Antidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression

Background: Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) is an experimental approach in treatment-resistant depression (TRD). Apart from its potential long-term antidepressant effects acute stimulation effects have been described. We investigated putative neuroanatomical clusters in which such acute effects accumulate and followed patients over the long-term.

Methods: We assessed safety and efficacy of DBS in six patients with TRD receiving bilateral DBS with electrodes implanted in the SCG. First, high intensity 130 Hz stimulation was applied on five consecutive days after surgery for 24 h comprising a sham condition in a double-blind, randomized design. Acute stimulation was conducted at all four homologous electrode contacts on both sides. Afterwards, chronic stimulation was initiated and the clinical effect was evaluated at 24-36 weeks compared to baseline (50% reduction in HAMD scores). The primary outcome criterion was depression severity as assessed with the Hamilton Depression Rating Scale (HAMD-24); secondary outcome parameters were the Montgomery-Åsberg Rating-Scale and Beck Depression Inventory following DBS. The clinical effect over the three scores was compared to sham stimulation and was correlated to the anatomical localization of active contacts by stereotactically delimiting the cluster of most effective contacts in responding patients.

Results: Acute 24 h of stimulation showed only moderate reductions in mean HAMD-24, MADRS and BDI scores. At the last observation (24-36 weeks), two patients were remitters (HAMD-24 < 10) and the four other patients were non-responders.

Conclusions: Our results confirm that stimulation of the SCG is capable of exerting moderate acute and chronic antidepressant effects. The predictive value of these findings needs to be addressed in future studies.