Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode XXXX .

@entity1 @entity146 @entity167 @entity161 @entity62 @entity734
CONTEXT: Progressive brain volume changes in @entity161 are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for @entity161 @entity1 , may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for @entity161 @entity1 and have increasingly widespread use in other @entity146 , it is imperative to determine their long-term effects on the @entity1 brain. OBJECTIVE: To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and @entity734 ) of brain volume change. DESIGN: Predictors of brain volume changes were assessed prospectively based on multiple informants. SETTING: Data from the Iowa Longitudinal Study. @entity1 : Two hundred eleven @entity1 with @entity161 who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each @entity1 had 3 scans (>= 2 and as many as 5) over 7.2 years (up to 14 years). MAIN OUTCOME MEASURE: Brain volumes. RESULTS: During longitudinal follow-up, antipsychotic treatment reflected national prescribing practices in 1991 through 2009. Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors. More antipsychotic treatment was associated with smaller gray matter volumes. Progressive @entity62 was most evident among @entity1 who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and @entity167 /illicit drug misuse had no significant associations when effects of the other variables were adjusted. CONCLUSIONS: Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.
