Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review

Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain.
Journal of Affective Disorders (Impact Factor: 3.38). 04/2008; 110(1-2):1-15. DOI: 10.1016/j.jad.2008.02.012
Source: PubMed


The main objective of this review of the literature was to evaluate the safety and efficacy of Vagus Nerve Stimulation (VNS) in treatment-resistant depression (TRD) by means of systematic review and meta-analysis.
A systematic review of the literature was made using the major databases (Medline, Psychological Abstracts, Current Contents), beginning in January 2000 and ending in September 2007. Ninety-eight references were found, but only 18 add-on studies met the required quality criteria and were included in this review. Only one double-blind, randomized study was available and therefore a meta-analysis was not feasible.
In a majority of the preliminary open studies selected for this review, VNS was associated with a significant reduction of the depressive symptoms (primary outcome: Hamilton Depression Rating Scale, HDRS) in the short and long term. Unfortunately, the only double-blind study gave rather inconclusive results. Generally, VNS is reported to be a safe and feasible procedure, despite its invasive nature.
VNS seems to be an interesting new approach to treating TRD. However, despite the promising results reported mainly in open studies, further clinical trials are needed to confirm its efficacy in major depression. Moreover, studies on its mechanism of action and cost-effectiveness are also required to better understand and develop VNS therapy for affective disorder.

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    • "Studies looking at the two-year outcome of VNS treatment show response rates of 42-53% and remission rates of 22-39%.40,41) Several single cases with positive effects of VNS have also been reported.42) Overall, these clinical studies show an increase in efficacy of VNS over time with the effect being sustained in most patients who respond.36,43) "
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    ABSTRACT: Treatment resistant depression (TRD) is a global health concern affecting a large proportion of depressed patients who then require novel therapeutic options. One such treatment option that has received some attention in the past several years is vagal nerve stimulation (VNS). The present review briefly describes the relevance of this treatment in the light of other existing pharmacological and non-pharmacological options. It then summarizes clinical findings with respect to the efficacy of VNS. The anatomical rationale for its efficacy and other potential mechanisms of its antidepressant effects as compared to those employed by classical antidepressant drugs are discussed. VNS has been approved in some countries and has been used for patients with TRD for quite some time. A newer, fast-acting, non-invasive pharmacological option called ketamine is currently in the limelight with reference to TRD. This drug is currently in the investigational phase but shows promise. The clinical and preclinical findings related to ketamine have also been summarized and compared with those for VNS. The role of neurotrophin factors, specifically brain derived neurotrophic factor and its receptor, in the beneficial effects of both VNS and ketamine have been highlighted. It can be concluded that both these therapeutic modalities, while effective, need further research that can reveal specific targets for intervention by novel drugs and address concerns related to side-effects, especially those seen with ketamine.
    Clinical Psychopharmacology and Neuroscience 08/2014; 12(2):83-93. DOI:10.9758/cpn.2014.12.2.83
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    • "These results led to speculation that some other mechanism might be at work beyond the baroreflex gains. One possible clue came from the recent research using vagal nerve stimulation for severe depression (and seizure disorders; Sackeim et al., 2001a,b; Nahas et al., 2005; Daban et al., 2008; George et al., 2008; Cristancho et al., 2011). An implanted electrical stimulation device is used to stimulate the vagal afferent pathways resulting in reduction of depressive symptoms. "
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    ABSTRACT: In recent years there has been substantial support for heart rate variability biofeedback (HRVB) as a treatment for a variety of disorders and for performance enhancement (Gevirtz, 2013). Since conditions as widely varied as asthma and depression seem to respond to this form of cardiorespiratory feedback training, the issue of possible mechanisms becomes more salient. The most supported possible mechanism is the strengthening of homeostasis in the baroreceptor (Vaschillo et al., 2002; Lehrer et al., 2003). Recently, the effect on the vagal afferent pathway to the frontal cortical areas has been proposed. In this article, we review these and other possible mechanisms that might explain the positive effects of HRVB.
    Frontiers in Psychology 07/2014; 5:756. DOI:10.3389/fpsyg.2014.00756 · 2.80 Impact Factor
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    • "Barowsky & Schwartz To establish state of the matter regarding augmentation Augmentation and (2006) and combining strategies with lithium, thyroid hormone combination and other compounds, for TRD Bauer et al. (2009) Meta-analysis of trials of Venlafaxine in the treatment Venlafaxine of MDD, including treatment resistant depression and long term relapse prevention Berlim & Turecki (2007) To summarize and discuss the conceptual and operational TRD definition definitions of TRD by systematically reviewing RCTs on its somatic treatments Bschor & Bauer (2006) It reviews the clinical evidence and hypotheses on the mode Augmentation with Lithium of action of lithium augmentation Bschor & Baethge To summarise the scientific findings on switching antidepressants Swtching ADs (2010) to manage TRD patients Daban et al. (2008) To evaluate the safety and efficacy of VNS in TRD VNS Dodd et al. (2005) To review published trials on combination antidepressants with a Combining ADs view to inform clinical practice Fekadu et al. (2009) To assess how people with TRD fare in the longer term, from Long-term outcomes information gathered in observational studies. We were not interested for TRD patients in acute treatment trials of TRD, but in studies which provided data on the longer term outcome of those who either had ongoing depressive symptoms after treatment or who had previously experienced TRD but responded successfully to treatment Lam et al. (2008) To find clear evidence of rTMS for TRD focusing on clinical outcomes rTMS that are relevant to clinicians Lam et al. (2002) To critically evaluate the evidence for efficacy of combining Combining ADs antidepressants McPherson et al. (2005) To evaluate psychological interventions with treatment resistant Psychological treatments depression Ruhé et al. (2012) To identify staging models for TRD and compare them regarding Staging methods predictive utility and reliability Stimpson et al. (2002) To give a summation of the findings of the clinical studies on DBS Deep Brain Stimulation and TRD that have been concluded thus far Sarnecki & Temel (2011) To summarise the findings from all RCTs that have assessed the Pharmacological and efficacy of a pharmacological or psychological intervention for TRD psychological interventions Thomas et al. (2010) To review all the evidence of lamotrigine's effectiveness in treatment Augmentation with resistant depression after at least one failed antidepressant trial Lamotrigine Trivedi et al. (2011) To examine the utility of psychotherapy in managing treatment Psychotherapy resistant depression Note. "
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    ABSTRACT: The objective of this research study was to assess pharmacological, somatic and/or psychological treatments in adults with a diagnosis of major depressive disorder who have not responded to at least one course of antidepressant medication. We conducted a systematic review to identify systematic scientific reviews and meta-analyses on treatment-resistant depression (TRD) published until February 2012. Of the sixty studies selected, sixteen met the inclusion criteria and were therefore included in the review. We considered eight main themes, including the definition of TRD, long-term results, and different treatment strategies, including so-called somatic therapies. Based on the review, the definition of TRD should be standardized in order to achieve a shared conceptualization of this disorder. This would allow a better understanding among clinicians and researchers in the field, promoting a homogeneous research methodology and thus leading to more reliable and comparable results. This essential conceptual clarification would also have a positive impact on patients with TRD, their families, and social and health systems.
    International Journal of Clinical and Health Psychology 05/2014; 14(2):145-153. DOI:10.1016/S1697-2600(14)70048-1 · 2.79 Impact Factor
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