Treatment-Resistant and Treatment-Refractory Obsessive Compulsive Disorder

Obsessive compulsive disorder (OCD) is defined as a complex, chronic, and often debilitating neuropyschiatric illness which is characterized by intrusive and disturbing thoughts (obsessions) and repetitive behaviors that a person feels driven to perform (compulsions) in order to combat the anxiety associated with their obsessions. This mental illness, which used to be categorized as a type of anxiety disorder, affects roughly 2.3% of the adult American population, and it has been treated for years with therapy and/or medications such as the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and the tricyclic antidepressant (TCA) clomipramine. But what happens when this disorder cannot be controlled by westernized medication or therapy alone? Studies have shown that as many as 60% of people diagnosed with and treated for OCD do not experience a strong enough response to treatment for their quality of life to be considered significantly improved. This article seeks to provide information on treatment-resistant and treatment-refractory OCD, as well as suggest coping mechanisms which have been shown to be beneficial for these types of OCD.

What makes OCD Treatment Resistant or Treatment Refractory?

Although the terms treatment resistant and treatment refractory are often used interchangeably, they refer to different levels of unresponsiveness to treatment. In obsessive compulsive disorder, treatment resistance refers to a failure to respond or to see significant improvement in OCD symptoms after two adequate trials with SRIs, a category of medications which includes the SSRIs and TCAs briefly mentioned above. An adequate trial is commonly considered to be a 12-week trial period of an SRI in at least moderate doses, so in order to be considered treatment-resistant, a person with OCD must have been on at least two different medications for a total of six months or more. This differs from a diagnosis of treatment-refractory OCD, which comes with a much longer trial time. Typically, a diagnosis of treatment-refractory OCD is not given until a person has tried at least three different SRIs at maximum dosage for at least 3–6 months each, has undergone therapy while on a “therapeutic dose” of an SRI, and has received at least two atypical anti-psychotics (such as risperidone and quetiapine) as augmenters in addition to behavioral therapy and another SRI. This process can take up to a few years to complete, but people often overlook the behavioral therapy requirement when trying to get a diagnosis of treatment-refractory OCD, making the process even longer.

Before continuing, it should be clarified that this article speaks of treatment resistance or refractoriness in terms of non-response to medications commonly thought to treat OCD, not in terms of non-response to CBT. While I did come across some studies which found CBT of little use to those with resistant and refractory OCD, there was enough evidence to support that CBT could be used to decrease symptoms and improve quality of life to include it as a possible solution. This article will cover ways to cope with both treatment-resistant and treatment-refractory obsessive compulsive disorder with respect to medication unresponsiveness and CBT responsiveness.

Why don’t Medications Work for Treatment-Refractory OCD?

Because treatment-resistant obsessive compulsive disorder is characterized by the failure of only two trials of medication, it wouldn’t be appropriate to say that this form of treatment doesn’t work; the person with the treatment-resistant form may just not have had the correct medication or combination of medications to ease their symptoms. However, this is not the case with treatment-refractory OCD. The people with this form of OCD have gone through enough medication trails to know that their illness is not treatable via pharmacotherapy, but they may not be aware of the reasons behind this phenomena.

[Discussion of the neurobiology of treatment-refractory OCD is under construction.]

How Can Treatment-Resistant and Treatment-Refractory OCD be Managed?

There are several ways to cope with treatment-resistant and treatment-refractory obsessive compulsive disorder, several of which utilize invasive techniques. The four techniques for managing resistant and refractory OCD suggested here are minimally invasive or do minimal damage to brain tissue if they are invasive. Embedded below is an infographic which provides an abridged version of the four coping mechanisms that will be covered in the remainder of this article.

1. Cognitive Behavioral Therapy & Exposure and Response Prevention

Although cognitive behavioral therapy (CBT) is one of the first line treatments for obsessive compulsive disorder, it has also been shown to have positive effects on both treatment-resistant and treatment-refractory OCD. There are several types of therapy which fall under the category of CBT, but exposure and response prevention therapy has been found to work best for those with obsessive compulsive disorder.

Exposure and response prevention, also known as ERP or exposure therapy, works by a process of habituation. In exposure therapy, a person with OCD will gradually be exposed to the thoughts, images, objects, and situations that make him or her anxious and/or cause his or her obsessions. Under the guidance of a therapist, the person undergoing ERP makes a conscious commitment not to give into and engage in compulsive behaviors. Over time, this program leads to habituation, or a decreased emotional response, to the things which originally caused intense anxiety. While traditional talk therapy can be useful for some people with OCD, ERP tends to be more helpful because it faces the person’s sources of anxiety directly as opposed to discussing the anxiety sources in order to gain insight into the disorder. However, ERP is not for the faint of heart, because exposure sessions can often include tasks which would even make those without OCD uncomfortable.

One major benefit of ERP is that it can be as effective for resistant and refractory OCD as the TCA cloipramine is for more treatable forms of the disorder. A 2005 study published in The American Journal of Psychiatry which consisted of one of the largest randomized, placebo-controlled trials of OCD treatments to date, found that after 12 weeks, 86% of participants responded well to ERP, while only 48% of those in the clomipramine group saw significant improvements in their symptoms. This study suggests that even if a person with OCD does not have a resistant or refractory form of the disorder, they should consider beginning their path to remission with exposure therapy, as it has a higher success rate and minimal side effects when compared to popular medications.

A lesser-examined result of exposure therapy is its ability to improve engagement in the external world. In an article published in the Journal of Clinical Psychiatry in 2015, the effectiveness of ERP on OCD in medication non-responders was examined. In this study, participants received up to 17 twice-weekly 90-minute sessions delivered by therapists who were trained in exposure and response prevention therapy, and participants who received ten or more of these sessions were designated treatment completers. The study found that, along with reduced OCD symptoms, participants made significant increases in social functioning. This could mean that because ERP works to eliminate sources of anxiety from a person’s life, the person may be more able to participate in daily activity and in society as a result of successful treatment.

2. Mindfulness

Mindfulness is a state of active, open awareness which allows a person to be fully present but also prevents them from overreacting to or being overwhelmed by their experiences. Practicing mindfulness has been shown to help with mental illness and is often associated with reductions in anxiety and stress levels.

One key aspect of mindfulness which is beneficial to those with treatment-resistant or treatment-refractory OCD is the change in relationship to thoughts that can occur. Cognitive distortions related to OCD, which consist of maladaptive thought patterns that lead to higher feelings of responsibility and guilt, are traditionally targeted though therapy techniques such as Socratic questioning. However, with appropriate practice of mindfulness, cognitive distortions such as thought-action fusion can be managed fairly well without such therapy techniques. The addition of mindfulness to a person’s routine has the potential to cultivate an attitude of nonjudgmentality. This attitude would allow the person to view all thoughts — even those that are generally thought of as intrusive — in a more open and accepting way, potentially discouraging thought suppression, increasing the likelihood of habituation toward obsessions, and decreasing reliance on compulsions for anxiety relief.

Self-regulation — or internally driven regulation of behavior, cognition, and emotion — is another important component of mindfulness with respect to OCD management. This component of mindfulness allows the person to have greater insight into their behaviors, which leads to this person making more thoughtful and voluntary decisions as opposed to making the reactive or impulsive decisions typically associated with compulsive behavior. Self-regulation can also help to decrease anxiety levels in those with OCD because they practice emotion regulation, a task which decreases a person’s reactivity to stressful events or objects and increases their tolerance for negative stimuli.

3. Deep Brain Stimulation

Deep brain stimulation (DBS) is a type of neurosurgery that is commonly used to treat neurological symptoms, especially those associated with movement and pain dysfunction. However, this procedure can be used for far more than the alleviation of symptoms associated with irregular movement or somatosensory functioning. Research has shown that deep brain stimulation can be an effective method for regulating obsessive-compulsive symptoms in those with treatment-resistant and treatment-refractory OCD.

DBS works via the implantation of tiny metal electrodes into a target area of the brain. These electrodes are attached to a computerized pulse generator, also called a neurostimulator, which lies just under the skin in the chest area of the patient. A programming computer held near the skin covering the neurostimulator is used to adjust the settings of the electrodes in order to best control the patient’s symptoms. Unlike other forms of neurosurgery, deep brain stimulation does not damage healthy brain tissue. Instead, the electrodes placed on the head alter abnormal brain functioning.

A 2015 meta-analysis of deep brain stimulation for obsessive compulsive disorder discussed the findings of thirty-one studies which examined the effects of DBS on severe treatment-resistant OCD. For the purposes of this article, the phrase “severe treatment-resistant OCD” will be taken to mean a type of resistance in between regular treatment resistance and treatment refractoriness. Twenty-four of the studies examined in this meta-analysis pointed to DBS being most effective in the “striatal areas,” which include the anterior limb of the internal capsule (ALIC), the ventral capsule and ventral striatum (VC/VS), the nucleus accumbens (NA) and the ventral caudate nucleus. For all studies, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to track severity of symptoms before and after exposure to DBS. In this scale, a higher score indicates that a person’s symptoms are more severe, and a low score indicates that the person is close to “normal” functioning. Overall, the meta-analysis found that there was a global percentage of Y-BOCS score reduction of 45.1%, and roughly 60% of the participants were considered responders (people whose scores had improved by more than 35%). These percentages show that deep brain stimulation should be considered an adequate treatment for resistant and refractory OCD, as neurosurgeries such as cingulotomy and capsulotomy have 56% and 64% response rates respectively and are generally more prone to causing adverse side effects.

4. Cannabidiol

Cannabidiol (CBD) is one of the main non-psychoactive cannabinoids of the cannabis sativa plant. CBD is known to have antipsychotic and anxiolytic effects, both of which may prove useful for the treatment of obsessive compulsive disorder. Although there is not a substantial amount of information regarding cannabidiol’s effects on mental health — mainly due to government restrictions that impede research on medicinal marijuana and its chemical constituents — several studies that have been conducted on the effects of cannabidiol on obsessive compulsive disorder or related disorders show promise.

One animal model of obsessive compulsive disorder published in Fundamental and Clinical Pharmacology in 2013 examined the role of cannabidiol in compulsion regulation. Mice were injected with mCPP, a nonspecific serotonergic agonist which reportedly increases OCD symptoms and blocks the anticompulsive effects of SRI medications. They were then subjected to a marble-burying test to determine their levels of compulsivity; more marbles buried indicated that a mouse had a higher level of compulsivity. Mice given doses of cannabidiol to combat the effects of mCPP were found to bury less marbles for up to 7 days after acute dosing, indicating that the mice behaved less compulsively when given CBD. The results of this study suggest that cannabidiol may be useful for the development of anticompulsive treatments.

In addition to this study, a review published in Neurotherapeutics in 2015 examined cannabidiol’s potential as a treatment for anxiety-related disorders which, in this case, included OCD. The authors found that acute dosing of CBD can be used to alleviate symptoms of OCD. Acute dosing was defined as repeated doses of CBD for less than 20 days; chronic dosing was defined as repeated doses for 21 or more days. This review prompts further study to determine the effects of chronic dosing of CBD in the treatment of anxiety disorders and obsessive compulsive disorder, as substantial evidence for its efficacy was not provided in the studies that were analyzed.

More research must be done in this field to provide a certain answer regarding whether CBD is an effective treatment for any form of obsessive compulsive disorder, but the studies that have been conducted on animal models of OCD and on the anxiolytic and antipsychotic effects of CBD indicate that cannabidiol may eventually become an approved method for treating OCD.


Although resistant and refractory forms of obsessive compulsive disorder are much more difficult to treat than their medication-responsive counterpart, there is still hope for remission. The coping strategies discussed above are just a few of several strategies that are used to combat OCD, and research is ongoing to find out what works best for each form of this disorder. If you believe that you or a loved one may have undiagnosed or untreated obsessive compulsive disorder, it is best to consult your primary care physician or a mental health expert before trying the strategies above, specifically deep brain stimulation and cannabidiol.