Long-term Antipsychotic Treatment and Brain Volumes
A Longitudinal Study of First-Episode Schizophrenia
http://archpsyc.ama-assn.org/cgi/content/short/68/2/128
Beng-Choon Ho, MRCPsych; Nancy C. Andreasen, MD, PhD; Steven Ziebell, BS; Ronald Pierson, MS; Vincent Magnotta, PhD
Arch Gen Psychiatry. 2011;68(2):128-137. doi:10.1001/archgenpsychiatry.2010.199
Context Progressive brain volume changes in schizophreniaare thought to be due principally to the disease. However, recentanimal studies indicate that antipsychotics, the mainstay oftreatment for schizophrenia patients, may also contribute tobrain tissue volume decrement. Because antipsychotics are prescribedfor long periods for schizophrenia patients and have increasinglywidespread use in other psychiatric disorders, it is imperativeto determine their long-term effects on the human brain.
Objective To evaluate relative contributions of 4 potentialpredictors (illness duration, antipsychotic treatment, illnessseverity, and substance abuse) of brain volume change.
Design Predictors of brain volume changes were assessedprospectively based on multiple informants.
Setting Data from the Iowa Longitudinal Study.
Patients Two hundred eleven patients with schizophreniawho underwent repeated neuroimaging beginning soon after illnessonset, yielding a total of 674 high-resolution magnetic resonancescans. On average, each patient had 3 scans (2 and as many as5) over 7.2 years (up to 14 years).
Main Outcome Measure Brain volumes.
Results During longitudinal follow-up, antipsychotic treatmentreflected national prescribing practices in 1991 through 2009.Longer follow-up correlated with smaller brain tissue volumesand larger cerebrospinal fluid volumes. Greater intensity ofantipsychotic treatment was associated with indicators of generalizedand specific brain tissue reduction after controlling for effectsof the other 3 predictors. More antipsychotic treatment wasassociated with smaller gray matter volumes. Progressive decrementin white matter volume was most evident among patients who receivedmore antipsychotic treatment. Illness severity had relativelymodest correlations with tissue volume reduction, and alcohol/illicitdrug misuse had no significant associations when effects ofthe other variables were adjusted.
Conclusions Viewed together with data from animal studies,our study suggests that antipsychotics have a subtle but measurableinfluence on brain tissue loss over time, suggesting the importanceof careful risk-benefit review of dosage and duration of treatmentas well as their off-label use.
Author Affiliations: Departments of Psychiatry (Drs Ho and Andreasen and Messrs Ziebell and Pierson) and Radiology (Dr Magnotta), University of Iowa Carver College of Medicine, Iowa City.
A Longitudinal Study of First-Episode Schizophrenia
http://archpsyc.ama-assn.org/cgi/content/short/68/2/128
Beng-Choon Ho, MRCPsych; Nancy C. Andreasen, MD, PhD; Steven Ziebell, BS; Ronald Pierson, MS; Vincent Magnotta, PhD
Arch Gen Psychiatry. 2011;68(2):128-137. doi:10.1001/archgenpsychiatry.2010.199
Context Progressive brain volume changes in schizophreniaare thought to be due principally to the disease. However, recentanimal studies indicate that antipsychotics, the mainstay oftreatment for schizophrenia patients, may also contribute tobrain tissue volume decrement. Because antipsychotics are prescribedfor long periods for schizophrenia patients and have increasinglywidespread use in other psychiatric disorders, it is imperativeto determine their long-term effects on the human brain.
Objective To evaluate relative contributions of 4 potentialpredictors (illness duration, antipsychotic treatment, illnessseverity, and substance abuse) of brain volume change.
Design Predictors of brain volume changes were assessedprospectively based on multiple informants.
Setting Data from the Iowa Longitudinal Study.
Patients Two hundred eleven patients with schizophreniawho underwent repeated neuroimaging beginning soon after illnessonset, yielding a total of 674 high-resolution magnetic resonancescans. On average, each patient had 3 scans (2 and as many as5) over 7.2 years (up to 14 years).
Main Outcome Measure Brain volumes.
Results During longitudinal follow-up, antipsychotic treatmentreflected national prescribing practices in 1991 through 2009.Longer follow-up correlated with smaller brain tissue volumesand larger cerebrospinal fluid volumes. Greater intensity ofantipsychotic treatment was associated with indicators of generalizedand specific brain tissue reduction after controlling for effectsof the other 3 predictors. More antipsychotic treatment wasassociated with smaller gray matter volumes. Progressive decrementin white matter volume was most evident among patients who receivedmore antipsychotic treatment. Illness severity had relativelymodest correlations with tissue volume reduction, and alcohol/illicitdrug misuse had no significant associations when effects ofthe other variables were adjusted.
Conclusions Viewed together with data from animal studies,our study suggests that antipsychotics have a subtle but measurableinfluence on brain tissue loss over time, suggesting the importanceof careful risk-benefit review of dosage and duration of treatmentas well as their off-label use.
Author Affiliations: Departments of Psychiatry (Drs Ho and Andreasen and Messrs Ziebell and Pierson) and Radiology (Dr Magnotta), University of Iowa Carver College of Medicine, Iowa City.
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