Oral clozapine, olanzapine LAI tied to fewer hospitalizations for schizophrenia

January 19, 2018

By Marilynn Larkin

NEW YORK (Reuters Health) – Oral clozapine and olanzapine long-acting injection (LAI) emerged as the most effective treatments for preventing hospitalization among patients with chronic and first-episode schizophrenia in a large, long-term comparative effectiveness study, researchers say.

As part of their ongoing work in this area, Dr. Jari Tiihonen of the Karolinska Institute in Stockholm and colleagues prospectively investigated the risk of all-cause and psychiatric hospitalization associated with novel antipsychotic drugs in a national Finnish registry of individuals with schizophrenia from 1972 through 2014.

A total of 62,250 people were included in the prevalent cohort and 8,719 in the incident (first-episode schizophrenia) cohort.

Follow-up for antipsychotic use started in 1996 for the prevalent cohort, and at the first discharge from inpatient care for the incident cases. To eliminate selection bias, risk models for psychiatric and all-cause hospitalization were constructed to compare risk during antipsychotic use and no use (using the individual as his/her own control).

As reported online December 20 in Schizophrenia Bulletin, 59% of people in the prevalent cohort were readmitted to psychiatric hospitals during a median 20 years of follow-up.

Overall, LAI use was associated with lower risk of psychiatric rehospitalization, especially among the incident cohort, which also had a lower risk with LAIs compared to oral antipsychotics. In the prevalent cohort, differences between the two classes of drugs were less pronounced.

With respect to specific antipsychotics used in monotherapy in the prevalent cohort, olanzapine LAI, oral clozapine, and paliperidone LAI were associated with the lowest risk of psychiatric rehospitalization compared to no antipsychotic use, with adjusted hazard ratios of 0.46, 0.51 and 0.51, respectively.

Among first-episode patients, the lowest risks were observed for flupentixol LAI, olanzapine LAI, and perphenazine LAI - with aHRs of 0.24, 0.26 and 0.39, respectively.

The authors report that the same antipsychotics were associated with the lowest psychiatric rehospitalization risks when compared to oral olanzapine and to no use of antipsychotics.

The same was true, for the most part, for risks of all-cause hospitalizations.

“LAIs were associated with a lower risk of psychiatric and all-cause hospitalization than oral antipsychotics,” they state. “This was seen both in the prevalent and the incident cohorts.”

“Of specific antipsychotics, olanzapine LAI and clozapine were associated with the lowest risk of hospitalization in all analyses,” they conclude.

That said, Dr. Tiihonen told Reuters Health by email, “there are patients who cannot use LAIs or clozapine for several reasons, such as tolerability or the fact that there are no LAI formulations for some antipsychotics.”

“LAIs should be used more widely,” he said, “especially among first-episode patients.”

Dr. Jeffrey Lieberman, Chairman of Psychiatry at Columbia University College of Physicians and Surgeons and Psychiatrist-in-Chief at New York Presbyterian Hospital-Columbia University Medical Center, stated, “These authors have provided yet another impressive and informative naturalistic study of the long-term outcomes of schizophrenia.”

“Their latest report is such a valuable contribution to our knowledge of the effectiveness of antipsychotic drug treatment that I believe it should serve as a guide to clinical practice,” he told Reuters Health.

“Indeed,” he said by email, “I would go further in saying that given the economic pressures and limited resources that our mental health care systems face and the fact that we have numerous different brands and formulations of these medications, the results of this study can be used to tier formularies and structure therapeutic algorithms to enhance the cost effectiveness of mental health care.”

“Adding to the resonance of the study’s findings, he added, “is the fact that they are almost wholly consistent with prior controlled studies in the scientific literature.”

“This report is a valuable contribution to our knowledge of the effectiveness of antipsychotic drugs in the treatment of schizophrenia,” he concluded. “I encourage all clinicians to read it and training programs to include in teaching psychiatric trainees.”

The study was funded in part by Eli Lilly, which makes Zyprexa (olanzapine). Dr. Tiihonen and two coauthors have received grants from Eli Lilly among other companies, and one coauthor is employed by a contract research organization that works in collaboration with various pharmaceutical companies.


Schizophr Bull 2017.

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