Preferential Serotonergic Reuptake Inhibitors
Preferential serotonergic reuptake inhibitors (PSRIs), the medications most effective in treating OCD, mainly inhibit there uptake of serotonin into nerve cells. These medications include clomipramine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine. Medications with noradrenergic reuptake inhibition produce no benefit and may counteract or diminish the efficacy of serotonergic reuptake inhibition. Among the PSRIs, clomipramine alone is a tricyclic antidepressant and has significant anticholinergic, antihistaminic, and anti--adrenergic side effects. Clomipramine is also metabolized to desmethyl clomipramine, a metabolite that will inhibit the uptake of noradrenaline. Meta-analyses of efficacy suggest that clomipramine may be more effective than other PSRIs in treating OCD; however, there is no direct evidence that any one of the PSRIs is more effective than any other. Except in the case of fluvoxamine, each of the multicenter trials for PSRIs showed nonsignificant trends for higher doses to be more effective in treating OCD, suggesting that the optimal doses for these medications may be at the higher end of the permissible prescription range.
While PSRIs exert their main effects in depression after 3–6 weeks of treatment, in OCD they must be administered for up to 12 weeks to determine their full range of benefits. Withdrawal from medication is frequently associated with relapse within 2–3 weeks; patients need, therefore, be advised to stay on their medication to prevent relapse. Tolerance to the beneficial effects of PSRIs rarely occurs.
If a patient has no response to medication after 8 weeks, or has an inadequate response after 12 weeks, the clinician should consider trying a different PSRI. Approximately 20% of patients who do not respond to one PSRI will respond to another. If the patient has not responded to a second PSRI, a third PSRI trial should be attempted. One of the three PSRI trials should involve clomipramine.
If a patient does not achieve an adequate response with proper trials of PSRIs, a second medication should be added. The combination of an SSRI and clomipramine should be considered first in this context. The combination of clomipramine and fluvoxamine may significantly augment serotonin uptake inhibition because fluvoxamine can inhibit the conversion of clomipramine to its noradrenergic desmethyl metabolite. Alternatively, low-dose, high-potency neuroleptics (e.g., risperidone, olanzapine, ziprasidone, aripiprazole, pimozide, haloperidol) may be used to augment PSRI treatment, particularly if the patient has comorbid tics, a family history of tics, or features of a schizotypal personality disorder. OCD symptoms in the latter group of patients can be refractory to conventional treatments, but show a response to augmentation with a neuroleptic. For patients whose OCD has a significant anxiety component, patients with a history of seizures, and patients with additional symptoms consistent with partial complex seizures, the addition of clonazepam (0.5–6 mg) should be considered. Clonazepam can also be considered as an adjunct to high-dose clomipramine treatment (greater than 250 mg daily) as a means of reducing the potential for seizures. Both low-dose neuroleptics and clonazepam should be added after the patient has been taking the optimal PSRI for at least 6–8 weeks and is on the maximal dose tolerated. These adjuncts may have beneficial effects within 1 week; however, an adequate adjunctive trial should be 4–6 weeks. Other medications that have been used as adjunctive treatments include tryptophan, pindolol plus tryptophan, mirtazapine, gabapentin, and fenfluramine. Lithium, buspirone, and pindolol appear to have little benefit as augmenting agents in the treatment of OCD.
Behavioral therapy for OCD involves exposure and response prevention. According to learning theorists, patients with OCD have learned an inappropriate active avoidance response to anxiety associated with circumstances that trigger their OCD symptoms. The clinician must encourage the patient to experience the aversive condition (exposure) without performing the compulsion (response prevention). Chronic exposure alone will reduce the anxiety associated with the exposure, but the compulsions will remain if not specifically restricted. Response prevention is critical. Typically, the individual is asked to hierarchally order his or her fears. A decision is then made as to which obsessive–compulsive dyad will be addressed. The patient is exposed by increasing degrees to the feared stimulus and is prohibited from carrying out the compulsive behavior. Anxiety with initial exposure is usually intense and enduring; however, with repeated exposure, the intensity and duration decrease. When it is not possible to expose the patient in the office, the therapist may accompany the patient to a location, such as the home or the street, where the feared stimuli are more prevalent. In an outpatient session the patient is typically instructed to repeatedly expose himself or herself to a specified set of circumstances on a proscribed number of occasions as "homework" between sessions. The patient should be encouraged to assess or question the validity of his or her obsessive thoughts as an adjunct to treatment. Such a cognitive approach may increase compliance, and when no compulsions are present, or when exposure is impractical, it may be the primary adjunct to treatment. In other cases, exposure to the actual fear (e.g., killing ones child) is not practicable, and the patient must engage in imaginal exposure. Typically, the therapist and patient will work on one symptom complex until the symptom has been reduced to an agreeable level or until a joint decision is made to address another symptom.
Behavioral therapy is effective in roughly 70% of individuals who agree to undergo the process. However, approximately 30% of individuals with OCD will decline this form of treatment. Behavioral therapy may be better tolerated if the patient has appropriate pharmacologic treatment.
Neurosurgery is the treatment of last resort. Neurosurgical procedures include bilateral cingulotomy, limbic leukotomy, anterior capsulotomy, and subcaudate tractotomy. Estimates of clinically significant improvement range from 25% to 90%, although controlled studies have not been undertaken. There is some disagreement regarding the optimal site of the lesion. In intractable cases, however, neurosurgery is a treatment that may offer relief from disabling symptoms and from extreme psychic pain. Improvement after surgery is not immediate but may occur over a period of up to 1 year. Adverse effects include seizures, disinhibition syndromes, and the attendant risks of general anesthesia.
Patients should not be referred for surgery unless they have had full trials of at least three PSRIs at appropriate dosages, including one trial of clomipramine, as well as trials of both a neuroleptic and clonazepam as adjunctive medications. A trial of an MAOI should have been attempted. The patient should have had a course of behavioral therapy with a qualified therapist, preferably occurring while the patient was receiving optimal pharmacologic treatment. Additionally, the OCD or its complications should have life-threatening consequences for the patient or cause extreme dysfunction or severe psychic pain. Patients should be referred to centers that have stringent presurgical entrance criteria and extensive experience with this treatment modality.