Objectives/Aims The habenular nucleus is a set of well-conserved structures involved in aversive reward and is inhibitory to major monoaminergic nuclei. Several cases indicated that it is a promising deep brain stimulation (DBS) target for treatment of major depressive disorder (MDD). In this study, we assess the effectiveness and safeness of bilateral habenula DBS in MDD patients.

Methods Six patients with MDD underwent DBS of bilateral habenula in the study (5 bipolar disorder and 1 unipolar disorder; 4 males and 2 females). Quantitative susceptibility mapping was used to visualize the habenula. Hamilton depression scale (HAM-D) and Montgomery-Asberg Depression Scale (MADRS) were used to qualify the severity of depressive symptoms and were the primary outcome measures.

Response to DBS was defined as a 50% decrease on the HAM-D and MADRS compared to baseline. The pittsburgh sleep quality index (PSQI), 36-Item short form survey (SF-36) and sheehan disability scale (SDS) were used to assess quality of sleep, quality of life and disability respectively. These measures were implemented at baseline and 1-month, 3-month, 6-month and 12-month after surgery.

Results At one-month follow-up, compared to the baseline, the HAM-D and MADRS mean scores significantly decreased from 24 (2.2), 31 (4.1) to 14 (7.3), 17.3 (9.8) respectively and four patients were categorized as responders to DBS (p=0.018, p<0.01). Moreover, the PSQI mean score dramatically decreased from 16.3 (2.1) to 9.7 (3.3) (p<0.01) and the SF-36 total mean score increased from 317 (119.4) to 540 (228.3) (p=0.012). The SDS mean score also significantly decreased (p<0.05). There were no permanent side effects observed.

Conclusions The results of one-month follow-up demonstrated that DBS of bilateral habenula may relieve the depressive symptoms rapidly. The quality of sleep, quality of life and functioning also improved.