Antipsychotic adherence helps keep lid on suicidal behaviour

Ensuring antipsychotic medication use as prescribed may be crucial for reducing the risk of suicidality among patients with schizophrenia, according to a study.

Analyses of 10-year data from patients who were consecutively admitted to an acute psychiatric unit showed that compared with nonuse, antipsychotic use was associated with a 70-percent lower risk of attempted or completed suicide (adjusted hazard ratio [aHR], 0.30, 95 percent confidence interval [CI], 0.14–0.65; p<0.01) and a 69-percent reduced risk of readmission with suicidal plans (aHR, 0.31, 95 percent CI, 0.18–0.55; p<0.01). [Psych Med 2024;54:4704-4712]

In contrast, benzodiazepines use was linked to a more than twofold increased risk of readmission with suicidal plans compared with nonuse (aHR, 2.26, 95 percent CI, 1.24–4.13; p=0.01).

“Our results … [are] in accordance with previous research, where nonadherence to antipsychotic drugs consistently emerges as a significant risk factor for suicidality in individuals with schizophrenia,” the investigators said. [Healthcare 2021;9:389; Schizophr Bull 2021;47:23-30; J Psychopharmacol 2010;24:81-90]

They explained that the efficacy of antipsychotics against suicidality likely stems from the medication’s efficacy in addressing hallucinations, delusions, and insomnia—all of which are known contributors to suicidal behaviour. [Schizophr Res 2020:221:44-56; Brain Behav 2021;11:e2381; JAMA Psychiatry 2019;76:1241-1255]

As for benzodiazepines and suicidality, the findings showed only a positive association for the risk of readmission with suicidal plans but not with the risk of attempted or completed suicide, unlike in previous studies, according to the investigators. [Prim Care Companion CNS Disord 2017;doi:10.4088/PCC.16r02037; Am J Psychiatry 2016;173:600-606; Arch Gen Psychiatry 2012;69:476-83]

“One potential explanation for the discrepancy between our results and previous studies may lie in the infrequency (n=32) of attempted and completed suicides within our study cohort. Moreover, confounding by indication is a well-known challenge in pharmacological cohort studies, as the use of medications is not randomized,” they said.

Finally, the investigators noted that benzodiazepines are commonly prescribed to patients with schizophrenia to manage aggression and agitation, and several studies showing an association between benzodiazepine use and suicide risk have failed to adjust for the patients’ levels of aggression and agitation. “In our study, we addressed this concern by adjusting for the baseline levels of overactive, aggressive, disrupted, or agitated behaviour. This adjustment might, at least partly, explain why our findings differ from those reported in previous studies.” [Cochrane Database Syst Rev 2012;11:CD006391]

Suicidality represents a major concern in patients with schizophrenia, according to the investigators, who emphasized that more studies are needed to identify causal associations and validate the findings before they could be used to inform treatment guidelines.

Study details

A total of 696 patients with schizophrenia who were consecutively admitted to a psychiatric acute unit during a 10-year period were enrolled for the study. The mean age at index admission was 41.1 years, and 61.9 percent were male. Most of the patients used antipsychotics (87.9 percent), while 18.8 percent used antidepressants and 21.0 percent used benzodiazepines.

During follow-up, 32 (4.6 percent) suicide events were recorded. Of these, nine (28 percent) were completed suicides and 23 (72 percent) were attempted suicides. Hospital readmission was required for 59 patients (8.5 percent) who had suicidal plans.

The use of antidepressants had a null association with the risk of either attempted or completed suicide or readmission with suicidal plans. Likewise, no significant associations were observed between readmission with suicidal plans and age, depressive mood, agitated behaviour, and excessive use of alcohol or illicit substances.

Meanwhile, female gender was associated with a 75-percent increased risk of readmission with suicidal plans (aHR, 1.75, 95 percent CI, 1.04–2.95; p=0.03). This is in line with the reported “gender paradox of suicidal behaviour” in research, indicating a higher prevalence of females with nonfatal suicidal incidents and a predominance of males with completed suicides, the investigators noted. However, they also stressed that they found no association between male gender and increased risk of attempted or completed suicide, most likely due to the primary outcome analyses including both attempted and completed suicides, not solely completed suicides. [Medicina 2019;55:361; J Affect Disord 2012;138:19-26]