Two cases of long-acting paliperidone in adolescence

Abstract

Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. We report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting. The cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. Given the lack of approved long acting injectable antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of such medications in children and adolescent patients are of importance.

Introduction

Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. Nevertheless, off-label use of antipsychotics in child and adolescent psychiatry is not uncommon [Baeza et al. 2014; Winterfeld et al. 2008]. Kowalski and colleagues reported one case of PPLAI treatment in a child with an autistic disorder [Kowalski et al. 2011], yet no study so far has described use of PPLAI in adolescents with psychotic disorders. In this context, we report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting.

Clinical cases

Subject A, a 14-year-old Caucasian male, was admitted following 2 years of total seclusion in his home. He had stopped attending school, having reported feeling observed in the street. He displayed no interest in social contact, his affect had become flattened, he was apathetic and had poor hygiene. He refused contact with any mental health professional and was admitted to hospital following the intervention of social services. He underwent a full medical and psychiatric assessment, and was administered a Wechsler Intelligence Scale for Children (4th edition) which revealed a total intelligence quotient score of 63 (95% confidence interval 51–78). He was diagnosed with undifferentiated schizophrenia [Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) 295.90] and mild intellectual disability (DSM-IV 317).

The initial treatment was aripiprazole 5 mg daily, but due to concerns regarding treatment compliance, the clinical team decided to change to a long-acting injection formulation (LAI). Off-label use of this medication was discussed with the family, who provided oral informed consent. First, oral paliperidone, at a dosage of 6 mg daily, was introduced; this was well tolerated and led to improvement of clinical symptoms. Subsequently, oral paliperidone was stopped and the first dose of PPLAI 50 mg was administered, followed by 50 mg 1 week later. The patient was discharged after 17 days of hospitalization. His symptoms were rated by two experienced child and adolescent psychiatrists (M.F. and I.B.) employing the Positive and Negative Syndrome Scale [Kay et al. 1987], the UKU side effects rating scale [Lingjaerde et al. 1987] and the Global Assessment of Functioning scale [Endicott et al. 1976]. Table 1 illustrates his symptoms at admission and discharge. As maintenance treatment, PPLAI 50 mg every 28 days was established. It was decided to program the injections every 28 days because this enabled us to establish a fixed pattern of administration, making it easier for the patient and their family to remember appointments.

Table 1.

Clinical symptoms at admission and discharge.

	Patient A		Patient B
	Admission	Discharge	Admission	Discharge
PANSS	P: 14	P: 8	P: 16	P: 15
	N: 36	N:27	N: 16	N: 15
	GP: 44	GP: 31	GP: 43	GP: 38
	Total: 94	Total: 66	Total: 75	Total: 68
UKU	No adverse effects		Psychic effects: 2 mild drowsiness and asthenia
			Neurological effects: 3: oculogyric dystonia
			No other adverse effects.
GAF	15	45	20	45

GAF, Global Assessment of Functioning; GP, general psychopathology; N, negative; P, positive; PANSS, Positive and Negative Syndrome Scale; UKU, The UKU side effects rating scale.

After 1 year, subject A still received PPLAI 50 mg every 28 days with no evidence of adverse effects. He attended a day hospital, and showed improvement in social skills and affective reactivity.

Subject B, a 17-year-old African male, adopted at the age of 10, was admitted for the fourth time to our inpatient unit due to disruptive behavior in the context of paranoid thoughts and coinciding with treatment noncompliance. He had been diagnosed with psychotic disorder NOS (DSM-IV 298.9) and conduct disorder (DSM-IV 312.9). Since the onset of his symptoms, 2 years before, he had received treatment with oxcarbazepine, methylphenidate, atomoxetine, aripiprazole and quetiapine. Given his lack of insight, treatment with a LAI was considered. After obtaining oral informed consent from B’s caregivers, oral paliperidone 3 mg daily, was initiated and was well tolerated; it was then changed to PPLAI administrating 50 mg as a loading dose. However, 3 days later he presented an oculogyric crisis, which reverted with biperiden 4 mg. After 1 week, PPLAI 50 mg was re-administrated with good tolerability and was maintained on a monthly basis in association with biperiden 4 mg daily. As a maintenance treatment, established 50 mg every 28 days was establisahed. He was discharged after 14 days of hospitalization. Table 1 depicts his symptoms at admission and discharge.

During the next 2 months, the patient reported somnolence and concentration difficulties, and eventually refused to receive treatment. A month later, he was readmitted due to behavioral disruption. Zuclopentixol decanoate 100 mg every 14 days together with biperiden 4 mg/day were introduced; this led to clinical improvement and was initially well tolerated. However, after 1 month as an outpatient, he began to refer concentration difficulties and diurnal somnolence, due to which the LAI was changed to oral aripiprazol 15 mg/day. However, noncompliance of this medication led to exacerbation of his behavioral difficulties and paranoid interpretations over the following months. On re-admission, a decision was reached together with the patient to reintroduce PPLAI in association with biperiden.

Discussion

The present cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. The American Academy of Child and Adolescent Psychiatry [McClellan et al. 2013] recommends the use of LAI antipsychotics in adolescents with schizophrenia with chronic psychotic symptoms and history of poor medication adherence. Poor insight is one of the main reasons of antipsychotic discontinuation and subsequent relapse in schizophrenia spectrum disorders [Tiihonen et al. 2011; Parellada et al. 2012] and may be more prevalent in younger ages [Parellada et al. 2011]. Therefore, given the lack of approved LAI antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of novel LAI in children and adolescent patients are important.