Obsessive-compulsive disorder - Emerging treatments

Neurosurgery

Ablative neurosurgery (anterior capsulotomy, limbic leucotomy, cingulotomy, and gamma knife radiosurgery) are procedures that are not Food and Drug Administration (FDA)-approved and are reserved for patients with severe, treatment-refractory OCD who have been unresponsive to first- and second-line treatments, including augmentation strategies.[56][63] The most commonly used neurosurgical intervention in recent times has been cingulotomy, a procedure that involves bilateral lesioning of the cingulate gyrus. In a review of stereotactic cingulotomy, cingulotomy was recommended as a safe procedure with limited adverse effects, although the review authors caution that it be reserved for only the most treatment-refractory cases.[128]

Deep brain stimulation (DBS)

DBS offers several important advantages over traditional lesioning procedures. Its effects are reversible and it is minimally invasive.[129] It has also been shown to be effective and tolerable in the long-term (mean follow-up, 6.8 years).[130] Sites targeted in studies have included the anterior limbs of the internal capsule bilaterally, the shell region of the right nucleus accumbens, the subthalamic nucleus, and the ventral caudate nucleus.[129][131][132][133][134][135][136] A systematic review has suggested that the strongest evidence exists for the use of bilateral subthalamic nuclei as a target, and that there is insufficient evidence to recommend the use of unilateral DBS in medically refractory patients with OCD.[137] The UK National Institute of Health and Care Excellence (NICE) recommends that DBS for chronic, severe treatment-resistant OCD in adults should only be used in a research context because of inadequate evidence for both efficacy and safety.[138]

Venlafaxine

Active comparator trials and open-label studies support the efficacy of venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), in OCD.[139][140][141] Nonresponders could be switched to venlafaxine, but there is conflicting evidence for this strategy and at least one study reported that venlafaxine was less effective than paroxetine if previous treatment with other selective serotonin-reuptake inhibitors (SSRIs) had failed.[56][63][139][140][141]

Augmentation with ondansetron

A possible mechanism of this agent’s anti-obsessional efficacy involves dopaminergic inhibition by 5-HT3 receptor blockade. One single-blind and one double-blind placebo-controlled trial showed the efficacy of ondansetron in combination with SSRIs in treatment-resistant patients.[142][143]

Augmentation with dextroamphetamine and caffeine

The increased release of dopamine induced by both dextroamphetamine and caffeine might increase D1 receptor stimulation in the prefrontal cortex, increasing the ability to shift attention away from obsessions, and thus decreasing urges to perform compulsions. Both caffeine and dextroamphetamine added after an adequate SSRI or SNRI trial were effective in treatment-resistant patients in a double-blind, placebo-controlled trial.[144]

Augmentation with opioids

Opioids alter the glutamatergic tone of the corticostriatal pathway. One double-blind crossover study demonstrated that adding morphine, with or without other augmenting agents, to treatment with SSRIs was superior to placebo in reducing symptoms in some treatment-resistant patients with OCD.[145]

Augmentation with topiramate

Topiramate alters the glutamatergic tone of the corticostriatal pathway. One case report suggested that augmentation of SSRI treatment with topiramate might be effective in improving OCD symptom severity in patients with treatment-resistant OCD.[146] However, a more recent double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant patients with OCD suggested that topiramate may be beneficial only for treatment of compulsions and not for treatment of obsessions.[147]

Augmentation with riluzole

Riluzole alters the glutamatergic tone of the corticostriatal pathway. An open-label trial showed significant efficacy of augmentation of existing pharmacotherapy with riluzole in treatment-resistant OCD.[148]

Augmentation with mirtazapine

Mirtazapine augmentation of SSRI treatment has been shown not only to be an effective pharmacotherapy for OCD, but also to accelerate the treatment response.[149][150] Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition.

Augmentation with buspirone

Augmentation with buspirone may be useful if residual symptoms are related to severe anxiety.[151][152]

Augmentation with naltrexone

Augmentation with naltrexone may be helpful if intensive grooming behaviors are present.

Cycloserine augmented exposure therapy

Augmentation of exposure and response prevention (ERP) with cycloserine may lead to a more rapid response to exposure treatment, although studies have found no difference in treatment outcome with cycloserine augmentation in either adult or pediatric patients.[153][154][155][156][157] In a study that examined whether antidepressant status influenced the response to cycloserine-augmented ERP in the treatment of OCD, patients who were not on antidepressants were more likely to achieve remission than those who were.[158]

Aqueous extract of Echium amoenum

An initial study indicates that Echium amoenum is efficacious in reducing obsessions and compulsions without adverse effects.[159]

Celecoxib

There is an increasing focus on the neuroinflammatory component of OCD as a means of therapeutic targeting.[35][25] Celecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor that prevents COX enzymes from catalyzing the formation of prostanoids. Preliminary evidence suggests that the anti-inflammatory effects of celecoxib may help modulate the behavioral symptoms of OCD if used alone in or in combination with SSRIs.[160][161] Clinical trials in individuals with OCD are ongoing.[162]

Computer-aided psychotherapy

Computer-aided psychotherapy is a promising emerging area of research in the psychotherapeutic treatment of anxiety disorders.[163] It may prove to be particularly useful in rural areas, in which trained clinical psychologists are not available.[164] However, one randomized controlled trial that included adults with moderate to severe OCD, who were already on the waiting list to receive therapist-led cognitive behavioral therapy (CBT), found that offering people book-based or computer-based CBT, together with phone support from a "psychological wellbeing practitioner", did not improve their obsessive compulsive symptoms after 3 or 12 months. This suggests that book-based and computer-based CBT is unlikely to be an effective strategy in patients with moderate to severe OCD symptoms, although further research is needed to determine its efficacy for patients with milder OCD symptoms.[165][166]

CBT plus motivational interviewing

Motivational interviewing is a widely used psychotherapeutic technique to increase motivation for behavior change. If used in conjunction with CBT for OCD, children between the ages of 6 and 17 years in a family-based OCD treatment required an average of three fewer therapy sessions to achieve the same outcomes as those receiving CBT alone.[167] Two sessions of motivational interviewing (with an additional thought-mapping technique) have also been a useful adjunct to standard CBT in adults with OCD.[168][169] Although there have been some promising results, at least one study did not find that an additional motivational interviewing component improved adherence or treatment outcome.[170]

Family-based CBT

Family-based CBT has also been examined for the treatment of OCD and was found to be superior to relaxation for the reduction of OCD symptoms and functional impairment in children ages 5 to 8 years.[171]

Inference-based CBT

In contrast to ERP, inference-based CBT focuses on adjusting cognitions upstream and, if successful, may eliminate the need for exposure work. Early evidence suggests inference-based CBT is effective and may be an alternative treatment option for those with OCD.[172]

Satiation therapy

In satiation therapy, individuals are instructed to increase their engagement with obsessions and compulsions, effectively doubling or tripling the amount that they think about their obsession and engage in their rituals. The goal is to reduce the pleasure in engaging in OCD symptoms, leading to their reduction. In one study in Iranian males, satiation therapy was found to be as effective as ERP in reducing Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores.[173]

Quality of life therapy (parenting intervention for mothers of children with OCD)

This is an intervention for mothers of children with OCD. It was found to be helpful in decreasing OCD symptoms in children and increasing quality of life for both mother and child.[174]

Third wave therapies

Third wave therapies include mindfulness and acceptance and commitment therapy (ACT). Studies evaluating the efficacy of third wave therapies in people with OCD have been small, with methodological limitations; further research is required.[175][176][177]

Augmentation with memantine

Memantine augmentation of first-line pharmacotherapy for moderate to severe OCD is effective after 8 weeks, while being well tolerated and with only mild and transient adverse effects.[178]