Tourettes Syndrome Tourettes Syndrome and Tic Disordersand Tic Disorders

Jess P. Shatkin, MD, MPHJess P. Shatkin, MD, MPH

Vice Chair for EducationVice Chair for Education

NYU Child Study CenterNYU Child Study Center

New York University School of MedicineNew York University School of Medicine

Learning ObjectivesLearning ObjectivesResidents will be able to:Residents will be able to:

1)1) Describe the two cardinal symptoms of Describe the two cardinal symptoms of TouretteTourette’’s Syndromes Syndrome2)2) Identify nine primary categories of rule-out Identify nine primary categories of rule-out diagnoses for Tourettediagnoses for Tourette’’s and two primary s and two primary comorbiditiescomorbidities3)3) Demonstrate an understanding of the natural Demonstrate an understanding of the natural history of the illness by matching the stages of history of the illness by matching the stages of TouretteTourette’’s with the correct age of the patient s with the correct age of the patient 4)4) Identify two psychosocial treatments and three Identify two psychosocial treatments and three pharmacological treatments for Tourettepharmacological treatments for Tourette’’ss5) Demonstrate comfort with rating scales for 5) Demonstrate comfort with rating scales for TouretteTourette’’s and Ti Disorderss and Ti Disorders

What is a tic?What is a tic?

A A ““tictic”” is a sudden, rapid, recurrent, non- is a sudden, rapid, recurrent, non-rhythmic, stereotyped motor movement or rhythmic, stereotyped motor movement or vocalizationvocalization

A tic may be simple (involving only a few A tic may be simple (involving only a few muscles or simple sounds) or complex muscles or simple sounds) or complex (involving multiple groups of muscles (involving multiple groups of muscles recruited in orchestrated bouts or words or recruited in orchestrated bouts or words or sentences)sentences)

Motor Tics (Simple)Motor Tics (Simple)

Generally lasting less than several hundred Generally lasting less than several hundred millisecondsmilliseconds

Examples include:Examples include:eye blinkingeye blinking

nose wrinklingnose wrinkling

neck jerkingneck jerking

shoulder shruggingshoulder shrugging

facial grimacingfacial grimacing

abdominal tensingabdominal tensing

Motor Tics (Complex)Motor Tics (Complex)

Longer in duration than simple tics; usually lasting Longer in duration than simple tics; usually lasting seconds or longerseconds or longerExamples include:Examples include:

hand gestureshand gesturesjumping, touching, pressing, or stompingjumping, touching, pressing, or stompingfacial contortionsfacial contortionsrepeatedly smelling an objectrepeatedly smelling an objectsquatting and/or deep knee bendssquatting and/or deep knee bendsretracing steps and/or twirling when walkingretracing steps and/or twirling when walkingassuming and holding unusual positions (including assuming and holding unusual positions (including ““dystonicdystonic”” tics, such as holding the neck in a tics, such as holding the neck in a particular tensed position)particular tensed position)

Copropraxia & EchopraxiaCopropraxia & Echopraxia

Both are considered complex motor ticsBoth are considered complex motor tics

Copopraxia = a sudden, tic-like vulgar, Copopraxia = a sudden, tic-like vulgar, sexual, or obscene gesturesexual, or obscene gesture

Echopraxia = a mirror phenomena, such Echopraxia = a mirror phenomena, such as involuntary, spontaneous imitation of as involuntary, spontaneous imitation of someone elsesomeone else’’s movementss movements

Vocal Tics (Simple)Vocal Tics (Simple)

Meaningless brief soundsMeaningless brief sounds

Examples include:Examples include:TThroat clearinghroat clearing

GruntingGrunting

SniffingSniffing

SnortingSnorting

ChirpingChirping

Vocal Tics (Complex)Vocal Tics (Complex)

More clearly involve speech and languageMore clearly involve speech and language

Examples include:Examples include:sudden, spontaneous expression of single words sudden, spontaneous expression of single words or phrasesor phrases

speech blockingspeech blocking

sudden and meaningless changes in pitch, sudden and meaningless changes in pitch, emphasis, or volume of speech; emphasis, or volume of speech;

The The ““LaliasLalias””

All are considered complex vocal ticsAll are considered complex vocal tics

Palilalia = repeating onePalilalia = repeating one’’s own sounds or wordss own sounds or words

Echolalia = repeating the last heard sound, word, Echolalia = repeating the last heard sound, word, or phraseor phrase

Coprolalia = the sudden, inappropriate expression Coprolalia = the sudden, inappropriate expression of a socially unacceptable word or phrase that may of a socially unacceptable word or phrase that may include obscenities as well as specific ethnic, include obscenities as well as specific ethnic, racial, or religious slurs (found in fewer than 10% racial, or religious slurs (found in fewer than 10% of individuals with tic disorders)of individuals with tic disorders)

History of TourettesHistory of TourettesThe first case was reported by a French physician, The first case was reported by a French physician, Itard, in 1825. He described the case of the Itard, in 1825. He described the case of the Marquise de Dampierre, a woman of nobility who Marquise de Dampierre, a woman of nobility who was quite important in her time. The Marquise was quite important in her time. The Marquise suffered motor tics, coprolalia, and echolalia from suffered motor tics, coprolalia, and echolalia from the age of 7. Itard wrote:the age of 7. Itard wrote:– ““The more she herself thinks her vulgarities will The more she herself thinks her vulgarities will

be revolting, the more she is tortured by the fear be revolting, the more she is tortured by the fear that she will utter them, and it is precisely this that she will utter them, and it is precisely this preoccupation, that when she can no longer preoccupation, that when she can no longer control it, puts these words at the tip of her control it, puts these words at the tip of her tongue.tongue.””

George Gilles de la TouretteGeorge Gilles de la TouretteIn 1885 another French doctor, Tourette, In 1885 another French doctor, Tourette, described nine cases with the syndrome that described nine cases with the syndrome that now carries his name. One of his cases was now carries his name. One of his cases was the Marquise de Dampierre, who by then the Marquise de Dampierre, who by then was in her nineties. was in her nineties. Throughout much of the 20Throughout much of the 20thth century, century, TouretteTourette’’s was believed to have a s was believed to have a psychogenic origin. More recent research, psychogenic origin. More recent research, however, has resulted in a return to however, has resulted in a return to TouretteTourette’’s initial impression of the disorder s initial impression of the disorder as a nonprogressive, hereditary neurological as a nonprogressive, hereditary neurological condition.condition.

Onset of TouretteOnset of Tourette’’ssTypically, the disorder begins with a Typically, the disorder begins with a simple motor tic on the face (e.g., simple motor tic on the face (e.g., blinking). blinking). The tics persist and generalize to other The tics persist and generalize to other parts of the body; waxing and waning is parts of the body; waxing and waning is typical.typical.Eventually, vocalizations (e.g., sniffing, Eventually, vocalizations (e.g., sniffing, snorting, throat clearing, barking, snorting, throat clearing, barking, hiccuping, or uttering nonsense words or hiccuping, or uttering nonsense words or intelligible words) ensue and are typically intelligible words) ensue and are typically ““explosive.explosive.””

Urges & PremonitionsUrges & Premonitions

Tics are generally experienced as Tics are generally experienced as irresistible but can be suppressed for irresistible but can be suppressed for various lengths of timevarious lengths of time

Some children are not aware of their tics Some children are not aware of their tics but with age a premonitory urge (a rising but with age a premonitory urge (a rising tension or somatic sensation that is tension or somatic sensation that is relieved when the tic occurs) may ariserelieved when the tic occurs) may arise

Premonitory UrgePremonitory Urge““I guess itI guess it’’s sort of an aching feeling in a limb or s sort of an aching feeling in a limb or a body area, or else in my throat if it proceeds a a body area, or else in my throat if it proceeds a vocalization. If I donvocalization. If I don’’t relieve it, it either drives t relieve it, it either drives me crazy or begins to hurt (or both) – in that me crazy or begins to hurt (or both) – in that way itway it’’s both mental and physical.s both mental and physical.””

““A need to tic is an intense feeling that unless I A need to tic is an intense feeling that unless I tic or twitch I feel as if Itic or twitch I feel as if I’’m going to burst. Unless m going to burst. Unless I can physically tic, all of my mental thoughts I can physically tic, all of my mental thoughts center on ticking until I am able to let it out. Itcenter on ticking until I am able to let it out. It’’s s a terrible urge that needs to be satisfied.”a terrible urge that needs to be satisfied.”

LeckmanLeckman

Frequency & Duration of TicsFrequency & Duration of TicsIndividuals may feel the need to perform the tic Individuals may feel the need to perform the tic repeatedly or in a specific way until it has been repeatedly or in a specific way until it has been done done ““just rightjust right””Tics are often emitted in bouts of one or several Tics are often emitted in bouts of one or several tics, separated by periods without tics lasting tics, separated by periods without tics lasting seconds to hoursseconds to hoursTics generally disappear during sleep and during Tics generally disappear during sleep and during intense sexual arousalintense sexual arousalTics generally change in severity over the course of Tics generally change in severity over the course of a day and may change in location over timea day and may change in location over timeTics may vary in their frequency and disruptivity Tics may vary in their frequency and disruptivity depending upon the circumstance (e.g., school, depending upon the circumstance (e.g., school, home, work, etc.)home, work, etc.)

When Do Tics Occur?When Do Tics Occur?

Tics are often more frequent when an Tics are often more frequent when an individual relaxes in private (e.g., watching individual relaxes in private (e.g., watching TV) and less frequent when an individual TV) and less frequent when an individual engages in directed, effortful activity (e.g., engages in directed, effortful activity (e.g., reading)reading)

Tics may be exacerbated during periods of Tics may be exacerbated during periods of stressstress

Other Symptoms of TouretteOther Symptoms of Tourette’’ss

Other abnormal movements and behavior Other abnormal movements and behavior patterns can also develop:patterns can also develop:

StutteringStuttering

Sticking out the tongueSticking out the tongue

Smelling objectsSmelling objects

Pounding the chest or bodyPounding the chest or body

Grabbing at oneGrabbing at one’’s genitalss genitals

Compulsive touchingCompulsive touching

Bruxism Bruxism

EchopraxiaEchopraxia

DSM-IV Diagnostic CriteriaDSM-IV Diagnostic CriteriaBoth multiple motor and one or more vocal tics have been Both multiple motor and one or more vocal tics have been present at some time during the illness, although not present at some time during the illness, although not necessarily concurrently. (A tic is a sudden, rapid, necessarily concurrently. (A tic is a sudden, rapid, recurrent, nonrhythmic, stereotyped motor movement or recurrent, nonrhythmic, stereotyped motor movement or vocalization.)vocalization.)The tics occur many times a day (usually in bouts) nearly The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of more than every day or intermittently throughout a period of more than 1 year, and during this period there was never a tic-free 1 year, and during this period there was never a tic-free period of more than 3 consecutive months.period of more than 3 consecutive months.The onset is before age 18 years.The onset is before age 18 years.The disturbance is not due to the direct physiological effects The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical of a substance (e.g., stimulants) or a general medical condition (e.g., Huntingtoncondition (e.g., Huntington’’s disease or postviral s disease or postviral encephalitis).encephalitis).

Differential Diagnosis of TourettesDifferential Diagnosis of Tourettes

Transient tics of childhoodTransient tics of childhood

Prenatal/perinatal insultsPrenatal/perinatal insults– Congenital CNS defectsCongenital CNS defects– Birth defectsBirth defects

Infections/post-infectiousInfections/post-infectious– Post-viral encephalitisPost-viral encephalitis– HIV infections of CNSHIV infections of CNS– Lyme diseaseLyme disease– PANDAS PANDAS

Differential Diagnosis of Tourettes (2)Differential Diagnosis of Tourettes (2)

Head traumaHead trauma

Toxin exposureToxin exposure– Carbon monoxide or gasolineCarbon monoxide or gasoline

DrugsDrugs– Neuroleptics, levodopa, opiate withdrawal, Neuroleptics, levodopa, opiate withdrawal,

amphetamines, lamotrigineamphetamines, lamotrigine

Chromosomal abnormalitiesChromosomal abnormalities– XYYXYY– XXYXXY– Fragile X syndromeFragile X syndrome

Differential Diagnosis of Tourettes (3)Differential Diagnosis of Tourettes (3)

Genetic disordersGenetic disorders– Hallervorden-Spatz DiseaseHallervorden-Spatz Disease– WilsonWilson’’s Disease s Disease – HyperekplexiasHyperekplexias– Rett SyndromeRett Syndrome– NeuroacanthocytosisNeuroacanthocytosis

Autism/AspergerAutism/Asperger’’s syndromes syndrome

Natural History of Tic DisordersNatural History of Tic Disorders20-25% of people will develop a transient tic at 20-25% of people will develop a transient tic at some point in their livessome point in their livesWith Tourettes after onset there is typically:With Tourettes after onset there is typically:– Prepubertal exacerbationPrepubertal exacerbation– Postpubertal attenuationPostpubertal attenuation– Adult stabilizationAdult stabilization

Once thought to be a lifelong disorder, retro-Once thought to be a lifelong disorder, retro-spective cohort studies have now demonstrated spective cohort studies have now demonstrated 50% of TS patients to be asymptomatic by age 1850% of TS patients to be asymptomatic by age 18The adulthood course of TS is generally stable with The adulthood course of TS is generally stable with up to 65% of patients not exhibiting any changes in up to 65% of patients not exhibiting any changes in symptomatology over 5 years.symptomatology over 5 years.

Epidemiology of TourettesEpidemiology of TourettesFound in all racial and ethnic groupsFound in all racial and ethnic groupsExact prevalence is unknown b/c of misdiagnosis, Exact prevalence is unknown b/c of misdiagnosis, underreporting, and few large epidemiological underreporting, and few large epidemiological studiesstudiesIn one large screening study of over 28,000 Israeli In one large screening study of over 28,000 Israeli army recruits (16-17 y/o), an overall rate of army recruits (16-17 y/o), an overall rate of 4.3/10,000 (4.9 in M; 3.1 in F)4.3/10,000 (4.9 in M; 3.1 in F)In a study of 4500 children aged 9, 11, & 13 in the In a study of 4500 children aged 9, 11, & 13 in the southeastern U.S. found a total prevalence of southeastern U.S. found a total prevalence of 10/10,00010/10,000DSM-IV reports a prevalence of 3-5/10,000 in DSM-IV reports a prevalence of 3-5/10,000 in children and 1-2/10,000 in adultschildren and 1-2/10,000 in adults

Structural Neuroimaging FindingsStructural Neuroimaging Findings

General neuroimaging and neuropathological General neuroimaging and neuropathological examination of TS brains is normalexamination of TS brains is normal

However, morphological abnormalities have However, morphological abnormalities have been reported in volumetric MRI studies:been reported in volumetric MRI studies:– A loss or reversal of normal asymmetries of the A loss or reversal of normal asymmetries of the

putamen and lenticular nucleus has been notedputamen and lenticular nucleus has been noted– Corpus callosum morphology (and therefore Corpus callosum morphology (and therefore

interhemispheric connectivity) appears to be interhemispheric connectivity) appears to be altered in (at least) males with TSaltered in (at least) males with TS

Functional Neuroimaging FindingsFunctional Neuroimaging FindingsSPET studies have detected hypoperfusion SPET studies have detected hypoperfusion in various brain structures bilaterally in various brain structures bilaterally (including the BG, orbitofrontal cortex, and (including the BG, orbitofrontal cortex, and temporal lobes)temporal lobes)PET scans have shown decreased activity in PET scans have shown decreased activity in prefrontal cortices and striatumprefrontal cortices and striatumfMRI studies have suggested:fMRI studies have suggested:

Increased utilization of the supplemental motor cortexIncreased utilization of the supplemental motor cortexSignificant b/l decrease in GP and putamen activitySignificant b/l decrease in GP and putamen activityAbnormal signals with tic occurrence in the primary Abnormal signals with tic occurrence in the primary motor and Brocamotor and Broca’’s areas, corresponding to motor and s areas, corresponding to motor and vocal tics; and striatal activityvocal tics; and striatal activity

Genetics of TourettesGenetics of TourettesNumerous family studies have demonstrated that Numerous family studies have demonstrated that TS is inherited and that 1TS is inherited and that 1stst degree relatives of a degree relatives of a proband are at increased riskproband are at increased riskIncreased rates of chronic & transient tics are also Increased rates of chronic & transient tics are also found among 1found among 1stst degree relatives, suggesting degree relatives, suggesting alternate expressions of TSalternate expressions of TSTwin studies demonstrate 8% concordance in Twin studies demonstrate 8% concordance in dizygotics and 53% in monozygotes; if all tic dizygotics and 53% in monozygotes; if all tic disorders are taken into account, dizygotes are disorders are taken into account, dizygotes are 22% concordant and monozygotes are 77%22% concordant and monozygotes are 77%Incomplete penetration/concordance suggests Incomplete penetration/concordance suggests other factors are at play (e.g., genomic imprinting)other factors are at play (e.g., genomic imprinting)

Comorbidities: ADHDComorbidities: ADHD

The rate of co-occurrence of ADHD and TS The rate of co-occurrence of ADHD and TS has been reported as being between 8 – 80%has been reported as being between 8 – 80%

Regardless of the precise frequency, it is Regardless of the precise frequency, it is apparent that ADHD and TS do frequently apparent that ADHD and TS do frequently occur together in those patients who seek occur together in those patients who seek medical attentionmedical attention

ADHD also occurs at an increased rate in the ADHD also occurs at an increased rate in the probands of patients with TSprobands of patients with TS

These facts suggest a shared group of genesThese facts suggest a shared group of genes

Comorbidities: OCDComorbidities: OCDObsessive compulsive symptoms and OCD are Obsessive compulsive symptoms and OCD are strongly associated with TSstrongly associated with TS– Approximately 8% of patients with OCD have TSApproximately 8% of patients with OCD have TS– Approximately 35% of patients with TS have OCDApproximately 35% of patients with TS have OCD

A number of studies have demonstrated a difference A number of studies have demonstrated a difference in the nature of obsessions and compulsions in TS in the nature of obsessions and compulsions in TS patients vs. pure OCD patientspatients vs. pure OCD patients– TS patients tend to have obsessions centered on TS patients tend to have obsessions centered on

symmetry and getting things symmetry and getting things ““just right;just right;”” in addition, they in addition, they tend to have more violent and sexual obsessions, are tend to have more violent and sexual obsessions, are more often male, have an earlier age of onset, and may more often male, have an earlier age of onset, and may be less responsive to treatment with SSRIsbe less responsive to treatment with SSRIs

– Also more touching, counting, blinking and staring Also more touching, counting, blinking and staring obsessionsobsessions

– Patients with pure OCD report more contamination Patients with pure OCD report more contamination obsessions and washing behaviorsobsessions and washing behaviors

Comorbidities: OtherComorbidities: Other

A variety of other behaviors and A variety of other behaviors and abnormalities have been reported to be abnormalities have been reported to be present in a higher than expected frequency present in a higher than expected frequency among TS patients:among TS patients:

Anxiety disorders (esp, phobias)Anxiety disorders (esp, phobias)

DepressionDepression

Oppositional Defiant DisorderOppositional Defiant Disorder

Restless Leg SyndromeRestless Leg Syndrome

StutteringStuttering

Comorbidities: PsychosocialComorbidities: Psychosocial

Children with TS often have difficulties at Children with TS often have difficulties at school, such as grade retention or special school, such as grade retention or special education placementeducation placement– Up to 1/3 may be diagnosed with an LD, which Up to 1/3 may be diagnosed with an LD, which

seems to be more related to comorbid ADHD seems to be more related to comorbid ADHD than the tic symptoms of TSthan the tic symptoms of TS

Children with TS have increased difficulties Children with TS have increased difficulties with peer relationships and social functioningwith peer relationships and social functioning

PANDASPANDASPPediatric ediatric AAutoimmune utoimmune NNeuropsychiatric europsychiatric DDisorders isorders AAssociated with ssociated with SStreptrepA possible cause of OCD and TourettesA possible cause of OCD and Tourettes– Group A Group A ββ-hemolytic streptococcal infection in -hemolytic streptococcal infection in

select individuals may induce neuronal damage select individuals may induce neuronal damage

Rat striata infused with sera from patients Rat striata infused with sera from patients with TS with a high level of strep antibodies with TS with a high level of strep antibodies demonstrated an increase in total and daily demonstrated an increase in total and daily oral stereotypies vs. rats with sera from oral stereotypies vs. rats with sera from normal controls and TS patients with low normal controls and TS patients with low levels of antibodieslevels of antibodies

Treatments: PsychosocialTreatments: Psychosocial

EducationEducation– Patient, family, and schoolPatient, family, and school

Counseling for family and patientCounseling for family and patient

Relaxation therapyRelaxation therapy

Supportive therapySupportive therapy

Habit Reversal TherapyHabit Reversal Therapy

HRTHRT4 Components:4 Components:1.1. Awareness trainingAwareness training

--learn to recognize when they--learn to recognize when they’’re tickingre ticking

2.2. Development of a competing responseDevelopment of a competing response--less noticeable, can be carried out for more than a few --less noticeable, can be carried out for more than a few

minutesminutes

3.3. Building motivationBuilding motivation--make a list of the problems caused by tics, all the bad --make a list of the problems caused by tics, all the bad

things it bringsthings it brings

4.4. Generalization of new skillsGeneralization of new skills--practice the skills in new contexts and locations--practice the skills in new contexts and locations

Treatments: PharmacologicalTreatments: PharmacologicalMild illness is unlikely to require medicationMild illness is unlikely to require medicationαα-2 agonists-2 agonists

TenexTenexClonidineClonidine

NeurolepticsNeurolepticsOther dopaminergic agentsOther dopaminergic agents

Metaclopramide (D-2 antagonist without antipsychotic properties)Metaclopramide (D-2 antagonist without antipsychotic properties)Pergolide (dopamine agonist)Pergolide (dopamine agonist)

OthersOthersFlunarizineFlunarizineNaloxoneNaloxoneOpiatesOpiatesTHCTHCBaclofenBaclofenNicotineNicotineDesipramineDesipramineSSRIsSSRIs

Antipsychotic TreatmentAntipsychotic Treatment

Historically high potency first generation Historically high potency first generation antipsychoticsantipsychotics– Pimozide (Orap) best studiedPimozide (Orap) best studied– HaloperidolHaloperidol

Severe side effects has led to search for Severe side effects has led to search for alternative 2alternative 2ndnd generation antipsychotics generation antipsychotics

Yale Global Tic Severity ScaleYale Global Tic Severity ScaleA simple tracking device for assessing the nature A simple tracking device for assessing the nature and severity of ticsand severity of tics

Addresses the following categories:Addresses the following categories:Simple motorSimple motor

Complex motorComplex motor

Simple phonicSimple phonic

Complex phonicComplex phonic

Behavior Behavior

Uses a Likert Scale Uses a Likert Scale

Most tic exacerbations will be identified with the Most tic exacerbations will be identified with the change on the YGTSS is greater than change on the YGTSS is greater than ““99”” and the and the total current YGTSS score exceeds total current YGTSS score exceeds ““1919””

AripiprazoleAripiprazole

A 12-week, open-label trial, flexible dosing of aripiprazole performed with 15 youth, aged 7-19 years. YGTSS at baseline, weeks 3, 5, 9, and end point scores were compared. – Significant decreases in the scores of motor and phonic tics, global

impairment, and global severity were demonstrated between baseline and week 3, and the scores continued to improve thereafter. (Seo et al, 2008)

Open-label, flexible-dose 6-week study of 16 youth (15 males) Open-label, flexible-dose 6-week study of 16 youth (15 males) aged 8-17 years; weekly ratings for OCD, tics, ADHD and Sefx; aged 8-17 years; weekly ratings for OCD, tics, ADHD and Sefx; ave dose was 3.3 mg/d. ave dose was 3.3 mg/d. – Significant pre-and post-treatment differences were ascertained for the Significant pre-and post-treatment differences were ascertained for the

YGTSS for motor, phonic, and total tics. Significant improvements in co-YGTSS for motor, phonic, and total tics. Significant improvements in co-morbid disorders as well, including OCD, ADHD, and depressive disorders. morbid disorders as well, including OCD, ADHD, and depressive disorders. (Murphy et al, 2009)(Murphy et al, 2009)

11 subjects (10 male), 9-19 years, who did not respond or couldn’t tolerate prior meds, treated with flexible dose for 10 weeks; mean dose 4.5 mg/d– YGTSS and CGI-tic severity scores showed significant improvement in 10 of

11 subjects (Lyon et al, 2009)

Treatments: Comorbid ConditionsTreatments: Comorbid Conditions

OCDOCDSSRIs +/- antipsychoticsSSRIs +/- antipsychotics

ADHDADHD– History of concern that stimulants would History of concern that stimulants would ““unmasunmas

kk”” tics tics– Multicenter, RDBPC study of MTP and clonidine Multicenter, RDBPC study of MTP and clonidine

(alone and in combination) in 136 children with (alone and in combination) in 136 children with Tourettes demonstrated:Tourettes demonstrated:

Significant improvement in ADHD with both treatmentsSignificant improvement in ADHD with both treatmentsGreatest benefit resulting from a combination of bothGreatest benefit resulting from a combination of bothThe proportion of subjects reporting a worsening of The proportion of subjects reporting a worsening of tics was no higher amongst those treated with MTP tics was no higher amongst those treated with MTP alone (20%) vs. clonidine (26%) vs. placebo (22%)alone (20%) vs. clonidine (26%) vs. placebo (22%)

Clonidine PatchClonidine Patch437 patients, who met Chinese Classification of Mental 437 patients, who met Chinese Classification of Mental Disorders-third edition diagnostic criteria for transient tic Disorders-third edition diagnostic criteria for transient tic disorder (5%), chronic motor or vocal tic disorder (40%) or disorder (5%), chronic motor or vocal tic disorder (40%) or TouretteTourette’’s disorder (55%), aged 6-18 yearss disorder (55%), aged 6-18 yearsParticipants in the active treatment group were treated with Participants in the active treatment group were treated with a clonidine adhesive patch and participants in the clinical a clonidine adhesive patch and participants in the clinical control group with a placebo adhesive patch for 4 weeks. control group with a placebo adhesive patch for 4 weeks. The dosage of the clonidine adhesive patch was 0.1mg, The dosage of the clonidine adhesive patch was 0.1mg, 0.15mg or 0.2mg per day, depending on each participant's 0.15mg or 0.2mg per day, depending on each participant's bodyweight. bodyweight. After 4 weeks of treatment the active treatment group After 4 weeks of treatment the active treatment group participants' YGTSS score was significantly lower than that participants' YGTSS score was significantly lower than that of the clinical control group (p=0.03). Further, the active of the clinical control group (p=0.03). Further, the active treatment group had a significantly better therapeutic treatment group had a significantly better therapeutic response than the clinical control group (p=0.003). The response than the clinical control group (p=0.003). The response rate in the active treatment group was 68.85% response rate in the active treatment group was 68.85% compared to 46.85% in the clinical control group (p=0.0001). compared to 46.85% in the clinical control group (p=0.0001).

Du et al, 2008Du et al, 2008

Risperidone vs. ClonidineRisperidone vs. Clonidine

7 to 14-day single-blind, placebo lead-in, 21 subjects (7-17 7 to 14-day single-blind, placebo lead-in, 21 subjects (7-17 years) randomly assigned to 8 weeks of double-blind years) randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Followed tics, OCD, treatment with clonidine or risperidone. Followed tics, OCD, and ADHD symptoms.and ADHD symptoms.

Risperidone and clonidine appeared equally effective in the Risperidone and clonidine appeared equally effective in the treatment of tics as rated by YGTSS. Risperidone produced treatment of tics as rated by YGTSS. Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. a 26% reduction.

Among subjects with comorbid obsessive-compulsive Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). clonidine group responded to treatment (not significant).

Gaffney et al, 2002Gaffney et al, 2002