LAIAs More Effective Than Oral Antipsychotics for Schizophrenia


A new study shows that for patients with schizophrenia, long-acting injectable antipsychotics (LAIAs) are associated with a lower risk of disease recurrence and hospitalization than oral antipsychotics (OA), and they do not carry an increased risk of side effects.

The researchers analyzed data from more than 70,000 patients with schizophrenia and found that, compared with OA, LAIAs were associated with a lower risk of hospitalizations for any reason, hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and suicide attempts.

Among patients who were fully treated with LAIA, there were fewer hospitalizations for medical disorders and cardiovascular diseases, as well as fewer extrapyramidal symptoms (EPS) compared with those who were fully treated with OA. In addition, among those in whom LAIA treatment was started early, the reduction in these outcomes was greater compared with patients in whom treatment was started later.


The results “confirmed that LAIAs were associated with a lower risk of hospitalizations, disease recurrence, and suicide attempts than OA, and this association persisted through subsequent treatment periods,” write the researchers, led by Esther Chan, Ph.D., Center for Safe Medical Practice. . and Research, Department of Pharmacology and Pharmacy, University of Hong Kong, China.

The results were published online on July 28 at the JAMA Network Open.


Table of contents


“Current clinical guidelines for the use of LAIA are based primarily on randomized clinical trials, where strict inclusion criteria limit generalization,” the researchers note. In addition, most of these trials were “of relatively short duration,” so long-term observational studies are “important in establishing the safety and efficacy of LAIA,” they write.

Moreover, most studies have been based on Western populations, and the results may not apply to Asian populations, which are less well understood.

Previous studies were also frequently subject to “exposure misclassification” as patients treated with LAIA alone and patients treated with both LAIA and OA were categorized as “LAIA” users and compared with OA-only users, the researchers note.


To investigate the long-term safety and efficacy of LAIA, they evaluated data from the Clinical Data Analysis and Reporting System, an electronic health record database of the Hong Kong Hospital Authority. They identified 70,396 patients with schizophrenia (52.8% women, mean age 44.2 years).

The researchers used a self-monitored case series design—”individual comparison based on a case-only approach”—to analyze the data. This model uses incidence rates (IRRs) obtained by “comparing the frequency of outcomes between exposed and unexposed or control periods for the same individual”. With this approach, “only people who have both an impact and an outcome are suitable.”

To be included, a patient must have received at least one OA and LAIA and must have had at least one baseline event during the follow-up period from January 2004 or date of first diagnosis of schizophrenia (whichever is later) until December 2019 or death (whichever comes first).

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The follow-up period was further divided into four periods: no treatment period, OA alone, LAIA alone, and OA and LAIA combined.

Primary outcomes included medical attention and relapses such as hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and suicidal attempts. Secondary outcomes included hospitalizations for medical conditions, hospitalizations for cardiovascular disease, and EPS.

LAIA Superior

Of the total population, 23,719 patients (33.7%) were prescribed both OA and LAIA (mean age 41.7 years). Of these participants, 15.4% died during the follow-up period.


The average duration of follow-up was 12.5 years. The mean duration of exposure to OA alone was 5 years; for LAIA exposure only, 1.4 years; and for OA plus LAIA exposure, 4.4 years.

During the follow-up period, almost all individuals (92.8%) had one or more emergency department (EED) visits, and the majority (88.4%) had one or more hospitalizations for any psychiatric disorder. More than three-quarters (77.5%) were hospitalized for schizophrenia, and a small percentage (6.1%) had a suicide attempt.

Almost all patients had EPS (93.5%); more than half (64.9%) were hospitalized for somatic diseases; and 15.6% were hospitalized for cardiovascular disease.

After adjustment, compared with OA, the use of LAIA was associated with a significantly lower risk for most outcomes.

Exodus % reduction in incidence rate (95% CI)
Hospitalization for any reason 37%
0.63 (0.61 – 0.65)
Hospitalizations for psychiatric disorders 48%
0.52 (0.50 – 0.53)
Hospitalization for schizophrenia 47%
0.53 (0.51 – 0.55)
Suicide attempts 44%
0.56 (0.44 – 0.71)
Hospitalization for somatic diseases 12%
0.88 (0.85 – 0.91)
Hospitalizations for cardiovascular diseases 12%
0.88 (0.81 – 0.96)
earnings per share fourteen%
0.86 (0.82 – 0.91)

There were no differences between LAIA and OA regarding ED visits.

The decrease in EPS suggests that LAIAs “were not associated with a higher risk of these side effects than OA,” the researchers wrote.

When patients were stratified by time of onset of LAIA, early initiators had 76% fewer hospitalizations for schizophrenia during LAIA compared with OA treatment (incidence rate ratio [IRR]0.24; 95% CI, 0.21–0.27), while late initiators of LAIA had 55% fewer hospitalizations for schizophrenia (IRR, 0.45; 95% CI, 0.40–0.49), “suggesting that early initiators of LAIA may have a greater reduction in disease relapses,” the researchers note.

Participants with comorbid substance use had a significantly lower risk of hospitalizations for any cause, hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, hospitalizations for medical disorders, suicide attempts, and EPS during treatment with LAIA compared with treatment time. with OA.

Older people (>65 years) who received LAIA had a lower risk of emergency room visits, hospitalizations for any reason, hospitalizations for psychiatric disorders, and hospitalizations for schizophrenia. They did not have an increased risk of hospitalizations for physical disorders or cardiovascular disease.

However, there was a higher risk of EPS during initial treatment with LAIA, so “caution should be exercised when initiating LAIA” in the elderly, the researchers wrote.

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Mentioned limitations of the study include the fact that pooled estimates were used for all LAIAs and not for individual antipsychotics. In addition, the dose of these antipsychotics “was not taken into account because disease information was recorded differently for LAIA and OA.”

Proactive approach

Commenting for Medscape Medical News, Brittany Goes, MD, associate professor at Boston University School of Medicine and psychiatrist in the Psychosis Health and Recovery Program at Boston Medical Center, Massachusetts, said the study “adds to a growing body of evidence supporting longitudinal benefits” of the LAIA for patients with schizophrenia spectrum disorders.

“In particular, switching to long-acting injectable antipsychotics during the first 2 years of illness may have a unique advantage,” said Goes, co-author of the accompanying editorial and not involved in the study.

She also called the study “important” as it suggests that early initiation of LAIA “may serve as an important tool to reduce morbidity and close the gap in premature mortality in schizophrenia.”

Gose emphasized the importance of prioritizing “tertiary prevention” from the onset of psychotic illness.

“Physicians should be proactive and include long-acting antipsychotics in general conversations with patients to make decisions during the first few years of illness,” she said.

The study was funded by the Distinguished Young Scientist Fund of the National Natural Science Foundation of China. Chan received grants from the National Natural Science Foundation of China during the research; non-financial support of the Wellcome Trust; grants from the Research Grants Council (RGC, HKSAR), Bureau of Food and Health Research Fund Secretariat (Medical and Medical Research Foundation, HKSAR), National Health and Medical Research Council (Australia), HKSAR Security Bureau Narcotics Division, Amgen , AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Pfizer, Takeda and Novartis; and personal fees from Pfizer, Novartis and the Hong Kong SAR Hospital Authority not related to the submitted work. The editors report a lack of relevant financial relationships.

JAMA The network is open. Published online July 28, 2022 Full article, editorial

Dad Swift Yasgur, Massachusetts, LSW, is a freelance writer with a consulting practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-focused health books, as well as Behind the Burqa: Our Life in Afghanistan and How We Fled to Freedom (a memoir of two brave Afghans ). sisters who told her their story).

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