Researchers from Canada have found that Zyprexa, an antipsychotic medication indicated for the treatment of depression, bipolar disorder and schizophrenia, may cause changes in the structure of users’ brains. According to the study authors, “Concerning animal and uncontrolled human data suggest antipsychotics are associated with change in brain structure, but to our knowledge, there are no controlled human studies that have yet addressed this question.” In order to examine the effects of antipsychotic drug treatment on brain structure in humans, the researchers conducted a double-blind, randomized trial involving 88 patients between the ages of 18 and 85, recruited from the multicenter Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). The research took place over a 36-week period at five academic centers and was published in the journal JAMA Psychiatry.
Zyprexa (olanzapine) is a popular antipsychotic drug manufactured by Eli Lilly and used to treat the symptoms of certain psychotic conditions, such as schizophrenia, and certain mood disorders, such as bipolar disorder. It may also be used in combination with other medications to treat depression. Zyprexa belongs to a class of drugs called atypical antipsychotics and works in the brain by restoring the balance of dopamine and serotonin in order to improve mood, thinking and behavior. Unfortunately, while Zyprexa and other atypical antipsychotics can be helpful in alleviating debilitating psychotic symptoms, the use of such powerful medications comes with a potential risk of serious, life-altering side effects.
The patients involved in this new JAMA Psychiatry study all suffered from major depressive disorder with psychotic features (psychotic depression) and were prescribed olanzapine (Zyprexa) and sertraline (Zoloft) for a period of 12 to 20 weeks, including eight weeks of remission of psychosis and remission/near remission of depression. The study participants were then randomized to either continue with the combination of Zyprexa and Zoloft or to be switched to Zoloft and a placebo for a subsequent 36-week period. The study participants underwent an MRI after phase one and phase two of the study in order for the researchers to analyze the impact of the drug treatment on their brain structure.
According to the researchers’ findings, there were significant decreases in cortical thickness in the left and right hemisphere among the study participants taking a combination of Zyprexa and Zoloft, but not among the patients taking Zoloft alone. Past research has established the fact that “human intellectual ability is related to brain structure including the thickness of the cerebral cortex” and a decrease in cortical thickness is often associated with neurological disorders like Alzheimer’s disease. The researchers noted that the average change in cortical thickness in aging adults 60-91 years old is between 0.35% and 0.59%. In the study, the researchers found that Zyprexa use was associated with an average loss of about 1.2% at 36 weeks, more than double the normal amount of thinning.
Antipsychotics like Zyprexa, Risperdal and Abilify are among the most widely prescribed medications in the United States, indicated to treat a wide variety of mental health disorders and also commonly prescribed off-label for attention-deficit/hyperactivity disorder (ADHD) and other behavioral disorders. And while antipsychotics can be helpful in alleviating psychotic symptoms like hallucinations, paranoia and delusions, critics argue that the drugs are being increasingly prescribed to patients without a mental health diagnosis, particularly among children, adolescents and young adults. In one 2019 study published in the journal JAMA Network Open, researchers noted that antipsychotic prescribing for youth in the United States increased by 50% from 1999 to 2014. And while some of these prescriptions were for clinical indications that have been approved by the FDA, such as bipolar disorder or schizophrenia, much of the increase has been associated with off-label use, most commonly ADHD.
The use of Zyprexa and other atypical antipsychotics has soared over the past decade, despite growing concerns about the safety and efficacy of the powerful psychotropic medications. In this new study, the researchers warn that among the potential side effects of Zyprexa is a significant change in users’ brain structure. “This information is important for prescribing in psychiatric conditions where alternatives are present,” the researchers write. “However, adverse effects of relapse on brain structure support antipsychotic treatment during active illness.”