Table 1.
A list of clinical studies on deep brain stimulation of the human subcallosal cingulate.
| Authors | Main Inclusion Criteria | No. of Patients | Stimulation Target & DBS Design | Stimulation Parameters | Clinical Evaluation | Major Outcomes | Adverse Effects |
|---|---|---|---|---|---|---|---|
| Sankar et al. 2020 [40] | TRD MDE; Current MDE ≥ 12 months; HRSD-17 score ≥ 20; Non-responsive (NR) ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20. |
27 | Target SCG |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3–6 V Pulse Width 90 μs |
Volumetric analysis, Whole brain grey and white matter analysis |
Left and average SCG volume significantly higher in responders compared to non-responders. Right and average amygdala volume significantly higher in responders compared to non-responders. Left, right, and average thalamus volume significantly higher in responders compared to non-responders. Brain grey matter volume significantly lower in responders compared to non-responders. Ratio of grey to white matter volume significantly higher in responders compared to non-responders. |
N.A. |
| Riva-Posse et al. (2019) [41] | TRD MDE; Current MDE ≥ 12 months; HRSD-17 score ≥ 20; Non-responsive (NR) ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF < 50. |
9 |
Target SCC Study Design Intraoperative Sessions: 6 min session of 3 min stimulation ON and 3 min stimulation OFF. Number of sessions: 12 trials (one at each of the eight available contacts. Four per hemisphere, plus four sham trials). Sham-controlled, double-blinded trials (one case w/single blind trial) |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 6 mA Pulse Width 90 μs |
ECG, EDA, MRI Volume of Tissue Activated, Structural Connectivity Analysis |
Autonomic changes with SCC-DBS correspond to salient behavioral responses. Distant effects of SCC-DBS in the midcingulate cortex. Increase in heart rate was only seen with left SCC-DBS. No significant relationship with skin conductance. These findings aid in the optimal selection of contacts and parameters in SCC-DBS surgery. |
N.A. |
| Eitan et al. (2018) [42] | Both sexes, 21–70 years; Non-psychotic MDD; First MDE onset before 45 years old with current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; MADRS ≥ 22; GAF < 50; MMSE > 24; No changes in current antidepressant treatments ≥ 4 wks prior to study. |
9 |
Target BA25 Study Design Double-blind, randomized. Two groups: High- OR low-frequency DBS for 12 months from 1 month after electrode implantation. |
Implantation Bilateral Stimulation Monopolar Frequency 20 Hz or 130 Hz Amplitude 4–8 mA Pulse Width 91 μs |
MADRS, HRSD-17, QIDS-SR, Q-LES-Q, GAF, HAM-A, CGI, PGI, CANTAB battery. | Four out of nine patients responded ◊ at the end of DBS (≥40% reduction in MADRS from baseline). The effect of DBS at 6–12 months was higher than DBS at 1–6 months. High-frequency DBS showed higher efficacy than low-frequency DBS. Non-responders crossed over after first 6 months of DBS. |
Severe One patient overdosed on medication (dothiepin and valium). |
| Merkl et al. (2018) [43] | Diagnosed MDD and disease lasted for >2 years; HAMD-24 score ≥ 20; ATHF Score ≥ 3; TRD: NR ≥ 2 antidepressant therapies; Failed to respond to antidepressants and ECT; No changes in current antidepressant treatments ≥6 wks prior to study. |
8 |
Target SCG Study Design Randomized; Two groups: sham-DBS (delayed onset) OR non-delayed onset group for the first 8 weeks in a blinded manner. Open-label DBS afterwards for up to 28 months. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 5–7 V Pulse Width 90 μs |
HAMD-24, BDI, MADRS. |
Three out of eight patients responded ** after 6 months DBS; three out of seven with the same criteria after 12 months. Two out of six responded ** at the end of DBS, follow-up at 28 months. Two out of six patients reached remission □ at the end of DBS, follow-up at 28 months. This study showed a delayed response in patients; no significant antidepressant effects between sham and active stimulation compared to baseline. |
Non-severe Headache; Pain; Scalp tingling; Dizziness; Light hypomania; Inconvenient movement; Severe NIL |
| Howell et al. (2018) [44] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
6 | Target SCC (Cingulum Bundle and Forceps Minor) |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 4 V Pulse Width 90 μs |
HDRS-17, MRI Field-cable modeling (non-VTA-based analysis) |
All of the subjects responded. Left and right cingulum bundles as well as forceps minor are the most likely therapeutic targets. Right cingulum bundle activation beyond a threshold may protract recovery. Uncinate fasciculus and frontal pole were activated to a lesser extent, may not be necessary for anti-depressive effect of SCC-DBS. Time to a stable response (TSR) was 8–189 days, 1-year HDRS-17 was 2–11. Field cable modeling was more accurate than volume of activated tissue at approximating axonal activation. Overstimulation of CB-DBS can be detrimental to the recovery process. |
N.A. |
| Waters et al. (2018) [45] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
4 |
Target SCC Study Design Single-blinded, Session 3 min |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3–5 V Pulse Width 90 μs |
HDRS-17, EEG |
Symptom severity scores decreased. three out of four patients in remission (HDRS-17 ≤ 7). Test-retest reliability across four repeated measures over 14 months met or exceeded standards for valid test construction in three out of four patients for cortical-evoked responses studied. |
N.A. |
| Smart et al. (2018) [46] | TRD patients enrolled from two separate clinical trials for Deep Brain Stimulation. Trial 1 Both sexes aged 18–70 years; Diagnosis of a Major Depressive Episode or Bipolar Type II—current episode depressed, Current episode duration of at least 1 year, Non-responsive (NR) ≥ 4 antidepressant therapies. Trial 2 Both sexes aged 25–70 years; Current depressive episode of at least 2 years duration OR a history of more than four lifetime depressive episodes, Non-responsive (NR) ≥ 4 antidepressant therapies. |
14 |
Target SCC Study Design Double-blinded. Intraoperative behavioral testing: Frequency: 130 Hz Pulse width: 90 μs Current: 6 mA Eight patients continued SCC local field potential. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 6–8 mA for St. Jude Medical devices, 3.5–5 V for Medtronic devices Pulse Width 90 μs |
HDRS-17, MRI, LFP. |
11 of 14 patients met the criteria for DBS antidepressant response by 6 months. Of the three 6 month non-responders, one responded after the 6 month study endpoint but without a contact change (Patient 2), one responded after a contact switch in the left hemisphere (Patient 7), and one remained a non-responder (Patient 6). Mean baseline HDRS-17 of 23.8 and SD of 2.8; HDRS-17 of 9.6 and SD of 4.5 at month 6; 19.9 weeks for stable response with SD of 20 weeks. Precision on the left may be more important than precision on the right, which is supported by theta decreases. |
N.A. |
| Choi et al. (2018) [47] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
15 |
Target SCC Study Design Patients went through SCC-DBS, followed by MRI scans. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 6 mA Pulse Width 90 μs |
HDRS-17, MRI, DWI, Volume of Tissue Activated |
Significant differences in the pathway activation changes over time between remitters and non-remitters. Non-remitters had significantly larger net changes in their pathway activation connection in both the near and long term relative to the initial plan. |
N.A. |
| Conen et al. (2018) [48] | TRD (unipolar); NR ≥ 4 antidepressant therapies; MADRS Score ≥ 22. |
7 |
Targets SCC followed by Ventral Anterior Capsule, nucleus accumbens (separately, unless patient in remission, and later combined, for non-responding patients). Study Design DBS was applied sequentially for 3 months per region, for a total period ranging from 16–45 months. |
N.A. | MADRS, HAM-D 17, GAF. |
Remitters had higher regional cerebral blood flow in the baseline prefrontal cortex and subsequent tests when compared to non-remitters and non-responders. Chronic DBS increased prefrontal cortex regional cerebral blood flow. Remitted patients had higher prefrontal cerebral blood flow at baseline. |
N.A. |
| Holtzheimer et al. (2017) [15] | Both sexes aged 21–70 years; Unipolar, non-psychotic MDD First MDE onset before 45 years old with current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies, MADRS Score > 22; GAF < 50; MMSE > 24; No changes in current antidepressant treatments ≥ 4 wks prior to study. |
60 (DBS) 30 (Sham) |
Target SCC Study Design DBS or sham stimulation 2 weeks after implantation for 6 months in randomized and double-blind manner. Two groups: DBS or sham then both groups received open-label stimulation for 6 months or 2 years. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 4–8 mA Pulse Width 91 μs |
MADRS, GAF HRSD-17, 30-item Inventory of Depressive Symptomatology, QIDS-SR, WSAS, PGI, CGI, QOL, HAM-A. |
Insignificant difference in response * between sham and DBS at the end of the 6-month double-blind phase. 38 patients responded * and 20 remitted □ after 6 month DBS. In 2 years of open-label active DBS, 48% achieved antidepressant response and 25% achieved remission—clinically meaningful long-term outcomes. |
Severe Eight of 40 events reported related to device or surgery: six infections (in five patients), one skin erosion over the extension wires, and one postoperative seizure. |
| McInerney et al. (2017) [14] | Current MDE ≥ 12 months; HRSD-17 Score ≥ 20; NR ≥ 4 antidepressant therapies. |
20 |
Target SCG Study Design DBS for 12 months open-label |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3.5–5 V Pulse Width 90 μs |
Wisconsin Card Sorting Task (WCST), Hopkins Verbal Learning Test, Controlled Oral Word Association Test (COWA), Finger Tap Test, Stroop Test, HRSD-17. |
Significant reduction in HRSD-17 from baseline to experimental follow-up. Baseline scores differed significantly between responders and non-responders. 11 patients responded ** and nine were non-responders. WCST Test results indicated that the total errors were predictive of responsiveness to DBS. No significant deterioration in cognition and psychomotor speed. Improvements in verbal memory and verbal fluency. |
N.A. |
| Riva-Posse et al. (2018) [49] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
11 |
Target SCC Study Design DBS from 4 weeks after surgery and lasted for 6 months, open-label. Stimulation contacts were changed in non-responders and they were stimulated for 6 more months. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 6–8 mA Pulse Width 91 μs |
HRSD-17 | Eight out of 11 responded ** and six remitted □□ after 6 month DBS. Nine responded ** and six remitted □□ after 12 month DBS. Two did not respond throughout the study. Tractography-based surgery reduced variability in the effects of stimulation on patient-specific brain circuitry. |
N.A. |
| Tsolaki et al. (2017) [50] | TRD | 2 | Target SCC |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 8 mA Pulse Width 91 μs |
MRI, DTI, CT, FSL Probabilistic tractography, Volume of Tissue Activated, MADRS. |
One patient was a responder (81% change in MADRS score). Responder’s contacts were closer to the Tractography-guided optimized target (TOT), unlike the non-responder. |
N.A. |
| Accolla et al. (2016) [51] | MDD; NR to treatments; Currently in a depressive episode as in DSM-IV Axis I disorders; HAMD-24 score of ≥ 20. |
5 |
Target BA25 Study Design Double-blind. Each homologous electrode pair was activated separately on 5 consecutive days, then antidepressant effects was assessed 24 h later. Open-label DBS for up to 24 months. Pre- and post-DBS MRI images were taken. |
Implantation N.A. Stimulation Monopolar Frequency 130 Hz Amplitude 5 V Pulse Width 90 μs |
HAMD-24, BDI. |
Four out of five patients did not show sustained response ** to DBS (also ≥50% reduction in DBI). One patient responded ** to DBS of the bilateral posterior gyrus rectus instead of the intended target (BA25). |
N.A. |
| Richieri et al. (2016) [52] | Diagnosed MDD; Severe cognitive defects and relapsed after ECT. |
1 |
Target BA25 Study Design DBS at Day 5 after electrode implantation. |
Implantation Bilateral Stimulation Bipolar Frequency 130 Hz Amplitude 4.2 V Pulse Width 90 μs |
QIDS SR-16 | Remitted (QIDS SR-16 3/48) at 1 month after DBS and maintained at the end of DBS. | Seizure |
| Hilimire et al. (2015) [53] | Both sexes aged 18–70 years; Current MDE ≥ 12 months, Non-responsive (NR) ≥ 4 antidepressant therapies, HRSD-17 score ≥ 20, GAF score ≤ 50. |
7 |
Target SCC Study Design DBS for 6 months, open-label. Behavioral testing and electrophysiological recording (i) before electrode implantation, (ii) after 1 month DBS and (iii) after 6 month DBS. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 4–8 mA Pulse Width 91 μs |
HDRS-17, Emotional self-referential task, EEG recording. |
Reduced proportion of negative self-descriptive words compared to baseline after 1 month and 6 month DBS. Significant reduction in P1 amplitude compared to baseline (for negative word self-description) after 1 month and 6 month DBS, and P3 amplitudes at 6 month DBS only Reduced depression severity. |
N.A. |
| Martin-Blanco et al. (2015) [54] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
7 |
Target SCG Study Design Chronic DBS for 9 months on average for clinical stabilization. A PET scan was acquired (i) during active stimulation and (ii) after 48 h of inactive stimulation. |
Implantation Bilateral Stimulation Monopolar Frequency 135 Hz Amplitude 3.5–5 V Pulse Width 120–210 μs |
HAMD-17, PET | Decreased metabolism in BA24, BA6, caudate putamen after 48 h DBS. This study suggests metabolic changes spread after longer periods of no stimulation. No clinical changes were detected according to HAMD-17. |
N.A. |
| Puigdemont et al. (2015) [55] | Severe TRD; Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
5 |
Target SCG Study Design Randomized, Double-blind. After stable clinical remission to DBS, patients were allocated to two groups, one with (i) 3 month DBS-ON, then (ii) 3 month sham stimulation (ON-OFF arm) or OFF-ON arm and the other, vice-versa. |
Implantation Bilateral Stimulation Monopolar Frequency 130–135 Hz Amplitude 3.5–5 V Pulse Width 120–240 μs |
Volume of Tissue Activated, HRSD-17 |
Active stimulation: four of five patients were remitted patients. Sham stimulation: Only two patients remained in remission, another two relapsed, and one showed a progressive worsening without reaching relapse criteria. |
N.A. |
| Serra-Blasco et al. (2015) [56] |
Treatment-Resistant Depression (TRD) Group Resistant to pharmacological treatment; min. stage IV of Thase-Rush scale; HDRS score ≥ 18. First Episode MDD (FE MDD) Group HDRS score ≥ 14; Newly diagnosed MDD. |
16 |
Target SCG Study Design DBS began at 48 h postoperative and ended when each patient had stabilized response for at least three consecutive visits, tests conducted before surgery, and 12 months after DBS treatment. |
Implantation Bilateral Stimulation Monopolar Frequency 135 Hz Amplitude 3.5–5 V Pulse Width 120–210 μs |
Rey Auditory Verbal Learning Test, Trail Making Tests-A and -B, Wechsler Adult Intelligence Scale III, Tower of London Test, HDRS-17. | FE MDD and TRD saw significant improvements over time in memory. No significant difference was observed in both groups on executive functioning, language, and processing speed. DBS was well tolerated and had no adverse effect on neuropsychological and cognitive function. |
N.A. |
| Choi et al. (2015) [57] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HDRS-17 score ≥ 20; GAF score ≤ 50. |
9 |
Target SCC Intraoperative Sessions: 6 min session of 3 min stimulation ON, and 3 min stimulation OFF. Number of sessions: 12 trials (one at each of the eight available contacts; four per hemisphere, plus four sham trials). Study Design Sham-controlled, Double-blind trials (one case w/single blind trial). |
Acute Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 6 mA Pulse Width 90 μs |
MRI with FSL analysis, Volume of Tissue Activated. |
Behavioral switch was apparent to patients within the first minute of the initiation of stimulation and effects were sustained while stimulation remained on. Three common white matter bundles were affected by stimulation: (i) the uncinate fasciculus, (ii) the forceps minor, and (iii) the left cingulum bundle.Seven of nine patients with left hemispheric contact had a response to treatment at 6 months. |
|
| Sun et al. (2015) [58] | NR ≥ 4 antidepressant therapies, Mean HRSD-17 score of 25 (3). |
20 |
Target SCC Session: 100 min, w/15 min break EEG recording sessions/day Session 1: DBS On Session 2: DBS Random (On/Off) Session 3: DBS (Off) |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 2–7.25 mA OR 2–6 V Pulse Width 90 μs |
EEG, HDRS-17. |
Suppression of gamma oscillations by DBS during working memory performance and the treatment efficacy of DBS for TRD may be associated with the improved GABAergic neurotransmission, previously shown to be deficient in MDD.The present study also suggests that modifying treatment parameters to achieve suppression of gamma oscillations and increased theta-gamma coupling may lead to optimized DBS efficacy for TRD. | N.A. |
| Perez-Caballero et al. (2014) [59] | 18–70 years old with MDE; Resistant to pharmacological treatment and at most, a partial response to ECT; HAMD-17 Score ≥ 18. |
8 |
Target SCG Study Design All patients received chronic DBS within 48 h after implantation. Four patients took NSAIDs for up to 30 days postoperative, four patients did not. |
Implantation Quadrupolar Stimulation 135 Hz Amplitude 3.5–5 V Pulse Width 120–210 µs |
HDRS-17 | At week 1 after surgery, all patients without NSAID prescription responded ** and two remitted □□□; three patients with NSAID responded **, and two remitted □□□. At week 4 after surgery, three patients without NSAID remitted □□□; no patients with NSAID responded ** |
N.A. |
| Merkl et al. (2013) [60] | MDD; NR to treatments; Currently in a depressive episode as in DSM-IV Axis I disorder; HAMD-24 score of ≥ 20; HDRS-24 score ≥ 24. |
6 |
Target SCG Study Design DBS on 11–19 days after electrode implantation, 24 h acute stimulation followed by sham stimulation for each of the three electrode pairs. Up to 6 months of chronic stimulation. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 2.5–10 V Pulse Width 90 µs |
HAMD-24, MADRS BDI, TMT-A, TMT-B, CVLT, TAP, Boston Naming Test, Stroop Test, Word Fluency Test. |
Non-significant reduction in HAMD-24, BDI, and MADRS scores for acute DBS and sham stimulation. 0/4 contact pair locations showed significant BDI and MADRS improvements. Contact pair 3/7 for Patient 4 saw a 77% reduction in HAMD-24 score and 62% reduction of MADRS score. Reduced HDRS-24, BDI, and MADRS scores at the end of chronic stimulation. Two out of six remissions □ at the end of chronic stimulation. |
Mild Headache; Pain; Scalp tingling; Dizziness; Sore throat; Hardware-related; Severe NIL |
| Ramasubbu et al. (2013) [61] | Aged between 20–60 years; Diagnosed MDD; HAMD-17 score ≥ 20; NR ≥ 4 antidepressant therapies. (Enrolled patients were among the most treatment resistant). |
4 |
Target SCC Study Design Double-blind DBS optimization. Open-label continuous DBS for 6 months after optimization period. Varied parameters for each patient during optimization. |
Implantation Bilateral Stimulation Monopolar Frequency 0/5/20/50/130/185 Hz Amplitude 0–10.5 V Pulse Width 0/90/150/ 270/450 μs |
HAMD-17, MADRS, HAM-A, CGI. |
Postoperative optimization: All four patients showed maximal response at longer pulse widths; three patients experienced a 50% reduction in HAMD-17 score. Longer pulse widths were correlated to short-term improvement. Longer pulse width also induced insomnia, confusion, and drowsiness; improved by turning off stimulation. Chronic stimulation: two patients responded ** at the end of open-label DBS, with longer pulse width. Electrode targets suggested to be individualized, as opposed to standard as in movement disorders, owing to the complexity of cortical gyral anatomy |
Mild Anxiety; Drowsiness; Confusion; Insomnia. |
| Torres et al. (2013) [62] | Type I bipolar depression; Poor response to ECT and pharmacotherapy. |
1 |
Target SCC Study Design DBS from 15 days after implantation and follow-up for 9 months. |
Implantation N.A. Stimulation Monopolar Frequency 130 Hz Amplitude 6 mA Pulse Width 91 µs |
HDRS-17, BDI, MADRS, GAF, Young Mania Scale. |
Scores improved across tests. Psychotic symptoms disappeared. Manic episodes reduced. |
N.A. |
| Broadway et al. (2012) [63] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
12 |
Target SCC Study Design DBS for up to 24 weeks. |
Implantation N.A. Stimulation Monopolar Frequency 130 Hz Amplitude 6–8 mA Pulse Width 90 µs |
HRSD-17, Frontal and posterior Theta cordance. |
Reduced HDRS-17 scores between baseline and the end of DBS among all patients. Six patients had significantly reduced HRSD-17 scores ** at the end of DBS. Increased frontal theta cordance between baseline and week 4 in responders correlated with their decreased depressive state at later time points. |
N.A. |
| Hamani et al. (2012) [64] | TRD; NR to respond to pharmacotherapy, psychotherapy, transcranial magnetic stimulation, ECT, vagus nerve stimulation. Relapsed after receiving 6 month SCC-DBS. |
1 |
Target SCC Study Design Administered tranylcypromine before surgery. DBS for 6 months. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 2.5 V Pulse Width 90 µs |
HAMD-17 |
Before relapse: SCC-DBS reduced HAMD-17 score from 22 to 9 after 4 month DBS. After relapse: MAOI supplementation restored the therapeutic effect of DBS; HAMD-17 score lowered from 22 to 16 (after 2 weeks), to 8 (after 2 months) and to 9 (after 4 months). |
N.A. |
| Holtzheimer et al. (2012) [65] | Both sexes aged 18–70 years; current MDE ≥ 12 months; NR ≥ 4 antidepressant therapies; HRSD-17 score ≥ 20; GAF score ≤ 50. |
17 |
Target SCC Study Design Intraoperative testing of electrode location for 12 or 17 patients. Stimulation: (i) 4 weeks of sham stimulation, followed by (ii) 24 weeks of open label DBS for 24 weeks, followed by (iii) single-blind discontinuation for 1 week and open label stimulation for up to 2 years. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 4–8 mA Pulse Width 91 µs |
HRSD-17, BDI-II, GAF. |
Reduced depression and increased function. 11 patients responded ** and seven further remitted □□ after 2 year DBS. Efficacy was similar for patients with MDD and those with BP. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention, but prior to entering the sham phase. |
Anxiety; Worsened depression; Nausea; Headache; Infection; Suicide attempts. |
| Lozano et al. (2012) [66] | Both sexes aged 30–60 years; First MDE before 35 years; HRSD-17 score ≥ 20; GAF < 50. |
21 |
Target SCG Study Design DBS for 12 months, open label. |
Implantation Bilateral Stimulation N.A. Frequency 110–140 Hz Amplitude 3.5–7 mA Pulse Width 65–182 µs |
HRSD-17, CGI-S. |
Improved global functioning and less severe depression. 13 patients responded ***, based on HRSD-17 scores. |
Gastrointestinal problems; Skin problem; Suicide; Spasms; Weight gain; Insomnia. |
| Puigdemont et al. (2012) [67] | 18–70 years old with MDE; Resistant to pharmacological treatment and at most, a partial response to ECT; HAMD-17 Score ≥ 18. |
8 |
Target SCG Study Design Intraoperative feedback was provided during surgery for electrode placement. DBS began at 48 h postoperative and ended when each patient had stabilized their response for at least three consecutive visits. |
Implantation Bilateral Stimulation Monopolar Frequency 135 Hz Amplitude 3.5–5 V Pulse Width 90 µs |
HAMD-17, MADRS, CGI. |
Seven patients responded ** and three remitted □□ after 6 month DBS. Five patients responded ** and four remitted □□ after 12 month DBS. Three out of four remitted patients after 12 month DBS had remitted after 3 month DBS. |
Suicide ideation; Neck pain; Recurrence; Depression; Cephalalgia. |
| Kennedy et al. (2011) [18] | Current MDE ≥ 12 months; HRSD-17 score ≥ 20; NR ≥ 4 antidepressant therapies. |
20 |
Target SCG DBS patients were monitored for 3–6 years. |
Implantation Bilateral Stimulation Monopolar Frequency 124.7 Hz (average) Amplitude 4.3 V (average) Pulse Width 70.6 µs |
HAMD-17 36-item Short-Form Healthy Survey Questionnaire. |
64.3% patients responded ** at the last follow-up visit. 35% patients remitted □□ at the last follow-up visit. Scores at the last visit tended towards maintenance of therapeutic scores at 3 years. |
Depression; Suicidal thoughts; Suicide (All determined to be unrelated to DBS). |
| Guinjoan et al. (2010) [68] | Chronic TRD; Family history of affective disorders; Poor response to antidepressants, ECT, and psychotherapy. |
1 |
Target BA25 Study Design Positioning was aided by intraoperative feedback. Bilateral DBS was conducted for 12 months. Followed by unilateral-left, then right DBS, for 6 months |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3.5–5 V Pulse Width 90 µs |
HAMD-17, BDI. |
Patient’s condition plateaued after 6 month bilateral DBS. Left unilateral DBS led to rapid worsening in mood. Right unilateral DBS reversed the symptoms and the patient made significant improvements over bilateral stimulation. Patient remitted at 18 months. |
Orthostatic hypotension. |
| Holtzheimer and Mayberg (2010) [69] | Showed signs and symptoms of MDD; Had suicidal ideation in current MDE; Did not improve in symptoms with pharmacotherapy, psychotherapy, and ECT HAM-D score was 25 |
1 |
Target SCC Study Design Positioning of electrodes was aided by intraoperative feedback 24 weeks of open-label DBS and chronic stimulation beyond the assessment |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 6 mA Pulse Width 91 µs |
HAMD-17 | HAMD-17 score lowered to 9 at the end of DBS follow-up. Sustained antidepressant response up to 2 years after surgery |
N.A. |
| Hamani et al. (2009) [70] | Diagnosed MDD; current MDE ≥ 12 months; HAMD-17 score >20; GAF ≤ 50; NR ≥ 4 antidepressant therapies. |
20 |
Target SCG Study Design DBS began at 2 weeks after surgery and lasted for 12 months |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3–5 V Pulse Width 90 µs |
HAMD-17 | 11 responded ** at the end of 6 month DBS follow-up. Electrodes in responders were positioned ventrally relative to the landmarks of the medial prefrontal lobe. |
N.A. |
| Puigdemont et al. (2009) [71] | Suffered from MDD, with several MDE accompanied by psychotic symptoms; Responded poorly to pharmacotherapy and ECT; Relapse following SCG-DBS with different features; Psychotic as opposed to depressive from previous episodes. |
1 |
Target SCG Study Design DBS for 4 months, then switched off because of relapse and administered ECT for 3 weeks Resumed DBS until 12 months from the beginning of DBS. |
Implantation Bilateral Stimulation Monopolar Frequency 135 Hz Amplitude 3.6 V Pulse Width 90 µs |
HAMD-17 | Sustained response without the need of ECT before relapse. Maintained remission in DBS after ECT until the end of follow-up. |
N.A. |
| Lozano et al. (2008) [72] | Current MDE ≥ 12 months; HRSD-17 score ≥ 20; NR ≥ 4 antidepressant therapies. |
20 |
Target SCG Study Design Blinded-DBS in between and after surgery, monitored for up to 1 year. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3.5–5 V Pulse Width 90 µs |
HRSD-17, Beck Anxiety Inventory, BDI, CGI-S, PET scans, Neuropsychological tests. |
Mean HRSD-17 score lower than baseline at all time points. 12 patients responded ** to DBS, 7 remitted □□ after 6 month DBS. 11 patients responded ** to DBS, 7 were nearly remitted or remitted □□ after 12 month DBS. Eight responses maintained from 6 month to 12 month DBS. PET Scans: decreases in orbital, medial prefrontal cortex, and insula. Increases in lateral prefrontal cortex, parietal, anterior, and posterior cingulate by 6 months; increases in metabolic activity in regions adjacent to SCG. |
Seven patients without adverse effects. Wound Infection; Headache; Pain; Seizure; Worsened mood; Irritability. |
| McNeely et al. (2008) [73] | Current MDE ≥ 12 months, HRSD-17 score ≥ 20, Non-responsive (NR) ≥ 4 antidepressant therapies, |
6 | Target BA25
Continuous DBS for 12 months. |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 3–4.5 V Pulse Width 60 µs |
HRSD-17 Object alternation Test Iowa gambling task Visual delayed recall memory Verbal delayed memory Verbal list learning Stroop color-word |
6 months: four responded at the end of DBS ** General Neuropsychological Performance: Manual Motor Skills: Improved for dominant and non-dominant hand by 12 months. Verbal learning: Restored impairments in two patients at the end of 12 months. No significant correlations between change in mood and neuropsychological function at 6 and 12 months. |
N.A. |
| Neimat et al. (2008) [74] | Family history of severe MDD. Failed to respond to antidepressants, adjuncts, and ECT. Relapsed after ablative cingulotomy |
1 |
Target BA25 Study Design Started DBS on the day after electrode implantation and lasted for 30 months |
Implantation Bilateral Stimulation Monopolar Frequency 130 Hz Amplitude 4.5 V Pulse Width 60 µs |
HAMD-17 | HAMD-17 score decreased from 19 before surgery to 8 at 6 months after DBS. Sustained remission until the end of DBS study (scored 7) |
N.A. |
| Mayberg et al. (2005) [19] | Current MDE ≥ 12 months, HRSD-17 score ≥ 20, Non-responsive (NR) ≥ 4 antidepressant therapies. |
6 |
Target BA25 Study Design 1–5 min on-off stimulation in acute DBS for 5 days postoperative. Chronic DBS for 6 months after pulse generator was implanted and optimized for 4 wks |
Implantation Bilateral Stimulation Monopolar Acute: Frequency 10–130 Hz Amplitude 0.0–9.0V Pulse Width 30–250 µs Chronic: Frequency 130 Hz Amplitude 4 V Pulse Width 60 µs |
HDRS-17, MADRS, CGI, Positive and Negative Affective Scale. |
Acute effects: Sudden feeling of calmness Chronic effects: five patients responded ** after 2 month DBS. Response maintained in four patients at the end of 6 month DBS. Three patients achieved remission □□ or near remission at the end of 6 month DBS. |
Mild Lightheadedness; Psychomotor slowing; Skin infection; Skin erosion. |
* ≥40% reduction in MADRS and average GAF in months 4–6 not worse than baseline; ** ≥50% reduction in HRSD-17 (HAMD-17) score from baseline; *** ≥40% reduction in HRSD-17 score from baseline; ◊ ≥40% reduction in MADRS compared to mean baseline; □ HAMD-24 scores or MADRS scores ≤ 10 after DBS; □□ HRSD score < 8. □□□ HRSD score ≤ 8; Abbreviations: ATHF = Anti-depressant Treatment History Form, BA25 = Brodmann Area 25, BDI/-II = Beck Depression Inventory/-II, CGI, PGI, CANTAB = Clinician and Patient Global Impression of Severity and Improvement (CGI; PGI) and cognitive function (CANTAB); CVLT = California verbal learning test, DBS = deep brain stimulation, DWI = Diffusion-weighted imaging, ECG = electrocardiogram, ECT = electroconvulsive therapy, EDA = electrodermal activity, EEG = electroencephalography, GAF = Global assessment function, HAM-A = Hamilton Anxiety Rating Scale, HRSD-17/HDRS-17 = Hamilton Rating Scale for Depression/ Hamilton Depression Rating Scale, (f)MRI = (functional) magnetic resonance imaging; MADRS/MARDS = Montgomery-Åsberg Depression Rating Scale, MAOI = monoamine oxidase inhibitors, MDD = major depressive disorder, MDE = major depressive episodes, MMSE = Mini-Mental State Examination, NSAID = non-steroidal anti-inflammatory drug, NR = non-responsive, PET = positron emission tomography, QIDS/-SR = Quick Inventory of Depressive Symptomatology/-self report, Q-LES-Q = Quality of Life and Satisfaction Questionnaire, SCC = subcallosal cingulate, SCG = subcallosal cingulate gyrus, SCR = skin conductance response, QOL = Quality of Life Enjoyment and Satisfaction Questionnaire, TRD = treatment-resistant depression, WSAS = Work and Social Adjustment Scale.