Stable Schizophrenia Not Necessarily Protective Against Relapse-Related Mortality

Just one relapse episode significantly increased all-cause mortality in people with relatively stable schizophrenia, a longitudinal study of database claims indicated.

Among 32,071 patients followed for an average of 40 months, any number of relapses was associated with a significantly higher risk for mortality, reported Christoph Correll, MD, of the Zucker School of Medicine at Hofstra/Northwell in New York City, at Psych Congress in Boston:

• One relapse: HR 1.20 (95% CI 1.14-1.26)
• Two relapses: HR 1.41 (95% CI 1.30-1.53)
• Three relapses: HR 1.62 (95% CI 1.45-1.81)
• Four relapses: HR 1.83 (95% CI 1.61-2.07)
• Five relapses: HR 2.02 (95% CI 1.77-2.32)
• 10 relapses: HR 2.63 (95% CI 2.02-3.42)

Estimated 5-year survival was 78% for patients with one relapse episode and only 58% for patients with 10 relapse episodes. For patients with five relapses, survival was only 50% within 7 years.

Schizophrenia significantly shortens life expectancy by an estimated 15 years with excess mortality arising from multiple causes, such as physical health complications and suicide, Correll told MedPage Today.

“The findings were both partially expected and also surprising, but very impactful in any case,” he said, adding how these data underscore the importance of preventing relapses in patients with schizophrenia.

“Clinicians should focus on early interventions and treatment adjustments, such as transitioning even stable patients to long-acting injectable (LAI) antipsychotics to improve adherence, reduce relapse rates, and also increase changes of patient survival,” he added. “Relapse prevention can be a crucial part of extending the lifespan of individuals with schizophrenia, also of increasing their health span through stabilized symptomatology, improved healthy lifestyle behaviors and increased functionality that are associated with absent relapsed and with LAI antipsychotic treatment.”

Relapse management isn’t just about controlling symptoms, but about addressing broader health implications that can impact long-term survival of patients with schizophrenia, said Correll. “Encouraging medication adherence, managing comorbidities, and providing comprehensive care are essential strategies to reduce relapse risks, improve the quality of life and increase life expectancy for patients with schizophrenia.”

Correll and colleagues looked at de-identified patient data in Optim’s Clinformatics Data Mart Database, which included events from January 2011 to December 2019. The final cohort included adults who had at least two outpatient claims on separate dates, or one or more inpatient claims with a schizophrenia diagnosis between 2012 and 2019. All were relatively stable with at least 12 months of continuous pre-index enrollment without a relapse, and received at least one antipsychotic medication during the year-long baseline period.

Relapses were considered as a claim of mental health-related inpatient hospitalization suicide attempt, self-inflicted harm, or injury, homicidal ideation, aggressive or violent behavior, hostility, or incarceration.

Among the coh9ort, 51% were male, average age was 57.6, and most were on a second-general oral antipsychotic (82.7%). Use of first-or second-generation LAI antipsychotics was uncommon (

During follow-up, the average number of relapses was 0.53 and 28.6% patients experienced a relapse. Most of the patients who had a relapse experienced one episode (53.4) or two episodes (20%). A total of 3,974 (12.4%) of patients died during the study period.

Because not all indicators of relapse were represented in the claims data, there may have been an undercounting of relapse episodes. Underreporting of patient deaths in the database were also possible, the researchers pointed out.

“Additional research evaluating cause-specific mortality associated with relapse would be helpful in identify key preventative strategies,” Correll’s group suggested.