Peripheral edema: An easily overlooked side effect of long-acting injectable paliperidone

To the Editor

Long-acting injectable (LAI) antipsychotics promote quality of life in psychiatric patients primarily through improving adherence. Peripheral edema has been reported as a side effect of LAI antipsychotics, such as risperidone LAI (Pelizza, 2008). However, there is scant literature regarding the relationship between paliperidone LAI and peripheral edema.

We report a case of paliperidone LAI-induced peripheral edema. A 62-year-old male with bipolar I disorder of 30 years’ duration had received numerous antipsychotics, including risperidone, olanzapine and quetiapine, without side effects. However, manic episodes relapsed frequently due to non-adherence. Because of the patient’s unsatisfactory treatment response, paliperidone LAI 100 mg was administered on days 1 and 8. On day 18, 2+ bilateral pitting pedal edema was observed. A complete medical evaluation was initiated, but yielded no significant findings. Because of persistent manic symptoms, paliperidone LAI 100 mg was repeated on day 36 and was followed by marked clinical improvement. Paliperidone LAI was suspected as the etiology of the edema because of the temporal relationship of its onset with therapy and by the exclusion of other potential causes. Consequently, paliperidone LAI was discontinued. The edema resolved entirely by day 51.

Although a previous case report suggested an association of peripheral edema and paliperidone LAI, the patient had been prescribed oral paliperidone for 3 months before LAI use (Cicek et al., 2017). Consequently, it is difficult to determine whether the edema was related to either oral or LAI formulations. To the best of our knowledge, this is the first reported case to unequivocally associate peripheral edema with paliperidone LAI.

Although various hypotheses have been offered, the mechanism of paliperidone LAI-induced edema is undetermined. In addition, an association of the severity of edema and paliperidone LAI dosage has not been confirmed. Due to paliperidone LAI pharmacokinetics, the maximum plasma concentration is not reached until 13 days after dosing (Kim et al., 2012). The temporality of the anticipated peak plasma level is close to the date of the onset of edema in our case. Therefore, our case also suggests that edema was related to peak plasma concentration. Although further studies are warranted to confirm these issues, it is still valuable to remind clinicians to be cognizant of paliperidone LAI-induced peripheral edema and its delayed onset based on pharmacokinetics.