A Synergistic Treatment Strategy for Severe Obsessive Compulsive Disorder

To the Editor: Deep brain stimulation (DBS) revolutionized the treatment of movement disorders such as Parkinson’s disease and is emerging into a promising tool as therapy for psychiatric disorders. Although DBS has been approved by the Food and Drug Administration (FDA) and the European authorities for treatment-resistant obsessive-compulsive disorder (OCD) for more than 4 years, its application still is controversial (1) and regarded with suspicion. National as well as international guidelines for OCD are rather reluctant to implement DBS, which is, if at all, recommended in the context of controlled clinical trials only (2). Indeed, scientific studies, including larger sample sizes, are definitely needed to tackle the still unsolved questions of response prediction or to determine the mechanisms of action underlying the therapeutic effects of DBS. Yet, large effect sizes (3) and meta-analytical results (4,5) underline that DBS constitutes a valid option for a subgroup of severely affected and treatment-resistant OCDpatients. Therefore, we advocate the extended integration of DBS into the overall therapeutic concept and propose a sequential approach based on the neurobiological underpinnings of OCD. OCD is amongst the most common and disabling mental disorders worldwide (6). It is characterized by recurrent and intrusive thoughts and/or repetitive behaviors that are time consuming, cause remarkable distress and often are perceived as inappropriate by the patient who, most often unsuccessfully tries to resist (7). International guidelines agree on cognitive behavioral therapy (CBT) being the first line treatment for OCD (2), thereby focusing on the exposure to anxiety-inducing situations while at the same time preventing the engagement in fear relieving compulsions (8). In more severe cases, or for patients suffering predominantly from obsessions or comorbid depressive symptoms, CBT should be combined with pharmacological interventions. The efficacy of serotonin reuptake inhibitors (SSRI) and clomipramine is well established in the treatment of OCD. SSRIs usually show a higher tolerability and are therefore given priority. If treatment response is unsatisfactory an augmentation with atypical antipsychotics or dual medications as venlafaxine should be considered (9). These therapeutic strategies are based on different concepts of the pathogenesis of OCD. Even though studies have shown, that CBT also influences the neurobiological substrate of OCD (10,11), it primarily addresses the psychological aspects via behavioral alterations and deconditioning, whereas pharmacotherapy aims to modulate neurobiological or neurochemical aspects of OCD in the first place. These different approaches are not contradictory but complementary. Typically OCD manifests in the second or third decade of life and often takes a chronic persistent course. Particularly early onset manifestations may support the idea of OCD being predominantly a neurodevelopmental disorder. Support for this assumption comes from structural imaging longitudinal studies showing neurodevelopmental abnormalities in cortico-striatal areas that play a crucial role in the pathogenesis of OCD (12,13). The reason for these structural impairments might not be fully explained by a delayed maturation theory. Next to this, indications for a neurobiological substrate of OCD can also be extracted from lesion studies reporting development of obsessive-compulsive symptoms following basal ganglia lesions (14). Since some patients neither respond to CBT nor pharmacotherapy, and therefore, remain severely affected (tr-OCD), the question arises whether these patients are characterized by a particular biological component. Obviously, standardized criteria for treatment response (15) have to be evaluated thoroughly to rule out a “pseudo-resistance” (16), which could be the case if, for instance, the number of CBT sessions is sufficient, but CBT was not conducted according to the guidelines. In contrast to these “pseudo-resistant” patients, a substantial group of patients remains severely affected; a circumstance referred to as “real” treatment-resistant (17). However, there is indeed evidence for a correlation between symptom severity and certain neurobiological peculiarities. For example, imaging data suggests that altered fronto-striatal connectivity correlates with symptom severity in unmedicated patients (18). Supposing that tr-OCD is based on a distinct or exclusive neurobiological impairment, biological procedures such as DBS may be of high relevance. The introduction of DBS by Benabid in the mid1980s marked the beginning of a whole new era of therapy for movement disorders (12). Owing to its high evidence-based efficacy, this procedure has, in the meantime, been applied to more than 130,000 patients with Parkinson’s disease worldwide. The DBS procedure involves the implantation of quadripolar electrodes that continuously emit short, high-frequency, low-voltage electrical pulses to the ambient neural tissue of subcortical brain regions after they have been connected to an implanted impulse generator. Despite many years of experience, the precise mode of action of DBS remains unclear. It is assumed that DBS functionally overwrites pathological hyperactivity in disturbed networks (13,14). In the context of OCD a milestone has been reached by a publication of Figee et al., who showed that DBS resulted not only in the reduction of hyperconnectivity in frontostriatal networks but also in a clinical