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.
To compare the effect of different medication combinations on psychiatric hospitalizations and other mental and physical health outcomes for people with schizophrenia
|Design||Observational: cohort study|
|Population||Medicaid claims of 81,921 adults with schizophrenia ages 18–64 currently taking an antipsychotic medication|
Primary: psychiatric hospitalization
Secondary: psychiatric ED visits, new-onset diabetes mellitus, all-cause mortality, self-injury, cardiovascular event
|Timeframe||1-year follow-up for primary outcome|
This retrospective cohort study examined treatment outcomes for people who already take an antipsychotic medication to treat their schizophrenia and who started another psychotropic medication. The research team compared the mental and physical health outcomes of people who added one of three different classes of psychotropic medications to those of people who added a second antipsychotic medication. The three classes of psychotropic medications were antidepressants, benzodiazepines, and mood stabilizers.
The research team reviewed Medicaid claims data from 2001 to 2010 across 44 states. The analysis included data for 81,921 adults with schizophrenia. Of these people, 39% were black, 36% were white, 3% were Asian, 2% were Hispanic, 1% was Hawaiian or Pacific Islander, 10% were more than one race, and 10% were unknown. The average age was 40, and 54% were male.
An advisory committee including patients, family members, policy makers, clinicians, and a health insurance representative provided input throughout the study. A patient advocate also contributed to discussions about analyses, results, and the implications of findings.
Compared with people who added a second antipsychotic medication,
- People who added an antidepressant had a lower risk of psychiatric hospitalization (hazard ratio [HR]=0.84; 95% confidence interval [CI]: 0.80, 0.88), psychiatric emergency department (ED) visits (HR=0.92; 95% CI: 0.88, 0.96), and developing diabetes (HR=0.88; 95% CI: 0.81, 0.96). They had a similar risk of death from all causes.
- People who added a benzodiazepine had a higher risk of psychiatric hospitalization (HR=1.08; 95% CI: 1.02, 1.15) and psychiatric ED visits (HR=1.12; 95% CI: 1.07, 1.19). They had a similar risk for developing diabetes and death from all causes.
- People who added a mood stabilizer had a similar risk for psychiatric hospitalizations, psychiatric ED visits, and developing diabetes. They had an increased risk of death from all causes (HR=1.31; 95% CI: 1.04, 1.66).
Patients across the treatment groups did not differ in risk for self-injury or cardiovascular events.
As an observational study, unknown variables may explain the associations the research team found. The study included adults ages 18–64 with Medicaid. Results may differ for older people and those with other types of insurance.
Conclusions and Relevance
For people in this study who were already taking an antipsychotic medication to treat schizophrenia, compared with adding a second antipsychotic medication, adding an antidepressant reduced the risk of negative outcomes and adding a benzodiazepine or a mood stabilizer increased those risks. These findings can help inform treatment decisions for people with schizophrenia when taking a single antipsychotic is not sufficient for managing their mental health symptoms.
Future Research Needs
Future research could test these findings using prospective or randomized study designs. Researchers could also explore when it is most beneficial to add antidepressants to treatment for schizophrenia.
Final Research Report
View this project's final research report.
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.
Results of This Project
Related Journal Citations
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
Study Registration Information
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