Article

Durability of antidepressant response to vagus nerve stimulation (VNS (TM))

Department of Psychiatry, Columbia University, New York, New York, United States
The International Journal of Neuropsychopharmacology (Impact Factor: 5.26). 01/2008; 10(6):817-26. DOI: 10.1017/S1461145706007425
Source: PubMed

ABSTRACT This study characterized the durability of improvement in patients who responded early or late while receiving vagus nerve stimulation (VNS). In both a pilot and pivotal study, patients were identified who had at least a 50% reduction in symptom scores 3 months (early responders) or 12 months (late responders) after starting VNS. Probabilities were determined for maintenance of response at 12-month and 24-month time-points. Consistency of improvement throughout the 24-month study period was evaluated, testing for change in serial depression ratings. In the pilot study, 30.5%, 23.7% and 45.8% were early responders, later responders, and non-responders, respectively. These rates were 14.6%, 19.5%, and 65.9% in the pivotal trial. The potential confound of alterations in antidepressant treatment was examined in the pivotal trial. In the pilot study, 72.2% and 61.1% of early responders (n=18) were responders at 12 and 24 months, respectively; 78.8% of late responders (n=14) were responders at 24 months. In the pivotal trial, of early responders (n=30), 63.3% and 76.7% maintained response at 12 and 24 months, respectively; of late responders (n=40), 65.0% maintained response at 24 months. Early and late responders had fewer changes in medication than non-responders across the pivotal study period. In both studies, analyses of serial depression ratings showed stable improvement in early and late responders. These samples had exceptional levels of chronicity and treatment resistance. Yet patients who showed substantial clinical benefit maintained the improvement at remarkably high rates. This durability of benefit was not attributable to alterations in other treatments.

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    • "L'efficacité s'améliore progressivement avec le temps comme démontré par la seule étude randomisée contrôlée en double-aveugle D-02 : 17 % de rémission et 30 % de réponse à un an [13]. La réponse thérapeutique est maintenue à deux ans chez 61 % des répondeurs « rapides » (trois mois de VNS) et chez 78,8 % des répondeurs « tardifs » (à 12 mois de VNS) [38]. On ne constate pas de troubles cognitifs ni d'interaction pharmacologique. "
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    • "Open-label series have found some evidence of beneficial effects in anxiety disorders (Greenberg et al. 2008). A trial of VNS, placed in the abdomen below the for up to 3 years in some cases (Sackeim et al. 2007). Novel effects of VNS have been seen in several animal models and may provide explanations for these slower but more durable clinical effects (Valdes-Cruz et al. 2008; Biggio et al. 2009; Manta et al. 2009). "
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    • "In this cohort, it was found that if patients responded beneficially to VNS after either 3 or 12 months of treatment, then efficacy was maintained for up to 24 months (Sackeim et al, 2007). How VNS produces its beneficial clinical effects is unknown. "
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    ABSTRACT: Vagus nerve stimulation (VNS) is used as therapy for treatment-resistant depression or epilepsy. This study used immunohistochemistry for biomarkers of short-term (c-Fos) and long-term (DeltaFosB) neuronal activation to map regions in brain that are activated by acute (2 h) or chronic (3 weeks) VNS in conscious Sprague-Dawley rats. Electrodes (Cyberonics Inc.) were implanted on the left vagus nerve and 1 week after surgery, stimulation began using parameters employed clinically (one burst of 20 Hz, 250 micros pulse width, 0.25 mA stimulation for 30 s every 5 min). Radio telemetry transmitters were used for monitoring blood pressure, heart rate, activity, and respiratory rate during VNS; neither acute nor chronic VNS significantly affected these parameters. Acute VNS significantly increased c-Fos staining in the nucleus of the solitary tract, paraventricular nucleus of the hypothalamus, parabrachial nucleus, ventral bed nucleus of the stria terminalis, and locus coeruleus but not in the cingulate cortex or dorsal raphe nucleus (DRN). Acute VNS did not affect DeltaFosB staining in any region. Chronic VNS significantly increased DeltaFosB and c-Fos staining bilaterally in each region affected by acute VNS as well as in the cingulate cortex and DRN. Using these stimulation parameters, VNS was tested for antidepressant-like activity using the forced swim test (FST). Both VNS and desipramine significantly decreased immobility in the FST; whereas desipramine decreased immobility by increasing climbing behavior, VNS did so by increasing swimming behavior. This study, then, identified potential sites in brain where VNS may produce its clinical effects.
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