Description of the goods or services required
The Health Technology Assessment Programme is accepting stage 1 applications to their commissioned workstream for this primary research topic:
18/194 Vagus nerve stimulation for highly treatment-resistant depression
The UK NIHR and the Australian National Health and Medical Research Council (NHMRC) are collaborating on this research priority and will consider joint funding for any collaborative research proposals submitted to this brief. Applications which include a research collaboration between UK and Australian institutions are most welcome. Please refer to the supplementary guidance for additional requirements related to NIHR/NHMRC collaborative applications. Applications from UK institutions without an Australian collaborative element are also welcome for consideration.
Treatment-resistant depression (TRD) is a major public health concern in terms of individual
suffering and cost to the NHS and wider society. Options are currently very limited for individuals
with an inadequate response to first- and second-line treatment approaches and there is a real
need for effective therapies for this group. Electroconvulsive therapy (ECT) may be offered and
has a high initial response rate, but relapse rate is high and there is a risk of cognitive
impairment. ECT also has a poor reputation with many service users.
VNS is a treatment where a small electrical pulse is administered through an implanted
neurostimulator to a wire connected to the left vagus nerve in the neck. VNS is a long-term
treatment and an increase in clinical response over months of use has been reported. NICE
currently recommends this procedure for adults and children with treatment-resistant epilepsy.
However, for people with treatment-resistant depression, NICE states that due to inadequate
evidence, the procedure should only be used with special arrangements or in research. Recent
Canadian guidelines for depression have recommended VNS as a third-line treatment and the
therapy has been FDA approved in the US for many years. VNS is being used in the UK in a few
centres. In England, it is currently NHS-funded via the Individual Funding Request mechanism.
Numerous non-randomised studies, often with long-term follow-up, have reported that VNS is
associated with a significant reduction in depressive symptoms, enduring benefits and high
treatment compliance. However, the only RCT failed to find any significant change in depression
rating scale, although it did demonstrate significance on its secondary outcome measures.
Several reasons for the lack of primary benefit in the RCT (which compared active VNS versus
implanted but not turned on VNS) have been discussed by experts but, currently, the positive
evidence to date comes from non-randomised or uncontrolled studies. In addition, whilst VNS is
viewed as cost-effective for use in epilepsy, the cost-effectiveness for TRD is unknown. A high
quality randomised controlled trial is needed to inform clinical practice regarding the use of VNS
for TRD and to inform future guidelines.
Recognising that a feasibility study will be required to assess the ability of the sham procedure to
act as a placebo, a step-wise approach is proposed as outlined above. This is a hard stop-go
criterion and applicants will need to take account of this in the design and costings of the study