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. |
When patients have been included in more than 1 publication, data are only provided for 1 of these reports. DBS, deep brain stimulation; OCD, obsessive-compulsive disorder; VC/VS, ventral internal capsule/ventral striatum; ICH, intracerebral hemorrhage; YBOCS, Yale-Brown Obsessive Compulsive Scale; IC, internal capsule; NA, nucleus accumbens; NC, nucleus caudatus; STN, subthalamic nucleus.
| 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 |
When multiple publications exist regarding the same patients, only 1 has been included here. DBS, deep brain stimulation; OCD, obsessive-compulsive disorder; VC/VS, ventral internal capsule/ventral striatum; NA, nucleus accumbens; STN, subthalamic nucleus; ITP: inferior thalamic peduncle; AC, anterior commissure; IC, internal capsule; ICL, intercommissural line; PC, posterior commissure; YBOCS, Yale-Brown Obsessive Compulsive Scale; HDRS, Hamilton Depression Rating Scale; HAMA, Hamilton Anxiety Scale; GAF, Global Assessment of Function Scale: SDSS, Sheehan Disability Scale score.
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.
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