Depression, Depressionen

Study Overview
Patients were excluded if they had

1) atypical or psychotic features in the current MDE;

2) a history of schizophrenia, schizoaffective disorder, or other non‐mood disorder psychosis;

3) rapid-cycling bipolar disorder; or 4) a current secondary diagnosis (or signs) of delirium, dementia, amnesia, or other cognitive disorder (by DSM-IV). Also excluded were patients with clinically significant, current suicidal intent and those with certain risks related to surgical implantation and treatment.

Study Overview

All patients followed the same treatment schedule. Following written informed consent, patients completed a “baseline period“ (up to 4 weeks) preimplantation during which clinical assessments were performed on two separate occasions. To qualify for implantation, patients had to score >20 on the HDRS₂₈ during both baseline visits. Patients on medications had to maintain a stable medication regimen for at least 4 weeks prior to the initial baseline visit.⁵

For 2 weeks following implantation, (single-blind “recovery period“), the NCP System remained off to allow for surgical recovery. Patients were told that “stimulation may or may not be turned on immediately after surgery.“ Clinical assessments were performed weekly. Further, during this recovery period, patients had to score >18 on the HDRS₂₈ for two consecutive visits (7 and 14 days postimplantation) before initiating stimulation.

At the end of the recovery period, the NCP System was turned on and the output current (mA setting) was progressively increased to the maximum, comfortably tolerated level over the next 2 weeks (“stimulation adjustment period“), with clinical assessments performed weekly.

At 4 weeks postimplantation (i.e., after 2 weeks of VNS), stimulation parameters were set and left unchanged for the remaining 8 weeks. (A decrease in stimulation parameters was permitted if intolerable side effects developed, but no patient required decreased stimulation.) Patients were seen weekly for the next 2 weeks and then every other week for another 6 weeks. This “fixed-dose stimulation period“ lasted 8 weeks; the total duration of stimulation was 10 weeks.

After completion of the acute study, patients were allowed to continue receiving VNS. All patients are being observed clinically at least 9 months after the acute study exit and for at least 12 months following implantation.⁷ During this long-term “follow-up period,“ either NCP stimulation parameters or concomitant medications may be changed based on investigator or primary physician judgment. As such, follow-up data provide descriptive information as to longer term outcomes.

⁵ Patients were allowed to continue stable medication regimen(s) rather than become medication free because 1) the medication(s) had provided some relief that could be lost if discontinued; 2) almost all patients, we believe, would have declined to stop taking even these modestly beneficial treatment(s); and 3) the medication discontinuation symptoms and possible significant clinical worsening were avoided using this scheme.

⁶ If patients had scored less than 18, they would hase had an extended visit and been observed weekly until the 28-item Hamilton Depression Rating Scale score was 18 or more, at which time the regular visit schedule would have been reinitiated. No patient required extended visits.

⁷ 1 year, patients can still continue to receive treatment.