A Psychiatry study” href="https://archpsyc.ama-assn.org/cgi/content/abstract/68/2/128" target="_blank">new study finds that one the fastest-growing classes of prescription drugs in the United States is linked to shrinkage in the brains of those who take it, raising some new questions about the widening use of NIH overview of antipsychotic medications” href="https://www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.shtml#pub4" target="_blank">antipsychotic medications.

Over a study period that spanned 14 years, 211 newly diagnosed schizophrenic patients had periodic brain scans that measured the volume of their brains overall, and of their brains’ principal component structures. Scanning each subject’s brain at least twice and as many as five times, researchers at the University of Iowa’s Carver College of Medicine sought to tease apart the factors that might contribute to a long-observed phenomenon: that patients with psychiatric disease—particularly those who suffer the delusional thinking, hallucinations and cognitive deficits of schizophrenia—appear to have smaller brains than those in good mental health.

What they found was that those whose treatment with antipsychotic medication was most “intensive”—those who took the largest doses over the longest time--had the greatest losses in brain volume. The intensity of a subject’s antipsychotic medication therapy was a far stronger predictor of brain-volume loss than was the severity of his or her psychiatric symptoms or of the extent of his or her illicit drug or alcohol abuse, the researchers found.

The volume losses were scattered throughout the brain, occurring in gray matter--the tightly packed clusters of brain cells that make up most of the brain’s lobes--as well as in the connective “white matter” that forms communication channels among the brain’s disparate regions and between its two hemispheres.


The study, published Monday in the Archives of General Psychiatry, comes against the backdrop of growing use of antipsychotic medications by younger and younger patients, as well as by patients with a wider range of psychiatric troubles, including anxiety or depression that has not yielded to first-line antidepressant drugs. Aggressive marketing of a new generation of antipsychotic drugs called the “atypicals” have made this class of drugs the top sellers in the U.S. prescription drug market, raking in $300.3 billion in sales in 2009 alone, according to IMS Health, which tracks trends in the healthcare and pharmaceutical markets.

The use of antipsychotic medications in treatment of a wider range of illnesses is also exposing more patients to these drugs, which also have been linked to metabolic changes and weight gain that can be extreme. In 2009, IMS Health estimates that U.S. consumers filled 52 million prescriptions for atypical antipsychotic medications, which account for the vast bulk of antipsychotic medications prescribed today.

“Given the sharp rise in antipsychotic utilization, especially among geriatric and pediatric populations, examining the possibility of antipsychotic brain tissue loss has important implications for assessing the risk benefit ratio in a large number of psychiatric patients,” the researchers wrote.

In an accompanying editorial, University of Pittsburgh psychiatrist David A. Lewis cautioned that the findings should not prompt discontinued use of the medications by those in treatment for schizophrenia. But he wrote that they “do highlight the need” for physicians to prescribe the minimal effective dose of these medications, to monitor their effectiveness in taming symptoms, and to consider other, non-drug treatments that can improve patients’ ability to function. While cautioning that the study falls short of demonstrating that antipsychotic medications caused the loss of brain volume, Lewis also called for continued efforts to find safer drugs for the treatment of serious mental illness.