A long-awaited, 14 year magnetic imaging (MRI) follow-up study by Dr. Nancy Andreasen, involving 211 patients, documents progressive shrinkage of brain tissue volume in patients prescribed antipsychotics when they first experienced an episode of psychosis.

The findings, published in The Archives of General Psychiatry (abstract below) show a direct causal relationship between dosage, duration of exposure to antipsychotics, and brain shrinkage:

• "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 decrement in white matter volume was most evident among  patients who received more antipsychotic treatment.

The finding corroborates animal studies:

• "The plausibility of long-term antipsychotic treatment leading to global brain volume reductions is further supported by recent controlled studies in macaque monkeys."

•  "These findings are also consistent with previous MRI studies suggesting that antipsychotics produce changes in the human brain that are measurable by in vivo neuroimaging techniques."

 The mechanism by which these drugs cause brain damage, as Dr. Andreasen explained in an interview in The New York Times (2008):

•  "these drugs... block basal ganglia activity. The prefrontal cortex doesn't get the input it needs and is being shut down by drugs. That reduces      the psychotic symptoms. It also causes the prefrontal cortex to slowly atrophy."

• "Another thing we've discovered is that the more drugs you've been given, the more brain tissue you lose."

See: http://www.ahrp.org/cms/content/view/606/9/

In the same NYT interview, Dr. Andreasen acknowledged that she "sat on these findings for a couple of years"--deliberately holding back publication.

Don't medical researchers have a public responsibility to disclose a finding of a causal relationship between a particular class of drugs and brain damage? 

 Antipsychotics have been shown to induce (iatrogenic) diseases, including: diabetes, metabolic, cardiovascular, hormonal abnormalities, and brain damage.

 Despite the debilitating, life-threatening risks posed by antipsychotics, US Psychiatrists embraced these drugs--prescribing them for ever more, unapproved, off-label uses--even for young children--despite the demonstrable ravages produced by antipsychotics.

 Psychiatry's academic leadership under the influence of industry $$$ have been the facilitators who helped manufacturers turn toxic drugs that undermine health and shorten lives, into industry's blockbuster profit makers. These psychiatrists should be held accountable.

Vera Hassner Sharav

Archives of General Psychiatry. 2011;68(2):128-137
Long-term Antipsychotic Treatment and Brain Volumes
A Longitudinal Study of First-Episode Schizophrenia

Beng-Choon Ho, MRCPsych; Nancy C. Andreasen, MD, PhD; Steven Ziebell, BS; Ronald Pierson, MS; Vincent Magnotta, PhD

Context:  Progressive brain volume changes in schizophrenia are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for schizophrenia patients, may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders, it is imperative to determine their long-term effects on the human brain.

 Objective:  To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change.

 Design: Predictors of brain volume changes were assessed prospectively based on multiple informants.

 Setting  Data from the Iowa Longitudinal Study.

 Patients  Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each patient 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 decrement in white matter volume was most evident among patients who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/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.