In 1991, Nancy Andreasen began a long-running study of first-episode patients, which involved periodically measuring their brain volumes with magnetic resonance scans. In articles published in 2003 and 2005, she reported finding "progressive brain volume reductions" in her patients, and that this shrinkage was associated with a worsening of negative symptoms, functional impairment and . But the implication was that this shrinkage was due to the disease, and that the drugs simply failed to stop it.

"The medications currently used cannot modify an injurious process occurring in the brain, which is the underlying basis of symptoms," Andreasen wrote in her 2003 paper.

However, even as she was publishing those findings, other research--in animals and schizophrenia patients--indicated that the drugs might exacerbate this brain shrinkage (or be the primary cause of it.) Then, in a 2008 interview with the New York Times, Andreasen confessed that the "more drugs you have been given, the more brain tissue you lose."

This was something of a bombshell, particularly since it came from Andreasen, who was editor-in-chief of the American Journal of Psychiatry from 1993 to 2005. Now, in the February issue of the Archives of General Psychiatry, she has published those findings, and thus the bombshell has officially landed in the scientific literature.

In this study, Andreasen took periodic MRI scans of 211 schizophrenia patients treated from seven years to 14 years. She found that long-term use of the old standard , the new atypical antipsycotics, and clozapine are all "associated with smaller brain tissue volumes."

Moreover, she found that this shrinkage was dose related. The more drug a person is given, the greater the "association with "smaller grey matter volumes," she reported. Similarly, the "progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment." Finally, Andreasen reported that this shrinkage "occurs independent of illness severity and ." Those two factors--illness severity and substance abuse--had "minimal or no effects" on brain volumes.

In this February report, Andreasen does not tie the drug-related brain shrinkage to an increase in negative symptoms, functional impairment, and cognitive decline. But in earlier articles, she did just that. And it is that larger context that makes this February report such a bombshell: When pieced together, this is a story of drug treatment that, over the long-term, causes long-term harm.

The other reason this is such a bombshell is that antipsychotics are widely prescribed now to children, often to control their "behavior," and to adults with diagnoses. They are being used to treat "non- " conditions. The risk-benefit analysis for those patients will be dramatically changed by the findings of this study.

One hopes that the study will be widely publicized in the media, and it will stir a vigorous discussion. Here are a few of the questions that I believe need to be asked:

Does long-term use of antipsychotics for people diagnosed with psychotic disorders need to be rethought?

Is there reason to prescribe these drugs to people with non-psychotic disorders?

Should the prescribing of these drugs to children and youth, whose brains are still developing, be halted (or, in essence, banned?)

Many adults diagnosed with disorders are mandated by court orders to take antipsychotics. Should society have the right to require such treatment, given that the drugs shrink brain volumes and this shrinkage is associated with cognitive decline?

For some time, here has been reason to believe that antipsychotics shrink the brain, and I wrote about this in Anatomy of an Epidemic. But this worry has largely been kept out of the public domain. Perhaps now it will become a public concern, and in particular, one hopes that our society now takes a hard look at whether prescribing such drugs to children is a good thing to do.