A 2026 German-Austrian study found that people with schizophrenia who were taking quetiapine scored modestly higher on demanding working-memory tests than matched patients who were not taking it. The result is an association, not proof that quetiapine improved cognition.
That distinction matters because the study was observational. Doctors, rather than researchers, selected treatments, and participants were not randomly assigned to quetiapine or another medication.
What the study found
The analysis included 106 quetiapine users and 106 patients matched with them by age and sex. On a composite measure of higher-demand working memory, the average scores were 101.1 for quetiapine users and 97.8 for non-users. The sample average was 100.
The 3.3-point difference was statistically significant. The groups did not differ significantly on the low-working-memory composite, which mainly assessed speed, attention and brief storage.
Quetiapine users performed better on each of the high-working-memory tests when results from both visits were considered, although the difference on Trail Making Test B was significant only at the second visit. The advantage was already present at the first assessment and was approximately the same six months later.
Why the result cannot establish a medication effect
The PsyCourse data came from a naturalistic study across 20 clinics in Germany and Austria. Participants were assessed every six months, while doctors decided which treatments to use. Most people in the comparison group—about 87%—were taking other second-generation antipsychotics.
The groups did not differ significantly in symptoms, depression, daily functioning, illness duration or education. Symptoms were somewhat lower in the quetiapine group, however, and the difference did not meet the study’s threshold for statistical significance. Other measured and unmeasured differences could still have influenced the cognitive results.
Many patients had probably started their current medication before the first study visit. The researchers did not have information on when treatment began or which medications participants had previously taken. As a result, the analysis cannot show whether quetiapine produced an earlier gradual change in cognition.
The dose finding needs particular caution
The average quetiapine dose was 543 milligrams per day. Within the quetiapine group, higher daily doses were associated with lower high-working-memory scores.
A smaller analysis of 29 people taking 300 milligrams per day or less found an average high-working-memory score of 103.9, compared with 97.0 among their matched partners. This was a stronger reported difference, but the sample was small.
The researchers did not present this finding as a dosing recommendation. People taking lower doses may have differed in important ways, including illness severity or whether quetiapine was being used for sleep or anxiety. Sedation at higher doses could also be relevant. These possibilities were not established as explanations by the study.
What genetics and earlier research add
The researchers examined 36 polygenic scores in 332 people, including scores related to hippocampal volume, white matter and cell-specific schizophrenia risk. None changed the observed association between quetiapine use and higher high-working-memory scores.
A lower schizophrenia genetic-risk score concentrated in genes active in human oligodendrocytes was weakly associated with better working-memory scores regardless of medication. The study described this as a preliminary signal. The genetic measures were indirect, and many tests were conducted without multiple-testing correction.
The study also did not directly measure myelin, the insulating material around nerve fibers, or brain changes in the hippocampus. Animal research has reported myelin-related effects of quetiapine, but those findings cannot establish that the same process occurred in these patients.
Evidence from randomized research provides additional context. In the CATIE trial, the two-month cognitive gain associated with quetiapine was small and did not differ significantly from gains associated with the other four antipsychotics tested.
What readers should take from the findings
The study raises a question about whether quetiapine and cognition may be related in some patients with schizophrenia. It does not show that quetiapine caused better working memory, that myelin repair explains the association or that the score difference improved work, education or everyday functioning.
The researchers called for randomized trials with repeated brain imaging, including measures of hippocampal myelination. Such studies could better test whether treatment changes cognition and brain structure in the same people over time.
For now, the findings are best understood as an observational signal rather than evidence for a particular medication choice or dose. The study does not support changing treatment based on working-memory scores alone.
AI tools were used to assist with the preparation of this article.
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