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Antipsychotics may reduce mortality in schizophrenia

 

Key clinical point: Antipsychotic agents appear to reduce all-cause mortality risk in schizophrenia.

Major finding: The all-cause mortality rate was 85% lower when patients with schizophrenia were on a second-generation long-acting injectable antipsychotic than when not taking an antipsychotic.

Data source: An observational study of the association between antipsychotic medication use and all-cause mortality over the course of more than half a decade in nearly 30,000 Swedish schizophrenia patients.

Disclosures: The study was funded by Janssen-Cilag. The presenter reported serving as a consultant to that pharmaceutical company and a half-dozen others.


 

AT THE ECNP CONGRESS

 

– All-cause mortality was 46% lower while schizophrenia patients were on antipsychotic agents than when off therapy in a nationwide observational study of nearly 30,000 Swedes with schizophrenia – and the biggest risk reduction occurred in patients on second-generation long-acting injectables, according to Jari Tiihonen, MD, PhD.

“The guidelines say there are special situations where you should consider using depot antipsychotics. I think the guidelines got it wrong. I think the right way to think of it is there are special situations where you might consider oral agents; otherwise you should use long-acting injectables,” said Dr. Tiihonen, who holds joint appointments as professor of psychiatry at the University of Eastern Finland in Kuopio and the Karolinska Institute in Stockholm.

Dr. Jari Tiihonen professor of psychiatry at the University of Eastern Finland in Kuopio and the Karolinska Institute in Stockholm Bruce Jancin/Frontline Medical News
Dr. Jari Tiihonen
At the annual congress of the European College of Neuropsychopharmacology, he presented an analysis of prospectively gathered national registry data on all 29,823 Swedes aged 16-64 who carried a diagnosis of schizophrenia during 2006.

During a mean follow-up of 5.7 years, 8.4% of the patients died. In a multivariate Cox regression analysis adjusted for 20 potential confounding variables, including age, sex, time since diagnosis, education, and comorbid conditions, the all-cause mortality was 46% lower when patients were on an antipsychotic agent than when off therapy.

The lowest mortality was observed in patients on a second-generation long-acting injectable (LAI) antipsychotic agent. Specifically, all-cause mortality was reduced by 89% while patients were on once-monthly palpiperidone palmitate LAI (Invega Sustenna) than during periods when they were not using an antipsychotic. They were 69% less likely to die while on risperidone LAI (Risperdal Consta), and 77% less likely to die while taking oral aripiprazole (Abilify).

In a pairwise comparison between the LAI and oral versions of antipsychotic agents, the LAIs were associated with a 33% lower mortality than the equivalent oral drugs.

Compared with periods of nonuse of any antipsychotic agent, the adjusted risk of mortality was reduced by 85% while patients were on a second-generation LAI, by 47% when on second-generation oral agents, by 36% with first-generation LAIs, and by 34% for first-generation oral antipsychotics.

Also at the ECNP congress, Dr. Tiihonen presented a separate analysis of the same cohort of 29,823 patients, this time examining the real-world effectiveness of various antipsychotic agents in preventing relapse, treatment failure, and rehospitalization. For this purpose, he and his coinvestigators performed a within-individual analysis in which each patient served as his or her own control. The advantage of this analytic strategy is that it corrects for selection bias and other forms of residual confounding inherent in observational studies.

During 7 years of follow-up, 44% of patients were rehospitalized. The risk of psychiatric rehospitalization was lowest when patients were on monotherapy with once-monthly palpiperidone LAI, as evidenced by a 49% reduction, compared with no use of antipsychotic agents. Clozapine (Clozaril) monotherapy and zuclopenthixol LAI (Clopixol) were similarly effective, with each conferring a 47% reduction in rehospitalization risk, compared with periods off therapy. Perphenazine LAI (Trilafon) and olanzapine LAI (Relprevv) each brought a 42% reduction in rehospitalization risk, while the oral version of perphenazine was associated with a 14% risk reduction.

In contrast, the risk of rehospitalization when patients were on oral flupentixol (Depixol) or quetiapine (Seroquel) was not significantly different from when they were off antipsychotic agents altogether.

Collectively, the LAIs were associated with a 22% lower risk of rehospitalization, compared with their equivalent oral versions. And among the 4,603 patients newly diagnosed with schizophrenia in 2006, the LAIs were associated with a more substantial 32% risk reduction, compared with their oral formulations.

Oral clozapine had the lowest treatment failure rate: 42% less than with oral olanzapine (Zyprexa), which served as the reference standard because it was the most commonly used antipsychotic agent. Treatment failure was defined as psychiatric rehospitalization, attempted suicide, treatment discontinuation or a switch to another antipsychotic agent, or death. The various LAIs were associated with 20%-35% lower treatment failure rates than oral olanzapine.

Dr. Tiihonen’s relapse prevention analysis has been published (JAMA Psychiatry. 2017 Jul 1;74[7]:686-93).

The two studies were funded by Janssen-Cilag. Dr. Tiihonen reported serving as a consultant to that pharmaceutical company and a half-dozen others.
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