Clinical results for patients with major depressive disorder in the Texas Medication Algorithm Project

CONTEXT: The Texas Medication Algorithm Project is an evaluation of an algorithm-based disease management program for the treatment of the self-declared persistently and seriously mentally ill in the public mental health sector. OBJECTIVE: To present clinical outcomes for patients with major depressive disorder (MDD) during 12-month algorithm-guided treatment (ALGO) compared with treatment as usual (TAU). DESIGN: Effectiveness, intent-to-treat, prospective trial comparing patient outcomes in clinics offering ALGO with matched clinics offering TAU. SETTING: Four ALGO clinics, 6 TAU clinics, and 4 clinics that offer TAU to patients with MDD but provide ALGO for schizophrenia or bipolar disorder.Patients Male and female outpatients with a clinical diagnosis of MDD (psychotic or nonpsychotic) were divided into ALGO and TAU groups. The ALGO group included patients who required an antidepressant medication change or were starting antidepressant therapy. The TAU group initially met the same criteria, but because medication changes were made less frequently in the TAU group, patients were also recruited if their Brief Psychiatric Rating Scale total score was higher than the median for that clinic's routine quarterly evaluation of each patient. MAIN OUTCOME MEASURES: Primary outcomes included (1) symptoms measured by the 30-item Inventory of Depressive Symptomatology-Clinician-Rated scale (IDS-C(30)) and (2) function measured by the Mental Health Summary score of the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) obtained every 3 months. A secondary outcome was the 30-item Inventory of Depressive Symptomatology-Self-Report scale (IDS-SR(30)). RESULTS: All patients improved during the study (P<.001), but ALGO patients had significantly greater symptom reduction on both the IDS-C(30) and IDS-SR(30) compared with TAU. ALGO was also associated with significantly greater improvement in the SF-12 mental health score (P =.046) than TAU. CONCLUSION: The ALGO intervention package during 1 year was superior to TAU for patients with MDD based on clinician-rated and self-reported symptoms and overall mental functioning.     

Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial.

BACKGROUND: Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy. METHODS: This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>/=50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD(24)]). RESULTS: At 10-weeks, HRSD(24) response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events. CONCLUSIONS: This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.     

Clinical issues in considering vagus nerve stimulation for treatment-resistant depression

This review briefly discusses the clinical and basic science rationale for vagus nerve stimulation (VNS) in treatment-resistant depression (TRD). As the number of treatment failures for depression increases, the likelihood of achieving remission during acute treatment decreases, and the risk of relapse increases with the number of treatment failures. Two open trials of adjunctive VNS for TRD showed positive acute results and a growing benefit over time. The results of the acute randomized controlled trial were not significant for the primary outcome (response by HRSD-24), but the secondary measure (IDS-SR-30) was significant for VNS. A 12-month nonrandomized comparative analysis of patients receiving adjunctive VNS with TRD patients receiving treatment as usual showed significant results favoring VNS. Post hoc analyses found that this difference was not accounted for baseline differences nor by intercurrent treatment. While VNS is well tolerated, the optimal dosing strategies have not been determined nor have clinically useful predictors of who will respond to the treatment. Given the profound effects of TRD upon the daily lives of patients and that a substantial number of VNS patients receive benefit, VNS is a useful option for managing patients with TRD.     

Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression

BACKGROUND: Treatment-resistant depression (TRD) is a long-term, disabling illness. We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with standard care. METHOD: This 2-year prospective, multicenter, observational study (patients enrolled from January 2001 through July 2004) tracked the outcomes of 124 patients with treatment-resistant, nonpsychotic major depressive disorder (N = 109) or bipolar depressed phase disorder (N = 15) who received treatment as usual (TAU) (i.e., any therapeutic regimen agreed to by patients and psychiatrists, including medications, electroconvulsive therapy [ECT], and psychotherapy). Treatments could be adjusted, started, and stopped as necessary. The primary outcome, treatment response, was defined a priori as > or = 50% improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR-30). Remission was defined as an IDS-SR-30 score of < or = 14. The Medical Outcomes Study (MOS) 36-item Short Form Health Survey (SF-36) was used to monitor quality-of-life changes. RESULTS: The 12- and 24-month IDS-SR-30 response rates were 11.6% (13/112) and 18.4% (19/103), respectively. Of the 13 responders at 12 months, only 5 were responders at 24 months. The 12- and 24-month IDS-SR-30 remission rates were 3.6% (4/112) and 7.8% (8/103), respectively. Only 1 of the 4 12-month remitters was also a remitter at 24 months. The SF-36 indicated globally poor quality of life in this sample. CONCLUSIONS: Despite the wide range of treatment options available for depression, the response rates, remission rates, and quality-of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU.     

Introduction of vagus nerve stimulation into a maintenance electroconvulsive therapy regimen: a case study and cost analysis

OBJECTIVE: This case report describes the outcome of a patient implanted with the vagus nerve stimulation (VNS) device while receiving maintenance electroconvulsive treatment (M-ECT) and compares the costs of treatment options for treatment-resistant depression. METHODS: The patient, a male, aged 47 years with bipolar I disorder, treatment-resistant depression, and a 13-year history of depressions, was receiving M-ECT at 2-week intervals as well as antidepressant medications when he was implanted with the VNS device. His depression was assessed with the Montgomery-Asberg Depression Rating Scale. The cost analysis of treatment modalities placed M-ECT at $800 to $1000 per treatment and VNS at approximately $3900 annually (surgery, device, and office visits, approximately $31,300, was prorated over 8 years). RESULTS: Antidepressants and other medications were used in combination and were gradually changed while the patient was receiving electroconvulsive therapy. The patient improved with VNS and was able to discontinue M-ECT. His Montgomery-Asberg Depression Rating Scale scores had fluctuated between 2 and 56, but, after VNS, the scores decreased to a level consistent with remission and have remained at those levels. The patient reported feeling as well as he had felt at any time he could remember, began an exercise program, and lost 30 lbs. During the 10 months before implantation, 14 electroconvulsive therapy treatments cost $11,200 to $14,000. For 10 months after implantation, 7 M-ECT treatments ($5600-$7000) plus prorated VNS ($3250) equaled $8850 to $10,250, $2350 to $3750 less than before implantation. CONCLUSIONS: This patient improved with VNS and was able to discontinue M-ECT. Introducing VNS effected a cost savings over M-ECT.     

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study.

BACKGROUND: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.     

Can a targeted psychological intervention be effective for young people following a first manic episode? Results from an 18‐month pilot study

Aim: There is a scarce literature describing psychological interventions for a young, first‐episode cohort who have experienced psychotic mania. This study aimed to assess whether a manualized psychological intervention could be effective in reducing symptomatology and relapse, and improve functional outcome in this population. Methods: The study was an open‐label design, drawn from a larger pharmacotherapy trial. All participants in the pharmacotherapy trial were offered a manualized psychological intervention in addition to case management. Inclusion in the psychotherapy group was based on participant's choice, and on completion of four or more of the eight modules offered. All clinical files were audited to ensure accuracy of group allocation. Forty young people aged 15 to 25 years old who had experienced a manic episode with psychotic features were recruited into the study, with 20 people in the combined treatment as usual plus psychotherapy group (P+TAU), and an equal number of matched control participants who received treatment as usual (TAU) within the same service. All participants were prescribed antipsychotic and mood‐stabilizing medication. Symptomatic, functional and relapse measures were taken both at baseline and at 18‐month follow‐up. Results: Manic symptoms improved significantly for both groups, with no differences between groups. Depression scores and overall symptom severity were significantly lower in the P + TAU group. No differences were evident between groups with regard to numbers or type of relapse. The P + TAU group had significantly better social and occupational functioning after 18 months. Conclusion: This study suggests that a manualized psychological intervention targeted to a first‐episode population can be effective in reducing depression and overall symptom severity, and can improve functional outcome following a first episode of psychotic mania.     

The application of vagus nerve stimulation and deep brain stimulation in depression

Despite the progress in the pharmacotherapy of depression, there is a substantial proportion of treatment-resistant patients. Recently, reversible invasive stimulation methods, i.e. vagus nerve stimulation (VNS) and deep brain stimulation (DBS), have been introduced into the management of treatment-resistant depression (TRD). VNS has already received regulatory approval for TRD. This paper reviews the available clinical evidence and neurobiology of VNS and DBS in TRD. The principle of VNS is a stimulation of the left cervical vagus nerve with a programmable neurostimulator. VNS was examined in 4 clinical trials with 355 patients. VNS demonstrated steadily increasing improvement with full benefit after 6-12 months, sustained up to 2 years. Patients who responded best had a low-to-moderate antidepressant resistance. However, the primary results of the only controlled trial were negative. DBS involves stereotactical implantation of electrodes powered by a pulse generator into the specific brain regions. For depression, the targeted areas are the subthalamic nucleus, internal globus pallidus, ventral internal capsule/ventral striatum, the subgenual cingulated region, and the nucleus accumbens. Antidepressant effects of DBS were examined in case series with a total number of 50 TRD patients. Stimulation of different brain regions resulted in a reduction of depressive symptoms. The clinical data on the use of VNS and DBS in TRD are encouraging. The major contribution of the methods is a novel approach that allows for precise targeting of the specific brain areas, nuclei and circuits implicated in the etiopathogenesis of neuropsychiatric disorders. For clinical practice, it is necessary to identify patients who may best benefit from VNS or DBS.     

Concomitant use of vagus nerve stimulation and electroconvulsive therapy for treatment-resistant depression

OBJECTIVE: This study explored the use of electroconvulsive therapy (ECT) in the pivotal study of vagus nerve stimulation (VNS) for treatment-resistant depression. METHODS: The clinical characteristics and outcomes of study participants who received ECT during the first 12 months of VNS were compared with those who did not receive ECT. Physicians were instructed to turn off VNS during administration of ECT. RESULTS: Of 205 (evaluable sample) patients who received VNS, 14 also received ECT. Participants who received ECT had a statistically significant greater number of hospital admissions (P = 0.037, Wilcoxon) and number of suicide attempts during their lifetimes (P= 0.022, Fisher exact test). Of 55 responders (> or =50% reduction in Hamilton Rating Scale for Depression-24 questions [HRSD-24] scores) after 12 months of VNS, 3 had received ECT. Of 32 remitters (HRSD-24 score, < or =9), 2 had received ECT. Administration of ECT did not affect the implanted VNS device, and the presence of the implanted VNS device did not affect the administration of ECT. CONCLUSIONS: Electroconvulsive therapy and VNS are not mutually exclusive. They can be used safely and effectively either sequentially or concurrently. Each can be prescribed as the depressive condition warrants-ECT for emergently worsening depressive symptoms and maintenance therapy and VNS for chronic, long-term therapy.     

Transcutaneous Vagal Nerve Stimulation in Treatment-Resistant Depression: A Feasibility Study

BackgroundMajor depression (MD) contributes significantly to the global burden of disease with up to one-third of patients being treatment resistant. Therefore, the development of new treatment options for treatment-resistant depression (TRD) is needed. Vagus nerve stimulation (VNS) has shown mood improvements in patients with TRD. However, due to high costs related to the implantation and the invasive nature of VNS, an application with transcutaneous VNS (t-VNS) has been developed stimulating a vagal nerve branch in the earlobe (Arnold's nerve). A few studies with t-VNS in MD have shown a possible antidepressant effect, but feasibility is poorly described and patients with TRD have not been investigated.ObjectivesAs the full antidepressant effect of t-VNS takes months we wanted to assess feasibility and side effects of daily treatments.Materials and MethodsSingle-arm feasibility trial assessing compliance, usability, side effects, cognitive speed, and depression in a four-week period with a recommended t-VNS stimulation duration of four hours per day in patients with TRD. The primary outcome was compliance with 80% of the recommended daily treatment time.ResultsCompliance threshold was reached for 80.0% of the 20 included participants. Usability was acceptable. Side effects were few, mild or moderate, mostly as local effects at the contact point in the ear. The device was difficult to use for some participants. A statistically significant reduction in depression severity and an increase in cognitive speed were seen with unchanged suicidal ideation and sleep.ConclusionsWe would recommend larger long-term randomized studies of t-VNS to access any antidepressant effect in TRD. The design of the device might be improved for higher usability.     

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.     

Vagus Nerve Stimulation Therapy Randomized to Different Amounts of Electrical Charge for Treatment-Resistant Depression: Acute and Chronic Effects

BackgroundMajor depressive disorder is a prevalent, disabling, and often chronic or recurrent psychiatric condition. About 35% of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression (TRD).ObjectiveWe compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of TRD.MethodsIn a multicenter, double blind study, 331 patients with TRD were randomized to one of three dose groups: LOW (0.25 mA current, 130 μs pulse width), MEDIUM (0.5–1.0 mA, 250 μs), or HIGH (1.25–1.5 mA, 250 μs). A highly treatment-resistant population (>97% had failed to respond to ≥6 previous treatments) was enrolled. Response and adverse effects were assessed for 22 weeks (end of acute phase), after which output current could be increased, if clinically warranted. Assessments then continued until Week 50 (end of long-term phase).ResultsVNS therapy was well tolerated. During the acute phase, all groups showed statistically significant improvement on the primary efficacy endpoint (change in Inventory of Depressive Symptomatology-Clinician Administered Version [IDS-C]), but not for any between-treatment group comparisons. In the long-term phase, mean change in IDS-C scores showed continued improvement. Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose.ConclusionsTRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline, and the effect was durable over 1 year. Higher electrical dose parameters were associated with response durability.     

Vagus Nerve Stimulation for Patients in Residential Treatment Facilities

This analysis compared the effectiveness of vagus nerve stimulation (VNS) therapy among patients with intractable seizures: a group living in residential treatment facilities (RTF) with a group not living in RTFs (non-RTF). Among a constant cohort of patients with baseline, 3-month, and 12-month data, the RTF group had significantly (P < 0.05) larger numbers of patients with generalized seizures, previous callosotomy, psychiatric disorders, behavioral problems, and Rett's syndrome. Median seizure reductions after 3 months were 33% in the RTF group and 49% in the non-RTF group (P < 0.001); after 12 months, 50% (RTF) and 56% (non-RTF). After both 3 and 12 months, alertness, mood, postictal recovery, and cluster seizures improved in more than a third of patients in both groups. Because VNS therapy does not interact with medications and is delivered automatically, it should be seriously considered for patients with intractable epilepsy who reside in RTFs.     

Neurostimulation therapies in depression: a review of new modalities

OBJECTIVE: In response to an increased understanding of the neurobiology of severe psychiatric disorders, new therapeutic modalities are entering clinical practice that involve the direct stimulation of the brain. METHOD: We provide a review of published literature regarding the clinical use of vagus nerve stimulation (VNS) therapy, transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) in psychiatric disorders, with an emphasis on treatment-resistant depression (TRD). RESULTS: Vagus nerve stimulation is approved for use in both the EU and US for TRD. TMS has been approved for TRD in Canada, Australia, New Zealand, the European Union and Israel, but not yet in the United States. DBS remains in the early stages of investigation. CONCLUSION: While additional studies are clearly warranted, treatments that directly stimulate the brain appear to hold great therapeutic promise for severe psychiatric disorders.     

Rapid titration protocol – Experiences with a dynamic novel titration regime for vagus nerve stimulation in a group of depressive patients

Vagus nerve stimulation (VNS) is an established tool in the psychiatric armamentarium for patients with therapy-resistant depression (TRD) with response rates of approximately 60%. So far, VNS is titrated slowly during ambulatory in-office visits. Thus, antidepressive effects can be expected after approximately six months.We report our experiences with a rapid dosing regime (RDR) with titration start shortly after VNS-implantation. We retrospectively analysed data of six patients with TRD who received VNS. Stimulation parameters were evaluated with regard to clinical side effects, heart rates (HR) and blood pressures (BP). Depressive symptoms were measured by Montgomery-Asberg Depression Rating Scale (MADRS) one week before and three months after implantation of the VNS.All patients received first stimulation between one and four days after surgery. We elevated output current using 0.25 mA titration steps. We increased output current between one and four days after the last titration. All patients received 1.0 mA output current after eight to 14 days post-surgery. HR and BP remained stable in all patients. All side effects were mild and temporary. MADRS scores were significantly lower three months after VNS-implantation (24 ± 8) than one week before VNS-implantation (42 ± 4; p = 0.028).The therapeutic range of VNS-parameters for antidepressive effect was reached quicker without finding increased numbers of side effects. Consequently, by using RDR the antidepressive effect of VNS-therapy for patients with TRD could be reached earlier than using slow titration. Our presented RDR might be able to significantly shorten the “clinical effect gap” due to the neurobiological and titration-related latency.     

Neurostimulation therapies for treatment resistant depression: A focus on vagus nerve stimulation and deep brain stimulation

Antidepressant treatments, including pharmacotherapy and psychotherapy, do not result in remission for the majority of patients with major depressive disorder. The high prevalence of treatment resistant depression (TRD) poses a significant issue for patients as well as both societal and economic costs. Due to the limited efficacy of existing therapies in this sub-population, alternative somatic treatments are being explored. Both vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are neurostimulation treatments for TRD. While VNS has Food Drug Administration approval as an adjunctive therapy for MDD, DBS is still in the experimental stages. This article will review the evidence supporting the clinical utility of these therapies.     

A randomized double-blind sham-controlled comparison of unilateral and bilateral repetitive transcranial magnetic stimulation for treatment-resistant major depression

Abstract

Objectives. High frequency left-sided (HFL) and low frequency right-sided (LFR) unilateral repetitive transcranial magnetic stimulation (rTMS) are efficacious in treatment-resistant major depression (TRD). Similar benefit has been suggested for sequential bilateral rTMS (LFR then HFL). There are few published reports on the efficacy of sequential bilateral rTMS compared to HFL and sham rTMS. Therefore, this study evaluated the efficacy of HFL and sequential bilateral rTMS compared to sham in TRD. Methods. Subjects between the ages of 18 and 85 were recruited from a tertiary care university hospital. Seventy-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS) greater than 21 were randomized to receive unilateral, bilateral, or sham rTMS. The rates of remission were compared among the three treatment groups. Results. The remission rates differed significantly among the three treatment groups using a modified intention to treat analysis that excluded subjects who did not respond to electroconvulsive therapy (ECT) during the current episode. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the unilateral group did not differ from either group. Conclusion. These findings warrant larger controlled studies that compare the efficacy of sequential bilateral rTMS and HFL rTMS in TRD.     

Neurostimulation therapies for treatment resistant depression: a focus on vagus nerve stimulation and deep brain stimulation

Antidepressant treatments, including pharmacotherapy and psychotherapy, do not result in remission for the majority of patients with major depressive disorder. The high prevalence of treatment resistant depression (TRD) poses a significant issue for patients as well as both societal and economic costs. Due to the limited efficacy of existing therapies in this sub-population, alternative somatic treatments are being explored. Both vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are neurostimulation treatments for TRD. While VNS has Food Drug Administration approval as an adjunctive therapy for MDD, DBS is still in the experimental stages. This article will review the evidence supporting the clinical utility of these therapies.     

Vagus nerve stimulation (VNS) for depression: What do we know now and what should be done next?

Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somatic clinical intervention for treatment-resistant depression (TRD). Long-term open data suggest a sustainable antidepressant response over time. Here we review the clinical data that exist so far and their limitations. We also discuss guidelines that may inform the clinical utilization of this procedure. Further clinical studies, in addition to prospective cost utilization and health economic investigations, are needed to better understand VNS therapy and the impact it holds on TRD care.     

Vagus nerve stimulation does not lead to significant changes in body weight in patients with epilepsy

BACKGROUND: Vagus nerve stimulation (VNS) is an FDA-approved treatment for medically intractable epilepsy. The effect of this therapy on body weight is unclear. VNS could cause weight loss by engaging vagal afferents from the gastrointestinal tract mediating satiety. METHODS: We performed a retrospective analysis of body weight changes over a period up to 2 years following VNS implantation. We studied 21 patients (13 M/8 F) 35 +/- 12 years old, who received a Cyberonics VNS Therapy System for medically intractable epilepsy between April 1998 and May 2004. The mean +/- SD duration of follow-up was 613.1 +/- 389.1 days. The study had 80% power with a type I error of 0.05 to detect a 5% weight change. Data were analyzed with repeated-measures ANOVA. RESULTS: Weight changes relative to baseline at 30, 60, 120, 360, 480, and 720 days were -0.17 +/- 2.33, +0.33 +/- 2.64, -0.32 +/- 3.56, +1.09 +/- 5.97, +1.06 +/- 7.47, and +0.33 +/- 3.69%, respectively. At all time points these differences failed to reach statistical significance. CONCLUSIONS: Vagus nerve stimulation with parameters typically used in the treatment of patients with epilepsy was not associated with clinically significant weight changes. A well-controlled prospective study is necessary for more precise evaluation of the effect of VNS therapy on body weight.