Outcome and follow-up
Before surgery, both patients had MADRS scores of 44 and 49 points and HAM-A scores of 40 points, corresponding to severe depressive and anxiety symptoms (Table 2).
Patient 1 received DBS in the BNST for the initial three months and experienced markedly reduced symptoms of depression and anxiety compared to pre-surgery (reductions: MADRS 77%, HAM-A 65%, Table 2). After switching to DBS in the MFB area, Patient 1 experienced an immediate worsening of symptoms. He continued to report severe anxiety and mild confusion and was offered to break the study protocol. However, the patient continued and by the end of the three-month stimulation, the depression and anxiety symptoms were only slightly reduced compared to pre-surgery levels.
After completion of the randomization phase, DBS was resumed in BNST and turned off in the MFB area. A week later the patient reported anxiety relief. Over the next six months of BNST-DBS, the patient reported a marked reduction in anxiety and therefore continued to receive BNST stimulation during the four-year follow-up. Due to remaining depressive symptoms, mainly apathy, DBS in the MFB area was reactivated, but the patient did not experience any positive effect on depression during the following months. When the current strength was increased, he experienced fatigue and MFB-DBS was again inactivated. In year four, MFB-DBS was reactivated at a low current level (0.5 volts), with the intention to gradually increase the current to avoid triggering additional side effects. Four years after surgery, stable improvements were observed, especially regarding anxiety symptoms, but also depression although the patient still reported feelings of apathy (reductions: MADRS 48%, HAM-A 70%, Table 2).
Patient 2 received DBS in the MFB area for three months, and minor reductions in depression and anxiety symptoms were recorded compared to pre-surgery (reductions: MADRS 10%, HAM-A 25%, Table 2). After switching to BNST-DBS, depressive symptoms were markedly reduced (reductions: MADRS 51%, HAM-A 13%). In the open-label phase, BNST-DBS was delivered and there was a gradual reduction of depression symptoms fulfilling the criteria of remission and for anxiety symptoms five years after surgery (reductions MADRS 55%, HAM-A 65%, Table 2). Attempts of combined stimulation in both targets (BNST and MFB area) were performed, but without any clear beneficial effects, and isolated BNST-DBS was used for chronic stimulation.