A Pilot Study to Explore the Effect of Long Acting Injectable Antipsychotics on Aggression

Abstract

Objectives

To explore the effect of switching from an oral antipsychotic to a long-acting injectable (LAI) antipsychotic on aggression, in terms of the changes of verbal and physical aggression, interventions required, self-injurious behavior, use of seclusion or restraint, antipsychotic medication refusal, and use of antipsychotics as needed (PRN).

Methods

This was a retrospective chart review at a long-term state forensic psychiatric facility. Patients treated with an oral antipsychotic for at least 6 months and then switched to a LAI antipsychotic for an additional 6 months during an 80-month period were included.

Results

Out of 70 patients evaluated, 18 were the study subjects. The median age of the cohort was 38 years with a majority being male. Of the seven patients who had an incident of aggression, two had an increase in aggressive incidents following the switch, three had a decrease, and two had no change. Thirty-six interventions occurred while patients were on an oral antipsychotic, which decreased by 30.6% to 25 interventions after the switch. Three patients had an incident of self-injurious behavior, and 6 patients required restraints/seclusions. Of the eight patients who had retrievable medication refusal and antipsychotic PRN use information, five had a decrease in antipsychotic medication refusals and five had an increase in PRN antipsychotic use after the switch.

Conclusion

The switch from an oral antipsychotic to a LAI antipsychotic did not appear to significantly increase or decrease incidents of aggression or self-injurious behavior, but seemed to decrease the number of restraints/seclusions required.

Introduction

Aggression often leads to psychiatric hospitalization, putting healthcare workers and other patients at risk of injury from violent acts. In the inpatient setting, approximately 85% of assaults are directed at healthcare workers, with 6% of the assaults resulting in medical interventions.¹ Patients with chronic aggression were more likely to target other patients with an organized or psychotic assault.² In addition, approximately 31% of patients admitted to an inpatient forensic psychiatric facility commit at least one violent assault on healthcare workers or other patients during hospitalization.³ Therefore, addressing violence for patients with aggression should be a priority for institutional leadership.

Pharmacologic treatments of violence can be divided into the treatment of acute agitation and the treatment of chronic aggression. The goal of treating acute agitation is to help patients regain self-control, which can be accomplished through oral or parenteral medications based on agitation severity.⁴ For example, preferred medications are benzodiazepines, especially lorazepam and diazepam, which have parenteral formulations.⁵ In addition, as needed (PRN) oral medications such as a benzodiazepine or antipsychotic could be considered. Treatment of chronic aggression is often based on the patient’s primary psychiatric diagnosis. For example, patients with a personality disorder or chronic psychosis are more likely to respond to clozapine than to antidepressants or mood stabilizers.^6,7 On the other hand, patients with aggression due to traumatic brain injuries are less likely to respond to antipsychotics and more likely to respond to beta-blockers such as propranolol.⁸ Furthermore, long-acting injectable (LAI) antipsychotics provide a more stable serum drug concentration than oral antipsychotics, resulting in better symptom control and a reduction in adverse effects.^9,10 Although LAI antipsychotics are an alternative option for patients with aggressive behavior, their effect on aggression remains unknown. The objective of this pilot study was to explore the effect of switching from an oral antipsychotic to a LAI antipsychotic on aggression. Aggression was measured in terms of the changes in routine rating of verbal and physical aggression, interventions required, self-injurious behavior, use of seclusion or restraint, antipsychotic medication refusal, and use of antipsychotics as needed (PRN). These parameters were chosen because the relevant reports are easily accessible and standardized across the hospital.

Methods

This pilot study was conducted at a long-term state forensic psychiatric facility. Patients who were treated with an oral antipsychotic for at least 6 months and then switched to a LAI antipsychotic for an additional 6 months between February 1, 2013 and September 30, 2019 (an 80-month period) were included. Patients were excluded if the LAI antipsychotic was discontinued within 6 months of initiation, if they received two or more concomitant LAI antipsychotics, or if the LAI antipsychotic chosen was not comparable to the parent oral antipsychotic. Disease states were identified by ICD-9 and ICD-10 codes. A LAI antipsychotic was considered comparable with the same active moiety or a similar metabolite. Aggression, self-injurious behavior, and restraint data were obtained from the hospital’s bi-weekly incident and injury reports. Other data collected included patient demographics (age, sex, and race), psychiatric diagnoses, oral antipsychotic and LAI antipsychotic dose and frequency, antipsychotic serum concentrations, and concomitant psychotropic medication changes. The University of Missouri-Columbia Institutional Review Board and the State of Missouri Department of Mental Health Professional Review Committee granted approval for this pilot study.

Results

Out of 70 patients evaluated during the study period, 18 met inclusion criteria and were the study subjects. The median age of the cohort was 38 years with a majority being male (94.4%). Fifty percent were African American and 44.4% were Caucasian (Table 1). Compared to the patient demographics at the facility,¹¹ the age of the study sample was consistent, but the percentage of African American was higher and the percentage of Caucasian was lower.

Table 1. Baseline Characteristics of Study Sample.

		Total Population (n = 18)
Age, median years (range)		38 (22–58)
Male Sex, n (%)		17 (94.4)
Race, n (%)
African American		9 (50)
Caucasian		8 (44.4)
Other		1 (5.6)
Primary Diagnosis, n (%)
Schizophrenia		9 (50)
Schizoaffective Disorder		6 (33.3)
Borderline Personality Disorder		1 (5.6)
Unspecified Personality Disorder		1 (5.6)
Disruptive Mood Dysregulation		1 (5.6)
Co-morbidities, n (%)
Substance Use Disorder		10 (55.6)
Vitamin D Deficiency		8 (44.4)
Antisocial Personality Disorder		7 (38.9)
Mild Intellectual Disability		3 (16.7)
Depressive Disorder		1 (5.6)
Autism		1 (5.6)
Oral Antipsychotics, n (%)
Haloperidol (dose range: 10–40 mg/day)		7 (38.9)
Risperidone (dose range: 3–8 mg/day)		7 (38.9)
Fluphenazine (dose range: 15–25 mg/day)		3 (16.7)
Paliperidone (dose range: 9 mg/day)		1 (5.6)
LAI Antipsychotics, n (%)
Haloperidol (dose range: 100–150 mg every 28 days)		7 (38.9)
Risperidone (dose range: 50 mg every 14 days)		2 (11.1)
Fluphenazine (dose range: 25–27.5 every 14–21 days)		3 (16.7)
Paliperidone (dose range: 117–234 mg every 28 days)		6 (33.3)
Dual Antipsychotic Therapy Utilization, n (%)		10 (55.6)
Olanzapine, n (dose range mg/day)		5 (15–30)
Quetiapine, n (dose range mg/day)		3 (100–1000)
Thiothixene, n (dose range mg/day)		1 (10)
Perphenazine, n (dose range mg/day)		1 (24–32)
Chlorpromazine, n (dose range mg/day)		1 (50)
Lurasidone, n (dose range mg/day)		1 (40)
Triple Antipsychotic Therapy Utilization, n (%)		2 (11.1%)

Nine patients (50%) had a primary diagnosis of schizophrenia and six (33.3%) of schizoaffective disorder. Seven patients (38.9%) were on oral haloperidol, and seven (38.9%) were on LAI haloperidol. Seven patients had an incident of aggression (verbal or physical) or self-injurious behavior prior to or after the switch from an oral antipsychotic to a LAI antipsychotic (Table 2). Of those seven patients, two had an increase in aggressive incidents following the switch, three had a decrease, and two had no change. Five patients had an episode of physical aggression leading to staff injury, compared to four patients causing peer injury. Sixty-one incidents required interventions. Thirty-six interventions (59%) occurred while patients were on an oral antipsychotic, which decreased from 36 to 25 interventions after the switch to a LAI antipsychotic. Additionally, once on a LAI antipsychotic, the number of medical interventions decreased from 14 to eight, and the number of interventions requiring no treatment decreased from 14 to six.

Table 2. Summary of Aggression Incidents.

		Oral Antipsychotic, n (%)		LAI Antipsychotic, n (%)		% Change (↓, ↑, ↔)
Incidents of Aggression		28 (100)		23 (100)		17.9 (↓)
Patient 1		1 (3.6)		0		100 (↓)
Patient 2		0		2 (8.7)		200 (↑)
Patient 3		0		0		0 (↔)
Patient 4		3 (10.7)		0		300 (↓)
Patient 5		0		2 (8.7)		200 (↑)
Patient 6		2 (7.1)		4 (17.4)		100 (↑)
Patient 7		22 (78.6)		15 (65.2)		31.82 (↓)
Interventions		36 (59)		25 (41)		30.6 (↓)
Medical Interventions		14 (38.9)		8 (32.0)		42.9 (↓)
Minor First Aid		8 (22.2)		11 (44.0)		37.5 (↑)
Assessment without Treatment		14 (38.9)		6 (24)		57.1 (↓)

Seven patients had an incident of aggression. Three patients had self-injurious behaviors before or after the switch. One had an increase in self-injurious behaviors after the switch, another had a decrease, and the other had no change. Patient 3’s self-injurious behaviors occurred while on the oral antipsychotic, and no incidents were reported once the patient switched to a LAI antipsychotic. Patient 6 had three incidents for self-injurious behavior while on the oral antipsychotic and three incidents while on the LAI antipsychotic. Patient 7’s self-injury occurred more often while on the LAI antipsychotic (n = 4) than on the oral antipsychotic (n = 1).

Six patients had required seclusion or restraints. One had an increase in the number of seclusion or restraint, and five had a decrease. Three patients required a 4-point restraint, two patients required a manual hold, and only one patient required seclusion. Patient 7 required 29 restraints, the highest number of restraints among all patients. The number of 4-point restraints decreased from 17 to seven after switching to a LAI antipsychotic, while the number of manual holds decreased from seven to five.

Eight patients had retrievable medication refusal and antipsychotic PRN use information. Five of them had a decrease in antipsychotic medication refusals after the switch, and three had no change. After the switch to the LAI antipsychotic, five patients had an increase in PRN antipsychotic use, two had a decrease, and one had no change.

Discussion

Managing aggressive behavior in psychiatric settings is an ongoing topic of discussion. This pilot study sheds light on the potential benefits and considerations of using LAI antipsychotics. The study found no significant difference in the incidence of aggression or self-injurious behavior between patients on oral antipsychotics and those who switched to LAI antipsychotics. However, further review of the three patients who had a reduction in aggressive behavior showed that none of them had significant medication changes other than the switch to LAI antipsychotics. This suggests that LAI antipsychotics could potentially play a role in reducing aggressive behavior. Nonetheless, it is important to recognize that aggression and self-injurious behavior can result from various factors, including underlying psychiatric diagnoses, environmental stressors, and individual patient characteristics. The lack of a clear overall effect may be due to the diversity of these contributing factors and underscores the need for larger studies to determine the potential benefits of LAI antipsychotics in specific patient subgroups. The study also found that switching to LAI antipsychotics reduced the number of restraints and seclusions required, which improves patient and staff safety and is consistent with the broader goal of de-escalation techniques and minimizing the use of coercive interventions. This reduction could also lead to improved job satisfaction among healthcare workers and potentially contribute to a reduction in turnover rates.

The analysis of antipsychotic medication refusals and PRN antipsychotic use provides interesting insights. The study found that medication refusals decreased after switching to LAI antipsychotics, but the use of PRN antipsychotics increased. This raises questions about patient acceptance of LAI antipsychotics and the role of PRN medications in managing acute symptoms of aggression. The increase in PRN antipsychotic use may reflect a need for more immediate symptom control, indicating that LAI antipsychotics require time to reach stable therapeutic levels. However, the benefits of improved adherence to LAI antipsychotics should not be overlooked, as maintaining consistent drug levels may contribute to better overall symptom control.

It is important to acknowledge the limitations of this pilot study, including the small sample size and the lack of adjustment for potential confounding variables such as staff turnover, unit dynamics, and environmental changes. Moreover, this analysis only included patients who switched from an oral antipsychotic to a LAI antipsychotic with a comparable drug molecule. These factors may have influenced the observed results, highlighting the need for larger studies with more comprehensive data. Future investigations should continue to explore the mechanisms underlying the potential benefits of LAI antipsychotics in treating aggression. Longitudinal studies that include a wider range of oral and LAI antipsychotics over an extended treatment duration may provide valuable insights into the sustainability of observed improvements and potential delayed effects.

Conclusion

Although the study did not clearly demonstrate a significant reduction in aggression, it suggests that LAI antipsychotics may hold promise in reducing the need for restraint and seclusion. The findings highlight the complexity of aggression management and the potential benefits of longer-acting antipsychotic formulations. However, the study’s limitations warrant cautious interpretation and underline the need for further research to elucidate the role of LAI antipsychotics in this context and guide clinical decision-making.