Abstract
Introduction:
The number of long-acting injectable antipsychotics (LAIA) has increased in recent years. The safety and efficacy of that treatment are not established in children. This study aims to address this gap of information by studying such treatments in a case series.
Methods:
This retrospective chart review of patients identified by the investigators at an academic acute inpatient psychiatric unit included all patients from the past 24 months who required new initial treatment with LAIA. This study included a case series of the nine patients along with Clinical Global Impression–Severity (CGI-S) scores from admission and discharge and Clinical Global Impression–Improvement (CGI-I) scores. Other observations included the presentation of primary psychiatric diagnosis, psychiatric and medical comorbidities, age, sex, previous and LAIA psychiatric medications, reasoning for LAIA treatment, adverse events, CGI-S and CGI-I scores, and outpatient resources utilized to continue treatment.
Results:
The case series included two females and seven males within the ages of 14–17 years. Of those patients, five were treated with paliperidone palmitate, one treated with risperidone, one treated with fluphenazine, and one treated with aripiprazole. Primary psychiatric diagnosis of the patients in the case series included five with schizophrenia, one with schizoaffective disorder, one with bipolar affective disorder-type I, one with bipolar affective disorder-not otherwise specified, and one with mood disorder-not otherwise specified. In all nine cases, noncompliance was a consideration in treatment with LAIA. Frequent running away and severity of illness were also considerations in one case each. All of the patients required community resources with injectable services.
Conclusion:
This study describes initiation of treatment with LAIA in 14–17-year olds in an acute inpatient psychiatric unit with serious mental illness. This study also demonstrates the need for outpatient community resources with the ability to provide long-acting injectable medication. Limitations of this study include a small patient population, other factors changing CGI-S and CGI-I scores beyond the medication, and the nature of the study as a retrospective chart review. This study did not compare medications between each other. Maintenance dosing and long-term safety were beyond the scope of this study. Future directives for safety studies, open-label trials, and randomized double-blinded control trails in the pediatric population would be needed.
Introduction
T
This study aims to address the gap in information regarding children and adolescents started on LAIA in an acute psychiatric hospital and including primary psychiatric diagnosis, psychiatric and medical comorbidities, previous psychiatric medications, reasoning into LAIA initiation, the LAIA started, age and sex of patient, adverse events (including divergent laboratory values, vitals, and physical examination findings), Clinical Global Impressions–Severity (CGI-S) and Clinical Global Impressions–Improvement (CGI-I) scores, and the resources needed after discharge. The authors could not find a collection of pediatric cases treated with LAIA in the literature at the time of this study and believe it to be a first of its kind. The hypothesis of this study is that minors starting LAIA are suffering with serious mental illnesses, the treatment is efficacious, and they require community outpatient resource with injectable services for treatment.
Methods
This study was a retrospective chart review completed in an academic acute inpatient psychiatric unit. Investigators identified patients who initiated LAIA treatment during an acute inpatient psychiatric hospitalization as minors. Inclusion criteria included patients initiating first-time treatment with LAIA within a 24-month period. Exclusion criteria included all patients who were already stabilized or previously stabilized on LAIA or those who turned 18 years old during their hospitalization. The investigators completed an electronic chart review and collected primary psychiatric diagnosis requiring inpatient treatment based on presenting symptoms, psychiatric and medical comorbidities, previous psychiatric medications, age, sex, LAIA, including dose and administration, clinical reasoning behind initiation of LAIA, adverse events and resulting changes to treatment, and outpatient resources required to continue treatment. Physical and psychiatric review of systems, laboratory values, and vitals were recorded daily as per hospital protocol and reviewed by the investigators for treatment-related adverse events. CGI-S scores were determined by the investigators at admission and discharge along with CGI-I scores. The time period in this chart review included the transition in this institution to the fifth edition from the fourth-text revision edition of the Diagnostic and Statistical Manual of Psychiatry (DSM). The diagnoses collected and presented here are as they were documented in the chart. The investigators would like to highlight that the diagnoses of these patients, except in cases of substance use, would fit criteria for the diagnoses given using the criteria in either DSM edition based on the information in the chart. In cases of substance use, the diagnoses presented here reflect the documentation in the chart and can be from either the fourth-TR or fifth edition of the DSM.
Cases
Patient 1
A 15-year-old female with a primary diagnosis of bipolar affective disorder-type I, comorbid posttraumatic stress disorder (PTSD), and cannabis abuse was admitted for 8 days due to suicidal thoughts. The seven past psychiatric medications included lithium, quetiapine, fluoxetine, aripiprazole, guanfacine ER, escitalopram, and sertraline. Considering her history of intermittent compliance due to running away from home frequently, LAIA were started. She began oral dosing of paliperidone ER bridging her to long-acting paliperidone palmitate 234 mg and then 156 mg a week later. She tolerated the medication well along with her chronic constipation. She was discharged to continue treatment at a community agency with pediatric injectable services and a plan to continue injections monthly. The admission CGI-S score was 6. The discharge CGI-S score was 2. The CGI-I score was 3.
Patient 2
A 15-year-old male with a primary diagnosis of bipolar affective disorder-not otherwise specified, attention-deficit/hyperactivity disorder (ADHD), and polysubstance dependence (cannabis, nicotine, and alcohol) was admitted for 9 days due to increasing out-of-control behaviors, aggression, impulsivity, and decreased sleep. His medical comorbidities include a history of prematurity (born at 26 weeks gestation) and well-controlled asthma. The seven past psychiatric medications included methylphenidate ER, aripiprazole, quetiapine, risperidone, lisdexamfetamine, haloperidol, and guanfacine ER. Considering his history of noncompliance, oral dosing of paliperidone ER was started and bridged to long-acting paliperidone palmitate injection of 234 mg. The medication was well tolerated and without adverse events. The patient was discharged to a community agency through his school with injectable services. His plan at discharge included paliperidone palmitate 156 mg a week after the 234 mg dose was given and then 117 mg a month later. The admission CGI-S score was 5. The discharge CGI-S score was 3. The CGI-I score was 3
Patient 3
A 17-year-old male with a primary diagnosis of schizophrenia and comorbid cannabis dependence was admitted for 10 days due to out-of-control behaviors and aggression. The three past psychiatric medications included risperidone, fluoxetine, and haloperidol. Considering his history of noncompliance, oral dosing of paliperidone ER bridging to long-acting paliperidone palmitate injection of 234 mg was started, with an156 mg dose one week later. Benztropine was concomitantly continued considering his history of dystonia with haloperidol administration. He tolerated the medication well without adverse events and was discharged with treatment at a community agency with pediatric injectable services. The admission CGI-S score was 7. The discharge CGI-S score was 1. The CGI-I score was 1.
Patient 4
A 14-year-old male with a primary diagnosis of schizophrenia and comorbid PTSD was admitted for 26 days due to suicidal and homicidal thoughts. Past medications included risperidone and fluoxetine as he was treated for depression before admission during what was most likely the prodromal phase of his illness. He was started on aripiprazole. Considering his self-reported history of noncompliance with oral medications after discharge, aripiprazole was changed to oral paliperidone ER and then to paliperidone palmitate injectable. He tolerated paliperidone palmitate 234 and 156 mg a week later without adverse events. He was discharged with treatment at a community agency with pediatric injectable services. The admission CGI-S score was 4. The discharge CGI-S score was 2. The CGI-I score was 2.
Patient 5
A 15-year-old male with a primary diagnosis of schizophrenia and comorbid cannabis use disorder was admitted for 6 days due to psychosis, including delusions and auditory and visual hallucinations. He had not been on psychiatric medications previously. During hospitalization, he was prescribed risperidone and clonazepam but adamantly refused these medications. He was then prescribed aripiprazole, which he eventually agreed to take. Then, for reasons not documented, he was started on paliperidone palpitate 156 mg, which he tolerated well without adverse events. He was discharged with treatment at a community agency with pediatric injectable services. The admission CGI-S score was 6. The discharge CGI-S score was 3. The CGI-I score was 3.
Patient 6
A 15-year-old female with a primary diagnosis of schizoaffective disorder was admitted for 15 days for worsening depression, including suicidal thoughts and auditory hallucinations. Previous medications included olanzapine and an unknown antipsychotic that reportedly caused galactorrhea. Considering her history of noncompliance, LAIA were considered. Paliperidone ER was started with a plan to bridge treatment to the injectable formulation, however, the serum prolactin level was found to be elevated and this medication was discontinued. Haloperidol was recommended, yet the patient's guardian refused. Fluphenazine was started and was tolerated well, so a 6.25 mg dose of fluphenazine decanoate every 2 weeks was started concomitantly. She tolerated the medication without adverse events. She was discharged with treatment at a community agency with pediatric injectable services. Later, it was found that follow-up injections were delayed due to intake procedures at the community agency. The admission CGI-S score was 6. The discharge CGI-S score was 2. The CGI-I score was 3.
Patient 7
A17-year-old male with a primary diagnosis of mood disorder-not otherwise specified and comorbid cannabis abuse was admitted for 14 days due to increased irritability and physical aggression. His previous medications included risperidone to which he was noncompliant. During hospitalization, risperidone was restarted and he experienced neck stiffness and believed to be experiencing extrapyramidal symptoms (EPS). Benztropine was added and the EPS resolved. Risperidone was increased for clinical effect and long-acting injectable risperidone 25 mg was also added with plans for him to receive a similar dose every 2 weeks as an outpatient. Oral risperidone was continued to bridge treatment to an outpatient provider. He tolerated both the oral and injectable medications without adverse events. He was discharged with treatment at his previous community agency, which could administer injectable medications. The admission CGI-S score was 4. The discharge CGI-S score was 3. The CGI-I score was 3.
Patient 8
A 16-year-old male with a history of ADHD was admitted for 21 days due to bizarre behavior, thought blocking, and disorganized movements. He was subsequently diagnosed with schizophrenia after a complete history was taken and was notable for symptoms starting several months earlier. Previous medications included lisdexamfetamine. He was started on risperidone to which he tolerated well. Considering the severity of his illness and his tendency to refuse oral medications, the plan changed to treatment with LAIA. The risperidone was switched to oral paliperidone ER and then to paliperidone palmitate 156 mg. He tolerated these changes well except for EPS, which was treated with concomitant benztropine. No other adverse events were noted. He was discharged with follow-up at a community agency with injectable services. The admission CGI-S score was 6. The discharge CGI-S score was 3. The CGI-I score was 3.
Patient 9
A 15-year-old male with a primary diagnosis of schizophrenia was admitted for 14 days due to worsening psychosis, including visual hallucinations, paranoia, and disorganized speech. Previous medications included risperidone, benztropine, and clonazepam. Before hospitalization, risperidone had caused dyslipidemia. Considering this, the medication was switched to aripiprazole. Aripiprazole was increased and his psychosis improved in the hospital. Considering his history of noncompliance and the effect of oral aripiprazole, treatment was started with long-acting injectable aripiprazole 400 mg. He was discharged with treatment at his previous community agency, which could administer injectable medications. The admission CGI-S score was 7. The discharge CGI-S score was 1. The CGI-I score was 2.
Results
There were a total of nine participants, two were females and seven were males. The participants ranged in age from 14 to 17. Data collected are presented in Table 1.
ψ Rx, psychiatric medications before admission (total); 1°ψ Dx, primary psychiatric diagnosis; ADHD, attention-deficit/hyperactivity disorder; AEs, adverse events; BAD-I, bipolar affective disorder-type I; BAD-NOS, bipolar affective disorder-not otherwise specified; CGI-S, Clinical Global Impression–Severity; CGI-S(A), CGI-S on admission; CGI-S(D), CGI-S on discharge; Days, days of inpatient psychiatric hospitalization; EPS, extrapyramidal symptoms; F, female; LAIA, long-acting injectable antipsychotics; M, male; Medical Dx, medical comorbidities; Mood, mood disorder not otherwise specified; NC, noncompliance; OP, outpatient psychiatric resources; Other ψ Dx, psychiatric comorbidities; PIS, pediatric injectable services; Polysub, polysubstance dependence; PTSD, posttraumatic stress disorder; SAD, schizoaffective disorder; Schz, schizophrenia; SIS, school injectable services; Why reasoning for long-acting injectable antipsychotic initiation.
Six of the participants were treated with paliperidone palmitate. Other LAIA used include risperidone, fluphenazine, and aripiprazole, each of which was administered to one patient.
With regard to primary diagnoses, five patients had schizophrenia, one patient had bipolar affective disorder-type I, one patient had bipolar affective disorder-not otherwise specified, one patient had mood disorder-not otherwise specified, and one patient had schizoaffective disorder. Psychiatric comorbidities included five patients with substance use disorders, two with PTSD, and two with ADHD. Previous medication trails before acute inpatient psychiatric hospitalization included a range of 0 to 7 with an average of 2.9. The length of acute inpatient psychiatric hospitalization included a range of 6 to 26 days with an average of 13.7. All of the participants required outpatient services with injectable resources. In the case of one participant, intake procedures hindered follow-up injections.
Conclusion
This retrospective case series describes a positive initial response to acute treatment with LAIA in youth aged 14–17 years with serious mental illnesses such as schizophrenia, schizoaffective disorders, and bipolar affective disorders in an acute inpatient psychiatric setting. LAIA were considered given the concerns for noncompliance in these patients. All of those requiring long-acting injectable required ongoing injectable services in the community for outpatient treatment and medication management.
Limitations of this study include a small number of participants and the nature of the study as a retrospective chart review. These findings are not generalizable and changes in CGI-S may be due to causes or associations beyond the long-acting injectable treatments. This study did not compare medications with each other. Maintenance dosing and safety were beyond the scope of this study. Further studies such as safety studies, open-label trials, and randomized double-blinded control trials of LAIA in the pediatric population would be needed.
Clinical Significance
This case series and resulting analysis highlight the efficacy of LAIA for the treatment of serious mental illnesses in adolescents. In all of these cases, significant outpatient resources were required, including injectable services and management. Long-acting injectable antipsychotic treatment should be considered in the pediatric population. This consideration can be difficult for a prescriber.
Considerations for use of a long-acting injectable antipsychotic for a patient include negative attitudes from the prescriber, negative attitude from the patient, and what could be seen as an imposition of treatment upon patients (Brissos et al. 2014). Meanwhile, the benefits of LAIA treatment is well established, including a higher quality of life and functionality (Kaplan et al. 2013), a lower risk of relapse (Kishimoto et al. 2013), and adherence (Schooler 2003). Although this literature focuses on adults receiving LAIA, more research should be completed in adolescents treated with LAIA.
Psychiatric disorders in childhood are associated with poor adult outcomes, including educational failure, criminality, addiction, suicidality, teenage parenthood, mental and physical health problems, social isolation, and early death (Costello et al. 2003; Copeland et al. 2015). The need for more research and clinical considerations of LAIA in children and adolescents is important for patients.
Footnotes
Disclosures
No competing financial interests exist.