Chronic motor tic (CMT) disorder is a condition consisting of sudden, recurrent, non-rhythmic and involuntary movements. It is characterized by persistent or episodic (motor or vocal) tics lasting more than 1 yr. Obsessive–compulsive disorder (OCD) is characterized by repetitive and intrusive thoughts with some compensatory actions to relieve the obsessive thought-related anxiety. Central dopamine dysregulation is believed to play an important role in the pathophysiological hypotheses of these disorders (Hershey et al.2004; Olver et al.2008). Second-generation antipsychotics, such as risperidone, quetiapine and olanzapine (Bloch et al.2006), have been suggested to be successful in the treatment of CMT disorder or serotonin reuptake inhibitor treatment-resistant OCD. However, these second-generation antipsychotics are associated with an increased risk of metabolic syndrome (Henderson, 2008). Aripiprazole, a new-generation antipsychotic with dopamine type 2 receptor (D2) partial agonist, 5-hydroxytryptamine (5-HT)1A partial agonist, and 5-HT2A and 5-HT2C antagonist properties, has been shown to be effective in the treatment of tic disorder (Yoo et al.2007) and refractory OCD augmentation therapy (Gao et al.2006). This report presents an adolescent suffering from CMT combined with refractory OCD who successfully responded to aripiprazole after previous treatment failure with risperidone and paroxetine.
Mr A was a 16-yr-old boy with onset of occasional grimacing, facial muscle twitch, eyebrow blinking, shoulder shrugging and head-nodding since age 14 yr. According to the patient his movements were involuntary; there were no simultaneous vocal tics observed. His symptoms became more severe over the course of 2 yr. Fearing being unclean and germs, he washed his hands almost 40 times a day, for approximately 10–30 min each time. He felt a strong urge to do so when having obsessive thoughts and a need for symmetry, ordering, counting and precision. The obsessive–compulsive symptoms occurred at a time similar to tics and both diagnoses were confirmed around age 16 yr. No previous exposure to amphetamine, no chronic partial seizures, or brain magnetic resonance imaging abnormalities were observed. The motor tic severity rating scores on the Yale Global Tic Severity Scale (YGTSS) were 17 (instrumental range 0–25), with marked impairments in self-esteem and school performances with scores of 40 (instrumental range 0–50). The OCD symptoms were rated by the New Jersey Center for Tourette Syndrome (NJCTS) and the Dimensional Yale–Brown Obsessive Compulsive Scale (DYBOCS), global severity rating scores were 25 (instrumental range 0–30) and symptom dimension scores of contamination and symmetry categories were 13 and 14, respectively (instrumental range 0–15).
Mr A started receiving 2 mg risperidone for CMT and 40 mg paroxetine for OCD in the first 2 wk, but his symptoms failed to improve (YGTSS 16; DYBOCS: global 26, contamination 14, symmetry 14) (see Table 1). Both dosages were titrated to 4 mg and 80 mg, respectively. During follow-up at 6 months with reasonable adherence, he had a 70–80% decrease of motor tics, but poor response in OCD symptoms (YGTSS 7; DYBOCS: global 24, contamination 13, symmetry 15). Due to treatment-resistant OCD, his medication was immediately switched to 10 mg/d aripiprazole. During initial aripiprazole treatment, neither intolerable side-effects nor paroxetine withdrawal syndrome were observed. OCD symptoms responded with less severity of contamination or symmetry-related obsession and compulsion after 1-month therapy (YGTSS 6; DYBOCS: global 19, contamination 11, symmetry 12). The aripiprazole dose was then titrated to 20 mg/d resulting in a further reduction of OCD symptoms being observed in the following 6 months (YGTSS 5; DYBOCS: global 12, contamination 6, symmetry 5). The only side-effect was slight dizziness.
YGTSS, Yale Global Tic Severity Scale; DYBOCS, Dimensional Yale–Brown Obsessive Compulsive Scale.
Recently, aripiprazole has been used for the treatment of CMT or Tourette's syndrome, in children or adolescents, possibly because of the fewer extrapyramidal side-effects or reduced risk of metabolic syndrome (Budman et al.2008). The characteristics of D2 partial agonists and 5-HT1A partial agonists were reported to be associated with dopamine release over prefrontal cortex (Lawler et al.1999). In addition, aripiprazole's 5-HT2C functional antagonist action was able to enhance dopamine release in the prefrontal cortex through activation of serotonin action over the nucleus accumbens (Giorgetti & Tecott, 2004). The prefrontal cortex dopamine activity can modulate the basal ganglion dopamine system through a top-down mechanism (Winter et al.2008) and thus the tic or OCD symptoms would be relieved through modulation of the serotonin–dopamine system. The reduction of anxiety was hypothesized to be associated with 5-HT2C antagonism, 5-HT1A partial agonism and dopamine partial agonism (Pae et al.2008). In a dopamine subtype 2 (D2) receptor dose-occupancy positron emission tomography study for normal humans, aripiprazole showed higher extrastriatal than striatal D2 receptor binding (Yokoi et al.2002). The successful experience of this patient with CMT and refractory OCD might be related to extrastriatal modulation towards striatal D2 receptors. Moreover, 5-HT2A antagonism and D2 partial agonism of aripiprazole might restore the phenomenon of lower 5-HT2A receptor availability over frontal cortex and D2 receptor uptake over basal ganglion in drug-naive OCD patients (Perani et al.2008). Possible reasons for the superiority of aripiprazole over risperidone in this case can be summarized as follows: (1) the dopamine system's stabilization effects from aripiprazole's partial agonist role, (2) the serotonin receptors' unique modulation, especially the direct 5-HT1A effects (Horacek et al.2006).
In summary, this is the first case report to describe the beneficial clinical effects of aripiprazole in the treatment of CMT and refractory OCD. The special 5-HT2A antagonist, 5-HT2C partial agonist, 5-HT1A partial agonist and D2 partial agonist neuropharmacological characteristics of aripiprazole might be of benefit for this type of patient.
Statement of Interest