Non-Pharma Approach a Potential 'Game Changer' in Schizophrenia?

Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.

A systematic review of 130 worldwide studies that included almost 9000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.

"Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient's personal recovery goals," the researchers write.

"We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized," lead author Antonio Vita, MD, PhD, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy, told Medscape Medical News.

Vita noted that he would also encourage clinicians to consider "proposing it for clinical practice."

The findings were presented at the virtual Congress of the Schizophrenia International Research Society (SIRS) 2021 and were published simultaneously in JAMA Psychiatry.

Resistance Continues

Cognition "should be a focus of treatment because most of the disability and functional consequences of the disease are related to...neurocognitive impairment and impairment of social cognition," Vita said.

He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.

However, despite a "solid body of evidence" supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators note.

The study's goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements. These core elements include

The presence of an active and trained therapist
Repeated practice of cognitive exercises
Structured development of cognitive strategies
Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation

The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also "hand-searched" meta-analyses, reviews, and reference lists.

Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8851 patients with schizophrenia spectrum disorders.

Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, four in Canada, four in Middle Eastern countries, three in Australia, and two in Brazil.

The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.

The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.

The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remainder interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).

Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen's d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).

Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).

The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).

Interventions that included all of the core elements had a "highly significant" association with global cognition (P = .02) and global functioning (P < .001), the investigators report. Longer treatments were significantly associated with greater functional improvement (P = .006).

The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).

The researchers note that CR should become more widely available because it has the "potential to be an element of standard care rather than an optional intervention targeting selected individuals."

An Overlooked Treatment Option

Commenting on the findings for Medscape Medical News, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York City, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.

"So this is a banner year for large reviews," she said. "It's great to have two studies like this [that] tell a very consistent story."

Medalia, who was not involved with the research, said individuals "don't really talk about cognition very much."

CR, she added, is "one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive heath needs addressed.

"If someone is having problems, and it's getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way," she said.

These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.

"But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available," Medalia said.

Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because "people just don't think about cognition and they don't know how to talk about it," she noted. In addition, she said, even when it is available, clinicians don't refer patients.

"That tells you something. The solution here is not to put a cognitive remediation program everywhere but...to get people comfortable talking about cognition and identifying when an intervention is needed," said Medalia.

One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Medalia have reported no relevant financial relationships.

Congress of the Schizophrenia International Research Society (SIRS) 2021: Abstract 3006850. Presented April 20, 2021.

JAMA Psychiatry. Published online April 20, 2021. Full article

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