Results Summary

What was the research about?

Schizophrenia is a serious mental health problem that can affect how a person thinks, feels, and behaves. It may cause people to see or hear things that aren’t there. Standard treatment includes medicine and therapy. Many people with schizophrenia take more than one medicine at a time to treat their mental health symptoms.

In this study, the research team wanted to learn how different combinations of medicines affected people with schizophrenia. The team looked at Medicaid records for people who were already taking an antipsychotic medicine, the most common type of medicine doctors use to treat schizophrenia, and then added one of the following types of medicines:

  • An antidepressant. This is a medicine doctors often use to treat depression.
  • A benzodiazepine. This is a medicine doctors often use to treat anxiety.
  • A mood stabilizer. This is a medicine doctors often use to treat strong mood swings.

The research team compared people who added one of these types of medicine with people who instead started using a second antipsychotic medicine.

What were the results?

Compared with people with schizophrenia who started using a second antipsychotic medicine,

  • People who instead added an antidepressant had a lower risk of going to an emergency room or a hospital for a mental health issue and a lower risk of getting diabetes
  • People who instead added a benzodiazepine had a higher risk of going to the hospital or emergency room for a mental health issue
  • People who instead added a mood stabilizer had a higher risk of dying from any cause

People across the groups had a similar risk of hurting themselves on purpose or having a heart attack or stroke.

Who was in the study?

The research team looked at Medicaid records for 81,921 adults ages 18–64 with schizophrenia. Of these people, 39 percent were black, 36 percent were white, 3 percent were Asian, 2 percent were Hispanic, and 1 percent was Hawaiian or Pacific Islander. In addition, 10 percent were more than one race, and 10 percent were an unknown race. The average age was 40, and 54 percent were men.

What did the research team do?

The research team looked at Medicaid records from 2001 to 2010 across 44 states. The team compared what happened to people already taking an antipsychotic for one year after they started one of the four additional types of medicines to treat their schizophrenia.

A patient advocate and a group including patients, family members, policy makers, and clinicians gave input to the research team throughout the study.

What were the limits of the study?

The research team didn’t assign people by chance to add the different medicines. For this reason, the team can’t say for sure that the type of medicine added was the reason for the difference in risks. This study only included people ages 18–64 who had Medicaid. Results may differ for people of other ages or with other insurance.

Future studies could follow patients taking the different types of medicines going forward instead of looking at past records. Researchers could also look more closely at when adding an antidepressant medicine is best for treating people with schizophrenia.

How can people use the results?

People with schizophrenia and their doctors can use these results when considering adding medicines to their treatment.

Final Research Report

View this project's final research report.

Journal Citations

Article Highlight: This study reviewed how different drug combinations work for people with schizophrenia, who often take several medications to treat different symptoms of their disease. Through a review of 81,921 Medicaid records, the researchers found that people already taking an antipsychotic drug had different benefits and negative outcomes when they used another antipsychotic or added an antidepressant, anti-anxiety medication or mood stabilizer. These results, in JAMA Psychiatry, can help people with schizophrenia and their doctors when they consider adding medicines to patients’ treatment plans.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented, and the researchers made changes or provided responses. The comments and responses included the following:

  • Reviewers asked if the individuals analyzed in this study had been required to stay on their original antipsychotic medication. The researchers responded that patients were not necessarily required to continue the first antipsychotic after the patients started a new psychotropic medication. However, patients had an active supply of antipsychotic medication when starting the new medication. For instance, if patients started a new antipsychotic medication, this could indicate a switch between two similar medications or an addition to their treatment regimen.
  • Reviewers noted, based on Figure 2, that psychotropic polypharmacy led to the exclusion of a large number of patients from the study and that this could effect the generalizability of findings. The researchers agreed. They added a comment to the discussion that because this polypharmacy is so common, it is an important topic to consider in future research.
  • Reviewers noted that the report mentioned surveying clinicians about treatment choices and suggested that surveying patients could have helped determine which outcomes matter most to them. The researchers responded that they had conducted a small survey with clinicians when applying for funding.  They acknowledged that patients would find other outcomes important as well, but also stated that patients saw hospitalizations, emergency department visits, and deaths as important outcomes.

Conflict of Interest Disclosures

Project Information

Thomas S. Stroup, MD, MPH
Columbia University Health Sciences
Comparative Effectiveness of Adaptive Pharmacotherapy Strategies for Schizophrenia

Key Dates

July 2014
June 2019

Study Registration Information


Has Results
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Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
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Last updated: January 20, 2023