Approach

Effective treatments have become available only in the past two decades. 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 behavioral therapy (CBT) in the form of exposure and response prevention (ERP). However, up to 40% of patients fail to benefit from these first-line treatments.[57][58][59][60][61]

Goals of therapy

The main goal of treatment for patients with obsessive-compulsive disorder (OCD) 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, by contrast, 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 ineligible for inclusion in clinical trials, because their Y-BOCS score is below the minimum score that is generally used as a criterion for participation in a study. Because recovery generally only occurs in the more episodic form of OCD, remission should be considered an adequate term to define the most successful outcome in the nonepisodic 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 as such on the basis of 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 ERP, is recommended as first-line treatment for patients with symptoms that are not severe.[56][62][63]

  • Pharmacotherapy alone is recommended if CBT is unavailable, the patient prefers drug treatment alone, or the patient has a history of responding well to a particular agent.[56][63]

The type of psychotherapy with the best evidence for the treatment of OCD is CBT, in the form of ERP.[56][63][64][65]​​​ In ERP, a graded hierarchy of symptom triggers is created with each patient. The therapist 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.[66] CBT interventions can also be successfully implemented in a group therapy format.[67][68]​​ There is no evidence to support the use of psychodynamic psychotherapy in the treatment of OCD.[56][63][69]

Drugs indicated for the treatment of OCD include clomipramine (a serotonin-specific tricyclic antidepressant) or an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline). Numerous studies have assessed the efficacy of SSRIs for this indication.[70][71][72][73]​ The controlled-release preparation of fluvoxamine has also been studied for OCD in adults.[74][75]​ SSRIs have also been studied for anxiety disorders in children and adolescents.[76] 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.[77] Caution is advised, however, if using escitalopram, because of its association with QT interval prolongation. Special caution is advised in those over 60 years of age or who have preexisting potential for QTc prolongation or arrhythmias, either due to inherent disease or due to other concomitant drugs.[63][78]

Clomipramine is generally less well tolerated than SSRIs; therefore, an SSRI is recommended as the initial pharmacologic treatment of choice.[56][63][79]​​ In choosing a particular SSRI, factors that should be considered include the individual adverse effect profiles of each agent, potential drug-drug interactions, comorbid medical conditions, patient age, and past treatment response.[56][63][80]​​ Children who have been prescribed SSRIs should be monitored closely for possible suicidal ideation.[80]  SSRIs are typically used at higher doses (the maximum recommended dose or maximum tolerated dose) and for longer periods (more than 12 weeks) to treat OCD than depression.[26][81][82]​ Initial research suggests that patients successfully treated with SSRIs could avoid symptom relapse with continued pharmacotherapy.[83] 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 1 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 1 year only, and so no evidence was available on the efficacy and tolerability of treatment beyond this point; this lack of evidence after a period of 1 year should not be interpreted as explicit advice to discontinue antidepressants after 1 year, however.[84]

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

Patients with severe symptoms are classified as such on the basis of a Y-BOCS score of 24 to 40.

Combined treatment with CBT and pharmacotherapy should be considered if OCD symptoms are severe. Drug treatment may alleviate symptoms to the extent that the patient may then be able to engage in CBT.[56][63] 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.[85] The application of CBT as an augmentation strategy may be particularly helpful for patients with comorbid personality disorders or dissociative symptoms.[86][87] Promising CBT treatments are being developed for individuals with comorbid depression and OCD.[88]

Inadequate response 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 drug.

At 12 weeks, if a patient has exhibited a partial response to an agent, augmentation strategies might be preferred to switching to a different drug. For this, three augmentation strategies exist:

  • Increasing the dose of the drug (sometimes to the highest tolerable dose beyond that which is licensed).

  • Combination regimens (e.g., an SSRI plus an antipsychotic, 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 if using citalopram, because of its association with QT interval prolongation. Special caution is advised in those over 60 years of age or who have preexisting potential for QTc prolongation or arrhythmias either due to inherent disease or due to other concomitant drugs.[63][78][89]

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 pharmacologic agent.[90] Although initial treatment most often enhances serotonergic transmission, other neurotransmitter systems may be targeted by augmentation strategies. The most frequently employed strategy utilizes antidopaminergic agents.

  • Evidence exists for a combination of fluoxetine and clomipramine in patients who do not respond to fluoxetine alone.[91]

  • Evidence exists for the efficacy of haloperidol, risperidone, and aripiprazole augmentation.[92][93][94][95][96][97][98]

  • Evidence supporting the efficacy of quetiapine and olanzapine is weaker.[99][100]

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

  • Weaker evidence also exists for augmentation with pimozide.[101][102][103]

Unfortunately, only one third of treatment-refractory patients with OCD show a meaningful treatment response to antipsychotic augmentation. The addition of second-generation antipsychotics is associated with less tolerability.[97][104]

Additional considerations here include a meta-analysis that found that when SSRIs 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.[99]

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.[105]

Transcranial magnetic stimulation (TMS), a form of noninvasive brain stimulation (NIBS), uses magnetic fields to stimulate neurons in the brain, and enhance neuroplasticity, mostly targeting the presupplementary motor area, the dorsolateral prefrontal cortex, and the anterior cingulate.[31][32][33][34]​​ Because TMS is an intervention that includes different patterns and locations of stimulation, treatment can be tailored to each individual’s underlying pathophysiology. It was approved in the US for the treatment of OCD in 2018.[106]​ Approval was based on the findings of a randomized placebo-controlled trial, in which 99 participants with OCD were allocated to either TMS or sham treatment.[107]​ Response rates (defined as ≥30% in Y-BOCS score) were significantly greater with TMS (38.1%) versus sham treatment (11.1%).[107]​ The most common adverse effect in both treatment groups was headache.[107]​ The study showed that treatment with TMS is safe and effective in improving OCD symptoms in patients unsuccessfully treated with CBT or SSRIs and should be considered after the first treatment failure (whether CBT or pharmacotherapy) in both mild to moderate and severe cases. In clinical practice, TMS may be most beneficial in resistant forms of OCD, especially if used in combination with pharmacologic therapy.[108][109]​​​ Concurrent CBT targets the same dysfunctional neural circuitry as TMS, enhancing neuroplasticity in the targeted neural circuit to improve outcomes.[110]

Identifying nonresponders

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.[26] Up to 40% to 60% of patients do not have a satisfactory response to first-line drug treatment at 12 weeks.[111][112][113][114][115][116][117][118]

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, because patients may respond to one drug better than another.[56][63]​ However, 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.[119]

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

Further evaluation of nonresponders

Given the variability of symptoms among nonresponders, the management of these cases should be dictated by the specific clinical situation; treatment guidelines should only be used as a general roadmap. At this point, referral to a specialist may be warranted because the selection of a 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, poststroke OCD phenomena, hypothyroidism, or other so-called "acquired" forms of OCD that can occur as a result of Huntington disease, Sydenham 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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