INTRODUCTION
Akathisia is a neurological side effect produced by antipsychotic or antiemetic drug therapy (Blaisdell, Reference Blaisdell1994). The clinical picture of akathisia is a feeling of inner restlessness in the limbs, especially in the legs (Gibb & Lee, Reference Gibb and Lee1986). However, reports have indicated that akathisia can occur in any area of the body, such as the arms or abdomen (Raskin, Reference Raskin1972; Ratey & Salzman, Reference Ratey and Salzman1984; Walters et al., Reference Walters, Hening and Chokroverty1989). A rare manifestation of akathisia reported by patients receiving antipsychotic treatment is an inner restlessness in respiration as dyspnea.
Prochlorperazine is an antiemetic agent frequently used by cancer patients taking opioids (e.g., morphine, oxycodone) for cancer pain. In oncological settings, prochlorperazine is used as an antiemetic drug for nausea, a side effect of opioid. It is a phenothiazine antiemetic that has central dopamine antagonist properties and that has been reported to cause acute extrapyramidal side effects, parkinsonism, dystonia, and akathisia (Bateman et al., Reference Bateman, Darling and Boys1989). It is well known that neuroleptic-induced akathisia may be difficult to recognize and can occur in the absence of other extrapyramidal signs. Furthermore, cases of akathisia due to antiemetic drugs used by cancer patients have been little reported.
CASE REPORT
The patient was an 66-year-old man with squamous cell carcinoma of the esophagus, stage II(T2N0M0). Due to his renal impairment and the presence of emphysema, surgical resection was not performed; furthermore, chemotherapy was not indicated. Therefore, he attempted radiation therapy and received a total dose of 70.2 Gy. He used opioid, 20 mg/day of morphine hydrochloride, for pain of esophagitis by irradiation, with taking prochlorperazine as an antiemetic drug. He complained of chest discomfort after receiving 5 mg/day of prochlorperazine p.o. for 3 weeks and was admitted to the hospital. When he arrived in the hospital, he acknowledged dyspnea with vague anxiety and a subjective restlessness in respiration, with a temperature of 36.8°C, blood pressure of 118/72 mm Hg, pulse 79 beats/min, respiratory rate 18 breaths/min. Resting room-air oxygen saturation was 98%. First, radiation pneumonitis was suspected, but chest X-ray was normal. He felt that he could not respire leisurely nor stop breathing at any time because of this restlessness in respiration. He denied restlessness in the limbs or other body areas except for the chest. He showed no signs or symptoms of parkinsonism. He was administered 5 mg of biperiden d.i.v.; his restlessness in respiration and dyspnea simultaneously disappeared approximately 1 h later (Hirose & Ashby, Reference Hirose and Ashby2000). Subsequently, 6 mg of oral biperiden was added to the treatment regimen. The next day, the dyspnea with vague anxiety and other restless movements completely ceased. No signs or symptoms of akathisia have appeared in this patient since that time.
DISCUSSION
We reported respiratory akathisia in cancer patients taking prochlorperazine as antiemetics. This is the first report of respiratory akathisia recognized in cancer patients.
It was necessary that other medical problems known to produce dyspnea, such as panic attacks and dyskinesia and dystonia or pulmonary diseases, could be ruled out as a cause of the respiratory restlessness (Hirose, Reference Hirose2000). In this case, the patient did not have anxiety about dying or a history of panic disorder before. Respiratory dyskinesia presents as involuntary movements of respiratory muscles, but not as a restless feeling in respiration, and is not improved on treatment with biperiden (Kruk et al., Reference Kruk, Sachdev and Singh1995; Esmail et al, Reference Esmail, Montgomery and Courtrn1999; Heard et al., Reference Heard, Daly and O'Malley1999). Furthermore, in this case, dystonia was ruled out by the absence of tonic contractions of respiratory muscles (Dressler & Benecke, Reference Dressler and Benecke2005).
Respiratory akathisia is uncommon, so one needs to ask specific questions about restlessness in breathing to recognize this type of akathisia. Therefore, if physicians is not aware of inner restlessness in respiration, it is possible that dyspnea in akathisia may be overlooked or misdiagnosed as a symptom of anxiety disorders, agitation, or respiratory symptoms of cancer itself (Hirose, Reference Hirose2000).
Antiemetics possessing a central antidopaminergic effect are suspected to have caused the akathisia (Seeman, Reference Seeman2002; Matsui-Sakata et al., Reference Matsui-Sakata, Ohtani and Sawada2005). Antiemetic-induced akathisia has been reported in cancer patients receiving metoclopramide or prochlorperazine to help control chemotherapy-related nausea and vomiting (Fleishman et al., Reference Fleishman, Lavin and Sattler1994; Tsuji et al., Reference Tsuji, Miyama and Uemura2006). In this case, prochlorperazine was used as an antiemetic drug for nausea and vomiting, a side effect of opioid.
Prochlorperazine is a phenothiazine antiemetic that has central dopamine antagonistic properties. It has been reported that the presumed community standard of prescribing prochlorperazine, dexamethasone, or a 5HT3 receptor antagonist after moderately high to highly emetogenic chemotherapy results in equivalent outcomes in terms of control of vomiting and measures of satisfaction and quality of life (Burris et al., Reference Burris, Hesketh and Cohn1996; Crucitt et al., Reference Crucitt, Hyman and Grote1996).
In Japan, many cancer patients taking opioids for cancer pain clinically use prochlorperazine as an antiemetic drug. Therefore, it should be noted that akathisia is considered a possible side effect during the management of cancer pain.
The clinicians' attitude toward akathisia is important to recognize. It is also important to consider the possibility of akathisia in patients that complain of vague anxiety, chest discomfort, or dyspnea following antipsychotic medication.
