Long-acting injectable paliperidone palmitate in a haemodialysis patient with schizophrenia

To the Editor

In patients with schizophrenia, poor medication adherence often necessitates administration of long-acting injectable antipsychotics. However, these patients have high chronic kidney disease risk (Tzeng et al., 2015), and recommendations on medication use in haemodialysis patients with schizophrenia are lacking.

A 48-year-old man was diagnosed as having paranoid schizophrenia at 16 years of age and end-stage renal disease at 45 years. His first psychiatric presentation revealed insomnia, self-talking and bizarre behaviours with auditory hallucinations; he was hospitalised three to four times every year thereafter due to poor medication adherence, psychotic symptoms and domestic violence. At 46 years of age, he began receiving haemodialysis treatment for uraemia at our hospital; he was also referred to our psychiatric outpatient department and prescribed clozapine (250 mg) and valproate (1000 mg) for schizophrenia. However, subsequent poor schizophrenia medication adherence led to poor control of psychotic symptoms and violent behaviour. After the first discharge from our psychiatric ward on 4 October 2018 (age, 47 years), he began receiving long-acting injectable paliperidone palmitate (150 mg, monthly), clozapine (25 mg/hours of sleep) and valproate (500 mg/hours of sleep). During follow-up over 2018–2019, he was hospitalised only twice, primarily due to physical problems, followed by amelioration of psychotic features and domestic violence behaviours.

Long-acting injectable paliperidone palmitate is a recommended antipsychotic, at a reduced dosage for patients with mild renal impairment (creatinine clearance rate 50–80 mL/min) but not those with moderate-to-severe renal impairment (creatinine clearance rate <50 mL/min) (Janssen Pharmaceutica, 2009); however, no dosage has been suggested specifically for haemodialysis patients, who have altered pharmacokinetics for some drugs, including long-acting paliperidone palmitate, largely because of the altered physiology (Inrig, 2019). For instance, intramuscularly administered paliperidone palmitate gradually hydrolyses to paliperidone, which is dialyzable (because of high water solubility and low molecular weight [664.89 Da]), increasing its clearance during haemodialysis (Janssen Pharmaceutica, 2009). Moreover, the dialyzability of paliperidone, with serum albumin binding rate of 74% (Inrig, 2019; Janssen Pharmaceutica, 2009), decreases with decreases in the fractions of the unbound drug. Therefore, the precise paliperidone clearance rate during haemodialysis remains uncertain. This complicates dosage adjustments for paliperidone palmitate in haemodialysis patients with schizophrenia, necessitating clinical symptoms, medication response and adverse effect assessment before drug administration.

Thus, long-acting injectable paliperidone palmitate may be effective in haemodialysis patients with schizophrenia, particularly those with poor medication adherence. However, its pharmacokinetic effects and relevant clinical results in haemodialysis patients with schizophrenia warrant further exploration.