Treatment of Negative Symptoms and Cognitive Impairment in Schizophrenia

This video describes therapeutic advancements that aim to improve functional outcomes in people living with schizophrenia.

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Video Transcript

Recovery, though, is the long-term goal, and recovery has two elements. It has symptom remission and functional outcomes, and response is different from remission. Symptom response is a relative term, so you have an improvement over baseline.

It depends on where you're starting, whereas remission is an absolute threshold that you want to go below a certain symptom severity. Here, we have data to suggest that the more and the earlier you get into symptom remission, the more likely it is to get into functional outcomes that are consistent with the recovery model. But still, even when you have—in addition, in terms of positive symptoms—there's often not the social and vocational functioning that we expect in order to give the label of recovery.

So, in a very important meta-analysis by Jääskeläinen E, et al., only 13.5 % of patients with schizophrenia achieved remission, symptomatically, and recovery by adding also the functional outcome. And over 50 years, this number has not shifted. Although we have pharmacologic advancements for positive symptoms, we have reduced the side effects. We have reduced, also, adherence problems with certain formulations; the recovery number has not moved.

Remission rates are about 30%. Now, recovery in first-episode patients—that was just a recent meta-analysis from a group in Denmark—is about 20%. So, that's also not much higher, even at the very beginning of treatment.

We need to do better, definitely. And to have that label be given, you need to be able to sustain both the symptomatic and functional outcomes for a year or, in this definition, even 2 years. There are currently no approved drugs for either cognitive impairment associated with schizophrenia or negative symptoms. There are also no apps, although they are in development. So, we are looking forward to something entering our hands that we can help patients with these two domains that are currently underserved.

There are a number of psychosocial interventions targeting negative symptoms that have shown efficacy. The challenge with them is they have shown efficacy in populations like veterans, who are coming into the hospital all the time anyway, so the idea of getting them to engage and come in is somewhat less of a challenge than getting someone in the community to do that. People need to be supported with antipsychotic treatment while they're getting psychosocial interventions, and psychosocial treatments can address those defeatist behaviors that seem to be a mediator.

A number of psychosocial interventions that involve rehabilitation strategies, like computerized cognitive training, really do work. They can be administered at home. In healthy populations, the benefits last for 10 years. But we got to get people to do the training. This is one of those things where it's not like you can take a medication, and it trains your brain. And, so, this has been the challenge with our whole psychosocial training program that we're running.

We don't really take people who don't have parents or other caregivers to monitor them because they don't train. They don't see the connection between training now and working later, or they don't care if they ever work again.

So, there is an urgent need to address these negative and cognitive symptoms if we want to improve outcomes. So, level of interaction, interest, engagement, body language, daily activities, regular daily behavior. We need to ask about it to get a picture and an image—as Phil was just saying— about also the functional capacity and the functional ability during the day. And you can ask different questions.

How do you spend your day? Do you enjoy things? How do you meet with people, and how often do you do that? So, basically, ask a little bit about the functioning that a patient has.  

Negative and cognitive symptoms are fairly prominent among people with schizophrenia, and they really impair real-world functioning. There's never been a treatment up to this point, but now there is some availability of both psychosocial and remediation-based approaches.

But assessments are critical! We need to identify the symptoms to make the referrals for the patients. When drugs come online, which may very well happen in the next few years, it's going to be very important to target who should get the medication and to be ready to deliver a rationale to an insurer.

Current antipsychotic medications don't do anything, one way or the other, for cognitive and negative symptoms. Their adverse impact is overstated, and their benefit is pretty negligible.

Yeah, obviously, if you have a lot of sedation or EPS, that can cause cognitive and negative symptoms in a secondary fashion. Still, we unfortunately don't improve much the primary cognitive and negative symptoms.