やせ薬（Fenfluramine）の離脱症状として錯乱状態を呈した1例

Acute Psychotic Episode Following Fenfluramine Withdrawal

　近年，若年女性を中心にダイエットが注目を浴びている。現在ダイエットを目的とした医薬品は日本では認可されておらず，病的肥満の治療薬としてβ-アドレナリン系を刺激して食欲を抑制するマジンドールだけが認められている。しかしダイエット先進国の欧米では，セロトニン作動薬のフェンフルラミン，そしてマジンドール同様β-アドレナリン作動薬であるフェンテルミンが幅広く使用されてきた。今回我々は，中国製フェンフルラミンを個人輸入し2年8か月にわたり内服し，内服中止後約2週目より不眠，多弁，感情不安定，易刺激性といった症状に始まり，1か月後に錯乱状態を呈した症例を経験したので，若干の考察を加えて報告する。

　Fenfluramine has been used for the treatment of obesity because of its serotoninergic effect. Although depression following fenfluramine withdrawal has been reported, we found no previous case of acute psychotic episodes following fenfluramine withdrawal in the literature.

　A 30-year-old Japanese woman received fenfluramine in Hong Kong and began to take this drug for weight reduction without a doctor's prescription in Japan. She had no previous psychiatric illness, but her younger brother had had depression at the age of 18. She took double the common dosage, 120mg per day, for 2 years and 8 months without any adverse effects. She stopped the drug abruptly because she succeeded in losing weight. One month later, she began to repeatedly perform unlawful acts such as embezzling and stealing goods from her work place and was advised to see a doctor by a colleague. Two months after discontinuation, she exhibited severe aggression, visual and auditory hallucinations as well as paranoid delusions, and was admitted to our hospital. One month after admission her symptoms resolved completely and she was discharged. She reported sleeplessness, irritability and emotional excitement that started 2 weeks after stopping fenfluramine and a few weeks of amnesia before and after admission.

　This case suggests that the abrupt discontinuation of fenfluramine may cause acute psychotic episodes. Fenfluramine stimulates serotoninergic activity by inhibiting serotonin reuptake into presynaptic neurons and by enhancing its release from neurons. Based on the serotonin hypothesis of appetite control, these effects are expected to reduce food intake. This pharmacological effect resembles that of serotoninergic antidepressants such as clomipramine or selective serotonin reuptake inhibitors (SSRIs). Hallucination, severe aggression, mania or confusion were reported as withdrawal symptoms of these antidepressants. It has been hypothesized that these symptoms may result from relative serotonin deficiency. In our case, a similar mechanism as that present with serotoninergic antidepressants may cause the withdrawal symptoms following the abrupt cessation of fenfluramine treatment for obesity.