Depression, Depressionen

Treatment

The NCP System implantation technique and the programming sequence used in this study were identical to those used in the studies of treatment-resistant epilepsy. The NCP System includes an implantable and multiprogrammable pulse generator that delivers electrical signals to the left vagus nerve (10th cranial nerve) via the bipolar lead. The pulse generator is programmed via a programming wand attached to a computer, which sets or adjusts stimulation parameters. Additional information about the NCP System has been provided in another article in this issue (George et al 2000).

After completion of the 2-week, postimplantation, single-blind “recovery period,“ the device was turned on with initial stimulation parameters of 0.25 mA, 20 or 30 Hz⁸, and 500 µsec, with stimulation on for 30 sec every 5 min. At this visit, the output current was increased gradually (in 0.25-mA increments) to allow accommodation to the stimulation until a comfortable tolerance level was reached. After a comfortably tolerated output current was attained, the patient left the clinic at these settings.

Additional increases (in 0.25-mA steps) in output current were made anytime during the “stimulation adjustment period“ over the next 2 weeks. Stimulation parameter settings were determined based on patient tolerance. Investigators were allowed by protocol a range of frequency (e.g., 20-‐30 Hz), pulse width (eg., 250-‐500 µsec), and on/off cycle parameters (eg., off 3 or 5 min). In general, the stimulation parameters commonly used for epilepsy were used in this study.

Concomitant Therapy

No patient received concomitant ECT, investigational drugs, or treatment with another investigational device during the study. Patients were allowed (but not required) to take antidepressant and/or mood stabilizer medications, as long as the same doses and same medication types were maintained during the baseline period and tor 12 weeks following implantation. Medications could be decreased, but not increased, during the acute study. Lorazepam (up to 3 mg/day) was allowed for anxiety and/or insomnia as needed. Other medications (i.e., antibiotics, decongestants, analgesics, and over-the-counter medications) were allowed (though investigators made all reasonable attempts to either limit or discourage over-the-counter medications during the study). Concomitant medications were recorded at each visit.

Evaluations and Outcome Measurements

Baseline evaluations included a medical and psychiatric history, physical and neurologic exams, and presurgical laboratory tests. Efficacy and safety data were gathered at the two baseline visits and at weeks 1 and 2 (recovery period), 3 and 4 (stimulation adjustment period), and 5, 6, 8, 10, and 12 (fixed-dose stimulation period) after implantation. Clinical assessments of depressive symptoms included the HDRS₂₈ and the 10-item Montgomery-Asberg Depression Rating Scale (MADRS; Montgomery and Asberg 1979). Manic/hypomanic symptoms were rated by the Young Mania Rating Scale (Young et al 1978). Overall status and response were gauged by the Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) indices (Guy 1976) and the GAF (American Psychiatric Association 1994). Functional outcomes were also assessed using the Medical Outcomes Study (MOS) 36-item short form (SF-36; Ware and Sherbourne 1992).

Stimulation parameter settings were documented at each visit (and at any additional visit if stimulation parameters were adjusted.)

⁸Standard frequency was changed from 30 Hz to 20 Hz in a protocol amendment - a change not expected to affect clinical outcome.