Similar benefits with once-quarterly and once-monthly paliperidone palmitate for schizophrenia in East Asians
Once-monthly and once-quarterly administration of paliperidone palmitate had similar efficacy in terms of relapse prevention for schizophrenia in an East Asian population, according to a subgroup analysis.
“Although the study was not powered to demonstrate noninferiority in any subgroup … the difference in relapse-free rates for [once-monthly and once-quarterly administration] for the East Asian population was consistent with the global findings,” said the researchers.
A total of 1,429 participants were included in the 17-week open-label phase. Of these, 510 were East Asians (58 percent from China, 34 percent from Japan, 4 percent from South Korea, and 4 percent from Taiwan), 344 of whom entered the 48-week double-blind (DB) phase. DB participants were randomized 1:1 to receive once-monthly or once-quarterly paliperidone palmitate, 285 of whom completed treatment (n=143 and 142, respectively). [Neuropsychiatr Dis Treat 2017;13:2193-2207]
Similar rates were observed in both the once-monthly and once-quarterly arms in terms of relapse events ie, psychiatric hospitalization, homicidal or suicidal ideation, or violent or aggressive behaviour (12 percent and 10 percent, respectively) and mean change in PANSS* (12.59 and 11.73), CGI-S** (0.80 and 0.89), and PSP*** scores (10.10 and 10.48).
These results reflected the potential benefit of once-quarterly administration of paliperidone palmitate given the overall improvement in efficacy parameters in both arms with sustained exposure despite the reduced dosing frequency, said the researchers.
Furthermore, 50 percent of the East Asian population achieved symptom remission at the end of the DB phase.
While it is a clinically important outcome for determining the success of antipsychotic treatment, symptom remission does not essentially translate to full functional recovery in patients with schizophrenia, the researchers pointed out. “As much as alleviation of symptoms is essential, improvement in social functioning remains the ultimate goal of clinicians.”
In the Japanese subgroup, however, there were high relapse rates in both the once-monthly and once-quarterly arms (23 percent and 18 percent, respectively), translating to a low symptom control or lack of improvement in social performance.
“Discontinuation of antipsychotics prior to study entry and switching to [paliperidone palmitate] … may have triggered relapse,” said the researchers, who noted that antipsychotic polypharmacy is particularly common for schizophrenia management in Japan.
Additionally, the social stigma related to mental illness and Japanese psychiatric treatment practices may have contributed to higher hospitalization rates which, in turn, could have resulted in further relapses in the Japanese subgroup, they said.
The researchers underscored the significance of reducing the dosing frequency in antipsychotic treatment, as frequent administration of oral antipsychotic agents may induce nonadherence and lead to increased risk of relapse and subsequent treatment failure. [Schizophr Res 2011;127:83-92; Schizophr Res 2011;133:36-41; BMC Med 2005;3:21]
Moreover, it is important to evaluate the clinical outcomes of reducing the paliperidone dosing frequency in Asians given their higher plasma concentrations of paliperidone due to their low body mass index. [BMC Psychiatry 2012;12:1-14]
“[Once-quarterly paliperidone palmitate] can be considered as maintenance therapy for relapse prevention in East Asian patients with schizophrenia following treatment with [once-monthly paliperidone palmitate],” said the researchers.
However, the results may not be representative of the Asian population given the relatively small sample which only included four East Asian countries, noted the researchers.