Vagus Nerve Stimulation Modulates Inflammation in Treatment-Resistant Depression Patients: A Pilot Study.

Vagal neurostimulation (VNS) is used for the treatment of epilepsy and major medical-refractory depression. VNS has neuropsychiatric functions and systemic anti-inflammatory activity. The objective of this study is to measure the clinical efficacy and impact of VNS modulation in depressive patients. Six patients with refractory depression were enrolled. Depression symptoms were assessed with the Montgomery-Asberg Depression Rating, and anxiety symptoms with the Hamilton Anxiety Rating Scale. Plasmas were harvested prospectively before the implantation of VNS (baseline) and up to 4 years or more after continuous therapy. Forty soluble molecules were measured in the plasma by multiplex assays. Following VNS, the reduction in the mean depression severity score was 59.9% and the response rate was 87%. Anxiety levels were also greatly reduced. IL-7, CXCL8, CCL2, CCL13, CCL17, CCL22, Flt-1 and VEGFc levels were significantly lowered, whereas bFGF levels were increased (p values ranging from 0.004 to 0.02). This exploratory study is the first to focus on the long-term efficacy of VNS and its consequences on inflammatory biomarkers. VNS may modulate inflammation via an increase in blood-brain barrier integrity and a reduction in inflammatory cell recruitment. This opens the door to new pathways involved in the treatment of refractory depression.

Electrocardiogram Corrected Q-T Interval Predicts Response to Vagus Nerve Stimulation in Depression.

INTRODUCTION: Recent studies have revealed a possible link between heart rate variability (HRV) and major depressive disorder (MDD), with decreased HRV in MDD compared with healthy subjects. Corrected Q-T interval (QTc) has been suggested to represent an indirect estimate of HRV, as QTc length is inversely correlated to parasympathetic activity in healthy subjects. This retrospective study assessed the ability of QTc length in predicting response to vagus nerve stimulation (VNS) treatment in refractory depression. METHODS: We measured QTc length in 19 patients suffering from refractory depression, selected to be implanted with VNS. Correlations were calculated between baseline QTc (preimplantation) and long-term mood response. RESULTS: Nineteen patients selected for VNS surgery were included in the study. Baseline 28-item Hamilton Depression Rating Scale scores were 28.5 ± 6.8 and decreased to 15.1 ± 9.5 at 12 months and 12.4 ± 10.4 at 24 months post-VNS. Among the 19 patients, 53% (10) were responders and 26% (5) were in remission at 12 months. Pretreatment QTc averaged 425.5 ± 22.0. Patients with longer baseline QTc displayed larger improvement, with a significant correlation between mood and QTc values after 12 months (r(18) = -0.526, P = 0.02) and also after 24 months of VNS therapy (r(17) = -0.573, P = 0.016). CONCLUSIONS: The presented analysis showed that increased QTc in patients with MDD might be used as a baseline biomarker for depressive episodes that might respond preferentially to VNS. The link between cardiovagal activity in depression and response to VNS treatment requires further investigation in larger cohorts and randomized controlled trials.

Safety and Efficacy of Accelerated Repetitive Transcranial Magnetic Stimulation Protocol in Elderly Depressed Unipolar and Bipolar Patients.

OBJECTIVE: Major depressive disorder (MDD) is a prevalent condition in older adults. Although antidepressant drugs are commonly prescribed, efficacy is variable, and older patients are more prone to side effects. Repetitive transcranial magnetic stimulation (rTMS) is an alternative therapy used increasingly in the treatment of MDD. Even though recent studies have shown efficacy of rTMS in elderly depressed patients, the safety and efficacy of accelerated rTMS has not been studied in this population. METHODS: Data were retrospectively analyzed for adults with treatment-resistant depression (N = 73, n = 19 ≥60years, n = 54 <60 years) who underwent an accelerated protocol of 30 sessions (2 sessions per day) of left dorsolateral prefrontal cortex high-frequency (20 Hz) rTMS. RESULTS: There were statistically significant improvements in depression and anxiety symptoms from baseline to post-treatment in both age groups, but those 60years and older showed statistically greater improvement in depression and anxiety symptom scores (p = 0.01) than those less than 60. There were significantly more responders (p = 0.001) and remitters (p = 0.023) in the older group. The age groups did not differ significantly in clinical and demographic characteristics or severity of current depressive episode, although baseline anxiety was less severe in those 60years and older. Unipolar and bipolar patients had a similar clinical response, and treatment appeared to be well tolerated by all patients. CONCLUSION: Our results suggest that accelerated rTMS protocol is a safe and effective treatment for unipolar and bipolar depressed subjects, including older adults.

Long-term Sustained Cognitive Benefits of Vagus Nerve Stimulation in Refractory Depression.

BACKGROUND: Treatment-resistant depression (TRD) is a serious chronic condition disabling patients functionally and cognitively. Chronic vagus nerve stimulation (VNS) is recognized for the management of TRD, but few studies have examined its long-term effects on cognitive dysfunction in unipolar and bipolar resistant depression. OBJECTIVE: The purpose of this study was to assess the course of cognitive functions and clinical symptoms in a cohort of patients treated with VNS for TRD. METHODS: In 14 TRD patients with VNS, standardized clinical and neuropsychological measures covering memory, attention/executive functions, and psychomotor speed were analyzed prestimulation and up to 2 years poststimulation. RESULTS: Vagus nerve stimulation patients significantly improved on cognitive and clinical measures. Learning and memory improved rapidly after 1 month of stimulation, and other cognitive functions improved gradually over time. Cognitive improvements were sustained up to 2 years of treatment. At 1 month, improvement in Montgomery-Åsberg Depression Rating Scale scores was not correlated with changes in any of the cognitive scores, whereas at 12 months, the change in Montgomery-Åsberg Depression Rating Scale score was significantly correlated with several measures (Stroop interference, verbal fluency, and Rey-Osterrieth Complex Figure delayed recall). CONCLUSIONS: In recent years, a growing interest in cognitive dysfunction in depression has emerged. Our results suggest that chronic VNS produces sustained clinical and cognitive improvements in TRD patients, with some mental functions improving as soon as 1 month after the initiation of the VNS therapy. Vagus nerve stimulation seems a very promising adjunctive therapy for TRD patients with cognitive impairment.

A 6-Year Follow-up Study of Vagus Nerve Stimulation Effect on Quality of Life in Treatment-Resistant Depression: A Pilot Study.

OBJECTIVES: Treatment-resistant depression (TRD) carries a major burden on those affected by this disease and significantly impacts their quality of life (QOL). Vagus nerve stimulation (VNS) has showed promising results on symptoms, but its impact on QOL remains underresearched. This study aims to evaluate the long-term effects of VNS on both QOL and clinical symptoms for TRD patients, through a naturalistic 6-year follow-up. METHOD: Outpatients with confirmed TRD were enrolled to receive VNS. None of the patients enrolled left the study or was lost at follow-up. Patients were evaluated at 1, 3, 6, 12, 24, 36, 48, 60, and 72 months for a total of 10 assessments using the 36 item Short Form questionnaire, Hamilton Rating Scale for Depression and Hamilton Anxiety Rating Scale. RESULTS: Ten patients were enrolled with a mean age of 50 years. This study shows a clinically and statistically significant improvement of the mental QOL (P = 0.012), physical QOL (P < 0.002), depressive symptoms (P < 0.001), and anxiety symptoms (P < 0.001). CONCLUSIONS: This long-term naturalistic study is the first to demonstrate that the therapeutic effect of VNS on TRD goes beyond clinical symptoms to improve the daily QOL of those affected.

Depressive Symptoms Negatively Impact Montreal Cognitive Assessment Performance: A Memory Clinic Experience.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a general cognitive screening tool that has shown sensitivity in detecting mild levels of cognitive impairment in various clinical populations. Although mood dysfunction is common in referrals to memory clinics, the influence of mood on the MoCA has to date been largely unexplored. METHOD: In this study, we examined the impact of mood dysfunction on the MoCA using a memory clinic sample of individuals with depressive symptoms who did not meet criteria for a neurodegenerative disease. RESULTS: Half of the group with depressive symptoms scored below the MoCA-suggested cutoff for cognitive impairment. As a group, they scored below healthy controls, but above individuals with Alzheimer's disease and frontotemporal dementia. A MoCA subtask analysis revealed a pattern of executive/attentional dysfunction in those with depressive symptoms. CONCLUSIONS: This observed negative impact of depressive symptomatology on the MoCA has interpretative implications for its utility as a cognitive screening tool in a memory clinic setting.