Abstract
Dear Editor:
Opioids are the mainstay for the treatment of cancer pain, although a major cause of nausea. Not only is the management of nausea important in terms of quality of life and care, but prognosis can also be improved where good nausea control results in greater treatment compliance with opioids. So far, opioid-induced nausea has been mainly treated with an antiemetic with strong selective blockade of the dopamine-2 (D2) receptor. However, it often induces extrapyramidal symptoms (EPS).
In Japan, perospirone is employed as an atypical antipsychotic drug that exerts strong antagonistic activities against the serotonergic-2 (5-HT2) receptor, D2 receptor, and histamine-1 receptor. 1 These antagonistic activities are understood to occur in the chemoreceptor trigger zone and vomiting center as well, making it an antiemetic agent. 2 Its strong antagonistic effect as 5-HT2 receptor also causes lower risk of EPS. 3 Moreover, perospirone can be given to diabetic patients, despite the fact that some atypical antipsychotics are contraindicated in them. However, there have been few clinical studies not only on its putative antiemetic action but also on its antiemetic effectiveness for opioid-induced nausea.
In our present study we conducted a retrospective chart review of opioid-naïve patients with advanced cancer who received perospirone as antiemetic against opioid-induced nausea from April 2012 to July 2013. They started on an opioid and subsequently developed nausea within 48 hours. We strictly excluded those patients developing nausea from other causes (chemotherapy, radiotherapy, nephropathy, hypercalcemia, intracranial lesion, and gastrointestinal dysfunction). Effectiveness was evaluated as follows: complete response (CR) defined as total elimination of nausea; partial response as a reduction in the severity of nausea or transient disappearance of nausea (with recurrence within four hours of the initial dosing); and no response shown as a lack of any change in the nausea.
All these patients (n = 5) revealed a CR to perospirone without any adverse effects (see Table 1). Two of them started on morphine (20 mg/day and 40 mg/day) and three started on oxycodone (dosage range 10–20 mg/day). Conventional antiemetic agents given before the initial dose of perospirone had resulted in no or partial antiemetic responses. The effective dose for a single administration was 4 mg (n = 4) or 8 mg (n = 1). One patient was administered three doses a day regularly. Four patients had the antiemetic effectiveness and did not require any more perospirone for at least 24 hours, although it is defined as short acting (e.g., Tmax: 1.4–2.3 h; t1/2α: 1.0–3.0 h; t1/2β: 5.0–8.0 h). 1 There were no adverse events, including EPS.
CR, complete antiemetic response defined as total elimination of nausea; FA, former antiemetics; MOR, controlled-release morphine; NR, no response, defined as a lack of any change in the nausea; OXC, controlled-release oxycodone; PR, partial response, defined as a reduction in the severity of nausea or transient disappearance of nausea with 4 hours of the initial dosing.
In our strictly conducted retrospective study, we first found that perospirone has antiemetic effectiveness against opioid-induced nausea in opioid-naïve patients. Nevertheless, the present study has some limitations due to its small number of subjects, retrospective design, and availability of perospirone only in Japan. Further studies can be designed as a prospective trial using a much larger number of patients to confirm this antiemetic effectiveness and the optimal dosage, which suggests its availability in other countries as well.