Effect of Long-Term Antipsychotic Use on Morbidity, Mortality Risk


Antipsychotics were not associated with an increased risk of morbidity and mortality in patients with schizophrenia in a new study. 

Mental Health

Long-term use of antipsychotic medications did not show an association with an increased the risk of morbidity and mortality in patients with schizophrenia, according to a new study published in World Psychiatry.1

Although antipsychotics can be effective in preventing relapses in those with schizophrenia, it has been thought that long-term use of these medications is associated with negative health outcomes. Even short-term use can result in several types of AEs, such as weight gain, dyslipidemias, glucose metabolism dysregulation, QTc prolongation, and sudden cardiac death. However, data on long-term physical morbidity and mortality associated with antipsychotic use are limited.

This study, which is the largest conducted in the field to date, assessed the risk of hospitalization due to physical health problems and the risk of all-cause mortality, as well as cardiovascular and suicidal death, associated with antipsychotic use.

A cohort of 62,250 patients treated for schizophrenia in inpatient care between 1972 and 2014 in Finland were included in the study, with up to 20 years of follow-up. The study investigated the use of antipsychotics compared with non-use, as well as the effects of specific antipsychotic medications.

Antipsychotic monotherapy was not associated with an increased risk of somatic hospitalizations (adjusted hazard ratio, aHR=1.00, 95% CI: 0.98-1.03) compared with non-exposure periods within the same individuals, according to the study. These results showed 153,149 somatic hospitalizations per 579,306 person-years of antipsychotic use versus 49,717 somatic hospitalizations per 188,107 person-years of non-use.

LAI fluphenazine was shown to be linked with the highest decrease of risk (HR-0.69, 95% CI: 0.56-0.85), according to the data. However, quetiapine, olanzapine, risperidone, and aripiprazole were associated with a slightly increased risk of somatic hospitalizations.

Antipsychotics did not appear to be associated with an increased risk of cardiovascular hospitalization (aHR-1.00, 95% CI: 0.92-1.07) compared with non-use periods within the same individuals, the study showed. LAI fluphenazine monotherapy was associated with a significantly decreased risk of cardiovascular hospitalization (aHR=0.46, 95% CI: 0.32-0.68).

Overall, all-cause mortality was significantly lower in patients being treated with antipsychotic compared with nonusers, as well. The cumulative mortality rate in the follow-up periods of medication and non-medication use was 26% and 46%, respectively, according to the researchers. Most of the specific antipsychotics in monotherapy in the analysis were associated with a lower risk of mortality.

In terms of all-cause, cardiovascular, and suicide mortality, clozapine was associated with the most beneficial mortality outcome, the study found. The least beneficial mortality outcome was observed with levomepromazine.

The researchers noted that the decreased mortality in patients receiving antipsychotics could be related to symptom and stress relief as a result of treatment, as well as improved adherence to healthy lifestyle behaviors and utilization of health care services.

“Antipsychotics get something of a bad press, which can make it difficult to reach out to the patient group with information on how important they are,” study author Jari Tiihonen, professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institutet, said in a press release.2 “We know from previous studies that only half of those who have been discharged from hospital after their first psychotic episode with a schizophrenia diagnosis take antipsychotic drugs. Besides, there are many people with schizophrenia who are on long-term benzodiazepine medication, which is in breach of existing guidelines and is associated with increased mortality risk. Building trust and understanding towards the efficacy and safety of antipsychotic drugs is important, and we hope that this study can contribute to this end.”


  • Tiihonen J, Taipale H, Tanskanen A, et al. 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). 2020. World Psychiatry. Doi: https://doi.org/10.1002/wps.20699

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