General description

Paliperidone palmitate is an atypical long acting antipsychotics，which can fast onset in acute phase and continuously improve the symptoms in maintenance phase． It has the solid efficacy and convenient ad[1]ministration，which offer a new option for schizophrenia treatment and will help patients to adhere the treatment and prevent relapse． As the sole long acting antipsychotics with monthly injection，it was approved by CFDA in 2011 and indicated for the acute and maintenance treatment of schizophrenia． Based on the published manuscripts and clinical experience，CSCG (China Schizophrenia Coordination Group) organized the experts to write this paper， which will discuss the characteristic of paliperidone palmitate on pharmacology，applicable patients，dosage information and adverse reaction．^[1]

3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-2-methyl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl hexadecanoate is a fatty acid ester obtained by the formal condensation of the carboxy group of hexadecanoic acid with the hydroxy group of 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. It is a member of 1,2-benzoxazoles, a heteroaryl piperidine, an organofluorine compound, a pyridopyrimidine and a fatty acid ester. A benzisoxazole derivative and active metabolite of RISPERIDONE.

Application and Pharmacology

The use of long-acting antipsychotics is a therapeutic option in psychiatry. The introduction of paliperidone palmitate (PALI) for the treatment of psychotic disorders constitutes a valuable broadening of therapeutic possibilities for patients who are mainly suffering from schizophrenia. Therefore, it is important to know the characteristics of this drug and its possibilities for use in clinical practice.

Paliperidone is an active metabolite of risperidone, which is a widely-used antipsychotic drug that has been used for years in the treatment of psychoses. Paliperidone palmitate is a long-acting formulation which possesses certain features that are important from the pharmacological and clinical point of view, differentiating the drug from other antipsychotics, and also from those which are available in long-acting injection forms. The effectiveness of paliperidone palmitate in the recommended doses, measured by a decrease in the severity of symptoms and an elongation of the duration of improvement period has been proved in many methodologically correct clinical trials. Paliperidone palmitate is recommended for the treatment of schizophrenia and is also recommended for early stages of the illness. The frequency and tolerance of paliperidone palmitate side-effects is similar to those found in placebo groups or in patients treated with an active comparator. Because of the good tolerance, paliperidone palmitate was better accepted by the patients that other antipsychotic drugs.^[2]

Toxicity

The studies revealed the effectiveness of paliperidone palmitate in the treatment of psychotic symptoms, mainly schizophrenia. The drug proved to be efficacious in both acute psychotic symptoms treatment and long-term treatment. Its efficacy in patients with schizophrenia was similar and sometimes even better than the efficacy of other long-acting drugs, such as risperidone or olanzapine. In the pharmacoeconomic studies, paliperidone proved to be cost-effective in comparison to risperidone or olanzapine. The review of the literature also underlined that paliperidone palmitate is well tolerated, compared with placebo. Frequency and severity of side-effects such as extrapyramidal symptoms, hyperprolactinemia and weight gain, was similar or less than those found in treatment with other atypical antipsychotics, including long-acting ones.^[3,4]

Time to relapse was significantly longer for patients receiving PALIPERIDONE PALMITATE compared with those receiving oral antipsychotics. The observed reduction in relative risk of relapse is comparable with recent clinical studies and meta-analyses A recent study of injectable aripiprazole failed to demonstrate an advantage on relapse rates over the oral formulation. However, patients were only followed for 38 weeks; an advantage may have become Paliperidone Palmitatearent in the longer term, as observed in the present study. The relapse rate reported herein for patients receiving PALIPERIDONE PALMITATE is comparable with that found in one of the few long-term studies of LATs in early illness, where 8% of patients with recent-onset psychosis who showed a clinical response to long-acting injectable risperidone (LAI-R) relapsed over 2 years. Another study found similar times to hospitalization between unstable patients with schizophrenia receiving oral antipsychotics and those receiving LAI-R. However, several factors may have contributed to this outcome, including the smaller sample size compared with that originally planned, biweekly frequency of study visits, and the chronicity and illness severity of included patients.

Reference

1.Zhang Hongyan, Huang Jizhong, Si Tianmei, etc.: Guidance on the clinical use of paliperidone palmitate, Chinese Journal of new drugs, 2014, No. 12, pp. 1410-1417.

2.Schreiner A., Aadamsoo K. & Altamura A. C. et al., "Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia," Schizophrenia Research, Vol.169, No.1-3(2015), pp.393-399.

3.Jarema M., Bieńkowski P. & Heitzman J. et al., "Paliperidone palmitate: effectiveness, safety, and the use for treatment of schizophrenia," Psychiatria Polska, Vol.51, No.1(2017), pp.7-21.

4."Paliperidone palmitate for schizophrenia (Review,".