A study, recently published in Psychological Medicine, examined the cognitive functioning of individuals with schizophrenia who discontinued antipsychotics, and those who maintained their antipsychotic use. The study adds to our understanding of the relationship between cognitive functioning and antipsychotic use. The authors found that persons who discontinued antipsychotic medication significantly improved when compared to those who stayed on antipsychotics in various cognitive domains.
“Findings suggest prolonged or higher dose antipsychotic use is associated with adverse cognitive outcomes. This could, at least partly, be explained by confounding by indication, meaning that patients treated with high dose antipsychotics for a longer time probably also have the worst illness trajectory.”
The presence of deficits in cognitive functioning in people with schizophrenia is well-established. Because antipsychotics (AP) are often the first-line treatment for folks identified as experiencing schizophrenia, it has been difficult to discern the effects of schizophrenia on cognition, independent of the effects of AP. The evidence is equivocal, with some research suggesting that AP improves cognitive functioning, while other research suggests that the drug worsens functioning.
The authors of the present study mention the caveat that the association between AP and worse cognitive functioning may also be partly because persons who are on AP longer-term likely have a worse illness trajectory.
Studies of discontinuation of AP have shown a risk of relapse for psychotic symptoms. However, discontinuing the drug might also result in improved cognition. The authors of this study aimed to compare the cognitive functioning of individuals who discontinued AP to the cognitive functioning of persons who stayed on AP.
The authors utilized data from a longitudinal study of the OPUS trial, extracting baseline and follow-up information about AP discontinuation and cognitive functioning. Give that the use of AP was decided on by the clinician and client, the study is a naturalistic examination, not a controlled trial.
The study included 189 participants who completed follow-up assessments. At the follow-up, 60 of the participants had discontinued AP use, while 129 continued their AP use.
Those who discontinued were significantly younger, had fewer negative symptoms, and had better functioning than the continuation group. Both groups demonstrated deficits in cognitive functioning. However, cognitive functioning was significantly better in the group that discontinued the drug.
At follow-up, the discontinuation group had a significantly higher level of employment, and more of them had a romantic partner. The discontinuation group also had a higher level of functioning, lower psychotic and negative symptoms, and more than half were in remission. Forty percent of participants in the continuation group were in remission at follow-up. Interestingly, 95% of participants in the discontinuation group said that they were the ones who chose to initiate the discontinuation, not their clinician.
At the five-year follow-up, the discontinuation group had improved on all six tests, three domains, and overall cognition. At follow-up, the continuation group’s cognition scores worsened on memory, but improved on motor abilities, verbal fluency, processing speed, and overall cognition. At the follow-up timepoint, the discontinuation group performed better on all cognitive scores. This finding remained significant after age, sex, level of functioning, and negative symptoms were all accounted for, except in the case of one test, “digit sequencing.” When comparing change between baseline and follow-up between the two groups, the discontinuation group saw significantly more change on motor tasks, processing speed, and overall cognition.
Understanding the trajectory of cognitive functioning in persons with schizophrenia is difficult because of the impact AP medications can have on cognition. In this study, those who discontinued AP had better cognitive scores at baseline and follow-up than those who continued AP use. The discontinuation group saw an improvement over time, while the continuation group worsened over time.
Albert, N., Randers, L., Allott, K., Jensen, H. D., Melau, M., Hjorthøj, C., Nordentoft, M. (2019). Cognitive functioning following discontinuation of antipsychotic medication. A naturalistic sub-group analysis from the OPUS II trial. Psychological Medicine, 49(7), 1138-1147. https://doi.org/10.1017/S0033291718001836 (Link)