Sustained use of the antipsychotic olanzapine in patients with remitted psychotic depression was associated with a thinning of the cortex, when compared with placebo, according to a study published online in JAMA Psychiatry.
“We found that the mean reduction in cortical thickness caused by 36 weeks of exposure to olanzapine is equivalent to loss of approximately 1.2% of a person’s cortex,” researchers wrote. “For context, mean annual change in cortical thickness across the adult life span is 0.35% and 0.59% in normal aging individuals aged 60 to 91 years.”
The double-blind, randomized study was a prespecified secondary analysis of a trial that took place at 5 academic centers. Adults up to 85 years of age who were diagnosed with major depressive disorder with psychotic features received olanzapine and the antidepressant sertraline for up to 5 months. After psychosis remission and remission or near remission of depression, participants were randomized to either continue olanzapine and sertraline or switch to placebo and sertraline for an additional 9 months.
Among 72 participants who received magnetic resonance imaging (MRI) scans at the time of randomization and then again after 36 weeks or at symptom relapse, researchers found significant decreases in cortical thickness in patients who continued olanzapine compared with those who switched to placebo.
However, MRI scans also revealed potential decreases in cortical thickness in another group of patients: those switched to placebo who went on to experience a relapse of psychotic symptoms (compared with patients switched to placebo who sustained remission).
“When taken together,” researchers wrote, “both olanzapine and illness relapse have an effect on brain structure.”
All in all, researchers believe their findings could have an immediate effect on current clinical practice.
“Antipsychotic medications remain the cornerstone of treatment for primary psychotic illnesses, but caution should be exercised with their off-label use for other conditions when psychosis is not present,” said researcher Aristotle Voineskos, MD, PhD, chief of the schizophrenia division at the Centre for Addiction and Mental Health in Toronto, Canada. “This may be especially true in children and the elderly, when the brain is changing more rapidly.”
Voineskos AN, Mulsant BH, Dickie EW, et al. Effects of antipsychotic medication on brain structure in patients with major depressive disorder and psychotic features: neuroimaging findings in the context of a randomized placebo-controlled clinical trial. JAMA Psychiatry. 2020 February 26;[Epub ahead of print].