Approach

OCD had been considered a treatment-resistant disorder for years. Effective treatments have become available only in the past two decades. According to international guidelines, two major approaches to treatment are considered first-choice options: drug treatment with selective serotonin-reuptake inhibitors (SSRIs) or the tricyclic antidepressant clomipramine, and cognitive behavioural therapy (CBT) in the form of exposure and response prevention. However, up to 40% of patients fail to benefit from these first-line treatments.[48][49][50][51][52]

Goals of therapy

The main goal of treatment for OCD patients is a full recovery, indicating an almost complete and objective disappearance of symptoms, corresponding to a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of 8 or below. Remission, on the other hand, indicates a response in which symptoms are reduced to a minimal level, with a Y-BOCS score of 16 or less. Based on this definition, patients in remission are usually not eligible to be included in clinical trials, as their Y-BOCS score is below the minimum score that is generally used as a criterion for participation in a study. Because recovery generally occurs only in the more episodic form of OCD, remission should be considered an adequate term to define the most successful outcome in the non-episodic form of OCD. Both recovery and remission should be considered high levels of response to treatment. Such levels of response are fairly rare, as treatment response is generally considered to be a reduction of at least 35% of the Y-BOCS score or a clinical global impression (CGI) score of 1 or 2.

Mild to moderate symptoms

Patients with mild to moderate symptoms are classified based on a Y-BOCS score of 8 to 23. Initial treatment consists of CBT (if available) or initiation of pharmacotherapy.

  • CBT alone in the form of exposure and response prevention is recommended as first-line treatment for patients with symptoms that are not severe.[53][54][55]

  • Pharmacotherapy alone is recommended when CBT is unavailable, when the patient prefers drug treatment alone, or when the patient has a history of responding well to a particular agent.[53][55]

The type of psychotherapy with the best evidence for the treatment of OCD is CBT in the form of exposure and response prevention (ERP).[53][55][56] In ERP, a graded hierarchy of symptom triggers is created with each patient. The therapist then encourages the patient to expose him- or herself to the trigger (e.g., dirt). The patient is then encouraged to refrain from engaging in compulsive rituals (e.g., hand washing). As symptoms begin to improve, more intense triggers are targeted. In addition, homework assignments focus on exposure to stimuli in naturalistic settings such as the home. A meta-analysis has provided further evidence that CBT is effective in patients with OCD.[57] CBT interventions can also be successfully implemented in a group therapy format .[58][59] There is no evidence to support the use of psychodynamic psychotherapy in the treatment of OCD.[53][55][60]

Drugs indicated for the treatment of OCD include clomipramine (a serotonin-specific tricyclic antidepressant) or an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, or sertraline). Numerous studies have assessed the efficacy of SSRIs for this indication.[61][62][63][64] The controlled-release preparation of fluvoxamine has also been studied for OCD in adults.[65][66] SSRIs have also been studied for anxiety disorders in children and adolescents.[67] Evidence is emerging for the effectiveness of escitalopram in OCD. In an open-label study escitalopram was shown to be effective, and in the second phase of the study it was significantly more effective than placebo in preventing relapse of OCD symptoms.[68] Caution is advised, however, when using escitalopram, due to its association with QT interval prolongation. Special caution is advised in those over 60 years of age or in those who have pre-existing potential for QTc prolongation or arrhythmias either due to inherent disease or due to other concomitant medications.[55][69]

Clomipramine is generally less well tolerated than SSRIs; therefore, an SSRI is recommended as the initial pharmacological treatment of choice.[53][55][70] In choosing a particular SSRI, factors that should be considered include the individual side effect profiles of each agent, potential drug-drug interactions, comorbid medical conditions, patient age, and past treatment response.[53][55][71] Children who have been prescribed SSRIs should be monitored closely for possible changes in suicidal ideation.[71] Initial research suggests that patients successfully treated with SSRIs could avoid symptom relapse with continued pharmacotherapy.[72] The results of one systematic review and meta-analysis of 28 studies suggest that in patients with anxiety disorders (including OCD) who respond to treatment with antidepressants, treatment for at least a year is associated with reduced rates of relapse, and is well tolerated. The studies included in the meta-analysis had a treatment duration of up to a year only, and so no evidence was available on the efficacy and tolerability of treatment beyond this point; this lack of evidence after this period should not be interpreted as explicit advice to discontinue antidepressants after one year, however.[73]

Severe symptoms, unresponsive to monotherapy, or patients with comorbid personality disorders or dissociative symptoms

Patients with severe symptoms are classified based on a Y-BOCS score of 24 to 40.

Combined treatment with CBT and pharmacotherapy should be considered when OCD symptoms are severe. Drug treatment may alleviate symptoms to the extent that the patient may then be able to engage in CBT.[53][55] In addition, combined treatment should be a first choice when patients have comorbid psychiatric illnesses such as depression, and combined treatment should be offered to patients with mild to moderate symptoms who do not respond to monotherapy.[74] The application of CBT as an augmentation strategy may be particularly helpful for patients with comorbid personality disorders or dissociative symptoms.[75][76] Promising CBT treatments are being developed for individuals with comorbid depression and OCD.[77]

Inadequate resonse to initial pharmacotherapy

The first step in the case of a partial responder (25% to 35% reduction in Y-BOCS score) at the sixth to eighth week of treatment should be to increase the dose of the current medication.

At 12 weeks, if a patient has exhibited a partial response to an agent, one might prefer to utilise augmentation strategies instead of switching to a different drug. For this, three augmentation strategies exist:

  • Increasing medication to the highest tolerable dose

  • Combination regimens (e.g., an SSRI plus antipsychotic medication, or an SSRI plus clomipramine)

  • Use of intravenous citalopram or clomipramine; however, these formulations are not available in general clinical settings in the US. Caution is advised when using citalopram, due to its association with QT interval prolongation. Special caution is advised in those over 60 years of age or in those who have pre-existing potential for QTc prolongation or arrhythmias either due to inherent disease or due to other concomitant medications.[55][69][78]

Patients with no response (<25% reduction in Y-BOCS score; CGI 4), as well as partial responders to initial SSRI treatment, may benefit from the addition of a second pharmacological agent.[79] Although initial treatment most often enhances serotonergic transmission, in employing augmentation strategies one may target other neurotransmitter systems. The most frequently employed strategy utilises antidopaminergic agents.

  • Evidence exists for a combination of fluoxetine and clomipramine in patients who do not respond to fluoxetine alone.[80]

  • Evidence exists for the efficacy of haloperidol, risperidone, and aripiprazole augmentation.[81][82][83][84][85][86][87]

  • Evidence supporting the efficacy of quetiapine and olanzapine is weaker.[88][89]

  • Risperidone can be particularly helpful in patients with poor insight.

  • Weaker evidence also exists for augmentation with pimozide.[90][91][92]

Unfortunately, only one third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. The addition of second-generation anti-psychotics is associated with less tolerability.[86][93]

Additional considerations here include a meta-analysis that found that when SRIs are continued at appropriate doses for a full 12 weeks, 25% more patients will respond who would otherwise have switched to antipsychotic augmentation before 12 weeks.[88]

In addition, a study comparing CBT (consisting of exposure and ritual prevention) augmentation and risperidone augmentation against placebo found that those in the CBT group had significantly greater reductions on Y-BOCS scores than those in either the placebo or risperidone groups. The study also found no significant difference in response rates between those in the risperidone and placebo groups.[94]

Identifying non-responders

Adequate trials are considered to be 12-week trials of at least moderate doses of the chosen drug. Not uncommonly, the maximally tolerated dose must be achieved before patients find them helpful.[25] Up to 40% to 60% of patients do not have a satisfactory response to first-line medication treatment at 12 weeks.[95][96][97][98][99][100][101][102]

If patients have not achieved at least a 25% reduction in Y-BOCS score or a 4 on the CGI scale after 12 weeks at full dose, switching to a different drug is recommended, as patients may respond to one drug better than another.[53][55] However, one should keep in mind that there is also evidence suggesting that patients who failed to respond to the initial drug may be less likely than treatment-naive patients to respond to further trials of other drugs.[103]

The label 'treatment-resistant' is generally used to describe patients who have not responded to at least two adequate trials of clomipramine or SSRI (at least 12 weeks). After trials with clomipramine and at least two SSRIs, with augmentation using CBT, a patient may be classified as a non-responder.

Further evaluation of non-responders

It should be noted that, given the variability of symptoms among non-responders, the management of these cases should be dictated by the specific clinical situation; treatment guidelines should be used only as a general roadmap. At this point, referral to a consultant may be warranted, as the selection of second-line therapy may vary widely depending on comorbidities or prevalent features in the individual patient's OCD symptomatology. Rarely, cases may be related to an organic cause: for example, neurodegenerative processes, post-stroke OCD phenomena, hypothyroidism, or other so-called 'acquired' forms of OCD that can occur as a result of Huntington's disease, Sydenham's chorea, rheumatic fever, bacterial or viral infection, or encephalitis. The characteristics of the residual clinical features should guide the choice of further treatment.

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