Question

What would you do next?

Allow patient to go for VNS

Insist on an MAOI or other augmentation strategy

Case outcome: interim follow-ups through six months

The patient enrolls in a trial, is implanted with the VNS pacemaker device, and allowed to heal for two weeks

The device is started and titrated to a reasonable, suspected therapeutic dose (0.75–1.5 mA charge every 5 min)

As the device sends small electrical currents afferently through the left vagus nerve, some charge dissipates toward the recurrent laryngeal nerve en route to the brainstem’s nucleus tractus solitarius, causing temporary voice changes and hoarseness when the device activates every five minutes. This side effect lasts for 30 s, which the patient states she will be able to tolerate

Other psychotropic medications continue as it is given that VNS is an adjunctive treatment and not studied as a monotherapy

There is no effect two to three months after starting VNS and her acute VNS treatment is considered a failure

How long is a therapeutic trial of VNS?

At the time of her enrollment in the study, this was unknown, but 8–10 weeks of treatment failed to separate from sham VNS treatments ultimately

Therapeutic dosing was estimated to occur at 0.75–1.5 mA with the VNS device sending this charge to the brain every five minutes

As this was an ongoing trial, the patient was allowed to continue VNS stimulation, despite its apparent acute failure, in a continuing manner while being evaluated for symptom reduction and tolerability over several years

Attending physician’s mental notes: interim follow-up, nine months (continued)

Patient is continued on the same medications

Patient continues to be depressed to the same degree

VNS continues at the same settings

VNS is again considered to be ineffective but is allowed to continue as the device is permanently implanted and being evaluated by the FDA

Case outcome and multiple interim follow-ups to 12–120 months

After one year of VNS treatment, the patient is unchanged and still depressed

The VNS study team and prescribing clinician feel that the patient has failed to respond and are disappointed in this VNS therapy outcome. VNS follow-up now is for safety monitoring and occurs every three months, and the patient is asked to consider removing the ineffective device

At 15 months of VNS treatment, the patient arrives with her spouse. Her hair is done and she is wearing makeup, which has not occurred in previous visits

Her psychomotor impairment is moderately better to the degree in which the study team can engage her in a reciprocal conversation. She is deemed to be 30% better based on Hamilton Depression Rating Scale (HDRS) analysis

After 18 months of VNS she is felt to be 70%–80% better, has no psychomotor or cognitive impairment, and informs the study team that she and her husband have purchased an RV camper, and they have planned several trips

Her medications are continued as she is tolerating them well. Her metabolic parameters are controlled and there is no TD/EPS. It is unclear if she is responding to VNS alone, VNS plus her complex medication regimen, or if her depression remitted on its own after three decades

Over a 10-year period of treatment with VNS

• – There has been no relapse into a full depression

• – The VNS dosing has increased in response to minor depression (threatened relapses detected as slight increases in scores on the HDRS) to where her device activates every 1.8 min, more than doubling her cumulative dose

• – The voice altering side effects gradually dissipated to the point of being undetectable by a layperson