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Pharmacological treatment of resistant OCD

In-depth: Eric Hollander

Eric Hollander is Professor of Psychiatry and Behavioural Sciences at the Albert Einstein College of Medicine and Director of the Autism and Obsessive Compulsive Spectrum Program, and the Anxiety and Depression Program, at Montefiore Medicine and the Albert Einstein College of Medicine (New York, USA).

He served as Chair of the DSM-V Research Planning Agenda for Obsessive Compulsive Behavior Spectrum Disorders, and as a member of the DSM-V Anxiety, Obsessive-Compulsive Spectrum, Post-Traumatic and Dissociative Disorders Workgroup, and the Behavioral and Substance Addictions Workgroup. He has published more than 500 scientific publications as well as having edited 20 books.

During the 31st ECNP Congress, Professor Hollander will speak on the topic of pharmacological treatment of resistant obsessive-compulsive disorder (OCD) during an educational update session dedicated to the topic.

Hollander has contributed to the investigation of pharmacological treatment strategies in the disorder as part of a cross-sectional study of nine international OCD centres1. He has also written about current pharmacological treatment strategies alongside more recent and experimental therapies2.

In 2013 he was a contributing author on to the Manifesto for a European research network into obsessive-compulsive and related disorders3. More recently he has written about the concept of OCD recovery with a view to guiding future research and clinical practice4, as well as a report on OCD in the elderly5 and a characterisation of suicide attempters with OCD6.

In an interview with ECNP he addressed the therapeutic choices open to patients with resistant and refractory OCD, describing the considerable morbidity and socioeconomic burden that, it is hoped, will be ameliorated via the development of more personalised care.

Could you describe how the research aims and priorities for OCD have evolved, perhaps since the publications of DSM V?

The publication of DSM V was an important landmark. For the first time, OCD was taken out of the anxiety disorders category. It was clustered in a chapter of obsessive compulsive and related disorders.

This grew out of a research planning agenda that many of the people at the symposium were involved with, where we looked at the five different criteria for understanding the association between different conditions – clinical features, comorbidities, underlying brain circuitry, treatment response and family history. That was felt primarily because OCD involves dysfunction in the basal ganglia and its associated circuits, like the fronto-striatal-thalamic circuits. This differs to some extent from other anxiety disorders, where the primary driver of the symptoms are the amygdala.

Many of these other obsessive-compulsive related disorders share features with OCD, including the underlying brain circuitry, familial transmission and treatment response. These include body dysmorphic disorder (which was previously a somatoform disorder), or trichotillomania (previously an impulse control disorder) and other conditions that weren’t specifically classified such as hoarding, skin-picking or nail biting.

The same year also saw the publication of the Manifesto for a European research network3. Could you summarise the research priorities this manifesto sets out, and their drivers?

The idea was that OCD and OCD-related disorders are still a large unmet need. These are conditions that begin relatively early in life, often in childhood and adolescence. There is substantial impact of these conditions, both in terms of quality of life, disability and caregiver burden. And there are big indirect costs in terms of impairment and work-related function, and large medical costs associated with these conditions. This is one group of conditions where, if you are aware of the conditions and if you assess for it early in course of development, you are going to pick it up. If you intervene early on then patients may have a much better long-term course of illness.

OCD is a common condition that has a big impact. But if you increase awareness and you pick it up early it differs from (for example) schizophrenia, where OCD sufferers can have a much better long-term prognosis, they may function better in society and may be less of a burden as well.

Unfortunately, many patients suffer on average for about 17 years before they get specific treatments7. By that time, their symptoms are pretty engrained. Many patients may be treatment-resistant to selective serotonin reuptake inhibitors (SSRI), cognitive behavioural therapy (CBT), or a combination of these.

That brings us to the whole idea of treatment resistant and treatment refractory OCD, and there are a range of different treatment approaches here. One option are pharmacologic treatments for OCD. Then there are the neuromodulation techniques, which could include transcranial magnetic stimulation (TMS) and deep TMS (recently approved by the FDA for resistant OCD). For patients who are more refractory, surgical treatments include cingulotomy or invasive modulation techniques like deep brain stimulation (DBS).

Our network has been looking at developing sequenced treatment alternatives for individuals who come in with treatment-refractory or treatment-resistant OCD. We want to better understand how genetic markers may be of benefit in terms of determining next-step treatments for resistant OCD. Understanding more about family history and comorbidity of illness may be very important in designing next steps in terms of psychopharmacology in treatment resistant OCD. Then there are other neural modulation techniques that may be helpful. There are other, more intensive types of treatment programmes that may be of benefit to patients – either in-patient programmes or intensive partial hospital-type programmes.

The International College of OC Spectrum Disorders (ICOCS) has published a white paper on developing a network of sites around the world that are certified to be able to provide expert treatment for treatment-resistant OCD8. One of the areas that is of interest in the UK is the National OCD Service for treatment-resistant OCD9. We have been thinking about what the criteria are for considering different sites around the world. Then we have also been looking at novel and experimental treatments.

What are some of the more recent ideas that have emerged in research into treatments of OCD and OCD-related disorders?

Some of the areas that we are working in for novel and experimental treatments are looking at treatments that may be helpful for immune-inflammatory or autoimmune conditions that present with severe rigidity. We have also been looking at using some of the new cannabinoid compounds (e.g. cannabidivarin (CBDV)) to treat some of the compulsive symptoms of autism spectrum disorder.

We have also been looking at some of the rare genetic syndromes that present with severe compulsive behaviours, such as Prader-Willi syndrome, and we have been matching symptoms with treatments such as intranasal oxytocin.

It turns out that up to about 25% of patients with resistant OCD may actually have Asperger’s or high functioning autism spectrum disorder. In fact, there are new experimental psychopharmacological treatments for autism spectrum disorder that may also be applied for patients with treatment-resistant OCD.

One very important clinical decision making point is that it is essential to assess comorbidity in people with resistant OCD. It is often that the comorbid conditions may inform and guide next step treatments in these patients. They may have comorbid bipolar disorder, panic disorder, OCD, or obsessive compulsive personality disorder; understanding these might be critical in terms of next step psychopharmacologic treatment. Also assessing and understanding family history (both comorbidity and treatment response) is also very important for next step pharmacology.

Returning to the notion of centres of excellence (as described in the 2013 Manifesto for a European research network), how do you think this will impact the implementation of tailored, comprehensive treatments – pharmacological, behavioural, or otherwise? And, with regard to OCD-tailored CBT in particular, given the reported shortage of well-trained therapists within the healthcare system10,11, what role will online resources play?

CBT is a very important element for OCD and certainly for treatment-resistant OCD. The quality of the CBT that is often administered out in the community may be very different than the type of CBT that may be
delivered in specialised centres. There is some variability.

The centres of excellences for treatment-resistant OCD are those that have expert psychopharmacological treatments for both standard and resistant OCD, that can deliver high-level CBT and that have access to other kinds of modalities that may be helpful for resistant or refractory OCD – like TMS or DBS.

With regard to increasing access, delivering CBT through the internet is a big advance because that increases access to CBT and it standardises it. It maybe also drives down the cost, not only for internet-delivered CBT, but in terms of mobile apps as well. These apps are being developed to monitor compulsive behaviours as well as delivering treatment interventions. Our site and other sites have been very interested in developing this.

On the subject of developing a personalised approach – tailoring interventions with the heterogeneity of OCD in mind – what work is ongoing here?

We have been involved in a large study with a company12  where we have a commercial common gene polymorphism database of about 16,000 patients (mostly around the US) who have come in with OCD and have also had other comorbid conditions.

We have a number of gene markers that, in particular, often go along with the comorbid conditions. In addition to that, they may be helpful for next step treatment selection in treatment-resistant OCD. This may lead to the selection for the use of, for example, stimulant medications, or anticonvulsant medicines, serotonin-norepinephrine reuptake inhibitors (SNRI), and other specific treatments based on genotype. It is important to include this kind of information in designing systematic prospective studies going forward.

Professor Hollander speaks during symposium E.01: Treatment of resistant obsessive compulsive disorder, which takes place on Saturday 6 October at 16.50.


1. Van Ameringen M, Simpson W, Patterson B et al. Pharmacological treatment strategies in obsessive compulsive disorder: A cross-sectional view in nine international OCD centers. J Psychopharmacol. 2014;28(6):596-602.
2. Pallanti, S., Hollander, E. Pharmacological, experimental therapeutic, and transcranial magnetic stimulation treatments for compulsivity and impulsivity. CNS Spectr. 2014;19(1):50-61.
3. Fineberg NA, Baldwin DS, Menchon JM et al. Manifesto for a European research network into obsessive-compulsive and related disorders. Eur Neuropsychopharmacol. 2013 Jul;23(7):561-8.
4. Burchi E, Hollander E, Pallanti S. From Treatment Response to Recovery - a Realistic Goal in OCD. Int J Neuropsychopharmacol. 2018 Sep 3.
5. Dell'Osso B, Benatti B, Rodriguez CI et al. Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). Eur Psychiatry. 2017 Sep;45:36-40.
6. Dell'Osso B, Benatti B, Arici C et al. Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS). CNS Spectr. 2018 Feb;23(1):59-66.
7. Hollander E, Kwon JH, Stein DJ et al. Obsessive-compulsive and spectrum disorders: overview and quality of life issues. J Clin Psychiatry. 1996;57 Suppl 8:3-6.
8. Menchón JM, van Ameringen M, Dell'Osso B et al. Standards of care for obsessive-compulsive disorder centres. Int J Psychiatry Clin Pract. 2016 Sep;20(3):204-8.
9. Drummond LM , Fineberg NA , Heyman I et al. National service for adolescents and adults with severe obsessive–compulsive and body dysmorphic disorders. Psychiatr. Bull. 2008 Sep;32:333-6.
10. Abramowitz, J. S., Blakey, S. M., Reuman, L., & Buchholz, J. L. New Directions in the Cognitive-Behavioral Treatment of OCD: Theory, Research, and Practice. Behavior Therapy. 2018;49(3):311-22.
11. Patel SR, Wheaton MG, Andersson E et al. Acceptability, Feasibility, and Effectiveness of Internet-Based Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in New York. Behav Ther. 2018 Jul;49(4):631-641.
12. Genomind. (accessed Sep 2018).
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