Bofu-tsusho-san effectively attenuates the weight gain observed after receiving olanzapine


*Nobutomo Yamamoto, MD, Department of Psychiatry, Seiwa Hospital, Institute of Neuropsychiatry, 91 Benten-cho, Shinjuku-ku, Tokyo 162-0851, Japan. Email:

THE INTRODUCTION OF second-generation antipsychotics has led to a reduction in extrapyramidal symptoms and cognitive dysfunction and improved adherence. The potential for adverse metabolic effects, however, such as weight gain, is markedly increased. We found that concomitant use of bofu-tsusho-san, a traditional oriental herbal medicine, effectively attenuates the weight gain observed after receiving such an antipsychotic, olanzapine. Here, we discuss a representative case.

A 20-year-old woman presented with a psychiatric diagnosis of disorganized schizophrenia (DSM-IV-TR: 295.10). Her height was 157 cm, weight 58.2 kg and body mass index (BMI), 23.6 kg/m2. The patient had begun to suffer from auditory hallucinations and was admitted to Shimofusa Psychiatric Medical Center. She received olanzapine 7.5 mg/day and promethazine 75 mg/day, and her psychosis improved. Her appetite and meal volume, however, increased. Her total Drug Attitute Inventory-10 (DAI-10) score, which indicates the level of drug compliance and ranges from −10 points to +10 points,1 was 1 at discharge from hospital. Three months after the start of treatment, her weight had increased by 4.5 kg (to 62.7 kg), and her BMI to 25.4 kg/m2. At this point she hinted that she intended to stop her treatment because of her weight gain. We therefore prescribed bofu-tsusho-san 7.5 g/day in addition to the medication. Subsequently, her weight decreased gradually but her appetite and meal volume remained unchanged. Six months after the start of concomitant use of bofu-tsusho-san, her weight had decreased to 60.0 kg, a 2.7-kg weight loss, and her BMI to 24.3 kg/m2. Her total DAI-10 score had increased to 5. She is currently continuing to visit hospital.

In a study of obese mice, bofu-tsusho-san produced a significant decrease in fat mass and weight compared with placebo, without affecting the amount of food ingested.2 Bofu-tsusho-san contains various herbal ingredients, including Ephedrae herba, Glycyrrhizae radix, Schizonepetae spica, Forsythiae fructus and Rhei rhizoma. Ephedrae herba contains ephedrine derivatives such as l-ephedrine, which stimulate the release of norepinephrine from nerve endings. One effect of this is to accelerate metabolism (as measured by heat production) in brown fat cells through the action of activated cyclic adenosine monophosphate (cAMP). Lipolysis in white fat cells is also promoted.3 The cAMP is inactivated by phosphodiesterase (PDE). Caffeine has an inhibitory action on PDE, and thus prolongs the activation of cAMP. Therefore, weight decreases significantly more in subjects treated with both caffeine and ephedrine than in those receiving ephedrine alone, and this effect lasts for an extended period.4Glycyrrhizae radix, Forsythiae fructus and Schizonepetae spica have a PDE-inhibiting effect approximately 2.5-fold greater than that of caffeine. Thus, cAMP activation is prolonged and whole-body metabolism accelerates.2

Second-generation antipsychotics have been used widely, but the resulting signs of metabolic syndrome such as weight gain and derangement of sugar and fat metabolism are attracting public attention. The present case and previous studies indicate that bofu-tsusho-san is effective in reversing these adverse effects.