Emerging treatments

Neurosurgery

Ablative neurosurgery (anterior capsulotomy, limbic leucotomy, cingulotomy, and gamma knife radiosurgery) are procedures that are not US 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.[53][55] 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 side effects, although the review authors caution that it be reserved for only the most treatment-refractory cases.[113]

Transcranial magnetic stimulation (TMS)

TMS uses magnetic fields to stimulate neurons in the brain, mostly targeting the presupplementary motor area, the dorsolateral prefrontal cortex, and the anterior cingulate. It was approved by the FDA for the treatment of OCD in 2018.[114] Approval was based on the findings of a randomised placebo-controlled trial, in which 99 participants with OCD were allocated to either TMS or sham treatment.[115] Response rates (defined as ≥30% in Yale-Brown Obsessive Compulsive Scale [YBOCS] score) were significantly greater with TMS (38.1%) versus sham treatment (11.1%).[115] The most common adverse event in both treatment groups was headache.[115] In clinical practice, TMS may be most beneficial in resistant forms of OCD, especially when used in combination with pharmacological therapy.

Deep brain stimulation (DBS)

DBS offers several important advantages over traditional lesioning procedures. Its effects are reversible and it is minimally invasive.[116] It has also been shown to be effective and tolerable in the long-term (mean follow-up 6.8 years).[117] 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.[116][118][119][120][121][122][123] A systematic review has suggested that the strongest evidence exists for the use of bilateral subthalamic nuclei as target, and that there is insufficient evidence to recommend the use of unilateral DBS in medically refractory OCD patients.[124] The UK National Institute of Health and Care Excellence (NICE) recommend that DBS for chronic, severe treatment-resistant OCD in adults should only be used in a research context due to inadequate evidence on both the efficacy and safety.[125]

Venlafaxine

Active comparator trials and open-label studies support efficacy in OCD.[37]​​​​​​​[42]​[126] One might consider switching non-responders to venlafaxine, but it should be noted that there is conflicting evidence for this strategy and at least one study reported that venlafaxine was less effective than paroxetine when previous treatment with other selective serotonin-reuptake inhibitors (SSRIs) had failed.[53][55][127][128][129]

Augmentation with 5-HT3 antagonist 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 as serotonin reuptake inhibitor augmentation in treatment-resistant patients.[130][131]

Augmentation with dextroamfetamine and caffeine

A possible explanation for the mechanism of this therapeutic effect could be that the increased release of dopamine induced by both drugs may increase D1 receptor stimulation in the pre-frontal cortex, increasing ability to shift attention away from obsessions, and thus decreasing urges to perform compulsions. Both caffeine and dextroamfetamine were effective in treatment-resistant patients in a double-blind placebo-controlled trial.[132]

Augmentation with opioids

Causes an alteration of the glutamatergic tone of the corticostriatal pathway. One double-blind crossover study demonstrated that adding morphine, with or without other augmenting agents, was superior to placebo.[133]

Augmentation with topiramate

Causes an alteration of the glutamatergic tone of the corticostriatal pathway. One case report suggested that topiramate augmentation was effective.[134] However, a double-blind, placebo-controlled trial of topiramate augmentation in OCD-resistant patients suggested that topiramate may be beneficial only for compulsions, and not for obsessions.[135]

Augmentation with riluzole

Causes an alteration of the glutamatergic tone of the corticostriatal pathway. An open-label trial showed efficacy of riluzole augmentation.[136]

Augmentation with mirtazapine

It should also be noted that augmentation with mirtazapine has been shown to accelerate selective serotonin-reuptake inhibitor (SSRI) response and to be an effective treatment for OCD.[137][138] Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition.

Augmentation with benzodiazepines, gabapentin, or buspirone

May be useful when residual symptoms are related to severe anxiety.[139][140]

Augmentation with naltrexone

May be helpful when intensive grooming behaviours are present.

D-cycloserine augmented exposure therapy

May lead to more rapid response to exposure treatment,[141] although studies have found no difference in treatment outcome with D-cycloserine augmentation in either adult or paediatric patients.[142][143] In a study that examined whether antidepressant status influenced response to D-cycloserine-augmented exposure therapy in the treatment of OCD, the authors found that patients who were not on antidepressants were more likely to achieve remission than those who were.[144]

Aqueous extract of Echium amoenum

An initial study indicates that this substance is efficacious in reducing obsessions and compulsions without side effects.[145]

Celecoxib

There is an increasing focus on the neuroinflammatory component of OCD as a means of therapeutic targeting.[146][147] Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor non-steroidal anti-inflammatory drug (NSAID) that prevents COX enzymes from catalysing the formation of prostanoids. Preliminary evidence suggests that the anti-inflammatory effects of celecoxib may help modulate the behavioural symptoms of OCD when used alone in or in combination with selective serotonin-reuptake inhibitors.[148][149] Clinical trials in individuals with OCD remain ongoing.[150]

Computer-aided psychotherapy

Computer-aided psychotherapy is a promising emerging area of research in the psychotherapeutic treatment of anxiety disorders.[151] It may prove to be particularly useful in rural areas where trained clinical psychologists are not available.[152] However one randomised controlled trial looking at adults with moderate to severe OCD, who were already on the waiting list to receive therapist-led cognitive behavioural 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 symptoms, although further research is needed to determine its efficacy for patients with milder symptoms.[153]

Cognitive behavioural therapy (CBT) plus motivational interviewing

Motivational interviewing is a widely used psychotherapeutic technique used to increase motivation for behavioural change. When used in conjunction with CBT for OCD, children between the ages of 6 and 17 in a family-based OCD treatment required an average of three fewer therapy sessions to achieve the same outcomes as those in CBT alone.[154] Two sessions of motivational interviewing (with an additional thought mapping technique) has also been a useful adjunct to standard CBT in adults with OCD.[155][156] 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.[157]

Family-based cognitive behavioural therapy (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 aged 5 to 8 years.[158]

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 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 exposure and response prevention in reducing Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores.[159]

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

This is an intervention with the mothers of children with OCD. It was found to be helpful with decreasing OCD symptoms in children and increasing quality of life for both mother and child.[160]

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.[161]

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