Subject:
DEPRESSION

Short Description:
Deep Brain Stimulation: A New Somatic Therapy for Depression?

Background:

Deep brain stimulation (DBS) has suddenly begun popping up in both the medical journals and the mainstream media as a potential treatment for treatment resistant depression. DBS involves the placement of tiny electrodes in the brain that deliver pulses of current and modulate activity of certain neural pathways. For many years, neurologists have used DBS to treat Parkinson disease and other movement disorders, and it has been used experimentally in some cases of depression and OCD. Several groups have already shown that stimulation of the subcallosal cingulate gyrus—an area known to be overactive in depression—can have an antidepressant effect (Lozano AM et al, Biol Psych2008;64(6):461–467). Most of the existing trials, however, were small, uncontrolled pilot studies. A recently published study offers additional evidence for a DBS effect in depression—including bipolar depression.

Investigators surgically implanted electrodes in the bilateral subcallosal cingulate of 17 adult patients with treatment-resistant unipolar or bipolar depression. All patients received open-label continuous stimulation for up to two years. Patients were permitted to continue antidepressant medication or therapy, but dose increases weren’t allowed during the first 24 weeks of the trial. There was a noticeable antidepressant effect of DBS in all patients, with gradual improvement in symptoms at 24 weeks, one year, and two years. In fact, after two full years of active stimulation, HAM-D scores had improved by an average of 70%. Nearly all (92%) patients showed a response (a decrease of >50% in HAM-D) and just over half (58%) entered remission (HAM-D score <8), with no spontaneous relapses of depression.

All patients had tried numerous antidepressants and had experienced at least a 12-month depressive episode prior to the trial, so these results are promising. However, there was no long-term control group, so it is unclear whether the long-term benefit was due to DBS or to medications, therapy, or the natural course of disease. All patients underwent a blind “sham” period immediately after the surgery; no current was delivered and no antidepressant effect was observed, but the sham phase was only four weeks in duration, making it difficult to draw a conclusion regarding a longer-term outcome.

There were few adverse events. Some, understandably, were from the surgery itself, while other minor complaints (nausea, headache, tingling in the hands) were most likely from the ongoing stimulation. The only side effect directly related to the device was infection in one patient. Two patients attempted suicide, but no one became manic or hypomanic, even those with bipolar depression. Interestingly, one patient accounted for 75% of the serious adverse events.

The investigators initially planned to include a discontinuation phase, during which patients would be observed for four weeks after the current was turned off. Three patients entered this phase, but all three reported increased suicidal ideation (and responded, but only gradually when stimulation was restarted), so this phase was eliminated from the design for the rest of the patients (Holtzheimer PE et al, Arch Gen Psych 2012;69(2):150–158).

TCPR's Take:
Several reports have shown DBS to be a safe and effective therapy for treatment-resistant depression. However, it’s an invasive procedure with its own unique risks, and it’s still not clear how much of patients’ improvement can be attributed to DBS. Also, discontinuation seems to be associated with rapid relapse. Nevertheless, DBS may represent a helpful adjunct to other interventions and deserves further controlled study as a novel somatic therapy for depression.