Patient Factors Associated with Schizophrenia

Peter Salgo, MD: Are there patient factors that would propel you even more strongly in favor of the long-acting injectables [LAIs] as opposed to the oral dosing? How do you evaluate a patient, and who’s the best candidate for these things? Henry, can you help us out?

Henry Nasrallah, MD: There are no best candidates, Peter, that’s the problem. People think that there are candidates for long-acting and candidates for oral. In my judgment, after 30 years of working with tens of thousands of patients, and as a researcher, every patient with schizophrenia is a candidate for long-acting at the beginning of the illness, right after the first episode, and there are many reasons for that. They have lack of insight, they’re not going to take their medicine because they don’t believe they’re sick, or they have cognitive impairment with poor memory—really bad memory, like 2 standard deviations below normal, and they forget a lot of things including pills.

They have negative symptoms like avolition, apathy, and lack of motivation that prevents them from taking pills every day, and then they have rampant substance use. Now that they live in the community, they’re either drinking alcohol or taking various drugs. People who are stoned or drunk are not going to take their prescription medicine. When you put all these things together, it is really a tragedy that psychiatrists do not treat those patients promptly with LAIs at the first episode. You don’t wait for patients to have 4 or 5 heart attacks before you implement a very aggressive regimen in cardiology; you do it after the first episode so they never get another myocardial infarction. The first 1 already damaged the heart, and you don’t want to damage it more because they will die outright. Same thing with psychiatry. We must adopt the same principles as cardiology.

One of the worst things that happened in psychiatry is that our own organization, the APA [American Psychiatric Association], because of the ignorance I told you about, had the 2004 guidelines, which fortunately have been revised in 2020. But if you look at the 2004 guidelines, they say, because of ignorance, use long-acting injectables in patients who have already proven not to be adherent as evidenced by multiple episodes. Excuse me? You want them to lose 40, 50 cm3 of brain, which is true by the way. Every episode, patients lose about 12 cm3 of brain tissue. If you wait for 3, 4, 5 episodes, they’re going to lose 40, 50, 60 cm3of brain tissue. Then you consider LAIs? That’s terribly ignorant and out of date.

The other reason we should do this is because patients who relapse again and again are going to end up with very bad outcomes, even after a second episode. One of the obsessions I have as a researcher in schizophrenia is to avoid the second episode by all means, which means keeping the patient well after the first episode. Never again do I want them to have another episode. The reasons: They will develop more brain tissue loss; they will develop treatment resistance, which was mentioned earlier; the patient needs higher doses with every episode; and the brain changes—it’s no longer the same receptors. Third, they get incarcerated because they become psychotic. They get arrested, and it’s off to jail and prisons they go, which explains why half our patients are incarcerated. Horrible. Fourth, suicide. Study after study has shown that patients who relapse are very likely to commit suicide. In fact, a paper just came out this month, they measured the blood level in patients with schizophrenia who died of suicide, and found that very few of them had any antipsychotics in their blood. They are not taking their medication. Finally, homelessness, which Joe Avelino mentioned earlier.

You’re talking about multiple negative outcomes that must be taken into account when we’re managing this serious neurological condition. I’m sorry, but it’s not a psychiatric condition. It’s a neurological condition wrapped under psychiatry by mistake over time, and this is what causes the poor reimbursement. Many of us are fighting very hard to change the classification of schizophrenia from a psychiatric disorder to a neurological disorder, like epilepsy, multiple sclerosis, Parkinson disease, and so on, because then the reimbursement will be much better. Even though it’s already known to be neurological, the government doesn’t see it that way.

Rahn Bailey, MD, DFAPA: That probably speaks to the issue of stigma. I would add that those points are 100% correct. It’s unfortunate that we have this duality: More persons are—as you mentioned, Henry—in the criminal justice system, in part because there’s a lack of adequate health care funding and resources on the department of mental health side for outpatient services and for hospital beds, and there’s too much money, energy, effort, and resources to find people, incarcerate them, and make laws in that setting. The bottom line is, in my career, we’ve tripled or quadrupled, at least in most states, the number of the chronically mentally ill who are in jails and prisons. This is 1 consideration of a place to start thinking about, where you’re likely to have individuals with evidence of serious mental illness but also who may have a history of medication noncompliance, real or perceived, and have sociological problems that likely will make it more difficult for them than others once they get to access care, to get their medications appropriately. If they are homeless, don’t have a place to go, there’s not a place to put your bottles of your pills in a certain place. Those are some additional structural reasons why there may be another population who is thinking about the use of LAIs initially, as well as long-term, can be helpful.

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Transcript Edited for Clarity