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.
Highlights
Neurocognitive deficits occur in the majority of persons with schizophrenia (Heinrichs and Zakzanis, 1998; Keefe et al, 2005)
Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days
In this study higher lifetime cumulative dose-years of any antipsychotics were significantly associated with poorer global cognition at the age of 43 years in schizophrenia, when the most important confounding factors related to duration and severity of illness were controlled for
Summary
Neurocognitive deficits occur in the majority of persons with schizophrenia (Heinrichs and Zakzanis, 1998; Keefe et al, 2005). They are present before the first psychotic episode, remain relatively stable over the illness course (Bora and Murray, 2014; Zipursky et al, 2013) and are strongly associated with functional outcome (Rajji et al, 2014). The cognitive effects of antipsychotic medication have mostly been studied early in the course of illness in relatively short follow-ups ranging from 1-3 weeks to 2-3 years. Information was gained in the interview at the 43-year study and for those with missing information it was ascertained from Finnish Centre for Pensions registers
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