Clomipramine—a nonselective tricyclic—was the first medication studied in treating OCD in children and adolescents. It is now usually considered only after two or three failed SSRI trials because of its potential for cardiac toxicity.15-17
Table 3
Suggested dosages (mg/d) for drug therapy of pediatric OCD
| Drug | Usual starting dosage | Approximate mean dosage* | Typical range | Usual maximum dosage |
|---|---|---|---|---|
| Citalopram | 20 | 40 | 20 to 60 | 80 |
| Clomipramine | 50 | 150 | 200 | 300 |
| Escitalopram | 5 | 10 | 10 to 20 | 30 |
| Fluoxetine | 20 | 40 | 40 to 60 | 80 |
| Fluvoxamine | 50 | 175 | 150 to 250 | 300 |
| Sertraline | 50 | 125 | 150 | 225 |
| *Mean dosage derived from registration trials, expert recommendation, and the authors’ clinical experience | ||||
Dosing. Fixed-dose studies suggest that dosing schedules for OCD are similar to those used for depression. For example, sertraline, 50 mg/d, or fluoxetine, 20 mg/d, are as effective as higher dosages.18
The common misconception that OCD requires higher dosages likely results from:
- increasing the dosage too early in the time-response window for a drug effect to emerge
- giving medication without concomitant exposure therapy.19
Delayed response. Although many patients respond early to an SSRI, others do not respond until 8 or even 12 weeks of treatment at therapeutic dosages. It often takes 3 to 4 weeks for evidence of benefit to emerge, so wait at least 3 weeks between dosage increases. Maintain therapeutic dosages at least 6 to 8 weeks before changing agents or beginning augmentation therapy.
Two-barrel approach.
In treating Adam, we began with sertraline, using a flexible titration schedule keyed to whether he experienced OCD symptom remission.
The starting dosage of 50 mg was titrated to 150 mg over 8 weeks while he was receiving behavioral therapy. We made adjustments with a time-response window of 2 to 3 weeks, allowing us to observe a response to each dosage escalation.
Adam’s OCD symptoms responded well to CBT plus sertraline. The maximum drug effect helped him confront the most difficult EX/RP tasks at the top of his stimulus hierarchy, which he attacked near the end of treatment.
Lessons learned. Multicenter trials have taught important lessons about drug therapy for OCD:
- OCD patients experience little or no placebo effect, unlike patients with depression.
- Clinical effects may appear as early as 2 to 3 weeks after medications are started and plateau at 10 to 12 weeks.
- Partial response is the rule; SSRIs reduce OCD symptoms by about 30%—which correlates with “moderately” to “markedly” improved ratings on patient satisfaction measures.
- Side effects and magnitude of improvement are comparable in pediatric and adult medication trials.
Acute-onset OCD may be bacterial
In some children, OCD or tic symptoms arise from or are exacerbated by group A beta hemolytic streptococcal infection (GABHS), which has been labeled pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS).21 Obsessive-compulsive symptoms are not uncommon in pediatric patients with Sydenham’s chorea, a neurologic variant of rheumatic fever. OCD is far more common in patients with rheumatic fever when chorea is present.
Acute-onset or dramatic exacerbation of OCD or tic symptoms should prompt investigation of GABHS infection. Immunomodulatory treatments—including antibiotics, plasmapheresis, or IV immunoglobulin G—may benefit some patients.22
MANAGING RESISTANT OCD
Adequate SSRI monotherapy trials fail to relieve OCD symptoms in one-third of patients. Some patients benefit from combination therapy—such as an SSRI plus risperidone—especially when comorbid schizotypal personality disorder or a tic-spectrum disorder is present.
Drug switching or augmentation trials often produce only partial response and cause unnecessary suffering. A more effective strategy for many patients is to augment drug treatment with CBT until symptoms normalize.
On the other hand, augmentation is appropriate when nonresponse or partial response to SSRI monotherapy leaves a patient clinically symptomatic and functionally impaired. Clonazepam, clomipramine, and the amino acid L-tryptophan have been used successfully. Lithium and buspirone also have been tried but seem not to be effective in controlled studies in adults and anecdotal experience in youth.
When augmenting an SSRI, adding clomipramine, 25 to 50 mg/d, is a reasonable choice. However, fluoxetine or paroxetine can inhibit clomipramine metabolism by cytochrome P-450 (CYP) 2D6, with potential for cardiac arrhythmias or seizures. Sertraline or fluvoxamine are less likely to elevate clomipramine levels.20 Fluvoxamine may be the most compatible SSRI with clomipramine because it inhibits CYP 1A2—the enzyme that demethylates clomipramine to its inactive desmethyl metabolite—thereby preserving more of the active parent compound.
Clinical evidence suggests that augmentation’s success may depend in part on a patient’s comorbidities. For example, clonazepam may be particularly helpful for children with comorbid panic symptoms.
MAINTENANCE THERAPY
We typically provide 14 weekly CBT sessions, followed by monthly contacts for a few months to ensure than a patient’s gains are maintained. Standard procedure with drug therapy is to continue maintenance treatment for up to 1 year, although some have suggested continuing maintenance treatment indefinitely.