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Do Antipsychotics Shrink Your Brain? Should You Care?

Blogger Natasha Tracy explores new research into the effects of antipsychotics—one form of treatment for bipolar disorder—and brain mass.

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A brain scanAntipsychotics (like quetiapine (Seroquel), olanzapine (Zyprexa), or aripiprazole (Abilify)) are actually now the highest-grossing psychiatric medication, ahead of even antidepressants. Antipsychotics (also known as neuroleptics or major tranquilizers) were initially prescribed for psychotic disorders like schizophrenia, but now are commonly prescribed for bipolar disorder and even hard-to-treat depression.

And while it has been shown that antidepressants can actually increase brain volume, there is a concern that antipsychotics decrease brain volume—they cause the brain to shrink.

Maybe.

Last year in the Archives of General Psychiatry, University of Iowa psychiatry professor Beng Choon Ho and colleagues published an article looking at the long-term effects of antipsychotics on the brain. This was a ground-breaking study in that it followed a relatively large group of people with schizophrenia for a fairly long time (211 patients, up to 14 years). Neuroimaging was used to look at brain masses to try and track the brain mass loss over the course of the illness and identify possible predictors.

This study did point out many interesting things, not the least of which was increasing brain volume loss over the course of the study as patients were treated with various antipsychotics. Patients were treated naturalistically (in other words, in a way decided upon by their individual doctor and not in a pre-set manner).

In short, Ho and colleagues found:

  • longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes
  • greater intensity of antipsychotic treatment (larger doses) was associated with indicators of generalized and specific brain tissue reduction 
  • 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 
  • alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted

Pretty damning evidence for antipsychotics.

But there are a few things to remember when looking at this data, and the important one is this: we know that people with schizophrenia already suffer brain volume loss before they are even treated. Moreover, the above study did not include a group of people with schizophrenia who received no treatment (for ethical reasons, obviously) with which to compare these results.

So for all we know, these brain volume losses may be primarily due to the schizophrenia and not the medication. There is also no comparison to another population (say, well people, or people with bipolar disorder) taking antipsychotics.

However, it does appear that some of the brain loss is related to the antipsychotic medication itself as differences were seen in brain volume loss when comparing different types of antipsychotics.

Should We Care About Brain Shrinkage?

While it seems natural to assume that brain shrinkage is bad, it may be the case that occasionally it is good. One theory of psychosis, for example, is that there is an overexcitement of dopamine in the brain and one must decrease the dopamine activity to treat the psychosis (this is partially how antipsychotics are thought to work).

Another study recently showed that electroconvulsive therapy may actually produce its antidepressant effect by reducing certain functional connectivity.

So it is possible that the reduction in certain areas of the brain may be therapeutic when treating schizophrenia? We just don’t know.

What does seem to be prudent, given the data, is to use fewer antipsychotics and not more—to reduce antipsychotic use and reduce dosage when possible. And it’s important to remember that even if we do determine that antipsychotics are shrinking parts of the brain, that risk may still be well worth the reward of treating a serious psychiatric disorder.

For all the details please see: Long-term Antipsychotic Treatment and Brain Volumes in the Archives of General Psychiatry.

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About the Author

Natasha Tracy is an award-winning writer who specializes in writing about bipolar disorder.

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