Advantages of LAIs in Schizophrenia


Examining the benefits of using long-acting injectables in managing schizophrenic episodes as it relates to patients and the overall health care system, as well as the disadvantages of psychotic relapse.

Henry Nasrallah, MD: Long acting injectables are primarily of great benefit to the patient but also to the system and the family. To the patient, the greatest advantage of long acting injectables is preventing psychotic recurrence, relapse. Which is like—very likely to happen in patients who take part of the medication or none at all. So even partial adherence can lead to a relapse. Of course, total non-adherence is a guarantee for relapse. Many studies have shown that patients, within a week of discharge, from the first episode, 25% have completely stopped their medication and within two or three months 50% have stopped their medication.

The few who are taking some days but not other days are guaranteed to relapse because studies have shown, and they're published in the American Journal of Psychiatry, that missing one day out of every four days, if you miss one dose every four days, it's enough to cause relapse. Because they measure the blood level over a year for patients discharged and every month when they came for the visit, they measured the blood level and they found that all it takes is a drop of 25% to cause a relapse. This is how fragile our patients are. So this is why it's so important to give long acting injectables, to avoid this erratic or total non-adherence, which is very, very common in schizophrenia. But another very important benefit, as I mentioned earlier, is avoiding brain tissue loss. 

Studies have repeatedly shown that patients lose about 12cc's of brain tissue with every psychotic episode, starting with the first one. 12cc's of brain tissue is a huge amount of cells. Because each cc has hundreds of millions of brain cells and billions of synapses. So it's very serious. Now we can recover from one episode and losing 12cc's. We have enough reserve in our brain. But you can't recover and become functional if you keep losing 12cc's every time. After four or five episodes, you've lost 50, 60cc's of brain tissue. There's no way you can remain normal. So avoiding brain tissue loss is a great importance and great advantage to the patient with long acting injectables. Then another very important issue is, it's been shown repeatedly in very important studies that in the first year after the psychotic episode, the initial psychotic episode, huge number of patients will kill themselves if they relapse. 

That psychosis will lead to suicide in huge numbers. A recent study just published three months ago showed, believe it or not, 17,000% higher suicide rate in young people with schizophrenia compared to the general population of young people, same age, same sex. This is enormous, 17,000% higher suicide rate. So that's the worst outcome in medicine, when they end up killing themselves when they realize that they are psychotic and they're experiencing the hallucinations, delusions, et cetera. It's very stigmatizing for them and they give up and decide to kill themself. The third outcome is incarceration. Nowadays we don't have state hospitals anymore, so whenever a patient becomes psychotic and behaves erratically on the street and talks aloud or assaults somebody or steals something because they're psychotic, they get shipped to jail and then they become criminals and they go to prison and serve a sentence. Again and again and again. 

This is terrible. Because the prisons do not treat our patients very well, frankly. It's very stigmatizing to become a criminal, a felon, not just mentally ill. Another disadvantage of relapse that we will prevent with the long acting injectable, it's been shown again and again with many studies that with every relapse, psychotic relapse, the brain no longer is the same brain. Because you lose all the tissue and all the connections and all the receptors. So treatment resistance develops. The same antipsychotic that used to work very well in the first episode, which is the best time that an antipsychotic works, the first episode, it no longer works once they have a second episode. Studies show about 18% of patients stop responding. Another episode, another 15 to 20 percent, and so on. Eventually, after multiple episodes, you need to use higher and higher doses with a lot of side effects and they still cannot suppress the delusions and hallucinations completely. That is a huge problem. 

Repetitive psychotic episodes leads to treatment resistance. You miss the opportunity of getting those patients completely in remission, back to their life, to their baseline, by stopping the illness in its tracks very early. This is not just unique to schizophrenia. Many neurological conditions, same thing. The earlier you intervene, the better. So here's an example of how dramatically better long acting injectables are, the group at UCLA, the schizophrenia research group, published a study in the Journal of Psychiatry, very prestigious journal, where they took patients in the first episode, treated them with orals. We always use orals in the hospital because nurses make sure they swallow them and we make sure they're not allergic to them, that they're working, et cetera. Treated them with an oral antipsychotic, second generation, as we always do now. 

Then at the time of discharge, half the patients were continued on oral medication, the same medication they were given, refilled every month, followed up for a whole year every month. The other group got injection of the same medication, no pills, just an injection. They compared the two groups at the end of a year. What did they publish? What did they report in that article? It's almost mind boggling the difference you can make by giving a long acting injectable. 650% higher relapse rate in the oral group compared to the injectable group with the same antipsychotic.

Now that's proof positive that long acting injectables can be tremendously protective of the patient compared to giving them the oral medication that worked for them in the hospital. They are not going to take it or they're going to take it very erratically. The relapse rate is 650% higher at the end of the year compared to the injectable group. This is the kind of data the I tell my patients about and the families to convince them that this is a huge—it makes a huge benefit for the patient. Not to take pills, but to just get the injection and the medication will slowly reach their brain every day at the right amount and you don't have to worry about getting psychotic again.

Transcript Edited for Clarity

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