Optimizing Management of Schizophrenia with LAIs - Episode 15
John M. Kane, MD: There are several long-acting formulations that are available. Two of the most commonly used drugs are paliperidone and aripiprazole. Paliperidone is available as either a monthly or 3- or 6-month formulation that’s under development. And there are different formulations of aripiprazole.
It’s great to have options for injections with long intervals. For example, when communicating with a patient and family about the 3-month option, we highlight the benefit of only 4 injections a year. This is a convenient way to get medicine. Some people think receiving injections 4 times a year means they aren’t getting any treatment. The reality is there should not be a link between the injection interval and the treatment that someone receives. Those are 2 different issues. If someone should be seen with various kinds of psychosocial treatment, that’s going to be determined by the clinical team, the patient, and the family. The injection interval doesn’t determine the frequency of therapy sessions.
Another advantage with the 3-month injection we’ve seen is that if someone stops their medicine, we know. When someone stops their oral medicine, we have no idea.
We don’t find out until they show up in the emergency department. If someone is on a 3-month injection and they were to stop it, they are protected from relapse for a longer interval than they would have been if they had been receiving just a once-monthly injection. It’s a reassuring aspect of using these long-acting formulations.
I would emphasize that we have some terrific options. These medicines are very well known and tolerated, and we have choices about injection intervals.
Henry A. Nasrallah, MD: We had only 2 first-generation injectables: Prolixin Decanoate, which came out in the mid-1970s, and haloperidol, which came out in the early 1980s. These are the only 2 first-generation [therapies] we used at the time. They work, but I never use them anymore because of literature in the last 20 years. Since 2000, there have been 31 studies showing that they’re actually killing brain cells. Both haloperidol and Prolixin kill neurons. They have good episodic efficacy but horrible neurotoxicity. The second-generation drugs are neuroprotective. They don’t kill any neurons, and 24 published studies have proven this. I don’t think clinicians read them because they are in neuroscience journals. The second-generation LAIs [long-acting injectables] are what we recommend for our patients.
Risperidone Consta came out in 2003. I did the clinical trials with it in 2000. Excellent drug, works very well. But it has to be given every 2 weeks, and you have to start with 4 to 6 weeks of oral before you get the necessary blood levels. It was great but not practical. The company Janssen Pharmaceuticals, Inc, makes risperidone and developed it into a long-acting in 2009. This came to the market as a monthly injectable with no oral supplementation. Then in 2013, Otsuka Pharmaceutical Co Ltd developed aripiprazole, which is given once a month. But you need to give it at least 2 weeks with oral in conjunction with the first injection, then you can stop the oral and continue once a month. Paliperidone comes with 5 doses, maintenance doses, and maintain it with 1.
In 2015, Alkermes plc developed another variation of aripiprazole lauroxil. In the body it becomes aripiprazole and tested 2 doses for 441, 882 mg. Both of them went well, but they needed 3 weeks of oral supplementation at the beginning. This same company did research and developed an injection of Initio, a formulation with crystals 1000 times smaller than the aripiprazole lauroxil, which can be given instead of the 3-week initiation of oral on the same day you give the first injection of aripiprazole lauroxil. Then you spare the patient having to take any oral.
They also developed the FDA-approved 661 mg every month and 882 mg every 6 weeks. Additionally, they developed the 1064 mg every 2 months. They have a variety of options. The 3-month came out 40 years ago. Every 3 months—it’s practical, with no oral supplementation. We shouldn’t ignore olanzapine, which was developed in 2000, around the same time Invega Sustenna came to the market. But hardly anybody uses it because it has a warning, and you have to put the patient on observation for 3 hours after the injection, and it causes metabolic adverse effects. Olanzapine is a great drug, but unfortunately it is plagued by its hyperbolic problems.
I tell my patients, “I can give you Invega Sustenna, 1 injection every month, or I can give you 6 mg of oral Invega AR. It would be equivalent to the injection I’d give you.” How many milligrams is 6 mg a day for a month? Six times 30 is 180—that’s exactly 180 mg if you take the oral. “How about I give you only 50 mg, which is what the Invega Sustenna 78 mg is; it’s really 50 mg. How about 50 mg? Don’t you want less medicine in your body?” Many patients are smart and they said, “Yeah, I prefer less medicine in my body.” It’s a logical argument I use with my patients.
This is amazing for Invega Sustenna. It’s not true for aripiprazole. You still have to do 400 mg, which is roughly 15 or 20 mg a day. The same idea with Aristada, which is aripiprazole lauroxil.
The final thing I want to mention is that Jari Tiihonen and his group published a paper last year in Sweden looking at mortality. We know mortality is terribly high in schizophrenia. They followed up on everybody in Sweden: 29,000 patients for 7 years.
And they kept them on whatever medication they were taking—oral, injectable, first-generation, second-generation—and counted the number of deaths. At the end of 7 years, the lowest mortality among all the ultra-psychotics in Sweden was Invega Sustenna and paliperidone. The injectable paliperidone had the lowest mortality. About 800% lower than Prolixin. This is another reason I don’t use Prolixin. There is an advantage of lowering mortality. Not just avoiding relapse and all its horrible consequences.
Transcript Edited for Clarity