Risperidone Treatment in a Case of Tourette Syndrome with Factor V Leiden Heterozygous Mutation

Abstract

To The Editor:

Tourette syndrome is a neuropsychiatric disorder with an age of onset <18 years. Symptoms are characterized by chronicity, and comprise sudden, quick, involuntary, repetitive, and rhythmic motor and vocal tics. Tourette syndrome is diagnosed by the existence of multiple motor and vocal tics for >1 year, even if they do not occur together. Symptoms may become more severe over time and may cause explicit functional losses (American Psychiatric Association 1994). Additionally, an associated disorder such as obsessive-compulsive disorder or attention-deficit/hyperactivity disorder is often diagnosed. Even though a significant role of family history has been detected in patterns of tics, the specific hereditary mechanism remains uncertain (Singer 2000). Patients diagnosed with head trauma, drug use, neurodegenerative diseases, movement disorders, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) should be evaluated for a differential diagnosis of Tourette syndrome (Singer 2000). For treatment, antipsychotic agents, psychotherapy, and neurosurgical approaches are often used (Cavanna and Termine 2012).

The factor V Leiden (FVL) mutation is one of the most common genetic polymorphisms, along with the G20210A mutation, causing a first episode of venous thromboembolism (VTE) (Marchiori et al. 2007). Several studies and case reports have indicated that psychiatric patients diagnosed with VTE mostly receive low-potency conventional antipsychotics (Zornberg and Jick 2000; Hägg and Spigset 2002). Additionally, two recent publications have suggested that VTE may be associated with olanzapine and risperidone use (Hägg et al. 2003; Kamijo et al. 2003; Waage and Gedde-Dahl 2003). However, the biochemical mechanisms underlying this association have not been fully established (Borras et al. 2008).

In this case report, the results of risperidone treatment in a patient with Tourette syndrome and FVL heterozygous mutation are discussed.

Case Report

The patient was a girl 11 years and 9 months of age. She exhibited tics that had changed location and had increased and decreased for the past 4 years. Previously, she had applied to another medical center, where physiological tests were performed and medication was recommended, but the family did not administer the medication. When the patient came to our clinic, she had shoulder tics. She was also becoming shy and had begun to withdraw from friendships, and she did not want to go to school. Her tics increased with anxiety and excitement. Previously, she had tics such as winks and coughs but the cough tic occurred for ∼1 year and 6 months and then disappeared. The patient's family reported no unusual difficulties during the pregnancy, delivery, or postnatal periods. The subsequent developmental stages proceeded successfully and at appropriate times.

The patient had the factor V R506-Q506 heterozygous mutation. The family history revealed that her older sister had Down syndrome, and there were no tic disorders in the family.

There were no findings other than the presence of tics during the mental state examination, and she had no attention deficits or obsessions. She had a score of 54 on the Yale Global Tic Severity Scale (YGTSS).

Complete blood count (CBC), thyroid-stimulating hormone (TSH), and vitamin B12 levels were normal, and serological tests showed no streptococcal infection.

The patient was diagnosed with Tourette syndrome, and 0.25 mg risperidone was prescribed; this dose was gradually increased to 1.5 mg. In the first month following treatment, she had severe foot and knee tics, and her score on the YGTSS rose to 75. After the first follow-up, her symptoms decreased as the drug dose increased. Blood tests (CBC, fasting blood glucose test, liver function tests [LFC], and serum prolactin [PRL] level) performed after 5 months showed no side effects. After 8 months of treatment with 1.5 mg risperidone, the dose was reduced to 1 mg. With treatment, there was a significant decline in her complaints, and her score on the YGTSS dropped to 11. No significant weight gain was observed during follow-up, and no VTE was observed for 14 months from the start of medication to the day of submission of this article.

Discussion

Past studies have found that schizophrenia is a risk factor for VTE and that risperidone increases that risk (Hamanaka et al. 2004). In this case, although risperidone was used, there was no evidence of VTE. This may be explained by the low dose of the drug or differences between schizophrenia and Tourette syndrome in terms of VTE causation. Borras et al. (2008) reported VTE in the 3rd month of the treatment in a case study of a schizophrenic patient who was treated with 3 mg risperidone. In two other cases of schizophrenia with catatonia, a 2 mg dose of risperidone was used, and VTE was also observed. There is no information about in which month of the treatment VTE was observed (Van Neste et al. 2009). In an autopsy study of schizophrenic patients by Hamanaka et al. (2004), VTE was observed in four patients who had used a minimum level of 3 mg of risperidone. In the current study, the maximum dose of risperidone was 1.5 mg, and there was no VTE.

The first 3 months after initiation of treatment with antipsychotics have the highest risk of pathological blood coagulation (Masopust et al. 2012). Similarly, Borras et al. observed VTE within the 3rd month of the treatment (Borras et al. 2008). Therefore, in our case, after 14 months of treatment, even though we cannot say that there is zero risk, we can conclude that the probability of VTE was reduced.

Mittal and Khan reported a case of a 19-year-old female patient with the heterozygous FVL mutation who exhibited psychotic symptoms following an infarction (Mittal and Khan 2010). She was medicated using 1 mg risperidone and aspirin, although the aspirin was subsequently considered unnecessary and was discontinued.

The biological mechanisms underlying the adverse reaction in such cases remain unknown, but several hypotheses have been offered. Antipsychotics such as olanzapine, risperidone, and clozapine are known to affect serotonergic 5HT2 receptors and to increase serotonin. This reaction may lead to an increase in the number of platelets, thereby increasing the risk for thrombosis (Koga and Nakayama 2005). The reason that VTE did not develop in this patient may be that the underlying mechanisms of the FVL mutation and the role of atypical antipsychotics in the development of VTE are independent of each other. A study by Lacut et al. found that the risk of VTE following treatment with atypical antipsychotics was independent of age, gender, and body mass index (BMI); was not related to major acquired risk factors (surgery, plaster cast immobilization, active malignancy, pregnancy, and delivery); and was independent of two major and frequently inherited risk factors, FVL and the prothrombin G20210A gene variation (Lacut et al. 2007). Seeman found that atypical antipsychotics may increase the risk of VTE via weight gain (Seeman 2009). In the current case, the absence of VTE may be explained by the absence of metabolic syndrome and its features.

Many studies have shown that heterozygous FVL increases the risk of VTE by three- to eightfold (Griffin et al. 1993; Koster et al. 1993; Svensson and Dahlback 1994; Ridker et al. 1995), whereas homozygous FVL increases the risk by a factor of 80 (Rosendaal et al. 1995). Despite this increased risk, the lack of VTE in the current patient may be because of the heterozygous nature of her mutation. Furthermore, her young age may have played a role, as the risk for developing VTE increases with age (Jaffer 2008).

Conclusions

In conclusion, this case report demonstrates that small doses of risperidone were effective for the treatment of Tourette syndrome in an adolescent with the FVL heterozygous mutation and did not result in VTE. To our knowledge, this is the first case reported of an adolescent with Tourette syndrome and the FVL heterozygous mutation treated with risperidone with no resulting VTE.

Disclosures

No competing financial interests exist.

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