2 The procedure
2.1.1 Depression is characterised by low mood, loss of interest in and enjoyment of life, and a range of associated emotional, cognitive, physical and behavioural symptoms. People with severe depression may also develop psychotic symptoms (hallucinations and/or delusions). Depression is associated with risk of suicide. The more severe the episode of depression, the less likely it is that remission will occur spontaneously.
2.1.2 Conventional treatment for depression includes antidepressant medication or psychological therapies (including cognitive behavioural therapies) or a combination of both. Electroconvulsive therapy (ECT) may be used to treat depression that has proven resistant to other treatments.
2.2.1 The aim of VNS for treatment-resistant depression is to improve mood regulation and reduce depression by stimulating the vagus nerve.
2.2.2 The procedure is carried out with the patient under general or local anaesthesia. An incision is made on the left side of the neck and the left vagus nerve is identified. A stimulator electrode is cuffed around the nerve and the leads of the stimulator electrode are tunnelled subcutaneously to the left chest wall and attached to a pulse generator unit, which is implanted into a subcutaneous pocket.
2.2.3 The vagus nerve is stimulated periodically (a short period of stimulation followed by a few minutes rest). The stimulation intensity and frequency can be programmed as required via an external (remote) electronic control. Patients may temporarily inhibit stimulation by activating a switch with a magnet.
Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.
2.3.1 Interpretation of the evidence was complicated by different publications reporting on the same patients but at different follow-up periods.
2.3.2 A systematic review of 18 studies (1 randomised controlled trial [RCT] and 17 case series) including 1251 VNS-treated patients with treatment-resistant depression (only defined in some of the studies) reported a satisfactory response (defined as a more than 50% reduction in baseline Hamilton Depression Rating Scale [HDRS] score). This ranged from 31% to 40% of patients in 'short-term' studies (up to 10-week follow-up) and from 27% to 58% of patients in 'long-term' studies (minimum 12-month follow-up). In the RCT (112 VNS-treated and 110 sham therapy patients) no significant differences were reported in the change in HDRS scores between treatment groups (absolute figures and follow-up not stated). A case series of 74 patients with severe depression (more than 2 years or at least 4 depressive episodes) reported that mean HDRS scores improved significantly compared with baseline at 12-month follow-up (p < 0.0001; absolute figures not stated), and that 55% of patients had a response to VNS.
2.3.3 The Specialist Advisers listed key efficacy outcomes as depression scale scores, quality of life indicators, and a decrease in the use of adjunctive antidepressant medication or support services.
2.4.1 The systematic review reported serious or clinically important adverse events (not otherwise described) in 17% (10/59) of patients in 1 case series, including 2 patients with worsening depression. In 6 short-term studies in the systematic review, 2 patients discontinued VNS treatment because of adverse events (not otherwise described).
2.4.2 In the case series of 74 patients, 2 of 61 patients were reported to have committed suicide at 12-month follow-up. In the RCT included in the systematic review, 1 of 112 VNS-treated patients were reported to have committed suicide (time after treatment not stated).
2.4.3 In the case series of 74 patients, 1% of patients developed a manic episode and 1% had worsening depression at 3-month follow-up (absolute figures not stated). Hypomania or mania was reported after VNS treatment in 5 patients across 2 case series (including 317 VNS-treated patients) in the systematic review.
2.4.4 Dyspnoea was reported in 10% of patients in the case series of 74 patients at 3-month follow-up (absolute figures not stated).
2.4.5 Pain (not otherwise defined) was reported in 20% of patients at 3-month follow-up in the case series of 74 patients.
2.4.6 In the case series of 74 patients, cough and voice alteration was reported in 26% and 63% of patients, respectively, at 3-month follow-up (absolute figures not stated).
2.4.7 The Specialist Advisers reported anecdotal adverse events including glottic spasm and hoarseness. They stated that theoretical adverse events include asystole, arrhythmias, cognitive disturbance, vocal cord paralysis, diarrhoea and local inflammation.