Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort

Abstract

This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.

Chronic clozapine treatment restrains via HDAC2 the performance of mGlu2 receptor agonism in a rodent model of antipsychotic activity

“…However, not all three domains of the disease respond equally to pharmacological intervention. In addition to impairments in cognitive domains associated with long-term use of antipsychotic medications [3][4][5][6][7], treatment discontinuation due to lack of therapeutic benefits and side effects is common [8]. These unmet clinical needs underline the necessity of novel and more efficient therapeutic targets for schizophrenia treatment.…”

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

“…This recommendation is nonspecific with no limitation on the maximum dose allowed. With this criterion, a participant taking haloperidol 60 mg and risperidone 16 mg could be enrolled in a study, and these high doses may interfere with signal detection [64]. Administration of chlorpromazine-equivalent doses ≥1,000 mg/day, which is suggestive of treatment resistance [65], lowers the likelihood of detecting a signal on cognition [66].…”

Considering the role of adolescent sex steroids in schizophrenia

“…Manipulation of steroid levels, through both gonadectomy and sex steroid treatment, has revealed much about sex steroid‐driven molecular actions on dopaminergic‐related behaviours. Oestrogen can potentiate the effects of dopamine receptor antagonists such as antipsychotics, which would be expected to help reduce positive symptoms in people with schizophrenia but may have a negative impact on some aspects of cognition . For example, DRD2 antagonism disrupts performance on an elevated plus maze response‐learning task in ovariectomised rats to a greater extent in the presence of high levels of oestradiol compared to no oestradiol, suggesting that oestrogen enhances the effects of dopamine receptor blockade, although it may be harmful to learning and memory when administered concurrently with antipsychotic drugs.…”

“…Oestrogen can potentiate the effects of dopamine receptor antagonists such as antipsychotics, which would be expected to help reduce positive symptoms in people with schizophrenia but may have a negative impact on some aspects of cognition. 28 For example, DRD2 antagonism disrupts performance on an elevated plus maze response-learning task in ovariectomised rats to a greater extent in the presence of high levels of oestradiol compared to no oestradiol, 29 suggesting that oestrogen enhances the effects of dopamine receptor blockade, although it may be harmful to learning and memory when administered concurrently with antipsychotic drugs. However, disruption of latent inhibition (the delayed learning of a conditioned response to a stimulus after pre-exposure to the stimulus) is seen in antipsychotic-naïve schizophrenia patients 30 and in ovariectomised rats.…”