Antipsychotic medications are the most common treatment for individuals with schizophrenia, helping to relieve some of the debilitating symptoms caused by the disorder. But according to a new study, long-term use of these drugs may also negatively impact brain structure.

[Illustration of the human brain and a pack of pills]Share on Pinterest
Researchers say long-term use of antipsychotic medications – particularly first-generation antipsychotics – may lead to gray matter loss in the brain.

First author Dr. Antonio Vita, professor of psychiatry at the University of Brescia in Italy, and colleagues publish their findings in the journal Biological Psychiatry.

Schizophrenia is estimated to affect around 1.1% of the US population. It is a chronic mental disorder characterized by dysfunctional thinking, delusions, hallucinations and agitated body movements.

The exact causes of schizophrenia remain unclear. As such, there is no cure for the disorder, with current treatments focusing on alleviating symptoms of the condition.

Antipsychotic medications are the first port of call for people with schizophrenia, relieving symptoms by altering the effects of chemicals in the brain that impact behavior, mood and emotion, such as dopamine and serotonin.

There are two classes of antipsychotic medications – first- and second-generation antipsychotics. First-generation antipsychotics – such as chlorpromazine and haloperidol – have been available since the mid-1950s. While effective, they been associated with severe neurological side effects.

Second-generation antipsychotics – such as clozapine and lurasidone – are costlier than first-generation medications, but they are preferred because they pose lower risk of serious side effects.

Previous studies involving brain imaging of patients with schizophrenia have identified continuous abnormalities in brain structure, which researchers have linked to duration of antipsychotic drug use.

However, Dr. Vita and colleagues point out that these studies failed to account for whether patients used first- or second-generation antipsychotics, which they say work differently in the brain.

As such, the team set out to investigate the impact of first- and second-generation antipsychotics on the brain structure of 1,155 individuals with schizophrenia, comparing them with 911 healthy controls. Participants were selected from 18 brain imaging studies.

The researchers found that individuals with schizophrenia treated with antipsychotics demonstrated progressive loss of gray matter in the brain, compared with healthy controls.

Perhaps most importantly, however, the team found that the long-term use of first-generation antipsychotics was associated with greater progressive loss of gray matter, while the use of second-generation medications “did not correlate with GM [gray matter] volume changes over time and was not associated with cortical tissue loss.”

The researchers add:

[…] There is evidence to suggest that antipsychotic treatment may have a contributory role in reducing the volume of cortical GM in schizophrenia, but this effect cannot be generalized and appears to be far less evident for SGAs [second-generation antipsychotics], which results in being associated with less loss of brain tissue.”

While Dr. Vita hails these results as “clinically meaningful,” he says issues remain that need to be addressed. For example, he notes that it is still unclear whether the effects of antipsychotics on the brain vary by a patient’s age or stage of illness, or whether there is a particular dosage that leads to changes in brain structure.

“Clarification of these issues will have crucial importance in the clinical management of schizophrenia and will allow a better understanding of the mechanisms underlying the progression of structural brain abnormalities in the disease,” adds Dr. Vita.

Medical News Today recently reported on a study that found individuals with schizophrenia have different throat microbes to those without the disorder – a finding researchers say could aid new diagnosis and treatment strategies for the condition.