Side Effects of Antipsychotic Zyprexa Linked to Changes in Brain Structure: Study

Use of the atypical antipsychotic drug Zyprexa for severe depression may lead to changes in the structure of the brain, according to the findings of new research.

In a study published last week in the medical journal JAMA Psychiatry, researchers from Canada report that side effects of olanzapine, known under the brand name Zyprexa, may lead to significantly reduced cortical thickness in the brain.

Researchers conducted a double-blind, randomized, placebo-controlled trial over a 36-week period at five academic centers. The study included 88 patients ages 18 to 85 recruited from the multi-center Study of the Pharmacotherapy of Psychotic Depression II.

The focus was on how antipsychotic medication affects brain structure. All participants had major depressive disorder with psychotic features, who were prescribed Zyprexa (olanzapine) and Zoloft (sertraline) for 12 to 20 weeks. Patients who experienced remission from their depressive symptoms for at least eight weeks were then randomized into two groups. The first continued with the combination of both medications. The second group was given a placebo instead of Zyprexa and only given Zoloft. This second phase was continued for 36 weeks.

Patients underwent a magnetic resonance imaging (MRI) study after the first phase before they were randomized. They were then given a second MRI at the end of the 36-week period.

Researchers noted significant changes in the brain structures of patients who had psychotic depression and were taking both Zyprexa and Zoloft, but not among the patients only taking Zoloft. The data indicated Zyprexa compared to placebo was linked to a decline in cortical thickness.

Cortex thickness is often associated with cognitive abilities. In aging patients, cortical thickness often begins to decrease. Cortical thinning is often linked to Alzheimer’s disease.

Patients who had a relapse of psychotic depression and were receiving Zyprexa experienced a decline in cortical thickness in both the left and right hemisphere of the brain.

Patients taking both Zyprexa and Zoloft did experience fewer depressive relapses once they were in remission.

Researchers noted the cortical thinning caused an average loss of about 1.2% of the cortex at 36 weeks of Zyprexa use. Comparatively, the average change in cortical thickness across the adult life span is 0.35% and 0.59% in normal aging individuals 60-91 years old. The thinning seen in the study was roughly double to triple the normal amounts.

The findings of the study should spur researchers and doctors to reconsider the risks and benefits of prescribing antipsychotics, the researchers determined.

“This information is important for prescribing in psychiatric conditions where alternatives are present,” wrote the study authors. “However, adverse effects of relapse on brain structure support antipsychotic treatment during active illness.”