TCR: Dr. Jibson, how do you go about deciding which atypical antipsychotic to prescribe for a particular patient?
Dr. Jibson: I begin with the assumption that all the atypicals are equally efficacious and that in large populations of patients they’re all equally well-tolerated. Which means that you’ve got to look for some unique feature of a patient that would point you toward one or the other, or some other factor unrelated to that particular patient, such as cost of the medication. I often think about what side effect I think the patient would be most susceptible to.
TCR: Is there any particular medication that you turn to first?
Dr. Jibson: If I’m seeing a patient who has no experience with any of these medications, then I’ll generally select the drug that I’ve been using for the longest and have the most experience with, and that’s generally going to be risperidone (Risperdal).
TCR: Do you use conventional agents?
Dr. Jibson: No I don’t, because with conventional agents the likelihood that the patient is going to have a bad experience early on in treatment is very high. Over the years I’ve treated lots of people who’ve told me that the first couple of times they took a dose of a conventional agent they’ve had EPS, particularly acute dystonic reactions, and it creates a very poor first impression. I’d much rather have people have a good first experience.
TCR: What sort of side effects are you most concerned about with the atypicals?
Dr. Jibson: Generally it’s going to be one big side effect for each of the atypicals. For example, with risperidone, it’s going to be EPS or akathisia. So if I see a patient who might be at a higher risk for that—a young, male patient, for example— then I’d tend to move away from that drug and to one of the others. If I see a patient for whom that’s a big risk, like a person with Parkinson’s Disease, than I’ll go over to quetiapine (Seroquel) which among the first-line atypicals (atypicals other than clozapine) clearly has the lowest EPS risk. If I have a patient who’s diabetic, who is overweight or is very concerned about weight gain, then I’ll steer away from olanzapine (Zyprexa). If a patient has cardiac problems, I’ll stay away from ziprasidone (Geodon). And if there’s a patient who is very sensitive to sedating medications or is already on sedating drugs, I’ll tend to stay away from quetiapine.
TCR: So you find quetiapine to be the most sedating of the first line atypicals?
Dr. Jibson: Right, especially early on. The most intense sedation usually doesn’t last more than a week or two, and then there’s a very dramatic drop-off. In the one head-to-head study between quetiapine and risperidone sedation was the main reason for dropout from the quetiapine arm.
TCR: Quetiapine is interesting because many psychiatrists have been using it as a non-addictive anti-anxiety agent at low doses. Do you use that way too?
Dr. Jibson: Yes I use it along those lines, most commonly as a substitute for thioridazine (Mellaril) in patients with borderline personality disorder. In the old days I would give them these tiny little doses of thioridazine which would be sedating, anxiolytic, and would cut down on the impulsivity and the distortions of thought that these patients have. Quetiapine has some of the same effects.
TCR: How would you typically dose quetiapine for that kind of patient?
Dr. Jibson: Usually I’ll start at 25 mg once or twice a day in addition to one or two prns a day. These patients really like to be able to manipulate the medication—they’re going to anyway, so I just make it official.
TCR: How do you dose quetiapine for psychotic patients?
Dr. Jibson: For outpatients, I’ll start around 25 mg. BID, wait for the sedation to subside, usually about a week, then I’ll titrate up fairly quickly to 300-400 mg per day. I generally follow the manufacturer’s guideline and dose it BID, but if my patient complains about sedation, I’ll dose it nightly.
TCR: You mentioned earlier that you have a lot of experience with risperidone. Any other reasons that you like it other than its long track record?
Dr. Jibson: Yes, it’s less expensive than the other atypicals. While the cost of these medications varies from region to region, in general, ziprasidone and risperidone are priced very closely together, olanzapine is about twice as expensive as risperidone and quetiapine is in the middle.
TCR: How do you deal with the hyperprolactinemia risk with risperidone? Do you always check prolactin levels?
Dr. Jibson: No, I very rarely get prolactin levels. Although many patients will show an elevated prolactin if you check them at random, the actual clinical risk is pretty small. So unless I get a report of amenorrhea or galactorhea, I don’t check levels.
TCR: How do you dose risperidone?
Dr. Jibson: I generally start risperidone at 2 mg QHS, and will go quickly to 4 mg if I’m treating an active psychosis. I’ll leave them at 4 mg for 3 to 4 weeks, and I’ll go up to 6 mg if I only have a partial response, but I will very rarely go above that. Once you go above that you’re losing the advantage of an atypical and you should think about switching.
TCR: What do you think about olanzapine? It certainly has received some bad press lately in terms of diabetes risk, weight gain, and so on.
Dr. Jibson: I think olanzapine still has its place among the first line atypicals. Yes, the risk of weight gain is a real issue, but it is one side effect among others, and it’s not really worse than having TD (tardive dyskinesia). Actually, my reason for using olanzapine less frequently is that it is more expensive than the other atypicals while having no real advantages over them.
TCR: And how do you dose olanzapine?
Dr. Jibson: I start at 10 mg, and I aim for 15 to 20 mg QHS, but I often go higher than that, as high as 30 or 40 mg. Above 40, you start to see EPS.
TCR: What do you make of the cardiac risk associated with ziprasidone?
Dr. Jibson: The post-marketing surveillance has revealed no cardiac events in 150,000 patients who have taken it so far. Once we get to a million patients we’ll be able to answer the question more definitively. On the other hand, when you look at thioridazine, 150,000 patients was enough to show that it causes cardiac problems, and similarly with sertindole (which was rejected by the FDA due to cardiac concerns). I certainly think about the issue in terms of prior history of cardiac problems and possible drug interactions, but other than that I don’t get too excited about it. I think about ziprasidone in much the way I think about the tricyclic antidepressants: the cardiac issue goes through my mind, but I don’t really have any hesitation to give it as a first line agent.
TCR: How do you dose ziprasidone?
Dr. Jibson: I start with 40 mg BID and usually titrate to 80 mg BID within one or two days. It tends to be very well tolerated, just a little bit of sedation early on, and virtually none later.
TCR: Do you have much experience with aripiprazole (Abilify)?
Dr. Jibson: Very little. If you look at the clinical trial data, it seems to have the same efficacy as the other atypicals. One potentially valuable thing about aripiprazole is that it cause no EPS, like quetiapine and clozapine, but unlike them it causes essentially no sedation.
TCR: Do you think all atypicals work for mania?
Dr. Jibson: Yes I do, even though olanzapine is the only one with the FDA indication. I use all the atypicals for mania, and I dose them the same way that I dose them for schizophrenia.
TCR: Is there any TD risk with the atypicals?
Dr. Jibson: They’re not completely free of TD risk. The best data suggests that there’s a tenfold improvement over the conventional agents. The risk of developing TD with conventional agents is 5-7% per year, and with the atypicals this risk drops to 0.5% per year. That’s a wonderful improvement. The big question is whether there’s a differential risk among the different atypicals, and right now we do not have enough data to answer this.
TCR: Do you combine antipsychotics?
Dr. Jibson: I try to avoid it if possible. One of the interesting things about the atypicals is that the same patient may respond to one and not the others, which is in contrast to the conventional agents. So I will generally run through at least three and often all four of the first line atypicals before I will go to clozapine, and only then will I consider combinations. Now having said that, I have to say that I do have patients who are on combinations, but usually not by design. What happens is that I’m cross-titrating from one atypical to another, and midway through this the patient walks into my office and says “This is the best I’ve ever felt, don’t change a thing.” There’s not a lot of solid pharmacologic basis to combining antipsychotics. The most common rationale in the community is that a patient can’t tolerate a full dose of any single atypical, so you give them a half dose of two.
Michael D. Jibson, M.D., Ph.D. is a Clinical Associate Professor of Psychiatry, University of Michigan, Ann Arbor, Michigan