A study at the University Clinics of Bonn and Cologne gives people with therapy-resistant depression reason for hope. The doctors treated two men and a woman with what is known as deep brain stimulation. All three patients have been suffering from very severe depression for several years which could neither be brought under control using medication nor by other therapies. During the simulation the condition of two of the three patients improved within a few days. Initial changes were even noticeable in a matter of minutes. The research team warn against exaggerated expectations in view of the small number of patients involved. Nevertheless, the results of the preliminary study are so sensational that they have now been published in the renowned journal Neuropsychopharmacology (doi: 10.1038/ sj.npp.1301408). In deep brain stimulation (DBS) electrodes are implanted selectively in certain areas of the brain and are stimulated using an electric pulse generator. Up to now the procedure has mainly been used in the treatment of Parkinson's. It is currently being investigated whether it also helps with certain psychiatric diseases such as compulsive behavioural disorders. Initial tests on about two dozen patients worldwide also show that it could possibly also have an effect in the case of severe depression. Previous tests have concentrated mainly on two areas of the brain in particular. "By contrast we stimulated a third region, the nucleus accumbens," the Bonn Professor of Psychiatry, Thomas E. Schläpfer, explains. The nucleus accumbens is an important part of what is known as the "reward system". It ensures that we remember good experiences and puts us in a state of pleasurable anticipation. Without the reward system we would not make plans for the future, simply because we could not enjoy the fruits of these plans. "Inactivity and inability to enjoy things are two important signs of depression," Profesor Schläpfer emphasises. "The conclusion is therefore obvious that the nucleus accumbens plays a key role in the genesis of the disease." Initial effects minutes after onset of therapy In their study the researchers report on two men and a woman who have been suffering from very severe depression for years. The researchers implanted electrodes in the nucleus accumbens, which they were able to stimulate using an electric pulse generator in the chest. Some of the effects were observable instantly. "One of the patients expressed the desire to go to the top of Cologne Cathedral a minute after the start of the stimulation and put this into practice the next day," Thomas Schläpfer says. "The woman treated was similar. She said she would enjoy going bowling again." Nevertheless, the patients did not notice a direct improvement in their mood. Nor could they tell whether the pulse generator was switched on or off. In the first few days of the DBS the symptoms of depression improved significantly in two of the three patients. Their condition remained constant for as long as they were undergoing treatment. However, as soon as the pulse generator was switched off, the depression recurred with full intensity. "The recurring symptoms were so severe that for ethical reasons we could not permit the treatment to be interrupted for as long as we had originally planned," Professor Schläpfer emphasises. While psychotropics generally interfere with the biochemistry of the brain, DBS acts locally in the affected areas. The doctors did not observe any side effects like those occurring after the use of antidepressants. The patients only complained about post-operative pain at the site of implantation. In the long term DBS does not seem to pose any major risks. There have been patients with Parkinson"s who have been using this kind of brain pacemaker for more than ten years without experiencing any problems. Preliminary results Even so, the research team caution against exaggerated expectations. "Of course, with so few patients, these are only fairly preliminary results," Professor Schläpfer says. "Our follow-up experiments are showing even now that by no means every patient will respond to this therapy." In the case of operations on the brain, in particular, ethical factors also need to be taken into account, not least because such operations are always risky. For that reason, there were particularly stringent conditions attached to the patients" consent. "One thing has certainly been demonstrated by our research and that of others: DBS can help some people with depression even in cases which were assumed to be resistant to therapy." ### Contact: Professor Thomas E. Schlaepfer