Trigeminal Nerve Stimulation for Depression: Dose Finding
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will aim to examine the use of external trigeminal nerve stimulation (TNS) as an
      adjunctive treatment for adults with major depressive disorder (MDD) when added onto
      antidepressant medications. Our primary objective is the examination of two different "doses"
      of TNS, in terms of pulse frequency.

      To accomplish our specific aims, the investigators will test the following specific
      hypotheses:

        1. Subjects will show greater improvement in ratings of mood and other symptoms of
           depression during the six-week of high frequency stimulation than during low frequency
           stimulation periods.

        2. Subjects will show greater improvement after 12 weeks of high frequency stimulation than
           after six weeks of high frequency stimulation.

        3. Subjects will show improvement in ratings of life functional capacity and quality of
           life with TNS.

        4. Subjects will report the TNS treatments to be acceptable in terms of side effects and
           burden of using the device.

        5. Subjects will show significant differences in regional brain function at the end of the
           high frequency stimulation period compared with baseline, and significant differences
           between high and low frequency stimulation conditions.
    

Detailed description: 
      A total of 20 subjects with Major Depressive Disorder (MDD), ages 18 to 65, will be consented
      and join this project at UCLA.

      The project has two phases: a 12 week treatment phase and a 6 month follow-up phase. In the
      first phase, a double-blind one-way cross-over design will allow us to compare the clinical
      and physiologic responses to TNS at two frequencies of stimulation, "high" (~120 Hz) and "low
      " (~20 Hz). Subjects will be randomized to start a six week period at either high or low
      frequency stimulation (n=10 in each); both subjects and the staff who interact with them will
      be blinded to assignment, and a separate member of the team will program the device settings.
      At the six week point, the low frequency group subjects will be crossed over to high
      frequency, while the high frequency group will continue at high frequency. At the end of the
      12 weeks, the TNS systems will be returned and the adjunctive treatment will end. All
      subjects will be followed for another six months with monthly telephone calls to monitor
      symptoms or changes in treatment that would signal a return of symptoms. The primary endpoint
      is the change in depression severity for the two groups at the week 6 visit.
    

Intervention name(s): Trigeminal Nerve Stimulation
Intervention type(s): Procedure
Intervention description(s): External trigeminal nerve stimulation (TNS) as an adjunctive treatment added onto antidepressant medications.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Depression; Major Depressive Disorder (MDD); EEG; Trigeminal Nerve Stimulation