Psychopharmacological treatment

Several randomized controlled clinical trials of pharmacological agents have been conducted in children and adolescents with OCD, demonstrating, as many more similar studies with adult patients, the selective and unique efficacy of SRIs (clomipramine, fluoxetine, sertraline) in the short-term treatment of the disorder; a few open studies have given preliminary positive results for other selective serotonin reuptake inhibitors ( SSRIs) (fluvoxamine, citalopram, paroxetine). The design and main results of these studies are summarized in Tab.l§...3.. Overall, it appears that:

Table 3 Percentage improvement from baseline on obsessive-compulsive symptoms measures during short-term pharmacological treatment of children and adolescents with OCD

1. the anti-obsessional effect is independent of the presence of depressive symptoms at baseline;

2. it takes longer to appear than the antidepressant effect;

3. the therapeutic response occurs gradually over a few weeks or a few months;

4. the final response is most often incomplete, with a mean reduction from baseline on scales measuring intensity of obsessive- compulsive symptoms between 20 and 44 per cent across measures and across studies.

A commonly used rating scale for measuring severity and change in OCD is the Children's Yale-Brown Obsessive-Compulsive Scale. (52)

Practice parameters for the assessment and treatment of children and adolescents with OCD(61> can be summarized as follows.

1. An adequate therapeutic trial of clomipramine generally consists of dosages up to 3 mg/kg/day for 3 months. Anticholinergic side-effects, typical of tricyclic antidepressants, might be dry mouth, somnolence, dizziness, tremor, headache, constipation, stomach ache, sweating, and insomnia. Risks of toxicity include seizures and ECG changes (ECG monitoring is recommended).

2. Initial studies suggest that the SSRIs are safe, effective, and well tolerated in children and adolescents, with a side-effect profile similar to that seen in adults. Although there are differences between them, the most common described side-effects include nausea, headache, tremor, gastrointestinal complaints, drowsiness, insomnia, akathisia, disinhibition, agitation, and hypomania.

3. Systematic dose-response data are not available for children, but side-effects generally appear dose-dependent. It is therefore recommended to start with a low dosage that is increased slowly up to the minimum dose found effective in adult patients (fluoxetine, 20 mg/day; sertraline, 50 mg/day; citalopram, 20 mg/day; paroxetine, 40 mg/day; no fixed-dose studies for fluvoxamine), although much higher doses have been used in published studies ( Tabje.,3).

4. Despite differences in potency and selectivity, it is not known whether one SRI is more effective than another for treating childhood OCD. If there is no clinical response after 10 to 12 weeks of treatment with one SRI, switching to another is reasonable.

5. The optimal duration of maintenance treatment is unclear, since relapses are frequent when discontinuing medication. Anti-obsessional medication should be maintained for at least 12 to 18 months after a satisfactory response has been obtained. Once the decision is made to attempt reduction or discontinuation, the tapering should be gradual.

In Tourette's disorder, the relatively selective D 2-receptor antagonists have consistently been shown to be effective in 80 to 90 per cent of patients, with at least 50 per cent reduction of tic severity.(62> Haloperidol has been used since the 1960s, but most patients discontinue their treatment because of emergent side-effects. In a placebo-controlled crossover study, Sallee et al.(63) evaluated the efficacy and safety of pimozide and haloperidol in 22 subjects aged 7 to 16 years. At equivalent dose, pimozide was superior to haloperidol for controlling tics, and haloperidol exhibited a threefold higher frequency of serious side-effects. In addition to the usual side-effects of neuroleptics, pimozide may cause ECG changes. The usual starting dose is 0.25 mg/day of haloperidol or 1 mg/day of pimozide. Increments (0.5 mg haloperidol or 1 mg pimozide) may be added at 7 to 14 days intervals, and daily dosages of 0.5 to 6 mg haloperidol, or 1 to 10 mg pimozide over a period of 4 to 8 weeks generally lead to adequate control of tic symptoms, which will often continue to wax and wane at a much lower level.

The a2-adrenergic receptor agonist clonidine may be effective for a proportion of Tourette's disorder subjects, presumably via acute and chronic downstream effects on dopamine. Clinical trials indicate an average 25 to 35 per cent reduction in symptoms over an 8- to 12-week period. (64> Clonidine seems especially useful in improving attentional problems and ameliorating complex motor tics. Treatment must be started at low dose (0.05 mg in the morning), and slowly increased to 0.15 to 0.3 mg in several doses throughout the day. The major side-effects of clonidine are sedation, hypotension, dizziness, and a decrease of salivatory flow.

For children and adolescents with OCD and comorbid tic disorder, SSRIs alone might have little anti-obsessional effect and there are reports suggesting that fluvoxamine and fluoxetine may exacerbate or even induce tics in some patients. In adults, a personal or family history of chronic tic disorder has been associated with a positive response to haloperidol augmentation of fluvoxamine. (65> For children and adolescents with OCD and comorbid tic disorder, combined treatment with an SSRI and a low dose of a dopamine antagonist is recommended.

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