Received date:April 24, 2015; Accepted May 30, 2015; Published date: June 06, 2015
Citation: Naguy A, At-Tajali A (2015) Ziprasidone Monotherapy for Tourette Syndrome with Comorbid ADHD. J Psychiatry S1:002 doi: 10.4172/2378-5756.S1-002
Copyright: © 2015 Naguy A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse, distribution, and reproduction in any medium, provided the original author andsource are credited
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TS: de la Tourette Syndrome; OCD: Obsessive- Compulsive Disorder; PANDAS: Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection; ADHD: Attention-Deficit/Hyperactivity Disorder; AAP: Atypical Antipsychotics; ECG: Electrocardiogram; OPD: Outpatient Department; HRT: Habit Reversal Therapy; Y-GTSS: Yale-Global Tic Severity Scale; IQ: Intelligence Quotient; DSST: Digital Symbol Substitution Test; CPT: Continuous Performance Test.
De la Tourette syndrome (TS), the most common childhood movement disorder, is defined by the presence of multiple motor and one or more phonic tics, with a rostral-caudal distribution, onset before age of 18, for more than 1 year with no 3-months tic-free interludes, waxing and waning course, male predominance (ratio of 3:1) and polygenetic transmission with variable penetrance  (SLITRK1 gene mutations were identified in some cases) . It was called “maladie de tics” by Charcot . Some authorities include TS in the impulsioncompulsion spectrum . Some cases are related to the controversial PANDAS . OCD is comorbid in 50% of cases and ADHD in 60-80% (Table 1). The infamous Coprolalia is present in only 10% and is not mandatory for diagnosis . Tics are brief, stereotyped, temporarily suppressible, suggestible, semi-voluntary, and, usually preceded by a premonitory urge . Tics could be classified according to semiology (Table 2). Secondary “tourettism” should be ruled out beforehand  (Table 3). Stimulants, the mainstay of treatment of ADHD, are notorious to exacerbate tics in TS, although this has been refuted recently and it is no longer a contraindication [9,10]. Nonetheless, great caution should be exercised when using stimulants, notably in high doses, for TS.
|• Low impulse control|
|• Affective disorders|
|• Sleep problems|
Table 1: Comorbidities in TS.
Table 2: Tics typology.
|• Head trauma|
|• Von Economo’s post-encephalitis lethargica|
|• Drugs: stimulants, levodopa, antipsychotics (tardive tics)|
|• Huntington’s disease|
|• Wilson’s disease|
Table 3: Secondary tourettism.
There is no hard and fast rule, but antipsychotics, especially atypical (AAPs), by and large, produce the most robust results controlling tics when socially-embarrassing or functionally impairing. Nonetheless, clinicians ’enthusiasm is commonly tempered by the ominous metabolic and/or neurologic syndromes subsequent to antipsychotic use. Pharmacologic options for TS are legion  (Table 4).
|• Antipsychotics (haloperidol, pimozide, risperidone, iprasidone, amisulpride…)|
|• DA depleters (tetrabenazine)|
|• α2 agonists(clonidine, guanfacine)|
|• BDZ (clonazepam)|
|• Anticonvulsants (topiramate)|
|• Dopaminomimetics (ropinirole)|
Table 4: Pharmacologic options in TS.
Here, we are reporting a case of adolescent TS with comorbid severe ADHD where stimulants were deleterious for tics, atomoxetine (Strattera®) was ineffective addressing ADHD, and clonidine (Catapres®) was too soporific to be tolerated. Risperidone (Risperidal®) trial was prematurely aborted due to hyperprolactinaemia and weight gain. Shift to Ziprasidone (Zeldox®) brought about significant control over tics, disruptive behaviours, but above all, meaningful improvement for the core symptoms of associated ADHD without an inherent risk for metabolic syndrome; a top priority in this population.
We assume the pharmacologic portfolio of Ziprasidone (Table 5), as D2 5HT 2A blocker with a unique SNRI activity might explain its impressive response in ADHD, akin to use of formal SNRIs, like Venlaxine (Effexor®) for ADHD [12,13]. This coupled with a benign metabolic profile might open new venues of treatment for complicated cases of TS with comorbid ADHD. Moreover, it could augment SSRIs response for concomitant OCD, if any. Large trials are definitely needed to gauge its proper placement in clinical practice. It is currently FDAapproved for10-17 years of age. QTc prolongation and torsadogenic effects were unduly exaggerated in the past [14,15]. However, we suggest a baseline ECG and subsequent monitoring with dose escalations.
|• D2 blockads|
|• 5HT2A,2C,1B/1D blockade|
|• H1 blockade|
|• Alfa-1 blocade|
|• 5HT1A agonism|
Table 5: Pharmacologic portfolio of Ziprasidone.
A 13-year-old Kuwaiti male youngster presented to our OPD clinic for assessment of bothersome composite motor (blinking, shoulder shrugging) and vocal tics (snorting), low impulse control and ostensible scholastic underachievement. He was diagnosed as a case of TS in a private setting. He had a trial on Methylphenidate for comorbid ADHD that caused marked exacerbation of tics. Atomoxetine was tried, in lieu, but response was very sluggish over 12 weeks despite adequate dosing (1.2 mg/d) and ascertained compliance. Clonidine was then introduced, but 150 μg/d (divided on 3 doses) was too sedating and counterintuitive. When felt socially ostracised, Risperidone was instituted and up titrated to 2 mg/d. S. Prolactin soon was X3. The youngster put on more than 7% from baseline body weight. HRT was time-consuming to pursue. Neurologic consult was summoned to rule out other dyskinesias and secondary causation. Y-GTSS, Vanderbilt, full-scale IQ and DSST& CPT were all administered to objectify clinical findings. We suggested a trial of Ziprasidone for tic control. ECG was done beforehand. At 80 mg/d (on 2 divided doses with meals), tics almost totally abated over 2 weeks, with dropped Y-GTSS scores. Impulsivity, as reported by both parents and teachers markedly diminished. Strikingly, scholastic performance began to improve cogently. Readminstered DSST and CPT confirmed the obvious improvement in cognitive domains. The response was well-sustained at W-4, W-8, and W-12. Efficacy of Ziprasidone in TS is well-documented in the literature . Case reports of utility in ASD with ADHD-like symptoms were also reported [17,18]. With metabolic syndrome borne in mind, established efficacy for tics that could extend to ADHD, disruptive behavioural repertoire and OCD, as this case portrays, clinicians should be vigilant to use Ziprasidone in such clinical scenarios as a viable option to simultaneously address a multitude of pharmacologic targets.