aripripazol y tourette

8/12/2019 Aripripazol y Tourette

1/8


2/8

The exact causes of TD are not yet well established (Leckman

2002). No clear single neurotransmitter system has so far been

clearly identified (Rickards 2009). However, dopamine release was

greater in patients with TD than in controls. Abnormal motor co-

ordination caused by the phasic dysfunction of dopamine trans-

mission may produce tics (Singer et al. 2002; Nikolaus et al. 2009).

Currently, the only medications formally approved for use in TD

are haloperidol and pimozide (Thompson 2007). However, sig-

nificant side effects, including extrapyramidal symptoms (EPS)such as acute dystonic reactions, Parkinsonism, akathisia, and

tardive dyskinesia (Shapiro et al. 1973), have limited their long-

term efficacy and safety prompted the development of the novel

atypical neuroleptics.

Aripiprazole is an atypical antipsychotic drug that is proposed to

have a unique mechanism of action (Bowles and Levin 2003;

Shapiro et al. 2003). The U.S. Food and Drug Administration

(FDA) approved indications for aripiprazole in adolescents ages

1317 with schizophrenia and bipolar disorder. There are only

limited data on the effects or side effects of aripiprazole in children

and adolescents with TD.

Few studies have investigated the effect of aripiprazole in chil-

dren and adolescents with TD, and the sample sizes of these studies

were all very small. A 12-week, open-label trial with a flexibledosing strategy of aripiprazole was performed with 15 children and

adolescents with TD or chronic tic disorders aged 719 years. This

study demonstrated that a relatively low dose of aripiprazole could

be used to control tic symptoms effectively in children and ado-

lescents with TD and chronic tic disorders without causing sig-

nificant weight gain (Seo et al. 2008). Another retrospective,

observational study suggested that aripiprazole could improve the

explosive outbursts symptoms of children and adolescents with TD

and aripiprazole was tolerated reasonably well (Budman et al.

2008). But a case reported an acute dystonic episode in a patient

with TD treated with the partial dopamine agonist aripiprazole

(Fountoulakis et al.2006).The preliminary evidence suggested that

aripiprazoles benefit-versus-risk profile merits should be further

explored for use in TD. Our hypotheses were that aripiprazolemight be effective in treating tic symptoms without causing serious

side effects and aripiprazole could be as an interesting option for

TD cases that did not respond to conventional therapies.

The aim of the study was to explore the use and tolerability of

aripiprazole as a treatment for tics and co-morbid symptoms in

youths with TD. This was a first study of aripiprazole on TD in

China.

Methods

Subjects

The subjects were recruited from outpatient units in three hospi-

tals in China over a period of 7 months from November, 2008, to

July, 2009. All subjects were Chinese and of Han nationality. Thestudy protocol was approved by Institutional Review Boards (IRBs)

in three sites. Written informed consent and assent were obtained.

All subjects were required to meet the following inclusion cri-

teria: (1) Between the ages of 6 and 18 years; (2) Diagnostic and

Statistical Manual of Mental Disorders, 4th edition (DSM-IV)

(American Psychiatric Association 1994) diagnosis of TD; (3)

minimum body weight of greater than or equal to 25 kg; (4) out-

patient status and not believed to require inpatient hospitalization

during the course of the study; (5) minimum Clinical Global

ImpressionsSeverity (CGI-S) score of moderately ill or greater

severity (rating of 4); (6) normal screening medical history and

physical examination; and (7) patient and parent/guardian must

provide written informed consent (or assent).

Subjects were excluded from participation in the study if they

had one or more of the following exclusion criteria: (1) Intelligence

quotient (IQ) score below 70 by Wechsler Intelligence Scale for

Children, 3rd

edition (WISC-III) (potential participants with a low

IQ were excluded from this study because they were not expected

to be able to describe their symptoms or the side effects of the

medication appropriately); (2) prior adequate treatment witharipiprazole; (3) hypersensitivity to aripiprazole; (4) need for

co-morbid psychotropic medication during the study period or

required concurrent medication that effects tics; (5) current use of

psychostimulants, mood stabilizers, or anticonvulsants; (6) pres-

ence of significant co-morbid medical illness; (7) history of seizure

disorder; (8) history of substance or alcohol abuse or dependence

within 6 months of screening; (9) pregnancy, lactation, or positive

pregnancy test; (10) absence of acceptable contraceptive method

for sexually active females; (11) detection of pregnancy during

the study, which would have led to withdrawal from the study; and

(12) concurrent behavioral treatment for tic symptoms during the

6-week treatment period.

Study design and measurements

This study was an 8-week, open-label flexible dose design in

outpatients with TD receiving monotherapy with aripiprazole. All

subjects had a 7- to 14-day screening period.

The tics and co-morbid symptoms of each participant at baseline

were evaluated by appointed psychiatrists Severity of tic symptoms

during the previous week was evaluated using the Yale Global Tic

Severity Scale (YGTSS) (Leckman et al. 1989). The YGTSS is a

semistructured interview designed to elicit information concerning

the specific character and anatomical distribution of tics. It has

robust psychometric properties as a measure of change in tic se-

verity and has been used in a number of studies internationally

(Storch et al. 2005; Storch et al. 2007). The interview began with

systemic assessment of current tic symptoms (both motor andphonic tic symptoms) that the clinician rated as present or absent

over the past week. This was followed by assessing the most severe

tic symptoms by the patients themselves. Motor and phonic tic

symptoms were rated according to number, frequency, intensity,

complexity, and interference on a 6-point ordinal scale. Patients

Current Total Tic score and Total Most Severe Tic score ranged

from mild to severe (0 absent, 15 for severity). The YGTSS was

evaluated at baseline, weeks 2 and 4, and end point through face-to-

face interviews with each participant.

Tic severity was also assessed using the Clinical Global

ImpressionsTics (CGITics) (Zhang 1998). The CGI consists of

07 points. It is used to evaluate the severity of clinical symptoms

and measure change in them over the course of the study. It has

robust psychometric properties as a measure of change in clinicalsymptoms and has been used in a number of studies internationally

(Zhang 1998). Operational definition of CGITics severity was as

follows: (1) Normal or no tics at all; (2) borderline, tics may or may

not be present; (3) mild, observable motor and/or vocal tics that

may or may not be noticed, would not call attention to the indi-

vidual, and are associated with no distress or impairment; (4)

moderate, observable motor and/or vocal tics that would always be

noticed, would call attention to the individual, and may be asso-

ciated with some distress or impairment; (5) marked, exaggerated

motor and/or vocal tics that are disruptive, would always call

attention to the individual, and are always associated with signifi-

292 CUI ET AL.


3/8

cant distress or impairment; and (6) severe, extremely exaggerated

motor and/or vocal tics that are disruptive, would always call at-

tention to the individual, and are associated with injury or inability

to carry out daily functions. The scale was evaluated at baseline,

weeks 2 and 4, and end point through face-to-face interviews with

each participant.

Staff for conducting clinician ratings all received extensive

training by the responsible author in the primary outcome mea-

sures, and satisfactory interrater reliability was documented. In-terrater reliability of YGTSS and CGITics in this study was

assessed with the Pearson correlation test. Interrater reliability of

YGTSS in this study was 0.87 and that of CGITics was 0.89. To

maximize interrater reliability between sites, thenumberof raters at

each site was minimized; they were all provided with identical

instructions for administering YGTSS and CGITics, and efforts

were to be made to ensure that the same rater administered the

scales for a given patient. Those raters who failed to achieve the

requisite level of interrater reliability were not allowed to rate

subjects in the trial.

The co-morbid symptoms of each participant were evaluated

with the Child Behavior Checklist (CBCL). The CBCL is a widely

used parent-reported questionnaire designed to assess the behav-

ioral problems and social competence of children 418 years ofage, which was revised by Achenbach and was used after being

translated into Chinese (Su et al. 1998). The CBCLChinese

(CBCL-C) consists of 20 items that assess social competence and

118 items concerning behavioral and emotional problems. The

questionnaires were scored using eight measures: Withdrawal,

somatic complaints, anxiety and depression, social problems,

cognitive problems, attention problems, delinquent behavior, and

aggressive behavior. They were grouped into two broad band

scores: Internalization behavior problem score, consisting of

withdrawal, somatic complaints, anxiety and depression, and ex-

ternalization behavior problem score, consisting of delinquent and

aggressive behaviors. Standardized T scores with a mean of 50

(standard deviation [SD] 10) were provided for each subscale.

A T score greater than 60 indicated a borderline clinical range.The higher the score, the more severe the childs behavioral and

psychological problems (Yang et al. 2000). The scale was evalu-

ated at baseline and end point.

All subjects had a complete review of their current health status,

which included a careful medical history. Vital signs, including

blood pressure and pulse rate, were assessed at screening, baseline,

weeks 2 and 4, and end point. Meanwhile, laboratory tests were

conducted and included routine hematology, prolactin, clinical

chemistry, and routine urinalysis. In addition, an ECG was done to

rule out any preexisting cardiac conditions. The side effects of

aripiprazole were evaluated using an adverse events chart made

by this study team. The chart was developed to evaluate extra-

pyramidal symptoms, gastrointestinal symptoms, neuromuscular

symptoms, sedation, or other cognitive symptoms. Height, weight,and body mass index (BMI) of each participant were checked at

baseline and end point, and the BMI of each participant was

compared between the two phases.

Dosing schedule

Aripiprazole was initiated at doses of 1.252.5 mg daily in

prepubertal children and at 2.55 mg in adolescents, and flexibly

titrated every 57 days as tolerated and clinically indicated.

Treatment duration was 8 weeks (with dosing generally titrated to

therapeutic range within about 4 weeks).

Data analyses

Analysis of variance (ANOVA) was performed to evaluate the

quantitative change in the scores pertaining to motor tic, phonic

tic, total tic, global impairment, and global severity in the YGTSS

at baseline, weeks 2 and 4, and end point. The same statistical

method was also used for CGITics. Change in the CBCL was

analyzed using a pairedt-test. Adverse effects were evaluated by

descriptive statistics. In addition, weight and prolactin were ex-

amined as primary side effects and were compared from baseline

to week 8, using paired t-tests and a one-sample t-test based on

percent change from baseline values. The last observation carried

forward (LOCF) was used as the end point for a participant. All

statistical analyses were performed using the SPSS statistical

package, version 15.0. All statistical tests were two-sided at the

5% level of significance.

Results

A total of 72 subjects were enrolled (age range 618;

10.23 2.47 years; 55 males, 17 females). A total of 25 participants

were drug nave to their tic symptoms, whereas 47 had a history of

using neuroleptics; 31 took lowdoses of neuroleptics (e.g.,less than

200 mg/day of tiapride or 1 mg/day of haloperidol or 1.5 mg/dayof risperidone); 16 took moderate-to-high doses of neuroleptics

(200400mg/day of tiapride or 14.5 mg/day of haloperidol or

1.53.5 mg/day of risperidone) (Table 1). Seven of 72 subjects

(9.7%) discontinued aripiprazole before 8 weeks. Of those 7 sub-

jects, 5 were adolescents and 2 were prepubertal children. Four of

the 7 dropouts discontinued at the end of 4 weeks because of no

significant reduction of symptoms. Two dropouts withdrew from

the study at the end of 4 weeks because of continuous sedation, and

another participant dropped out because of skin hypersensitivity at

the end of 2 weeks, a symptom that disappeared 2 days after

stopping the drug. In the cases of early withdrawal, data were ob-

tained using the LOCF method. All 72 subjects provided data over

2 weeks of the study, and these were used for analyses. There were

no differences in outcomes stratified by site.The initial dosage of aripiprazole was 1.252.5 mg daily in

prepubertal children and at 2.55 mg in adolescents, and flexibly

titrated every 57 days as tolerated and clinically indicated. The

mean daily dosages of aripiprazole were 4.880.63 mg,

7.33 2.06 mg during weeks 2 and 4, and the final dose of ar-

ipiprazole was 8.17 2.41 mg or 0.19 mg/kg (range from 0.1 to

0.60 mg/kg).

Table 1. Demographics and Prior History of Treatment

n (%)

Total of subjects 72 (100%)Males 55 (76.4%)Females 17 (23.6%)Mean age (SD) 10.23 (2.47)

Never used medications 25 (34.7%)Ever used medications 47 (65.3%)

Tiapride (


4/8


5/8

et al. 2009; Seo et al. 2008; Kawohl et al. 2009; Murphy et al.

2009). Outcomes in all six studies were measured by the YGTSS

at baseline and end point. In all the six studies, significant re-ductions in the YGTSS were noted in participants aged 719 years

with doses ranging between 2.520 mg/day. In three of the six

studies, significant improvement was shown from CGI scales at

end point. In addition to these open-label studies there was a pilot

study (Yoo et al. 2006), three case series (Murphy et al. 2005;

Davies et al. 2006; Duane 2006), and one retrospective study

(Budman et al., 2008), all finding clinical improvement with

reasonable tolerability with use of aripiprazole in the treatment of

tic disorders.

A small dose of aripiprazole was found to be effective in con-

trolling tic symptoms in the above-mentioned studies investigating

tic disorders. However, the sample size of these studies was rela-

tively small, even including some case reports. Aripiprazole is

relatively new, even in the adult population, and without the ex-perience of time and the relative lack of excellent efficacy and

safety data, there is not enough evidence to support its use in tic

disorders. To the best of our knowledge, there have been not any

data regarding the administration of aripiprazole to patients with tic

disorders in China. So our study was a first study investigating the

use of aripriprazole to treat children and adolescents with TD in

China.

In our open-label, acute treatment trial of children and adoles-

cents with moderate-to-severe TD, aripiprazole administration was

associated with noticeable improvement on dimensional measures

across a variety of symptomatic areas, including reduced total tic

frequency, intensity, interference, impairment, and severity and

decreased behavior problems.

The magnitude and significance of effect of aripiprazole onmeasures of tic severity was in line with an array of other similar

reports. Aripiprazole was associated with a statistically significant

decrease in the YGTSS Total Tic score of 50.3%. Yoo et al. (2007)

reported that there was a 52.8% reduction in the mean YGTSS

Total Tic scores after a mean of 9.8 4.8mg/day of aripiprazolefor

8 weeks. Seo et al. (2008) reported that the degree of symptom

reduction according to YGTSS was 5064.8% with a mean end

point dosage of 8.174.06 mg. Another 12-week case series of 6

children and adolescents with TD and OCD, mean decrease of

YGTSS was 56% with a mean dose of 11.7 mg of aripiprazole

(Murphy et al. 2005). It seems thatthere was a greater magnitude of

effect of aripiprazole than for most other medications used in

treating tics in childhood, such as those reported for olanzapine

(30%; McCracken et al. 2008), ziprasidone (35%; Sallee et al.2000), risperidone (2142%; Gaffney et al. 2002; Scahill et al.

2003; Gilbert et al. 2004), and pimozide (21%; Gilbert et al. 2004).

The difference was notable, but it needs further exploration. Taken

together with the significant drop in YGTSS Impairment ratings,

the data (56.5%) from this study suggest that the overall clinical

benefit for tic control per se is meaningful. The mean CGITics

severity score was 4.77 1.69 at baseline and decreased to

2.20 1.39 at end point (t 10.698, p0.000). The significant

improvement observed according to CGITics severity also con-

firmed this finding.

An important aim of this study was to evaluate the possible

broader effectiveness of aripiprazole on commonly co-occurring

behavior symptoms in TD. A significant reduction of behavior

symptoms was noticed according to the CBCL and its subscalesbetween baseline and end point in this study. This finding ex-

panded on the observations (Stigler et al. 2004; Valicenti-

McDermott et al. 2006; Owen et al. 2008a; Owen et al. 2008b;

Stigler et al. 2009; Bastiaens et al. 2009) that rating of behavioral

problems decreased with aripiprazole treatment. Given that

behavior problems in TD often form the primary source of

impairment and stress, we believe aripiprazoles beneficial

effects are clinically important. The effectiveness of aripiprazole

on behavior symptoms in TD may have contributed to the

improvement of impairment.

With regard to dosing aripiprazole in TD and tic disorders,

there are no clear guidelines (Greenaway et al.2009). In ourstudy,

the initial dosage of aripiprazole was 1.252.5 mg daily in pre-

pubertal children and at 2.55 mg in adolescents, and flexiblytitrated every 57 days as tolerated and clinically indicated. The

final mean daily dose of aripiprazole was 8.17 mg (range 2.5

17.5 mg). This dosage was consistent with the available reports

(from 6.7 to 14.5 mg/day)(Murphy et al. 2005; Davies et al. 2006;

Yoo et al. 2006; Miranda et al. 2007; Yoo et al. 2007; Seo et al.

2008; Budmanet al. 2008;Findling et al. 2008b). A dose of 10 mg/

day appears to be a reasonable target dose for these conditions for

many children and must adolescents. Given that younger children

are more susceptible to the side effects of aripiprazole, they

should be started at lower initial doses with a lower target dose

(Greenaway et al. 2009).

Table 3. Comparison of the Mean Scores of CBCL(T-Scores) Between Baseline and End Point (n 72)

CBCL scoresBaseline

(mean SD)End point

(mean SD) T-testp

value

Total 56.36 8.54 49.46 8.39 4.93 0.000Externalizing 52.14 6.33 48.38 7.92 2.81 0.007Internalizing 56.28 8.44 52.14 9.48 3.07 0.003

Withdrawn 57.40 8.07 56.16 8.14 1.81 0.075Somatic complaints 54.66 7.76 53.94 7.60 2.14 0.037Anxious/ Depressed 57.978.06 54.82 9.29 3.13 0.003Social problems 54.187.63 52.88 9.68 0.92 0.363Thought problems 56.318.35 52.16 9.22 3.24 0.002Attention problems 57.829.11 55.08 8.65 2.26 0.027Delinquent behavior 52.9110.97 51.74 8.72 1.04 0.301Aggressive behavior 55.0910.15 51.88 7.43 2.06 0.043

Abbreviations: CBCLChild Behavior Checklist; SD standarddeviation.

Table 4. Safety Report Comparison BetweenInitial and Final Visit (n 72)

Inspection

item

Initial value

(mean SD)

Final value

(mean SD) T-test p

value

ALB 44.36 11.10 41.53 11.74 2.04 0.046ALT 20.38 8.13 24.72 10.38 3.48 0.001AST 21.92 10.02 24.26 9.68 2.48 0.016Cre 57.61 28.03 53.97 29.49 2.08 0.041Bun 3.64 1.58 3.68 1.77 0.51 0.610PRL 11.49 4.00 11.25 4.69 0.70 0 .484BMI 20.71 9.80 21.57 8.11 0.94 0.352QTc interval 401.78 16.85 399.75 12.41 0.87 0.387

Abbreviations: SDStandard deviation; ALB albumin(g/L);ALT alanine aminotransferase (U/L); AST aspartate aminotransferase(U/L); CreCreatinine(mmol/L); Bun blood urea nitrogen(mmol/L);PRL prolactin(ng/ml); BMI body mass index.

ARIPIPRAZOLE IN TOURETTES DISORDER 295


6/8

In this acute trial, aripiprazole was reasonably tolerated, as 65

of 72 (90.3%) of subjects were able to complete the protocol, and

adverse events were generally mild to moderate in severity.

Aripiprazole is associated with a relatively low risk of weight

gain (Murphy et al. 2005; Haupt 2006; Correll et al. 2009;

Reynolds et al. 2009). However, it resulted in rapid and robust

weight gain in an animal model (Kalinichev et al. 2005). An

open-label aripiprazole study in the treatment of youth with tic

disorders (Murphy et al. 2009) also reported that although ar-ipiprazole was well tolerated increases in weight were found.

Even though there was no significant weight gain in this study, it

is not conclusive. A relatively small dose of aripiprazole was

administered, and some of the participants complained of nausea

in the beginning of this study. These two factors may have af-

fected the weight changes of the participants. An additional long-

term study investigating the weight change associated with

aripiprazole will be needed to confirm the effect of aripiprazole

on weight. Furthermore, the other side effects such as nausea and

sedation were transient, and not as serious as those observed in

other trials of aripiprazole (Findling et al. 2003; Yoo et al. 2007;

Seo et al. 2008; Robert et al. 2009). Nausea remitted in 2 weeks,

and sedation remitted after changing aripiprazole from daytime to

nighttime administration. Although none of the trials specificallyassessed changes in sleep parameters or use of concurrent hyp-

notic medications, it may be logical to administer this medication

at bedtime to take advantage of its sedating effects (Greenaway

et al. 2009).

There have been a few case reports describing EPS, including

one report of Parkinsonism (Lua et al. 2009) and another of acute

dystonia (Singh et al. 2007). However Osorio et al. (2009) re-

ported three cases of psychiatric geriatric patients who suffered

from tardive dyskinesia that were resolved after switching treat-

ment from haloperidol to aripiprazole. The EPS symptoms during

this study were negligible, which may be due to a relatively small

dose and a relatively slow titration of aripiprazole. Because a

number of patients taking aripiprazole developed EPS, there is

recommendation that patients be informed of the possibility of,and assessed routinely for these adverse effects (Greenaway et al.

2009).

Aripiprazole has no warnings pertaining to cardiac functioning

(Bristol-Myers Squibb Canada 2009) and may even decrease QTc

intervals (Goodnick et al. 2002). No statistically significant chan-

ges in ECG readings were found in this study. However, further

research using a larger sample size and longer treatment period is

clearly needed to draw firm conclusions. There were no clinically

significant laboratory abnormalities noted during aripiprazole ex-

posure, including for prolactin; therefore, aripiprazole could be

used when individuals are particularly susceptible to hyperpro-

lactinemia induced by other agents. Finally, the impact of ar-

ipiprazole treatment on metabolic parameters such as weight,

fasting glucose, and lipids does appear to be less than some of theother available atypical agents when used in children and adoles-

cents (Greenaway et al. 2009).

Although a small dose of aripiprazole was found to be effective

in controlling tic symptoms and behavior symptoms, several lim-

itations of this study must be taken into account. First, this study

was an open-label trial, not placebo or another active drug con-

trolled, and both the participants and their parents were not blinded.

Second, the sample size was relatively small. Third, the co-morbid

conditions were not considered enough to profile diagnostically.

Fourth, the lack of statistical correction for multiple hypothesis

testing was another limitation. Allof these limitations mean that the

findings of this study cannot be easily generalized to all the children

and adolescents with TD.

Conclusions

In conclusion, this short-term study suggests that aripiprazole

shows effectiveness in treating tic symptoms without causing sig-

nificant weight gain or other serious side effects. Aripiprazole could

be an possible option for TD cases that do not respond to con-

ventional therapies. Further controlled, double-blind studies need

to be conducted with a larger sample size to evaluate the safety and

efficacy of aripiprazole in treating TD.

Disclosures

The studys authors do not promote for any pharmaceutical

companies, and there are no other conflicts of interest.

References

American Psychiatric Association: Diagnostic and Statistical Manual

of Mental Disorders, 4th edition (DSM-IV-TR). Washington (DC):

American Psychiatric Association, 2000.

Bastiaens L: A non-randomized, open study with aripiprazole andziprasidone for the treatment of aggressive behavior in youth in a

community clinic. Commun Mental Health J 45:7377, 2009.

Bowles TM, Levin GM: Aripiprazole: A new atypical antipsychotic

drug. Ann Pharmacother 37:687694, 2003.

Bristol Myers Squibb Canada: Abilify Product Monograph. Mon-

treal, QC: Bristol Myers Squibb Canada, 2009.

Budman C, Coffey BJ, Shechter R, Schrock M, Wieland N, Spirgel A,

Simon E: Aripiprazole in children and adolescents with Tourette

disorder with and without explosive outbursts. J Child Adolesc

Psychopharmacol 18:509515, 2008.

Chao KY, Wang HS, See LC: Recognition and management of

Tourette syndrome. Hu Li Za Zhi 56:6974, 2009.

Coffey BJ, Biederman J, Geller DA, Spencer T, Park KS, Shapiro SJ,

Garfield SB: The course of Tourettes disorder: A literature review.

Harv Rev Psychiatry 8:192198, 2000a.Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra

AK: Cardiometabolic risk of second-generation antipsychotic

medications during first-time use in children and adolescents.

JAMA 302:17651773, 2009.

Davies L, Stern JS, Agrawal N, Robertson MM: A case series of

patients with Tourettes syndrome in the United Kingdom treated

with aripiprazole. Hum Psychopharmacol 21:447453, 2006.

Duane DD: Aripiprazole in childhood and adolescence for Tourette

syndrome. J Child Neurol 21:358, 2006.

Findling RL, Blumer JL, Kauffman R, Batterson JR, Gilbert DL,

Bramer S, Marcus R: Pharmacokinetic effects of aripiprazole in

conduct disorder. AACAP Annual Meeting, October, 2003.

Fountoulakis KN, Siamouli M, Kantartzis S, Panagiotidis P, Iacovides

A, Kaprinis GS: Acute dystonia with low-dosage aripiprazole in

Tourettes disorder. Ann Pharmacother 40:775777, 2006.

Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor

P: An international perspective on Tourette syndrome: Selected

findings from 3,500 individuals in 22 countries. Dev Med Child

Neurol 42:436447, 2000.

Gaffney GR, Perry PJ, Lund BC, Bever-Stille KA, Arndt S, Kuperman

S: Risperidone versus clonidine in the treatment of children and

adolescents with Tourettes syndrome. J Am Acad Child Adolesc

Psychiatry 41:330336, 2002.

Gilbert DL, Batterson JR, Sethuraman G, Sallee FR: Tic reduction with

risperidone versus pimozide in a randomized, double-blind, cross-

over trial. J Am Acad Child Adolesc Psychiatry 43:206214, 2004.

296 CUI ET AL.


7/8

Goodnick PJ, Jerry J, Parra F: Psychotropic drugs and the ECG: Focus

on the QTc interval. Exp Opin Pharmacother 3:479498, 2002.

Greenaway M, Elbe D: Focus on Aripiprazole: A Review of its use in

child and adolescent psychiatry. J Can Acad Child Adolesc Psy-

chiatry 18:250260, 2009.

Haupt DW. Differential metabolic effects of antipsychotic treatments.

Eur Neuropsychopharmacol 16:149155, 2006.

Kadesjo B, Gillberg C: Tourettes disorder: Epidemiology and co-

morbidity in primary school children. J Am Acad Child Adolesc

Psychiatry 39:548555, 2000.

Kalinichev M, Rourke C, Daniels AJ, Grizzle MK, Britt CS, Ignar

DM, Jones DN: Characterisation of olanzapine-induced weight gain

and effect of aripiprazole vs olanzapine on body weight and pro-

lactin secretion in female rats. Psychopharmacology 182:220231,

2005.

Kawohl W, Schneider F, Vernaleken I, Neuner I: Aripiprazole in the

pharmacotherapy of Gilles de la Tourette syndrome in adult

patients. World J Biol Psychiatry 10:827831, 2009.

Leckman JF: Tourettes syndrome. Lancet 360:15771586, 2002.

Leckman JF, Riddle MA, Hardin MT: The Yale Global Tic Severity

Scale: Initial testing of a clinician-rated scale of tic severity. J Am

Acad Child Adolesc Psychiatry 28:566573, 1989.

Lua LL, Zhang L: Development of Parkinsonism following exposure

to aripiprazole: Two case reports. J Med Case Reports 3:6448,2009.

Lyon GJ, Samar S, Jummani R, Hirsch S, Spirgel A, Goldman R,

Coffey BJ: Aripiprazole in children and adolescents with Tourettes

disorder: An open-label safety and tolerability study. J Child

Adolesc Psychopharmacol 9:623633, 2009.

McCracken JT: Tourette and the Tic disorders, in Textbook of Psy-

chiatry/VII, Kaplan HI, Sadock, B, eds. New York: Williams and

Wilkins, pp 27112719, 1999.

McCracken JT, Suddath R, Chang S, Thakur S, Piacentini J: Effec-

tiveness and tolerability of open label olanzapine in children and

adolescents with Tourette syndrome. J Child Adolesc Psycho-

pharmacol 18:501508, 2008.

Miranda CM, Castiglioni TC. Aripiprazole for the treatment of

Tourette syndrome. Experience in 10 patients. Rev Med Chil

135:773776, 2007.

Moss AJ: Measurement of the QT interval and the risk associated with

QTc interval prolongation: A review. Am J Cardiol 72:23B25B,

1993.

Murphy TK, Bengtson MA, Soto O, Edge PJ, Sajid MW, Shapira N,

Yang M: Case series on the use of aripiprazole for Tourette syn-

drome. Int J Neuropsychopharmacol 8:489490, 2005.

Murphy TK, Mutch PJ, Reid JM, Edge PJ, Storch EA, Bengtson M,

Yang M: Open label aripiprazole in the treatment of youth with tic

disorders. J Child Adolesc Psychopharmacol 19:441447, 2009.

Nikolaus S, Antke C, Muller HW: In vivo imaging of synaptic

function in the central nervous system: II. Mental and affective

disorders. Behav Brain Res 204:3266, 2009.

Osorio RS, Aguera-Ortiz L, Hurtado de Mendoza A, Ramos I, Palomo

T: Treatment of tardive dyskinesia with aripiprazole. Neurotox Res17:432434, 2009.

Owen R, Findling, RL Carlson G, Nyilas M, Iwamoto T, Mankoski R

et al.: Efficacy and Safety of Aripiprazole in the Treatment of

Serious Behavioral Problems Associated with Autistic Disorder in

Children and Adolescents (617 Years Old): Results from a Dou-

ble-Blind, Randomized, Placebo-Controlled Trial (Study CN138-

178). Poster presented at the 55th Annual Meeting of the American

Academy of Child & Adolescent Psychiatry, Chicago, Illinois,

2008a.

Owen R, Marcus R, Aman MG, Manos G, Mankoski R, Assuncao-

Talbott S. et al.: Efficacy and Safety of Aripiprazole in the Treat-

ment of Serious Behavioral Problems Associated with Autistic

Disorder in Children and Adolescents (617 years old): Results

from a Fixed-Dose, Double-Blind, Randomized, Placebo-

Controlled Trial (Study CN138-179). Poster presented at the 55th

Annual Meeting of the American Academy of Child & Adolescent

Psychiatry, Chicago, Ilinois, 2008b.

Reynolds GP, Kirk SL: Metabolic side effects of antipsychotic drug-

pharmacological mechanisms. Pharmacol Ther 2009 Nov 17. [Epub

ahead of print].

Rickards H: Functional neuroimaging in Tourette syndrome. J Psy-

chosom Res 67:575584, 2009.

Robert S, Hamner MB, Durkalski VL, Brown MW, Ulmer HG: An

open-label assessment of aripiprazole in the treatment of PTSD.

Psychopharmacol Bull 42:6980, 2009.

Sallee FR, Kurlan R, Goetz CG, Singer H, Scahill L, Law G, Dittman

VM, Chappell PB: Ziprasidone treatment of children and adoles-

cents with Tourettes syndrome: A pilot study. J Am Acad Child

Adoles Psychiatry 39:292299, 2000.

Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS: A

placebo-controlled trial of risperidone in Tourette syndrome. Neu-

rology 60:11301135, 2003.

Seo WS, Sung HM, Sea HS, Bai DS: Aripiprazole treatment of

children and adolescents with Tourette disorder or chronic tic dis-

order. J Child Adolesc Psychopharmacol 18:197205, 2008.Shapiro AK, Shapiro E, Wayne H: Treatment of Tourettes syndrome

with haloperidol, review of 34 cases. Arch Gen Psychiatry 28:92

97, 1973.

Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR,

Roth BL, Mailman R: Aripiprazole, a novel atypical antipsychotic

drug with a unique and robust pharmacology. Neuropsycho-

pharmacology 28:14001411, 2003.

Singer HS, Szymanski S, Giuliano J, Yokoi F, Dogan AS, Brasic JR,

Zhow Y, Grace AA, Wong DF: Elevated intrasynaptic dopamine

release in Tourettes syndrome measured by PET. Am J Psychiatry

159:13291336, 2002.

Singh MK, Delello M, Adler C. Acute dystonia associated with ar-

ipiprazole in a child. J Am Acad Child Adolesc Psychiatry 46:306

307, 2007.

Stephens RJ, Bassel C, Sandor P: Olanzapine in the treatment of

aggression and tics in children with Tourettes syndromeA pilot

study. J Child Adolesc Psychopharmacol 14: 255266, 2004.

Stigler KA, Diener JT, Kohn AE, Li L, Erickson CA, Posey DJ,

McDougle CJ. Aripiprazole in pervasive developmental disorder

not otherwise specified and Aspergers disorder: A 14-week, pro-

spective, open-label study. J Child Adolesc Psychopharmacol

19:265274, 2009.

Storch EA, Murphy TK, Geffken GR: Reliability and validity of the

Yale Global Tic Severity Scale. Psychol Assess 17:486491,

2005.

Storch EA, Murphy TK, Fernandez M: Factor-analytic study of the

Yale Global Tic Severity Scale. Psychiatry Res 149:231237, 2007.

Su LY, Li XR, Luo XR: The newly revised norms of Child Behavior

Checklist in Hunan Province. Chinese Mental Health Journal12:6769, 1998.

Thompson PDR: Physicians Desk Reference, 61st ed. Montvale (New

Jersey): Thompson Healthcare, 2007.

Valicenti-McDermott MR, Demb H: Clinical effects and adverse re-

actions of off-label use of aripiprazole in children and adolescents

with developmental disabilities. J Child Adolesc Psychopharmacol

16:549560, 2006.

Yang HJ, Soong WT, Chiang CN, Chen WJ: Competence and

behavior/emotional problems among Taiwanese adolescents as re-

ported by parents and teachers. J Am Acad Child Adolesc Psy-

chiatry 39:232239, 2000.

ARIPIPRAZOLE IN TOURETTES DISORDER 297


8/8

Yoo HK, Kim JY, Kim CY: A pilot study of aripiprazole in children

and adolescents with Tourettes disorder. J Child Adolesc Psy-

chopharmacol 16:505506, 2006.

Yoo HK, Choi SH, Park S, Wang HR, Hong JP, Kim CY: An open-

label study of the efficacy and tolerability of aripiprazole for

children and adolescents with tic disorders. J Clin Psychiatry 68:

10881093, 2007.

Zhang MY: Rating scales manual for mental health. Hunan: Hunan

Science and Technology Press, 1998.

Address correspondence to:

Yi Zheng, M.D.

Yun-ping Yang, M.D.

Beijing Anding Hospital

Capital Medical University

XiCheng District

Beijing, China, 100088

E-mail:[email protected]

298 CUI ET AL.

aripripazol y tourette

Documents