Deep Brain Stimulation in the Treatment of Obsessive-Compulsive Disorder
Abstract
Background:
Deep brain stimulation (DBS) has emerged as a treatment for severe cases of therapy-refractory obsessive-compulsive disorder (OCD), and promising results have been reported. The literature might, however, be somewhat unclear, considering the different targets used, and due to repeated inclusion of individual patients in multiple publications. The aim of this report was to review the literature on DBS for OCD.
Methods:
The modern literature concerning studies conducted on DBS in the treatment of OCD was reviewed.
Results:
The results of DBS in OCD have been presented in 25 reports with 130 patients, of which, however, only 90 contained individual patients. Five of these reports included at least 5 individual patients not presented elsewhere. Sixty-eight of these patients underwent implantation in the region of the internal capsule/ventral striatum, including the nucleus accumbens. The target in this region has varied between groups and over time, but the latest results from bilateral procedures in this area have shown a 50% reduction of OCD scores, depression, and anxiety. The subthalamic nucleus has been suggested as an alternative target. Although beneficial effects have been demonstrated, the efficacy of this procedure cannot be decided, because only results after 3 months of active stimulation have been presented so far.
Conclusions:
DBS is a promising treatment for therapy-refractory OCD, but the published experience is limited and the method is at present an experimental therapy.
Reprinted with permission from World Neurosurgery 2013; 80(6):E245–E253
Introduction
Obsessive-compulsive disorder (OCD) is a chronic disorder characterized by persistent obsessive, intrusive thoughts generating anxiety, and related compulsions (tasks or rituals) with the function of neutralizing the distress. It is the 10th most common cause of disability in the world, affecting approximately 2% of the population (11). It is considered to be one of the most disabling psychiatric disorders, creating manifest functional impairment that will influence work, leisure activities, and interaction with family and the social environment. OCD is, however, not only associated with suffering for the patients, and a reduced quality of life, but also with a significant mortality (3). Recent studies suggest that 10% to 27% of the patients might attempt suicide during their lifetime (3).
Even though the majority of patients with OCD will respond at least partly to selective serotonin-reuptake inhibitors and cognitive-behavioral psychotherapy (CBT), there remains a significant portion in whom these methods will cause little or no relief of the patient’s symptoms (36). It is estimated that about 10% of the patients will demonstrate severe therapy-refractory symptoms (16, 17).
In these patients, stereotactic lesional procedures (capsulotomy and cingulotomy) have constituted an alternative for a few well-selected patients. The results have varied, and the irreversibility of the procedure has raised concern regarding nontransient side effects (38, 59).
Recently, stereotactic deep brain stimulation (DBS) has emerged as a possible treatment for therapy-refractory OCD. Although chronic electrical stimulation using stereotactically implanted electrodes have a long history going back to the 1950s, the modern era began in the end of the 1980s and has expanded, especially during the last decade (9, 12, 28, 69). Today DBS is an established treatment for movement disorders such as Parkinson disease (PD), and more than 60,000 patients have undergone operations worldwide (46).
New indications for DBS are emerging, and regarding psychiatric disorders, several studies have been presented regarding Tourette syndrome (2, 8, 18, 29, 31, 63, 64, 75), major depressive disorder (10, 14, 34, 39, 44, 60), and OCD (1, 4-7, 15, 17, 22-27, 30, 32, 33, 38, 42, 45, 50-53, 55, 65, 67, 68). The goal of this report is to review the modern literature regarding DBS in the treatment of OCD.
Studies and Methods
The literature was searched regarding DBS for OCD. Relevant publications were obtained using the PubMed database and references from the consulted reports. Duplicate inclusion of patients included in multiple publications from the same institution was avoided.
DBS
The surgical procedure differs little between OCD and movement disorders (14). After mounting of the stereotactic frame, magnetic resonance imaging is performed for identification of the target. A burr hole is made a few centimeters from the midline in accordance with the precalculated trajectory, and the electrode is advanced to the target. The DBS electrode has a diameter of 1.27 mm and 4 contacts of 1.5 or 3 mm in length, separated by 0.5, 1.5, or 4 mm, depending on the model. The effect and side effects of stimulation, both of which tend to be discrete in OCD, are then evaluated, which is why the procedure most often is performed under local anesthesia.
DBS in movement disorders has been demonstrated to be a safe method associated with few complications or side effects of a more serious nature. The major risk in these procedures is intracerebral hemorrhages, occurring in 1% to 2% in larger studies, small and asymptomatic intracerebral hemorrhage included (74). Complications related to the implants occur, but these do not normally pose any serious threat to the patient. A wide variety of stimulation-induced side effects have been reported from DBS in different targets, such as dysarthria, paresthesias, sweating, hypomania, etc. The advantage of DBS over lesions is that these side effects can be abolished by altering the stimulation parameters or by simply turning off the implantable pulse generator.
DBS in the Treatment of Ocd
Pathophysiology
Although recent neuroimaging studies are increasing our knowledge regarding the mechanism behind OCD, the understanding of the pathophysiological background is still limited (30, 38, 48, 56-58, 61, 73). The suggested models are instructive, but there must be little doubt that the reality is far more complex. Even if functional neuroimaging holds promise for the future, it has as yet had limited impact on the current status of DBS for OCD. The best target for an intervention with DBS cannot be identified based on our current understanding of the pathophysiological mechanisms behind OCD. The current targets are therefore mainly based on the experience from the lesional era, as well as from the continuous evaluation of the effect of DBS in relation to lead location, or as in the cases of DBS, of the subthalamic nucleus (STN), on observations during surgery for other conditions (30).
Clinical studies have demonstrated promising results of DBS from different targets, and the same targets has in many cases also been used successfully in the treatment of isolated depression (10, 34, 35, 40, 44, 62, 71, 72) and Tourette syndrome (19, 37, 49, 76). This is in analogy with the situation regarding DBS for movement disorders, in which different targets are used to treat the same symptoms, and the same targets are used to treat different symptoms (14). This is in accordance with the present understanding of these conditions as disturbances in one, or several, circuits, rather than in circumscribed isolated functional entities (66).
The pathophysiological background of OCD seems to involve a dysfunction in an orbito-fronto-striato-thalamo-cortical circuit, in which the orbitofrontal cortex and the anterior cingulate cortex are especially implicated on the cortical level, and the striatum in the basal ganglia. The striatum is divided by the internal capsule (IC), and consists of the putamen lateral to the IC, the caudate nucleus medially, and the nucleus accumbens (NA) ventral to the IC. The IC is a large anatomical structure, and the target within the IC has varied substantially over time, both regarding capsulotomies and DBS. The effect of these procedures is believed to be caused mainly by an inhibitory effect on connections between the frontal lobe and the basal ganglia traversing the IC (33). It is, however, difficult to know which adjacent structures might contribute to the effect of DBS, especially considering the very high stimulation strength used in OCD. In the first patients who underwent surgery with DBS for OCD, the anterior IC was the target, but a possible contribution to the effect from the surrounding striatal structures was acknowledged (51), and the target area is now often referred to as the ventral capsule/ventral striatum (VC/VS) (26). The groups targeting the IC will often place the deepest part of the electrode in the NA, whereas the groups targeting the NA will have their highest contacts located in the IC, and in 1 group intentionally in the caudate nucleus. Somewhat posterior-medial to these targets is the newly suggested bed nucleus of the stria terminalis, which has connections with the cortico-striato-thalamo-cortical circuitry, and is currently being evaluated (70). Slightly medial-posterior to the bed nucleus of the stria terminalis, we find yet another target, the inferior thalamic peduncle (ITP), which has been used in a few patients (33). The mechanism of action is unclear regarding the ITP, but it has been suggested to be mitigated by an effect on the projections from striatum and orbitofrontal cortex entering the thalamus (48). Clearly separated from this area is the STN, which plays an important role regarding integration of emotional, cognitive, and motor components of behavior. It has been suggested that the effect of STN DBS in OCD is due to an effect on the decision-deferring process, as has been demonstrated in patients with STN DBS for PD (21, 42, 43, 54).
Clinical Studies
In the literature, a total of 25 publications presenting the clinical effects of DBS for OCD were identified (1, 4-7, 15, 17, 22-27, 32, 33, 42, 45, 50-53, 55, 65, 67, 68). These publications included a total of 130 patients. After consideration of multiple inclusions of the same patients in several publications, a total of 90 individual patients could be identified. The target was in 32 patients the internal capsule/ventral striatum (1, 4, 15, 23-26, 50-53, 65, 67), 36 NA (5-7, 17, 22, 27, 32, 45, 55, 68), 17 STN (42), and in 5 the ITP (33). Further mentioned, but without any clinical data, were 2 patients with IC DBS (51) and 6 STN DBS (54). Three patients with STN DBS for PD with concomitant OCD were also reported (20, 41). These publications are presented briefly (Table 1). Nine reports presented more than 2 individual patients not presented elsewhere (1, 17, 22, 25, 27, 32, 33, 42, 68). Five reports presented 5 or more individual patients. These reports regarding VC/VS by Greenberg et al. (25), unilateral NA by Huff et al. (32), bilateral NA by Denys et al. (17), ITP by Jiménez-Ponce et al. (33), and STN by Mallet et al. (42) are presented in some detail (Table 2) and are further discussed later.
Author | Patients/Procedures | Complications of Surgery/Stimulation | Results and Comments |
---|---|---|---|
Greenberg et al., 2010 (25) | 26 patients Bilateral VC/VS | Adverse events of interest: 1 asymptomatic ICH, 1 ICH with transient apathy, 1 seizure, 1 wound infection, 2 hardware-related complications, stimulation-induced reversible effects, including hypomania | Several subgroups; varying follow-up (minimum 3 months, mean 24 months). |
YBOCS reduced by 38% after 3 months and after 3 years. Anxiety and depressive symptoms reduced by half at last follow-up. | |||
The target was changed during the study, which improved the results. In the last 17 patients, YBOCS was improved by 54% at last follow-up (72% >35% improvement). | |||
Greenberg et al., 2006 (26) | 10 patients included in Greenberg et al. (25) | ||
Goodman et al., 2010 (24) | 5 of the 6 patients included in Greenberg et al. (25) | Double-blind staggered onset. | |
Okun et al., 2006 (53) | 5 patients included in Greenberg et al. (25) and Goodman et al. (24) | ||
Burdick et al., 2010 (15) | 1 patient included in Greenberg et al. (25), Goodman et al. (24), and Okun et al. (53) | ||
Shapira et al., 2006 (65) | 1 patient included in Greenberg et al. (25), Goodman et al. (24), and Okun et al. (53) | ||
Springer et al., 2006 (67) | 1 patient included in Greenberg et al. (25), Goodman et al. (24), and Okun et al. (53) | ||
Okun et al., 2004 (52) | 1 patient included in Greenberg et al. (25), Goodman et al. (24), Okun et al. (53), and Springer et al. (67) | ||
Nuttin et al., 2003 (51) | 4 patients included in Greenberg et al. (25); 2 other patients with poor results briefly mentioned | Double-blind crossover in 4 patients. | |
Gabriëls et al., 2003 (23) | 3 patients included in Greenberg et al. (25) and Nuttin et al. (51) | ||
Nuttin et al., 1999 (50) | 4 patients included in Greenberg et al. (25), Nuttin et al., (51) and Gabriëls et al. (23) | ||
Abelson et al., 2005 (1) | 4 patients Bilateral IC | 1 electrode breakage 1 suicide not considered to be caused by the therapy | Double-blind crossover; follow-up 4 to 23 months. |
The largest reduction of YBOCS during the follow-up period was a mean 29.8%. Two patients responded with 57.6% reduction. | |||
Anderson et al., 2003 (4) | 1 patient Bilateral IC | None | YBOCS reduced by 81.1% after 3 months. |
Sturm et al., 2003 (68) | 3 NA unilateral right 1 NA bilateral | None | “Nearly total recovery from both anxiety and OCD symptoms” in 3 patients. |
Huff et al., 2010 (32) | 10 patients Unilateral right NA | Adverse events of interest: 4 stimulation-induced reversible agitation/anxiety, 1 affection of memory/concentration, 2 hypomania, 1 temporary suicidal thoughts not clearly related to DBS | Double-blind crossover. YBOCS reduced by a mean 21% after 1 year (1 responder with >35% improvement). Anxiety and depressive symptoms reduced by 29% and 23%, respectively. |
Plewnia et al., 2008 (55) | 1 patient Unilateral right NA | Wound infection | OCD and residual schizophrenia. YBOCS reduced by 25% after 1 year. |
Franzini et al., 2010 (22) | 2 patients Bilateral NA | None | YBOCS reduced with by a mean 38% after about 2 years. |
Denys et al., 2010 (17) | 16 patients Bilateral NA | Adverse events of interest: 1 wound infection, 8 stimulation-induced mild reversible hypomania, 5 mild forgetfulness, 3 mild word-finding problems, 7 increased (normalized?) libido | Double-blind crossover. YBOCS reduced by a mean 47% after 1 year; 52% after 21 months (9 responders with a mean reduction of 72%). Anxiety and depressive symptoms reduced by half. |
Mantione et al., 2010 (45) | 1 patient included in Denys et al. (17) | ||
Guehl et al., 2008 (27) | 3 OCD Bilateral NA/NC | None | YBOCS reduced by 35% to 60% after 1 year. |
Aouizerate et al., 2004 (6) | 1 patient included in Guehl et al. (27) | ||
Aouizerate et al., 2005 (7) | 1 patient included in Guehl et al. (27) and Aouizerate et al. (6) | ||
Aouizerate et al., 2009 (5) | 2 patients included in Guehl et al. (27) and Aouizerate et al. (6, 7) | ||
Jiménez-Ponce et al., 2010 (33) | 5 patients | Only stimulation-induced reversible side effects | Three patients had addiction, 1 schizoid personality. YBOCS reduced by 49% after 12 months. |
Mallet et al., 2008 (42) | 17 patients Bilateral STN | Adverse events of interest: 1 ICH with permanent finger palsy, 2 infections, 1 transient clumsiness and diplopia Stimulation-induced reversible side effects, including hypomania | Double-blind crossover. YBOCS reduced by 41% after 3 months of active stimulation. |
Piallat et al., 2011 (54) | 9 patients, of which 3 were included in Mallet et al. (42) | Analysis of neuronal firing. No clinical data. | |
Mallet et al., 2002 (41) | Beneficial effect of STN DBS in Parkinson disease reported in 2 patients with concomitant OCD. | ||
Fontaine et al., 2004 (20) | Beneficial effect of STN DBS in Parkinson disease reported in 1 patient with concomitant OCD. |
Table 1. Reports Concerning Deep Brain Stimulation for Obsessive-Compulsive Disorder
Greenberg et al., 2008 (25) | Huff et al., 2010 (32) | Denys et al., 2010 (17) | Mallet et al., 2008 (42) | Jiménez-Ponce et al., 2010 (33) | |
---|---|---|---|---|---|
Target | VC/VS | Unilateral right NA | NA bilateral | STN | ITP |
Coordinates | Gradually changed from 15 mm anterior of AC to within 1 to 2 mm of the posterior border of the AC, further somewhat more medially and more inferior to include most often the caudal NA | Visual targeting based on the IC and the band of Broca | 3 mm anterior of the anterior border of AC, laterality 7 mm, 4 mm inferior of ICL | “2 mm anterior to and 1 mm medial to the target that is used in patients with Parkinson’s disease” | 3.5 mm lateral to the wall of the 3rd ventricle, 5 mm behind the AC, at the AC-PC-plane |
Number of patients | 26 | 10 | 16 | 16 | 5 |
Male/female | 14/12 | 6/4 | 9/7 | 9/7 | 3/2 |
Age at onset (years) | 15.1 | 14.2 | |||
Duration (years) | 22 | 22.2 | 28.4 | 17 | |
Age at surgery (years) | 37.1 | 36.3 | 42.6 | 43.8 | 37 |
Evaluation presented here | Last follow-up, after a mean 24 months | 12 months | 12 months | 3 months of active stimulation | 12 months |
YBOCS preoperative/postoperative | 34.0/∼21 | 32.2/25.4 | 33.7/17.8 | 32.1/19 | 35/17.8 |
HDRS preoperative/postoperative | 52.8% reduction | HDRS: 21.6/16.6 | HDRS-17: 19.5/10.3 | ||
HAMA preoperative/postoperative | 50.0% reduction | 21.2/15.0 | 20.9/9.7 | ||
GAF preoperative/postoperative | 34.8/59.0 | 36.6/53.1 | 31.6/56 | 18/72 | |
SDSS preoperative/1 year | 8.6/4.8 | ||||
Stimulation parameters | Monopolar, 2 to 3 contacts, 4.5 to 6.5 V, 90 to 140 μS, 145 Hz | Monopolar, 2 contacts, 3.5 to 5 V (mean 4.3), 90 μS, 130 Hz | 27 electrodes monopolar, 2 bipolar, 2.0 V | Bipolar, 5.0 V, 450 μS, 130 Hz | |
Number of responders | 61.5% | 1/10 | 9/16 |
Table 2. Patient Characteristics in Reports of >5 Individual Patients with Deep Brain Stimulation for Obsessive-Compulsive Disorder
Patients
The inclusion criteria were quite uniform in the whole study. Although there were slight variations, DBS was offered to patients suffering for at least 5 years from severe OCD, defined as a minimum Yale-Brown Obsessive Compulsive Scale (YBOCS) of 25 to 28. The symptoms should be therapy-refractory, typically described as no or insufficient improvement after adequate administration during adequate time of: 1) three treatment attempts with selective serotonin-reuptake inhibitors, of which one had to be clomipramine; 2) augmentation with a neuroleptic and/or a benzodiazepine; 3) a minimum of 16 to 20 sessions of CBT. In reality these inclusion criteria seem to have been well surpassed. The mean YBOCS on inclusion varied from 32 to 34, and the mean duration of disease from 22 to 28 years. Patient characteristics are presented in Table 2.
Results
The results are summarized in Table 1 and presented in further detail regarding the larger studies in Table 2.
The first patients treated with DBS for OCD underwent implantation in the anterior IC in the same target as used for capsulotomies (25, 50, 51). Four collaborating groups have individually and in various combinations presented parts of a study recently summarized by Greenberg et al. (25). The results were reported for 26 patients after a mean time of 24 months. Cases lost to follow-up or converted to capsulotomies were excluded. The effect of DBS in the original target was limited, and battery consumption was high. The target was therefore gradually moved posteriorly during the study, and the study was divided into 3 different groups based on the posterior position of the electrodes. The mean reduction of YBOCS was 29% in the first group with the most anterior electrodes, and 54% in the group with the most posterior electrodes. One third were responders in the first group (improvement ≥35%) and three fourths in the last 2 groups, at last follow-up. Anxiety and depressive symptoms were reduced by about half in the whole study. Stimulation strength was reduced from approximately 8.5 V and >300 μS to <5 V and 200 μS from the first to the last group. The name of the target has further been changed from the IC to the VC/VS to reflect the modified target.
The observation that the ventral-caudal part of the IC adjacent to the NA is of importance for the result in capsulotomies, in combination with the high stimulation levels for IC DBS, motivated Sturm et al. to suggest the NA as a target (32, 68). The result was initially encouraging, and unilateral DBS of the right NA was performed because the first patient did not benefit more from bilateral DBS (68). Their further results were, however, modest. Only 1 of 10 patients was a responder, and the mean reduction of YBOCS was 21% after 1 year. Anxiety and depressive symptoms were reduced 29% and 23%, respectively (32). Voltage varied between 4.5 and 6.5 V and pulse-width 90 to i40 μS.
The effects of bilateral NA DBS were presented by Denys et al. in 16 patients (42). YBOCS was reduced by 47% after 1 year, and 52% after 21 months. Nine of the patients were responders, with a mean reduction of 72%. Anxiety and depressive symptoms were reduced by half. Mean voltage was 4.3 V, and pulse-width was 90 μS.
Jiménez-Ponce et al. (33) presented 5 patients with bilateral DBS in the ITP, where YBOCS was reduced by 49% after 12 months. The included patients deviated from other studies in that 1 patient had a schizoid personality and 3 had substance abuse (47). The voltage was 5.0 V, and pulse-width was 450 μS.
In 3 patients suffering from PD and concomitant OCD, STN DBS had an effect also on the OCD (20, 41). This led to the French multicenter study of STN DBS for OCD presented in 2008 (42). The electrodes had been slightly misplaced toward the medial zona incerta in the PD patients, and the target for OCD was chosen in the limbic part of the STN, 2 mm anterior and 1 mm medial to the traditional target in PD. The study was designed as a 10-month double-blind crossover study in which the patients were randomized either to 3 months of sham stimulation followed by 3 months of active stimulation or vice versa. Of the original 17 patients, 16 were available for evaluation. Of these, 14 received bilateral stimulation and 2 received unilateral stimulation, due to infection and stimulation-induced side effects, respectively. YBOCS was reduced by a mean 41% after 3 months of active stimulation, as compared with the preoperative baseline, and 32% when compared with sham stimulation. No significant differences were seen regarding anxiety or depression. The mean voltage was 2.0 V.
Blinded, randomized designs have also been used in some other studies. Nuttin et al. (51) attempted a blinded crossover study in 4 patients. The on and off phases were planned for a duration of 3 months each, but the off phases were substantially shortened due to worsening of symptoms. Abelson et al. (1) performed a double-blind test in 4 patients early after surgery, with four 3-week periods on or off stimulation, with modest differences. Huff et al. (32) performed a double-blind crossover study in 10 patients with stimulation on or off for 3 months, in which no significant changes were seen. Denys et al. (17) performed a double-blind crossover study 8 months after surgery in 14 patients with 2 weeks on and off stimulation. YBOCS was reduced by 25% as compared to off stimulation. Goodman et al. (24) performed a blinded staggered-onset study, in which DBS was initiated in 3 patients 1 month after surgery, and in the remaining 3 after an additional month. The authors wrote that the data “suggests that little improvement occurred in either group until the device was activated”.
Complications
A selection of surgical and stimulation-related complications of interest are presented in Table 1. The major studies have meticulously documented adverse events, even when not related to the surgical therapy. Most side effects were minor and transient; however, 3 intracerebral hemorrhages were reported, of which 1 resulted in a permanent sequelae in the form of a finger palsy (25, 42). Regarding stimulation-induced side effects, the most interesting finding was that hypomania could be induced in several patients.
Discussion
Although the study is limited, the effects of unilateral NA DBS are modest compared to the bilateral procedures. It is of interest that an effect was only achieved by Huff et al. (32) when using the 2 deepest contacts in the NA, whereas Denys et al. (17) had no effect here, but only at the above-lying contacts in the IC. At the same time, the target in the IC has been moved to a more posterior and somewhat deeper location: this is why the deepest contact will often be in the NA (25). Thus, when ignoring what the procedure is called, and comparing the location of the contacts actually used for stimulation, it becomes evident that the areas used for stimulation in bilateral NA DBS and IC DBS are so close that it might be considered a single target. The results of bilateral DBS in this area also seem to be similar, with a mean improvement of about 50% concerning OCD symptoms, as well as depression and anxiety.
Some difficulties arise when comparing the different studies. The follow-up period varies from 3 months to a mean of 24 months. The study design varies considerably, and with the exception of YBOCS and the Hamilton Anxiety Scale, a wide variety of different scales has been used.
These difficulties are most pronounced regarding STN DBS, in which the focus was put on the difference between active and sham stimulation. Because most evaluations are reported in relation to a postoperative baseline 3 months after surgery, before initiation of stimulation, and presented with a mix of mean and median values, it is difficult to compare the results with those from other studies. However, the improvement regarding OCD symptoms was lower in the STN, and no benefit was seen concerning anxiety or depression. These are, however, the results after 3 months, whereas other groups have demonstrated that the period of improvement is more extended (17, 22). Further, these patients did not receive CBT (Dr. Mallet, personal communication, 30 November 2010), whereas CBT was encouraged in the study by Greenberg et al. (25), and Denys et al. (17) have stressed the contribution of CBT to the improvement of YBOCS. The fact that the effect of DBS is not immediate, but seems to develop over months or even years, might also explain the modest results presented in the other studies when comparing the effect of DBS to sham stimulation (1, 17, 32).
The surgical complications in these studies were minor, with the exception of 3 intracerebral hemorrhages (4%), however, with only a minor sequelae in 1 of the patients (25, 42). This figure is high in comparison to what has been reported in DBS for movement disorders (13, 74). This should, however, probably be attributed to chance. The surgical complications are not specific for the targets presented here, and can probably be better estimated from the experience of DBS in movement disorders than from this limited study. The advantage of DBS was demonstrated by the fact that all stimulation-induced side effects were transient and could be abolished by altering the stimulation.
Stimulation parameters are of interest because the higher the stimulation, the faster the battery will be depleted, necessitating replacement of the expensive implantable pulse generator, with an inherent risk for infection. The battery consumption was very high when the target for capsulotomies was used. In the present targets in the VC/NA region, the stimulation strength is reduced but still high. The recently introduced rechargeable neuropacemakers might diminish this problem. However, in our own experience we have found the time spent on recharging and checking the battery level to be inconveniently high, probably due to the patient’s OCD, so some caution is advisable. The stimulation levels were low in the study of STN DBS, but only short-term data have been reported.
Due to the differences in evaluation and follow-up, it is not possible to decide further on the relative efficacy and safety of the different targets. Whether any of the suggested targets will prove to be the optimal target for OCD remains to be decided. It is further possible that an optimal target will not be identified, but that different targets might be considered depending on the characteristics of the OCD symptoms, or on associated symptoms such as depression or anxiety.
A therapy that will improve about one third of patients from severe to moderate OCD, and one third from severe to mild or no OCD, is promising for many patients suffering from severe therapy-refractory symptoms. However, the presented study comes mainly from nonrandomized studies of limited size. Further, no consensus exists regarding the target of choice for DBS in this condition. It must therefore be emphasized that DBS for OCD is currently an experimental therapy that should only be performed in clinical studies by multidisciplinary teams with substantial experience with DBS from other conditions.
1. : Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry 57:510–516, 2005.Crossref, Google Scholar
2. : Deep brain stimulation in Tourette’s syndrome: two targets? Mov Disord 21: 709–713, 2006.Crossref, Google Scholar
3. : Suicide in patients treated for obsessive-compulsive disorder: a prospective follow-up study. J Affect Disord 124:300–308, 2010.Crossref, Google Scholar
4. : Treatment of patients with intractable obsessive-compulsive disorder with anterior capsular stimulation. Case report. J Neurosurg 98:1104–1108, 2003.Crossref, Google Scholar
5. : Distinct striatal targets in treating obsessive-compulsive disorder and major depression. J Neurosurg 111:775–779, 2009.Crossref, Google Scholar
6. : Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg 101:682–686, 2004.Crossref, Google Scholar
7. : Deep brain stimulation for OCD and major depression. Am J Psychiatry 162:2192, 2005.Google Scholar
8. : Deep brain stimulation in Tourette’s syndrome. Mov Disord 22:1346–1350, 2007.Crossref, Google Scholar
9. : Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 50:344–346, 1987.Google Scholar
10. : Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry 67:110–116, 2010.Crossref, Google Scholar
11. : Obsessive-compulsive disorder: update on assessment and treatment. J Psychiatr Pract 13:362–372, 2007.Crossref, Google Scholar
12. : Analysis of deep brain stimulation and ablative lesions in surgical treatment of movement disorders–with emphasis on safety aspects. Thesis. Umeå, Sweden: University of Umeå, April 2007.Google Scholar
13. : Are complications less common in deep brain stimulation than in ablative procedures for movement disorders? Stereotact Funct Neurosurg 84:72–81, 2006.Crossref, Google Scholar
14. : Deep brain stimulation in the treatment of depression. Acta Psychiatr Scand 123:4–11, 2011.Crossref, Google Scholar
15. : Lack of benefit of accumbens/capsular deep brain stimulation in a patient with both tics and obsessive-compulsive disorder. Neurocase 16:321–330, 2010.Crossref, Google Scholar
16. : Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders. Psychiatr Clin North Am 29:553–584, 2006.Crossref, Google Scholar
17. : Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 67:1061–1068, 2010.Crossref, Google Scholar
18. : Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report. Mov Disord 20:1496–1499, 2005.Crossref, Google Scholar
19. : Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report. Neurosurgery 57:E403, 2005.Crossref, Google Scholar
20. : Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease. Case report. J Neurosurg 100:1084–1086, 2004.Crossref, Google Scholar
21. : Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism. Science 318:1309–1312, 2007.Crossref, Google Scholar
22. : Deep-brain stimulation of the nucleus accumbens in obsessive-compulsive disorder: clinical, surgical and electrophysiological considerations in two consecutive patients. Neurol Sci 31:353–359, 2010.Crossref, Google Scholar
23. : Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases. Acta Psychiatr Scand 107:275–282, 2003.Crossref, Google Scholar
24. : Deep brain stimulation for intractable obsessive-compulsive disorder: pilot study using a blinded, staggered-onset design. Biol Psychiatry 15:535–542, 2010.Crossref, Google Scholar
25. : Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry 15:64–79, 2008.Crossref, Google Scholar
26. : Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuro-psychopharmacology 31:2384–2393, 2006.Crossref, Google Scholar
27. : Neuronal correlates of obsessions in the caudate nucleus. Biological psychiatry 63:557–562, 2008.Crossref, Google Scholar
28. : Deep brain stimulation between 1947 and 1987: the untold story. Neurosurg Focus 29:E1, 2010.Crossref, Google Scholar
29. : Gilles de la Tourette syndrome and deep brain stimulation. Eur J Neurosci 32:1128–1134, 2010.Crossref, Google Scholar
30. : High-frequency stimulation of deep brain structures in obsessive-compulsive disorder: the search for a valid circuit. Eur J Neurosci 32:1118–1127, 2010.Crossref, Google Scholar
31. : Tourette’s syndrome and deep brain stimulation. J Neurol Neurosurg Psychiatry 76:992–995, 2005.Crossref, Google Scholar
32. : Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: outcomes after one year. Clin Neurol Neurosurg 112:137–143, 2010.Crossref, Google Scholar
33. : Preliminary study in patients with obsessive-compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle. Neurosurgery 65:203–209, 2009.Crossref, Google Scholar
34. : A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery 57:585–593, 2005.Crossref, Google Scholar
35. : Neuro-modulation of the inferior thalamic peduncle for major depression and obsessive-compulsive disorder. Acta Neurochir Suppl 97:393–398, 2007.Crossref, Google Scholar
36. : American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Available at: http://www.psychiatryonline.com/pracGuide/PracticePDFs/OCDPracticeGuidelineFinal05-04-07.pdf 2007. Accessed January 20, 2012.Google Scholar
37. : Deep brain stimulation of the nucleus accumbens and the internal capsule in therapeutically refractory Tourette-syndrome. J Neurol 254:963–965, 2007.Crossref, Google Scholar
38. : Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: the search for a valid target. Neurosurgery 61:1–11, 2007.Crossref, Google Scholar
39. : Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64:461–467, 2008.Crossref, Google Scholar
40. : Functional topography of the ventral striatum and anterior limb of the internal capsule determined by electrical stimulation of awake patients. Clin Neurophysiol 120:1941–1948, 2009.Crossref, Google Scholar
41. : Compulsions, Parkinson’s disease, and stimulation. Lancet 360:1302–1304, 2002.Crossref, Google Scholar
42. : Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med 359:2121–2134, 2008.Crossref, Google Scholar
43. : Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior. Proc Natl Acad Sci U S A 104:10661–10666, 2007.Crossref, Google Scholar
44. : Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 65:267–275, 2009.Crossref, Google Scholar
45. : Smoking cessation and weight loss after chronic deep brain stimulation of the nucleus accumbens: therapeutic and research implications: case report. Neurosurgery 66:E218, 2010.Crossref, Google Scholar
46. Medtronic: Available at: http://professional.medtronic.com/interventions/deep-brain-stimulation/overview/index.htm 2010. Accessed February 15, 2012.Google Scholar
47. : Comments. Neurosurgery 65:209, 2009.Google Scholar
48. : Deep brain stimulation for obsessive-compulsive disorder: past, present, and future. Neurosurg Focus 29:E10, 2010.Crossref, Google Scholar
49. : Deep brain stimulation in the nucleus accumbens for intractable Tourette’s syndrome: follow-up report of 36 months. Biol Psychiatry 65:e5–e6, 2009.Crossref, Google Scholar
50. : Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. Lancet 354:1526, 1999.Crossref, Google Scholar
51. : Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 52:1263–1272, 2003.Crossref, Google Scholar
52. : What’s in a “smile?” Intra-operative observations of contralateral smiles induced by deep brain stimulation. Neurocase 10:271–279, 2004.Crossref, Google Scholar
53. : Internal capsule and nucleus accumbens region DBS: responses observed during active and sham programming. J Neurol Neurosurg Psychiatry 78:310–314, 2007.Crossref, Google Scholar
54. : Subthalamic neuronal firing in obsessive-compulsive disorder and Parkinson disease. Ann Neurol 69:793–802, 2011.Crossref, Google Scholar
55. : Sustained improvement of obsessive-compulsive disorder by deep brain stimulation in a woman with residual schizophrenia. Int J Neuropsychopharmacol 11:1181–1183, 2008.Crossref, Google Scholar
56. : Provocation of obsessive-compulsive symptoms: a quantitative voxel-based meta-analysis of functional neuroimaging studies. J Psychiatry Neurosci 33:405–412, 2008.Google Scholar
57. : Meta-analysis of brain volume changes in obsessive-compulsive disorder. Biol Psychiatry 65:75–83, 2009.Crossref, Google Scholar
58. : Gray matter alterations in obsessive-compulsive disorder: an anatomic likelihood estimation meta-analysis. Neuropsychopharmacology 35:686–691, 2010.Crossref, Google Scholar
59. : Capsulotomy for refractory anxiety disorders: long-term follow-up of 26 patients. Am J Psychiatry 160:513–521, 2003.Crossref, Google Scholar
60. : Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry 67:e9–e11, 2010.Crossref, Google Scholar
61. : Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am 23:563–586, 2000.Crossref, Google Scholar
62. : Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology 33:368–377, 2008.Crossref, Google Scholar
63. : Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. J Neurol Neurosurg Psychiatry 79:136–142, 2008.Crossref, Google Scholar
64. : GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities. Neurology 68:159–160, 2007.Crossref, Google Scholar
65. : Panic and fear induced by deep brain stimulation. J Neurol Neurosurg Psychiatry 77:410–412, 2006.Crossref, Google Scholar
66. : The psychological neuroscience of depression: implications for understanding effects of deep brain stimulation. Scand J Psychol 52:411–419, 2011.Crossref, Google Scholar
67. : Long-term habituation of the smile response with deep brain stimulation. Neurocase 12:191–196, 2006.Crossref, Google Scholar
68. : The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders. I Chem Neuroanat 26:293–299, 2003.Crossref, Google Scholar
69. : Brain control. New York: Wiley-Interscience; 1973.Google Scholar
70. : Comparative study of the effects of electrical stimulation in the nucleus accumbens, the mediodorsal thalamic nucleus and the bed nucleus of the stria terminalis in rats with schedule-induced polydipsia. Brain Res 1201:93–99, 2008.Crossref, Google Scholar
71. : Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders. Neurosurgery 57:439–448, 2005.Crossref, Google Scholar
72. : Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder. Clin Neurophysiol 117:320–327, 2006.Crossref, Google Scholar
73. : A meta-analysis of functional neuroimaging in obsessive-compulsive disorder. Psychiatry Res 132:69–79, 2004.Crossref, Google Scholar
74. : Deep brain stimulation for Parkinson’s disease: prevalence of adverse events and need for standardized reporting. Mov Disord 23:343–349, 2008.Crossref, Google Scholar
75. : Chronic bilateral thalamic stimulation: a new therapeutic approach in intractable Tourette syndrome. Report of three cases. J Neurosurg 99:1094–1100, 2003.Crossref, Google Scholar
76. : Deep brain stimulation of the right nucleus accumbens in a patient with Tourette syndrome. Case report. Neurol Neurochir Pol 42:554–559, 2008.Google Scholar