria for metabolic syndrome. The reason is that when people gain weight, some tend to gain that weight in their extremities, whereas others gain in the waist, which we term abdominal obesity. Abdominal obesity is a specific risk factor for diabetes. But it’s far more important to simply measure weight, and then to calculate the BMI (Body Mass Index), which is weight (in kg) divided by the square of the height (in meters). There is also a formula for calculating BMI using pounds and inches, and the easiest way to do this is to go to one of many BMI calculator websites, such as the NIH site at http://www.nhlbisupport.com/bmi/. Patients with a BMI above 25 are considered overweight, and those above 30 are considered obese.
TCPR: So how do we help patients manage weight gain?
Dr. Yohanan: The first thing is to minimize the impact of the patient’s medication. For example, in one study, Zyprexa (olanzapine) led to an average weight gain of 37 pounds in a year (Strassnig M et al., Schizophr Res 2007 Jul;93:90-8). It is generally more damaging than most of the other atypicals. If you have a patient who has gained five to 10 pounds on Zyprexa in a brief period of time, you should consider switching to a different medication to keep the problem from worsening.
TCPR: Aside from switching to a medication with a lower weight gain liability, how else can we be helpful to these patients?
Dr. Yohanan: Simply having a scale in the office and weighing patients at each visit is helpful, because this reminds patients that this is an issue they should be thinking about. But I have found that the best intervention is having patients keep a simple food diary. If people get into the habit of writing down every single bite, that seems to make a bigger difference than any anti-obesity pill that I know of.
TCPR: What about treatment with metformin (Glucophage)?
Dr. Yohanan: There have been some hopes that people could potentially head off both obesity and diabetes induced by atypical antipsychotics by pretreating with metformin. Recently, two big studies of this approach have been published. One did not show any significant decrease in weight (Baptista T, et al., Can J Psychiatry 2006;51(3):192-6), and one did (Wu R, et al., JAMA 2008;299(2):185-93). But the study that showed a positive effect used an inpatient sample and it is not clear how generalizable this would be to the real world of outpatient care. There is also Orlistat, which prevents the absorption of fat, but people tend not to tolerate this very well because of side effects. Frankly, I just don’t think there are any great pills for obesity yet. However, gastric bypass can be incredibly beneficial for patients who are morbidly obese, and it ends up for many people quite literally curing them of their diabetes.
TCPR: Let’s move on to diabetes. What is the latest on the diagnosis of diabetes?
Dr. Yohanan: A significant development is that in 2008 the American Diabetes Association (ADA) changed the criteria so that a single random glucose of 200 mg/dl or above makes the diagnosis. It used to require two random glucoses of 200 or one high random glucose plus symptoms of diabetes. There are two other ways to diagnose diabetes: a fasting glucose of 126 mg/dl, or a glucose tolerance test level between 100 and 125.
TCPR: So assuming that you make a diagnosis via either random or fasting glucose, or impaired glucose tolerance, what is the standard approach now to beginning treatment with patients once they get that diagnosis?
Dr. Yohanan: It depends on whether the patient has Type 1 or Type 2 diabetes.
TCPR: Can you remind us of the difference between the two types?
Dr. Yohanan: Type 1 diabetes used to be referred to as juvenile diabetes. It tends to be an autoimmune disease where you lose a lot of insulin-secreting cells, leading to low insulin levels. The treatment is exogenous insulin.
TCPR: And type 2 diabetes?
Dr. Yohanan: Type 2 diabetes is a combination of a decrease in secreting ability and an increase in insulin resistance of the cells. The mainstay of treatment for type 2 diabetes is Glucophage (metformin), if somebody doesn’t have liver or renal dysfunction. It has several advantages; it tends not to be associated with low blood sugar or hyperglycemia, it is cheap, and it has been around forever. The secondary drugs are the sulfonylurea like glipizide or glyburide, and the thiazolidinediones like Avandia (rosiglitazone) or Actos (pioglitazone).
TCPR: There has been a lot of controversy about whether the atypicals directly cause Type 2 diabetes or whether they cause it indirectly by causing weight gain. What is your opinion about that?
Dr. Yohanan: I would say it is probably a little of both. A little over half of people with type 2 diabetes meet criteria for obesity. So it is likely that weight gain, especially if it is abdominal weight gain, plays a role. I believe that atypicals probably increase the risk of diabetes independent of weight gain, but it is hard to quantify the degree of this risk.
TCPR: Do you think that we are being too liberal with our prescriptions of atypicals?
Dr. Yohanan: The literature on this is somewhat mixed. These medications probably precipitate metabolic syndrome in some patients, but there also seems to be a genetic predisposition to developing obesity, diabetes, and hyperlipidemia in certain patients with serious mental illness (Mulder H et al., J Clin Psychopharmacol 2007;27(4):338-43). Interestingly, younger people are more susceptible to the metabolic effects of atypicals than the elderly: the odds ratio for developing type 2 diabetes in patients under 40 who are placed on atypicals is 1.63 but we don’t see the same elevation of risk in older patients (Sernyak MJ et al., Am J Psychiatry 2002;159:561–566). I believe there is a large group of patients who have an elevated baseline risk for developing the metabolic syndrome for whom atypicals seem to serve as a trigger of sorts. This can cause cardiovascular problems to present themselves decades before they would have otherwise.
TCPR: Thank you for you advice, Dr. Yohanan. It is sure to be helpful for many frontline psychiatrists.