Clinical Effectiveness of Quetiapine in Children with Tourette's Syndrome

Abstract and Introduction

Background and Objective: Tourette's syndrome is a relatively common biological genetic disorder with a broad spectrum of neurobehavioural manifestations. Unfortunately, treatment of the condition is often unsatisfactory and all available drugs are associated with potential adverse effects. We therefore aimed to investigate the efficacy of quetiapine, a newer atypical antipsychotic, in the treatment of children and adolescents with Tourette's syndrome.
Methods:This was a retrospective study carried out in outpatient clinics. Twelve patients aged 8-18 years with Tourette's syndrome (diagnosed according to Diagnostic and Statistical Manual IV criteria) who were receiving quetiapine therapy and had no diagnosis of epilepsy, major depression or psychotic disorder, were included in the study. The main outcome measure was the Yale Global Tic Severity Scale (YGTSS) score.
Results: The initial dose of quetiapine was 25 mg/day, but the mean dose was increased to 114.6 ± 51.6 mg/day and 175.0 ± 116.8 mg/day at the fourth and eighth weeks of treatment, respectively. The YGTSS score, which was 21.6 ± 4.0 at baseline, showed significant decreases at 4 and 8 weeks (reducing to 7.5 ± 7.4 and 5.6 ± 8.1, respectively; p < 0.003). Routine laboratory parameters and serum prolactin level were all normal and did not change throughout treatment. Mild but significant increases in both bodyweight and body mass index at 4 and 8 weeks compared with baseline were observed.
Conclusion: Other than causing mild weight gain, quetiapine appears to be an effective, safe and well tolerated drug in children and adolescents with Tourette's syndrome.

Tourette's syndrome is a relatively common biological genetic disorder with a broad spectrum of neurobehavioural manifestations that fluctuate in severity and frequency, and which vary markedly from one individual to another, often contributing to misdiagnoses.^[1] According to the Diagnostic and Statistical Manual IV (DSM-IV-TR), Tourette's syndrome is characterised by the following: multiple motor and one or more vocal tics, not due to substances or medical conditions; duration >1 year; and onset at age <18 years.^[2] Since a large proportion of individuals with Tourette's syndrome remain undiagnosed, making a correct diagnosis is particularly important and should be considered the first step in management.

There is a consensus that Tourette's syndrome occurs in about 0.5% of school-age children.^[3,4,5,6,7] The disorder generally begins between 3 and 8 years of age and often persists throughout life with weekly or monthly remissions. In most cases, the frequency, severity and type of symptoms subside or even disappear in adolescence and adulthood.^[2]

Drugs used in the treatment of patients with Tourette's syndrome include dopamine receptor antagonists (antipsychotics), CNS stimulants, selective serotonin reuptake inhibitors (SSRIs), nicotinergic drugs^[8,9] and other serotoninergic drugs, including buspirone.^[10]

In a large international study of 3500 individuals from 22 countries diagnosed with Tourette's syndrome, behavioural problems were associated with attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive behaviour, depression, anxiety, self-injurious behaviour, aggression, rage, learning disorders, conduct and oppositional behaviour.^[1] Similar results have also been reported in other studies.^[11,12] These co-morbid behavioural conditions often interfere with functioning and with school and work performance to a greater extent than the tics. Indeed, the majority of patients experience mild to moderate tics; extreme tic severity is rare and, in some patients, the behavioural manifestations are more severe than the tics. Therefore, Tourette's syndrome is often called a neuropsychiatric disorder as well as a spectrum disorder.^[13]

Treatment of Tourette's syndrome is often unsatisfactory. All available drugs are associated with potential adverse effects. Thus, drug therapy is usually limited to those patients in whom symptoms cause impairment. However, not only severe tics are functionally disabling; milder tics can also cause psychosocial problems, such as loss of self-esteem or difficulty in participating in work and social activities.^[13]

Classes of medication used in the treatment of patients with Tourette's syndrome include conventional antipsychotic agents. However, studies suggest that the prevalence of extrapyramidal symptoms is lower in children treated with atypical anti-psychotics than in those given drugs such as haloperidol and pimozide, CNS stimulants or SSRIs. Nevertheless, antipsychotics are usually associated with the occurrence of extrapyramidal adverse events and other adverse effects such as sedation, depression, weight gain, school phobia and hepatotoxicity.^[14] Over the last few years, various atypical antipsychotics have been developed for the treatment of neuropsychiatric disorders. Their profile of potent antagonism at specific serotonin and dopamine receptors offers certain advantages compared with typical antipsychotics, and they have been shown to have superior safety and similar efficacy profiles to conventional antipsychotics.^[15,16]

The newer atypical antipsychotic drugs have also demonstrated potential in the treatment of Tourette's syndrome. For example, risperidone and clozapine have been found to reduce tic severity with mild to moderate adverse events in children and adolescents with Tourette's syndrome.^{[17,18,19,20,21,22]} Furthermore, a recent study by Mukaddes and Abali investigating the short-term safety and effectiveness of quetiapine suggests that quetiapine may be effective in reducing motor and phonic tics in children and adolescents diagnosed with Tourette's syndrome.^[23] A significant reduction in Yale Global Tic Severity Scale (YGTSS) scores has been reported in two studies: the first of these was a 15-case study with risperidone^[24] and the second one a study in which 21 cases diagnosed as Tourette's disorder were treated with risperidone and clonidine.^[25] Another case series in which olanzapine was used also showed that olanzapine may be an effective treatment for aggression and tics in children with Tourette's syndrome.^[26]

In light of these findings, the present study was conducted to investigate the efficacy of an atypical antipsychotic drug, quetiapine, in the treatment of children and adolescents with Tourette's syndrome.

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