Fourteen patients were treated over 2 years with cervical vagus nerve stimulation (VNS) for adjunctive therapy of severe, treatment-resistant depression. Here, we report the serendipitous observation that this treatment was associated with highly significant, gradual weight loss despite the patients' report of not dieting or exercising. The weight loss was proportional to the initial BMI, that is, the more severe the obesity, the greater the weight loss. Weight loss did not correlate with changes in mood symptoms. The vagus nerve carries visceral information to and from the brain; modulation of its activity may alter eating behavior. Chronic cervical VNS may merit controlled study for the treatment of severe obesity. Table 1. Psychiatric diagnoses were determined using a structured clinical interview (SCID). 1 One patient had bipolar depression; all others had recurrent, unipolar, major depression. These severely depressed patients (mean Hamilton 2 depression score 29, range 24-37) had failed standard treatments: average duration of illness, 24 years; average duration of current episode, 2.5 years; average number of failed, but adequate, medications trials, 4. The medications on intake and psychiatric co-morbidities are also listed in Table 1.The VNS device (NCP Model 101, Cyberonics Inc., Houston, TX, USA) was approved in 2005 for the adjunctive therapy of severe depression refractory to conventional therapies. It consists of a pacemaker-like device implanted subcutaneously just below the left clavicle. An electrode from the device courses subcutaneously and attaches to the trunk of the left vagus nerve about half way between the clavicle and the mastoid. The right vagus is not used typically because of greater vagal side effects upon the heart. The device is programmed to deliver preset stimuli using an external, magnetic, programming wand. The protocol and device parameters have been previously described. 3 The output current frequently varied either up or down depending upon the patients' side effects and depression symptoms, since the precise relationship between dose and efficacy remains unsettled. At 1 year, the current outputs varied between 0.25 and 1.5 mA. The stimulation frequency was 30 Hz with a pulse width of 500 ms, except for two patients who had 250 ms. The device cycled continuously with stimulation on for 30 s and off for 5 min.After continuous VNS therapy for 6-12 months, several obese patients showed marked weight loss. The mean weight on intake was 91 kg (s.d. 727, range 46-137 kg) with a body mass index (BMI) of 43 kg/m 2 (s.d. 75, range 18-49 kg/m 2 ). The average weight loss at 1 year was 7 kg (s.d. 73, range -6 to þ 24) with mean drop in BMI at 1 year of 2 kg/m 2 (s.d. 73, range -2 to þ 8). The heaviest patient weighed initially 137 kg (BMI 49 kg/m 2 ) and after 1 year of VNS, 114 kg (BMI 40 kg/m 2 ), a decrease of 23 kg. Figure 1 shows that the decrease in BMI at 1 year of individual patients was
