Concomitant Use of Maintenance ECT and Vagus Nerve Stimulation for More Than 10 Years in Treatment-Resistant Depression

To the Editor: Vagus nerve stimulation (VNS) has been approved by the U.S. Food and Drug Administration as an adjunctive treatment for certain types of intractable epilepsy and treatment-resistant depression. Maintenance ECT is used for patients with treatment-resistant depression who had a positive response to ECT in the acute phase (1). ECT is likely to cause adverse cognitive effects, and preliminary studies have shown that VNS may have potential benefits for patients with cognitive disorders (2, 3). VNS is also known to have effects on cardiac electrophysiology, including increased risk of arrhythmias such as sinus bradycardia, asystole, atrial fibrillation, or atrioventricular conduction block (4). Similarly, ECT is likely to influence atrial conduction by causing significant prolongation of P wave duration and dispersion (5). The long-term effects of concomitant ECT and VNS in patients with treatment-resistant depression are not known. We present here the case of a 57-year-old man with VNS for intractable epilepsy who was on maintenance ECT for treatment-resistant depression for more than 10 years.

Case Report

“Mr. A” is a 57-year-old white man with a lifelong history of recurrent major depressive disorder. He had multiple trials of antidepressants, including antidepressant combination (selective serotonin reuptake inhibitors, tricyclic antidepressants, and venlafaxine) and augmentation with mood stabilizers (lithium) and antipsychotic medications (quetiapine and aripiprazole). However, he had achieved suboptimal response and experienced significant adverse effects with the medications, including decreasing seizure threshold. Intensive psychotherapy was also ineffective. He received intermittent short-term ECT and had achieved adequate response, but as soon as ECT was discontinued, his depression worsened and he presented with suicidal ideation. Treatment maintenance was a challenge because of his intolerance to antidepressants, which led to frequent psychiatric hospitalization.

Mr. A was also diagnosed with complex partial seizure with secondary generalizations at age 40. A brain MRI did not reveal any abnormalities. Despite multiple trials of anticonvulsants, including combinations of antiepileptics, he continued to have seizures. As a result, he underwent implantation of a vagus nerve stimulator (Cyberonics, Houston) for intractable epilepsy in 2002. His epilepsy responded well to VNS with a combination of antiepileptic medications. His VNS parameters were set at 0.5 mA, 250 ms pulse width, 30 seconds on and 5 minutes off time. His seizures were well controlled at this VNS dosage, and increases in VNS parameters resulted in shortness of breath. As a result, he was maintained at a relatively low VNS dosage, so he did not require battery replacement until recently.

Because Mr. A continued to have relapses in depressive symptoms after short-term ECT, he was started on weekly maintenance bilateral ECT. During the ECT procedure, the VNS therapy magnet was placed over the VNS generator to temporarily turn off VNS. In a patient taking antiepileptics with long-term maintenance ECT, achieving optimal therapeutic seizure duration was a challenge. However, pretreatment with caffeine, amniophylline, and hyperventilation helped us to achieve optimal seizure duration. An attempt was made to space out maintenance ECT, but worsening suicidal ideation and sleep disturbances were the major limiting factors. Concomitant maintenance ECT and VNS prevented further inpatient hospitalization and produced significant improvement in socio-occupational functioning. Mr. A has been on weekly maintenance ECT with VNS for the last 10 years without any short- or long-term complications. His Mini-Mental State Examination score has remained between 28 and 30 during these treatments, and there were no adverse cardiac effects.

Discussion

Although ECT has been found to be safe in patients with VNS (6), to our knowledge no studies have reported long-term ECT use in a patient with VNS with treatment-resistant depression. In Mr. A, the implanted VNS device did not affect the administration of ECT and the administration of ECT did not affect the functioning of VNS. A previous case report (7) found that initiation of VNS in patients with treatment-resistant depression who were also on maintenance ECT helped in the discontinuation of maintenance ECT, with significant reductions in the cost of treatment for the depression. It is possible that if our patient was able to tolerate a higher VNS dosage, he might not have required maintenance ECT or could have been maintained on less-frequent ECT. ECT is indicated for worsening depressive symptoms and maintenance therapy, while VNS is indicated for chronic long-term therapy. The longest reported durations of maintenance ECT in the literature are 5 years in a combined prospective and retrospective study and 7 years in a clinical case report (8). Neurocognitive side effects are a major concern with ECT. In the case of Mr. A, maintenance ECT and VNS were used concomitantly for more than 10 years without any cognitive or cardiac adverse influences or other complications. It is possible that VNS may have improved any possible cognitive effects of ECT. Maintenance ECT seems to be a safe treatment option for patients with treatment-resistant depression with VNS.