Antipsychotic medication for schizophrenia
associated with subtle loss in brain volume
Patients with schizophrenia who take antipsychotic medications
appear to lose a small but measurable amount of brain tissue over time, according
to a report in the February issue of Archives of General Psychiatry, one of the
JAMA/Archives journals.
Schizophrenia affects 1 percent of the worldwide population and remains a leading
cause of chronic disability among young adults, according to background information
in the article. Progressive changes in brain volume observed in patients with
schizophrenia have been thought to be an effect of the disease. "However,
recent animal studies indicate that antipsychotics, the mainstay of treatment
for schizophrenia patients, may also contribute to brain tissue volume decrement,"
the authors write. "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."
Beng-Choon Ho, M.R.C.Psych., and colleagues at University of Iowa Carver College
of Medicine, Iowa City, studied 211 patients with schizophrenia who underwent
repeated neuroimaging beginning soon after their illness. Each patient had an
average of three magnetic resonance imaging (MRI) scans over 7.2 years, for a
total of 674 scans. The authors then assessed the relative contributions of four
predictors-illness duration, antipsychotic treatment, illness severity and substance
abuse?on changes in brain volume over time.
Patients who were followed for longer periods of time experienced more reductions
in brain volume. Antipsychotic treatment was also associated with brain tissue
reduction after controlling for the other three predictors. More intense antipsychotic
treatment was associated with overall measures of brain tissue loss, smaller gray
matter volume and progressive declines in white matter volume.
The other two variables, illness severity and substance abuse, had no or minimal
association with brain changes after the effects of illness duration and antipsychotic
treatment were considered.
"Findings from the present study raise several clinical questions. Are
antipsychotic-associated gray matter and white matter volume reductions 'bad'
for patients?" the authors write. Although they are assumed to be undesirable,
the benefits of long-term treatment may outweigh the risks, they note. "However,
our findings point toward the importance of prescribing the lowest doses necessary
to control symptoms."
In addition, the results raise concerns about the use of antipsychotics for
people who do not have schizophrenia, including children, older adults and patients
with bipolar or depressive disorders.
"Antipsychotics are effective medications for reducing some of the target
clinical symptoms of schizophrenia: psychotic symptoms. In medicine we are aware
of many instances in which improving target symptoms worsens other symptoms,"
the authors conclude. "It is possible that, although antipsychotics relieve
psychosis and its attendant suffering, these drugs may not arrest the pathophysiologic
processes underlying schizophrenia and may even aggravate progressive brain tissue
volume reductions."
"Although proof that antipsychotic medications cause reductions in brain
volume in individuals with schizophrenia remains elusive, the findings of Ho and
colleagues, in concert with those of the aforementioned animal studies and prior
reports in humans, raise the important question of the clinical significance of
the observed brain volume changes," writes David A. Lewis, M.D., of the University
of Pittsburgh, in an accompanying editorial.
"A classic maxim in clinical medicine is to treat the patient, not the
laboratory test?or in this case, the MRI," Dr. Lewis writes. "Thus,
the findings of Ho and colleagues should not be construed as an indication for
discontinuing the use of antipsychotic medications as a treatment for schizophrenia.
But they do highlight the need to closely monitor the benefits and adverse effects
of these medications in individual patients, to prescribe the minimal amount needed
to achieve the therapeutic goal, to consider the addition of non-pharmacological
approaches that may improve outcomes and to continue the pursuit of new antipsychotic
medications with different mechanisms of action and more favorable benefit to
harm ratios."
This research was supported in part by grants from the National Institute of
Mental Health.
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