Case debrief

The patient has a lengthy history of chronic MDD that was not comorbid with other psychiatric or medical conditions, which is quite rare. This made her a good candidate for a VNS study focusing on TRD

She failed to respond to many medications and solid psychotherapy attempts. Albeit, her psychotherapy did not give her formal CBT or PDP approaches

She likely represents the most optimal, and by no means typical, response to long-term VNS. The study team and the prescribing clinician reported that they saw little hope of response given her chronic treatment history and ECT failure

The learning curve in this case involved dosing VNS effectively and to wait out its longer therapeutic duration needed for effectiveness when compared to medication and psychotherapy trials

Given the typically poor outcomes of sustaining a remission after successful treatment with medication or ECT, her VNS and all of her medications were continued over the long term. It appears that this patient meets the endpoint whereby those patients who achieve a remission by VNS tend to maintain remission for at least two years (69%). In this case, it has been 10 years

This patient also fell into the category where one out of six patients is expected to achieve a remission that is based on less stringent open-label regulatory trial data

However, her remission via VNS occurred well after a year of treatment where many patients see effects after three months but within one year

Take-home points

This case emphasizes the need for full therapeutic trials of antidepressant treatments, augmentations, combinations, psychotherapy, and VNS

VNS generally takes weeks or months to become effective

Therapeutic dosing should be considered at 1–1.5 mA electrical charge with device activation every 1.8–5 min

Cumulative dosing (dosing charge times frequency) seems to be a determining factor as well as longitudinal use over time. This is a newer finding

VNS, when effective, appears to maintain its response equal to or better than medications alone

VNS was FDA approved based upon long-term, open-label data and its comparison to an equally ill, depressed cohort not receiving VNS treatment. The VNS TRD patient has a 2:1 response rate over patients who received non-VNS but otherwise treatment as usual

These data appear to have been compelling to the FDA, who deemed it approved for treating depression in 2005, but many insurance companies consider it experimental as there was never a long-term trial of VNS versus a sham control proving the device may become effective over a one-year period

As a counterargument, investigators felt that giving a severely depressed patient a sham placebo treatment over 12–18 months would be unethical. The controversy about this treatment and adequate insurance coverage continues

Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Was the patient on too many medications at the time of VNS?

• – Should the patient have been directed more toward the MAOI monotherapy, or use of more classic augmentations?

Possible action items for improvement in practice

• – Make sure that augmentation/combination strategies are all considered and weighed against device-based treatments

• – Discussing options outside medications is always warranted. Psychotherapy or device-based treatments offer a way to treat MDD outside the norm and likely utilizes different mechanisms of action compared to our usual monoamine facilitation strategies. Sometimes this makes a difference in outcome

• – Of course, this means pushing the clinician’s clinical envelope with regard to knowledge base. Outside being up-to-date on new medications, clinicians have to be aware of the indications, risks, and benefits of new device-based treatments