The placebo effect is a powerful and well-documented phenomenon: Patients improve because they think they are receiving a medication, yet they are actually taking a sugar pill. How the brain creates the placebo effect is an ongoing area of research, but the need for quick answers is acute for researchers doing clinical trials of psychiatric medications. In antipsychotic trials for the treatment of schizophrenia and bipolar disorder, and in antidepressant trials, the placebo effect is growing stronger over time, making it more difficult for a new medication to be proven effective against placebo.

The difficulty in proving efficacy in current medications has discouraged many major pharmaceutical companies from continuing to invest in new psychiatric medication development. Given the serious limitations of the antipsychotics that are currently available, identifying and reducing the factors that contribute to such a powerful placebo response is critical to support the development of new treatments.

2009 NARSAD Young Investigator Grantee Bret Rutherford, M.D., of Columbia University, recently led an analysis of 105 clinical trials of antipsychotic medications conducted between 1960 and 2013 with patients with schizophrenia or schizoaffective disorder. The research team examined the placebo response over time in an effort to pinpoint possible contributors to the problem. Their results were published online October 8th in JAMA Psychiatry.

Consistent with previous studies, the researchers confirmed that patients in the placebo group over the course of the past 50 years have reported increasing levels of symptom improvement. Dr. Rutherford and colleagues, including Foundation Scientific Council Member and two-time NARSAD Distinguished Investigator Grantee Jeffrey Lieberman, M.D., also of Columbia University, identified several factors that may be responsible for this effect: increasing patient expectations of symptom improvement (patients believing that they are receiving a medication that will help them get better); a shift from clinical trials conducted primarily at a few academic centers to a large number of non-academic trial sites; and an increasing recruitment of patients with less severe symptoms.

The researchers recommend that future clinical trials should be designed to minimize the patients’ expectations of receiving the active medication and that recruitment for trials should exclude patients with only mild symptoms.  

Read the abstract of this research paper.

Read more about this research from the Schizophrenia Research Forum.