Abstract
Objective: Although new treatment modalities are recommended for the treatment resistant depression, it has been estimated that some depressive episodes treated for an adequate duration with recommended dose of an antidepressant exhibit treatment resistance. Direct evidence supporting a role for the vagal nerve stimulation (VNS) therapy in depression came from early observation of mood improvement in treatment resistant epileptic patients who were performed VNS. Results of the clinical and experimental studies recommended that VNS therapy could be a choice for long-term treatment of chronic or recurrent treatment resistant depression (TRD). The aim of this study was to review the literature which evaluates the affectivity and mechanism of the VNS which have been used as an alternative therapy modality in the treatment resistant major depressive disorders.
Method: Medline/ Index Medicus (PubMED) was searched and the reports which investigated the properties of the VNS (such as application procedures, mechanisms of effect, therapeutic affectivity and reliability of VNS in chronic or recurrent TRD episodes) were reviewed in a wide perspective in this article.
Results: It has been reported in several studies that large number of patients receiving conventional treatment could not show full remission of depressive episodes, and the results of these studies support that new therapy modalities are needed. Numerous studies had been conducted regarding the effect mechanisms of VNS in treatment-resistant depressive episodes. However, in these studies which area of the brain -and how- was affected not fully understood. The effectiveness and the reliability of the VNS methods in intractable depressive episodes have been investigated by using different methods and study design. In some of these VNS studies for treatment of TRD episodes, showed an increase in the rate of treatment response and remission; however, some studies showed an increase only in the rate of treatment response. In these studies, the research group received a large portion of patints with unipolar disorder who had TRD episodes in general, and less portion of patients were bipolar disorders. And, the authors suggested future studies contained large sample size, because their study samples, which were conducted to investigate the effectiveness and reliability of VNS, consisted of relatively small number of the patients with bipolar disorder. In studies, the most commonly reported side effects in patients treated with VNS were incision side pain, hoarseness, neck pain, headache, cough, difficulty in swallowing, and shortness of breath.
Conclusion: VNS in TRD episodes may seem an efficient and reliable treatment method to use, but this method more widely on this subject to be able to use more controlled studies are needed.

Key words: bipolar disorder, major depression, vagal nerve stimulation