Trigeminal nerve stimulation in major depressive disorder: acute outcomes in an open pilot study.

Most patients with major depressive disorder (MDD) do not recover with initial pharmacotherapy, and many pursue combination treatments. Combining a medication with neuromodulation offers an alternative to purely pharmacologic strategies. In prior open and double-blind controlled trials for drug-resistant epilepsy, adjunctive external trigeminal nerve stimulation (eTNS) was found to be safe and well tolerated, to significantly reduce seizures, and to be associated with an improvement in depressive symptoms. Here, we present a comprehensive description of the first open pilot investigation in MDD. In this 8-week trial, eleven adults with unipolar MDD received nightly stimulation (V(1) branch). All entered with moderate to severe symptom levels despite at least two antidepressant medication trials in this episode. All the eleven adults completed the acute trial, without serious adverse events. Symptoms of depression improved significantly, whether assessed with clinician- or self-rated scales (all p < 0.01; effect sizes d 1.0-1.8), as did quality of life (p < 0.02). Four of the 11 achieved remission. These improvements from nightly adjunctive eTNS in treatment-resistant depression merit replication under double-blind conditions.