Long-Acting Injectable Antipsychotics Cut Suicide Death Risk in Half

Megan Brooks

May 18, 2021

Results from a large study make a strong case for offering long-acting injectable antipsychotics (LAIs) to patients newly diagnosed with schizophrenia.

Investigators found that among patients who switched to LAIs, mortality was lower and tthat here were fewer suicide attempts in comparison with patients who continued taking the corresponding oral antipsychotic (OAP).

In addition, switching to an LAI antipsychotic within the first 2 years of OAP cut the risk for suicide death by 47%.

"With newly diagnosed schizophrenia, more active consideration of LAIs in this stage for better long-term outcomes (ie, mortality and suicide risk) should be encouraged, particularly for those who have already exhibited poor adherence attitudes," Cheng-yi Huang, MD, Bali Psychiatric Center, Ministry of Health and Welfare, New Taipei City, Taiwan, told Medscape Medical News.

The study was published online May 11 in JAMA Network Open.

Powerful Incentive to Switch

Using data from the Taiwan National Health Insurance Research Database, the investigators identified patients newly diagnosed with schizophrenia who received OAPs from 2002 to 2017.

Within this cohort, they defined the LAI group as patients who switched to LAIs and were prescribed LAIs at least four times within 1 year. The LAI group was propensity matched to patients who continued receiving OAPs of the same compounds. There were 2614 patients in each group (median age, 30 years).

During the 16-year follow-up period, compared with patients who continued taking the OAP, those who switched to the LAI had a 34% lower risk for all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.54 – 0.81), a 37% lower risk for natural-cause mortality (aHR, 0.63; 95% CI, 0.52 – 0.76), and a 28% lower risk for suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55 – 0.93).

The risk for suicide mortality was 47% lower for patients who switched to LAIs within the first 2 years of having begun taking the OAP (aHR, 0.53; 95% CI, 0.30 – 0.92).

A recent study from Canada found that the suicide rate among patients with schizophrenia spectrum disorders was more than 20 times higher than that of the general population.

"Clinically, most psychiatrists use LAIs with a conservative attitude, and the reasons for this attitude are generally not well supported by current scientific evidence," Huang and colleagues note in their article.

Huang said the study provides a powerful incentive to begin treatment with LAIs for patients newly diagnosed with schizophrenia.

"Because this study compared depot vs the same oral compound, as soon as patients show response and tolerability to the OAP, they will benefit much more when switching to LAI of the same compound," Huang told Medscape Medical News.

"Remarkably Underutilized"

Commenting on the study for Medscape Medical News, William Carpenter, Jr, MD, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, said this report is "very important and in a high-quality journal.

"LAIs have been remarkably underutilized in the US and not considered as main line and initial treatment. All of this is unfortunate attitude, not science," Carpenter said.

There is now evidence that the field is shifting toward LAIs as frontline treatment, "at least conceptually and by research leaders," he noted.

"In this report, the health and suicide information is new, extremely important, and robust. This report should alert clinicians to possible advantage of LAI in suicide prevention," Carpenter added.

Also commenting for Medscape Medical News, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences, Staten Island University Hospital, New York City, said the findings provide "another very robust argument for LAIs.

"The decrease in all-cause mortality is really interesting," said Sullivan, "and it would be interesting to find out whether some of this reflects improved metabolic states" with LAIs vs OAPs.

The finding that people who switched to LAIs within 2 years were at much lower risk for suicide and other mortality represents a "powerful argument for switching within 2 years," Sullivan said.

However, in current clinical practice, clinicians often don't suggest LAIs until patients have suffered repeated acute episodes of illness after not taking their oral antipsychotics. Such episodes have an impact on the individual and on their nervous system, Sullivan explained.

"That's really undesirable. We know from other data that the more episodes someone has, the harder it is to get the illness symptoms under control," he noted.

"We really ought to be thinking preventively about approaches that will decrease the risk of recurrence, and the evidence in this study is pretty compelling that the LAI was a significant intervention that decreased the risks. Thinking about LAIs as a preventive measure is a message that hasn't gotten out to the practice community yet," Sullivan added.

The study was supported by the Bali Psychiatric Center, Taiwan, through a grant from the Ministry of Health and Welfare. Huang, Carpenter, and Sullivan have disclosed no relevant financial relationships.

JAMA Netw Open. Published May 11, 2021. Full text

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