Thomas Schwartz, MD.
Professor and Interim Chair of Psychiatry and Behavioral Sciences, Upstate Medical University, Syracuse, NY.
Dr. Schwartz has disclosed that he has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
TCPR: Dr. Schwartz, there are so many antipsychotics available. How do you choose in your own practice?
Dr. Schwartz: Any drugs that have an FDA indication for a particular diagnosis are likely to be effective. I especially like to use those that have less risk of metabolic complications, such as ziprasidone, lurasidone, etc. If we are discussing effectiveness with schizophrenia, none are better than clozapine (Clozaril), so I am willing to move to this drug when initial medications fail to help. For me, though, it comes down to side effect profile, so my personal preference is to avoid risperidone, olanzapine, paliperidone, and quetiapine.
TCPR: Why do you avoid those medications?
Dr. Schwartz: Because they are the most metabolically unfriendly products we have. There’s a hassle factor—more blood draws, more calls to the family practice doctor, more help managing diabetes and lipids. So, I like to start with a safer drug with less metabolic risk. That said, my inpatient colleagues really like olanzapine and risperidone, and with difficult inpatients, they tell me those drugs “cut the mustard” and work better. But my inpatient colleagues only manage these patients for 10 days. I work with the patients for 10 to 20 years, and must manage those metabolic issues. A lot of trials seem to indicate that maybe generic risperidone and generic olanzapine are better in schizophrenia, but because of their side effect profile, I like to hold them in reserve.
TCPR: That makes a lot of sense. But what happens when your patient doesn’t respond to other drugs and you need to consider using olanzapine? There are various guidelines for what we’re supposed to do in terms of monitoring, but what do you do, and what do you tell your patients?
Dr. Schwartz: With every atypical, there are class warnings for weight gain, hyperlipidemia, increased blood sugar, abdominal girth, tardive dyskinesia, and extrapyramidal symptoms (EPS). I have a conversation in layman’s terms with the patient and say, “You might gain weight. Your cholesterol, your blood sugars might go up, you may get muscle shakes, muscle twitches, and some of those will be permanent (Wei Xin Chong J et al, Mental Health Clinician 2016;6(4):178–184).” I tell them that their risks with these drugs are greater than some of the other drugs. That’s how I pitch it in the end, and I think that does get me through an informed consent process. For monitoring with all of the atypicals, we get vital signs—blood pressure, height, and weight. We check labs for sugars and lipids.
TCPR: Earlier, you mentioned clozapine in the context of saying none of the other antipsychotics are better. Do you have any advice on how to make the process of prescribing it a little less scary?
Dr. Schwartz: Yes. Good question. As we are finding more people with schizophrenia that are treatment-resistant and treatment-refractory, I think clozapine is making a comeback. I think if you march through the 11 or 12 atypical antipsychotics, spending 3 months on each, you have someone who might go 3 or 4 years with unmitigated psychosis. To me, that is too much of a delay and can worsen the patient’s prognosis. I would say that, if you fail with 2 or 3 antipsychotics and you still have psychosis going on, go with clozapine. It’s a great drug. [Ed note: See this issue’s article on clozapine.]
TCPR: Do you find that you’re doing the same monitoring with all the medications? And how do you manage the problematic issue of weight gain for patients?
Dr. Schwartz: Most of my patients have a scale at home, and I’ll say, “I might not see you for 90 days, and if you gain more than 5 pounds I want you to call me, since I know that some people can gain 15 pounds in 3 months.” So, I do try to empower my patients to self-monitor with their scale, but I don’t necessarily bring them in every couple of weeks just to measure their weight. I tell them, “If you’re consistently above 5 pounds, I’m going to give you a speech about diet and exercise. If that fails, I’m going to probably put you on weight loss meds.”
TCPR: I’m guessing that first conversation about weight doesn’t always work for your patients. When it doesn’t, what else do you say to them?
Dr. Schwartz: What works the best in my practice is that I tell patients, “You don’t have to count calories. You actually don’t have to exercise.” I start by telling them all the things they don’t have to do, and their defenses drop some. It’s about portion control, and my quick speech is: “You can eat everything that you normally eat, but I want you to take 25% of the food off your plate.” And I joke about it by saying, “You can feed it to your dog. You can give it to your spouse. You can save it for another time. But you’re not going to eat a quarter of what’s on your plate. You can eat a candy bar, but eat three-quarters of it.” That’s portion control. A very simple explanation about portion control dieting has been my most effective approach. After that, if the portion control approach doesn’t work, I move to weight loss methods.
TCPR: Which weight loss antidotes do you recommend?
Dr. Schwartz: The one with the most evidence is metformin. It’s off label; it’s a $5 generic. There are at least 20 trials, and this is almost a standard of care. It clearly knocks off 5 to 10 pounds in our patients. It does not make people hypoglycemic like insulin would (Zheng W et al, Journ Clin Psychopharm 2015;35(5):499–509). There’s nausea and diarrhea, and you must watch out for acidosis. You need a basic metabolic panel once a year to make sure the bicarb isn’t too low. But in my practice, it is a very well-tolerated drug.
TCPR: And what dosing of metformin do you use?
Dr. Schwartz: I start off at 500 mg twice a day, and I give that 2 to 3 months to settle in. After that, if there’s no significant weight loss, I will go up to 1,000 mg BID, and I’ll give that another couple of months. If it works and the weight is staying off, I may keep the patient on the metformin.
TCPR: What labs do you recommend before starting an atypical antipsychotic?
Dr. Schwartz: I’ll get baseline labs. Before I start the drug, I’ll get a lipid panel and either a fasting glucose or a hemoglobin A1C. Because I’m doing a blood draw regardless for atypical monitoring, I usually get a CBC because there are general precautions about agranulocytosis. Then I’ll titrate the drug, and once I’m up to a reasonable dose, which could be anywhere from 2 weeks to several weeks, I’ll get a new blood draw. Then I’ll wait 3 or 4 months, and then get another blood draw. After that, if the patient’s labs are clean, I’m happy with once-a-year blood draws. If the patient shows some inkling toward more weight gain, and one of the labs has peaked a little bit, then I’ll probably get blood every 6 months.
TCPR: That reminds me to ask you about labs in general. Clinicians are pretty good about ordering labs, but when we get a result that’s flagged as abnormal, how should we respond?
Dr. Schwartz: I recommend asking for training from a colleague who’s a family medicine doctor or an internist. Get 30 minutes of the person’s time and ask, “What do you look for in a lipid panel, and how do you test for elevated blood sugars?” Also ask, “What scares you in a lab profile, and what should I worry about?” That’s what I did—I talked to my uncle, who’s an endocrinologist. If you don’t feel comfortable interpreting labs yourself, you can always shoot off a quick letter to your patient’s primary care doctor to ask for help.
TCPR: Using that approach, what are some of the things that you’ve learned that we should take note of in the labs?
Dr. Schwartz: Fasting glucose is one area that comes to mind, and it should be below 100. If patients are between 100 and 120 twice, they’re prediabetic. If they’re above 120 twice, they’re diabetic. When somebody gets in that 120 range, I start getting worried, and that’s my cue to get help. In terms of lipids, I focus on triglycerides, which in my experience usually spike first in a metabolic disorder. When triglycerides spike above 150, I get worried. At that point I’ll prescribe fish oil, but I’ll also refer the patient to primary care.
TCPR: When you use fish oil, is there any particular brand that you favor?
Dr. Schwartz: Lovaza and Epanova are the only FDA-approved ones, but it can be hard to get coverage, so over-the-counter fish oil works as well. I usually use about 4,000 mg per day. And there’s some data regarding fish oil helping ADHD and depression, so every now and then I get lucky and it helps the other medications that are on board.
TCPR: Switching gears a little, let’s discuss some of the relatively new antipsychotics. Many of us have very little experience prescribing them. What are some of their advantages?
Dr. Schwartz: Let’s start with cariprazine (Vraylar) and brexpiprazole (Rexulti). These are sometimes called third-generation antipsychotics. They’re very similar to aripiprazole. These 3 drugs have a different mechanism than other antipsychotics—they partially agonize D2 and D3 receptors. They’re not full antagonists, so I put them into their own family. I think aripiprazole (Abilify) is a great drug. It’s generic; it’s $5; it has a lot of FDA-approved indications. So, I usually start with Abilify, and if patients can’t tolerate Abilify, I then switch them to Rexulti. Vraylar is interesting to me; it is probably the best at manipulating the D3 receptor, which is one of the wakefulness and executive functioning receptors.
TCPR: What has been your experience with Latuda?
Dr. Schwartz: Because it rarely causes weight gain or lipid abnormalities, Latuda (lurasidone) is a fantastic drug, and it’s approved for bipolar depression. The problem with Latuda is that, to be fully absorbed, it must be taken with food. I’ve had a couple patients who could not absorb it even after eating enough calories. I even had a gentleman—just to demonstrate that he was in fact taking it correctly—come to my practice each day to take his Latuda along with a donut, but he still could not absorb it. As for side effects with Latuda, you can see some EPS, some headaches and stomachaches; you get some fatigue. These are the kinds of constitutional nickel-and-dime side effects that you can get from several psychiatric medications.
TCPR: What about Geodon as an option to avoid metabolic effects?
Dr. Schwartz: From a metabolic point of view, ziprasidone (Geodon) is my second favorite behind lurasidone. The issue I have with ziprasidone is that, although it works for schizophrenia and bipolar mania, there are only a couple of small studies showing that it helps depression. The other problem is that dosing is unpredictable. I have some people who get sedated on low doses of around 20 mg twice a day with food; others get horrible akathisia. So, in terms of doing informed consent with patients, I tell them, “We are starting on a low dose, but I have no idea if you’re going to get tired and sedated, or if you’re going to feel like you are caffeinated with akathisia. You might get none of those side effects.” But again, this is why I prefer Latuda, which seems to have fewer side effects and is more predictable.
TCPR: And when you do prescribe ziprasidone, what do you do about cardiac issues?
Dr. Schwartz: I follow the FDA guidance. Unless a person has previous heart issues or a family history of heart issues, I don’t do an ECG. If I ever end up super-dosing it and going off label by pushing the drug higher, I will get an ECG.