Clinical Effectiveness of Quetiapine in Children and Adolescents with Tourette's Syndrome

Mazlum Copur1; Baki Arpaci2; Turkay Demir1; Halis Narin3

Disclosures

Clin Drug Invest. 2007;27(2):123-130. 

In This Article

Discussion

During the last few years, several atypical anti- psychotics have been developed to reduce the risk of extrapyramidal symptoms. These drugs are characterised by antagonism of both serotonergic 5-HT2 receptors and, at higher doses, dopamine D2 receptors.[34]

It has been stated that quetiapine is not a potent D2-blocking agent,[34,35,36] and there is evidence that it is effective in tic suppression and is better tolerated in some patients than typical antipsychotics.

Studies have reported efficacy for atypical anti- psychotics in chronic tic and Tourette disorders[22,24,37] as well as in schizophrenia, bipolar mania and depression, schizoaffective disorder, delusional disorder, agitated delirium and dementia.[33,35,36,38,39,40] Quetiapine is an atypical antipsychotic (dibenzothiazepine derivative) that has been indicated for the management of patients with psychotic disorders.

In a study of adolescents (aged 12.3-15.9 years) with DSM-IV-defined chronic or intermittent psychotic disorder, patients received quetiapine twice daily starting at 25mg and reaching 400mg by day 20.[41] No unexpected adverse effects or clinically important changes in haematology or clinical chemistry variables were recorded. The most commonly reported adverse events were postural tachycardia and insomnia. Consistent with other studies of quetiapine in children and adolescents, it appears that the drug was less likely to induce extrapyramidal symptoms.[41,42] Clinical observations and standardised rating scales suggest that this drug is also beneficial in patients with tics.[21,23] Parraga and Woodward described two children with Tourette's syndrome who responded favourably to quetiapine at doses of up to 150 mg/day.[43]

In this study, we evaluated the records of 12 patients >18 years of age to determine the efficacy of quetiapine in the treatment of Tourette's syndrome. The initial dose in these patients was quetiapine 25 mg/day. The dose was then increased to 175 mg/day at week 8 of therapy according to patient efficacy and tolerability. The Y-BOCS scores of these patients revealed that they did not have an obsessive-compulsive disorder. The CTRS-28 (rated by teachers) and the ADHDS score (rated by parents) demonstrated the presence of mild to moderate hyperactivity. In this study, the efficacy of quetiapine as a means of reducing tics was observed, but no effect on ADHD was evident. However, the objective of the study was to evaluate the efficacy of quetiapine in relation to tics.

Quetiapine treatment did not alter laboratory findings compared with baseline values. Although it is known that all conventional and some atypical antipsychotics (e.g. risperidone) increase serum prolactin levels,[23] we did not observe hyperprolactinaemia during treatment with quetiapine.

Although their profile of potent antagonism at specific 5-HT and dopamine receptors offers certain advantages compared with typical antipsychotics, atypical antipsychotics are reported to cause significant weight gain.[42] In this study, we observed gains of approximately 3% in bodyweight and BMI during quetiapine treatment. The patients had gained a mean of 1.4kg in weight by the fourth week and a mean of 2.1kg by the eighth week. A recent retrospective study of quetiapine in children and adolescents demonstrated a mean weight gain of 0.03kg and a mean increase in BMI of 0.2 kg/m2.[44] Published data suggest that clozapine and olanzapine are associated with considerable weight gain, whereas risperidone and quetiapine have a moderate risk.[45] After 10 weeks of treatment, clozapine, olanzapine, risperidone and ziprasidone were associated with weight gains of 4.45kg, 4.15kg, 2.10kg and 0.04kg, respectively.[46] A review of data from short-term clinical trials with the atypical antipsychotics risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole showed that a higher percentage of patients who received olanzapine experienced weight gain than patients who received any of the other atypical antipsychotics.[47] Risperidone has a lesser effect on weight, associated with a mean weight gain of 2.6kg in 1200 patients treated for 30 weeks,[48] and quetiapine is weight-neutral in long-term treatment, as shown by data from 427 patients treated with quetiapine.[49] Thus, these data suggest that weight gain with quetiapine is lower than with other atypical antipsychotics.

In this study, the efficacy of quetiapine was evaluated by comparing YGTSS scores during treatment with those at baseline. Measurement of YGTSS scores during treatment showed that quetiapine caused a marked improvement in tic severity. The severity of motor tics improved by 66.1% and 73.2% at weeks 4 and 8, respectively, and that of phonic tics by 62.5% and 75%, respectively. More-over, the improvements in total tic severity score by 65.3% and 74.1% with quetiapine treatment at weeks 4 and 8 revealed that tic severity was more improved at week 8 than at week 4. In a study by Lee et al., the YGTSS score was 66.8 ± 10.8 at baseline and improved to a mean of 73.1 ± 10.1 after 6 weeks of treatment with risperidone.[24]

This study has certain limitations that should be recognised. As a retrospective study, the study results depend on hospital records, where evaluation of the data might be limited. Furthermore, being an open-label study, it lacks a control group, which again might limit the evidence status of the study.

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