7262019

1

Update on

Tourette

DisorderREBECCA K LEHMAN MD FAAN

ASSOCIATE PROFESSOR OF CLINICAL PEDIATRICS (CHILD NEUROLOGY)

PALMETTO HEALTH-UNIVERSITY OF SOUTH CAROLINA MEDICAL GROUP

PRISMA HEALTH CHILDRENrsquoS HOSPITAL-MIDLANDS

AUGUST 9 2019

Disclosures

Financial disclosures

Reimbursement from TAA for travel to MAB meeting and lectures

Participating (Sub-IPIRater) in clinical trials for Neurocrine Teva and Emalex Reimbursed for travel to investigator meetings No other financial conflicts

All of the treatments for Tourette Disorder are off-label with the following exceptions

Haloperidol (3 years and older)

Pimozide (12 years and older)

Aripiprazole (6-18 years)

Tetrabenazine (orphan drug designation for children 5-16 years)

1

2

7262019

2

Objectives

By the end of the lecture attendees should be able to

Describe the clinical characteristics of tics

Define Tourette Disorder (Syndrome)

Review the symptom criteria for the diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections)

Examine the controversies surrounding the diagnosis and treatment of PANDAS

List the neuropsychiatric conditions that commonly co-occur with TD

Outline the range of management strategies for TD

Identify resources that are available for patient education and support

What are tics

Movements or vocalizations that are

Sudden

Abrupt

Transient

Repetitive

Coordinated (stereotyped)

3

4

7262019

3

Premonitory Urge

Leckman JF Walker DE Cohen DJ 1993

Other Characteristics of Tics

bull Variable in appearance and frequency over time

bull Briefly suppressible

bull Worsened by stress and excitement

bull Often reduced by focused concentration

bull May persist in sleep but often abate

5

6

7262019

4

Classification of Tics

Tic Symptom Dimensions Examples

Simple motor tics Sudden brief

meaningless movementsEye blinking nose twitching grimacing grinning pouting

mouth opening head jerking shoulder shrugging abdominal

or buttock tensing kicking finger movements rapid jerking of

any part of the body

Complex motor tics Slower longer more

ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching

objectsself thrusting arms throwing banging gestures with

hands gyrating and bending dystonic postures copropraxia

(obscene gestures)

Simple phonic tics Sudden meaningless

sounds or noises

Throat clearing coughing sniffing spitting screeching

barking grunting gurgling clacking hissing sucking animal

noises and innumerable other sounds

Complex phonic tics Sudden more

ldquomeaningfulrdquo utterances

Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)

speech atypicalities (variations in pitch volume etc)

palilalia (repetition of onersquos own words) or echolalia

(repetition of anotherrsquos words or phrases) coprolalia

(obscene or inappropriate words or phrases)

I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me

7

8

7262019

2

Objectives

By the end of the lecture attendees should be able to

Describe the clinical characteristics of tics

Define Tourette Disorder (Syndrome)

Review the symptom criteria for the diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections)

Examine the controversies surrounding the diagnosis and treatment of PANDAS

List the neuropsychiatric conditions that commonly co-occur with TD

Outline the range of management strategies for TD

Identify resources that are available for patient education and support

What are tics

Movements or vocalizations that are

Sudden

Abrupt

Transient

Repetitive

Coordinated (stereotyped)

3

4

7262019

3

Premonitory Urge

Leckman JF Walker DE Cohen DJ 1993

Other Characteristics of Tics

bull Variable in appearance and frequency over time

bull Briefly suppressible

bull Worsened by stress and excitement

bull Often reduced by focused concentration

bull May persist in sleep but often abate

5

6

7262019

4

Classification of Tics

Tic Symptom Dimensions Examples

Simple motor tics Sudden brief

meaningless movementsEye blinking nose twitching grimacing grinning pouting

mouth opening head jerking shoulder shrugging abdominal

or buttock tensing kicking finger movements rapid jerking of

any part of the body

Complex motor tics Slower longer more

ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching

objectsself thrusting arms throwing banging gestures with

hands gyrating and bending dystonic postures copropraxia

(obscene gestures)

Simple phonic tics Sudden meaningless

sounds or noises

Throat clearing coughing sniffing spitting screeching

barking grunting gurgling clacking hissing sucking animal

noises and innumerable other sounds

Complex phonic tics Sudden more

ldquomeaningfulrdquo utterances

Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)

speech atypicalities (variations in pitch volume etc)

palilalia (repetition of onersquos own words) or echolalia

(repetition of anotherrsquos words or phrases) coprolalia

(obscene or inappropriate words or phrases)

I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me

7

8

7262019

3

Premonitory Urge

Leckman JF Walker DE Cohen DJ 1993

Other Characteristics of Tics

bull Variable in appearance and frequency over time

bull Briefly suppressible

bull Worsened by stress and excitement

bull Often reduced by focused concentration

bull May persist in sleep but often abate

5

6

7262019

4

Classification of Tics

Tic Symptom Dimensions Examples

Simple motor tics Sudden brief

meaningless movementsEye blinking nose twitching grimacing grinning pouting

mouth opening head jerking shoulder shrugging abdominal

or buttock tensing kicking finger movements rapid jerking of

any part of the body

Complex motor tics Slower longer more

ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching

objectsself thrusting arms throwing banging gestures with

hands gyrating and bending dystonic postures copropraxia

(obscene gestures)

Simple phonic tics Sudden meaningless

sounds or noises

Throat clearing coughing sniffing spitting screeching

barking grunting gurgling clacking hissing sucking animal

noises and innumerable other sounds

Complex phonic tics Sudden more

ldquomeaningfulrdquo utterances

Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)

speech atypicalities (variations in pitch volume etc)

palilalia (repetition of onersquos own words) or echolalia

(repetition of anotherrsquos words or phrases) coprolalia

(obscene or inappropriate words or phrases)

I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me

7

8

7262019

4

Classification of Tics

Tic Symptom Dimensions Examples

Simple motor tics Sudden brief

meaningless movementsEye blinking nose twitching grimacing grinning pouting

mouth opening head jerking shoulder shrugging abdominal

or buttock tensing kicking finger movements rapid jerking of

any part of the body

Complex motor tics Slower longer more

ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching

objectsself thrusting arms throwing banging gestures with

hands gyrating and bending dystonic postures copropraxia

(obscene gestures)

Simple phonic tics Sudden meaningless

sounds or noises

Throat clearing coughing sniffing spitting screeching

barking grunting gurgling clacking hissing sucking animal

noises and innumerable other sounds

Complex phonic tics Sudden more

ldquomeaningfulrdquo utterances

Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)

speech atypicalities (variations in pitch volume etc)

palilalia (repetition of onersquos own words) or echolalia

(repetition of anotherrsquos words or phrases) coprolalia

(obscene or inappropriate words or phrases)

I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me

7

8

7262019

5

Tourette Disorder

(Syndrome)

A Both multiple motor and gt= 1 vocal tics have been present at some time during the illness although not necessarily concurrently

B The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of gt1 year and during this period there was never a tic-free period of gt3 consecutive months

C Onset before age 18 years

D The disturbance is not due to the direct physiological effects of a substance (eg stimulants) or a general medical condition (eg HD or post-viral encephalitis)

9

10

7262019

6

Other Tic Disorders

bull Persistent (Chronic) Motor Tic Disorder

bull Multiple motor tics

bull Duration gt1 year

bull Persistent (Chronic) Vocal Tic Disorder

bull Multiple vocal tics

bull Duration gt1 year

Other Tic Disorders

Provisional Tic Disorder

Single or multiple motor andor vocal tics

Duration gt4 weeks but lt12 consecutive months

Other Specified Tic Disorder Unspecified Tic

Disorder

Any tic disorder that does not meet criteria for a

specific tic disorder (eg tics lasting lt4 weeks onset

after age 18)

11

12

7262019

7

Epidemiology

bull Boys girls = 3-4 1

bull Affects all ethnic groups

bull Prevalence among school-age children

Provisional (transient) tic disorders ndash 20-25

Chronic tic disorders ndash ~1

Tourette syndrome ndash 03-08

Prevalence of TD

Community studies 06

Diagnosed + Not Diagnosed

Ages 0-19 years

National survey data 03

Diagnosed only

Ages 6-17 years

Suggests that ~50 of

children with TS are

undiagnosed

Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)

13

14

7262019

8

Copyright copy1998 American Academy of Pediatrics

Leckman J F et al Pediatrics 199810214-19

Take Home Point 1

15

16

7262019

9

Differential Diagnosis

Eye rolling -gt Absence seizures

Blinking -gt Allergy poor vision blepharospasm

Facial grimacing -gt Dystonia

Sniffing -gt Allergy

Scratching -gt Scabies lice skin disorders

Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias

Extremely exaggerated tics -gt Functional movement disorder

Other movement disorders (myoclonus tremor chorea dystonia)

Compulsions

PANDAS

Pediatric Autoimmune Neuropsychiatric Disorder

Associated with Streptococcal Infections (Swedo

et al 1998)

OCD and or tics

Prepubertal onset

Episodic (saw-tooth) course

Associated with Group A beta-hemolytic Strep

infections

Association with neurological signs

17

18

7262019

10

PANS

Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)

Abrupt dramatic onset

OCD or severely restricted food intake

Two or more of

Anxiety

Emotional lability or depression

Irritability aggression andor severely oppositional behavior

Behavioral regression

Deterioration in school

Sensory or motor abnormalities

Somatic symptoms including sleep disturbances enuresis and urinary frequency

Symptoms not better explained by another neurological or medical disorder

Cunningham Panel

Antibody Moleculara Upper

Limit of Normal

Hesselmark Upper

Limit of Normal

Calcium

Calmodulin Kinase II

130 197

Anti-Dopamine

Receptor 1

8000 15200

Anti-Dopamine

Receptor 2

16000 18400

Lysoganglioside

GM01 Antibody

640 1280

Beta-Tubulin

Antibody

1000 8000

19

20

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

6

Other Tic Disorders

bull Persistent (Chronic) Motor Tic Disorder

bull Multiple motor tics

bull Duration gt1 year

bull Persistent (Chronic) Vocal Tic Disorder

bull Multiple vocal tics

bull Duration gt1 year

Other Tic Disorders

Provisional Tic Disorder

Single or multiple motor andor vocal tics

Duration gt4 weeks but lt12 consecutive months

Other Specified Tic Disorder Unspecified Tic

Disorder

Any tic disorder that does not meet criteria for a

specific tic disorder (eg tics lasting lt4 weeks onset

after age 18)

11

12

7262019

7

Epidemiology

bull Boys girls = 3-4 1

bull Affects all ethnic groups

bull Prevalence among school-age children

Provisional (transient) tic disorders ndash 20-25

Chronic tic disorders ndash ~1

Tourette syndrome ndash 03-08

Prevalence of TD

Community studies 06

Diagnosed + Not Diagnosed

Ages 0-19 years

National survey data 03

Diagnosed only

Ages 6-17 years

Suggests that ~50 of

children with TS are

undiagnosed

Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)

13

14

7262019

8

Copyright copy1998 American Academy of Pediatrics

Leckman J F et al Pediatrics 199810214-19

Take Home Point 1

15

16

7262019

9

Differential Diagnosis

Eye rolling -gt Absence seizures

Blinking -gt Allergy poor vision blepharospasm

Facial grimacing -gt Dystonia

Sniffing -gt Allergy

Scratching -gt Scabies lice skin disorders

Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias

Extremely exaggerated tics -gt Functional movement disorder

Other movement disorders (myoclonus tremor chorea dystonia)

Compulsions

PANDAS

Pediatric Autoimmune Neuropsychiatric Disorder

Associated with Streptococcal Infections (Swedo

et al 1998)

OCD and or tics

Prepubertal onset

Episodic (saw-tooth) course

Associated with Group A beta-hemolytic Strep

infections

Association with neurological signs

17

18

7262019

10

PANS

Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)

Abrupt dramatic onset

OCD or severely restricted food intake

Two or more of

Anxiety

Emotional lability or depression

Irritability aggression andor severely oppositional behavior

Behavioral regression

Deterioration in school

Sensory or motor abnormalities

Somatic symptoms including sleep disturbances enuresis and urinary frequency

Symptoms not better explained by another neurological or medical disorder

Cunningham Panel

Antibody Moleculara Upper

Limit of Normal

Hesselmark Upper

Limit of Normal

Calcium

Calmodulin Kinase II

130 197

Anti-Dopamine

Receptor 1

8000 15200

Anti-Dopamine

Receptor 2

16000 18400

Lysoganglioside

GM01 Antibody

640 1280

Beta-Tubulin

Antibody

1000 8000

19

20

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

7

Epidemiology

bull Boys girls = 3-4 1

bull Affects all ethnic groups

bull Prevalence among school-age children

Provisional (transient) tic disorders ndash 20-25

Chronic tic disorders ndash ~1

Tourette syndrome ndash 03-08

Prevalence of TD

Community studies 06

Diagnosed + Not Diagnosed

Ages 0-19 years

National survey data 03

Diagnosed only

Ages 6-17 years

Suggests that ~50 of

children with TS are

undiagnosed

Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)

13

14

7262019

8

Copyright copy1998 American Academy of Pediatrics

Leckman J F et al Pediatrics 199810214-19

Take Home Point 1

15

16

7262019

9

Differential Diagnosis

Eye rolling -gt Absence seizures

Blinking -gt Allergy poor vision blepharospasm

Facial grimacing -gt Dystonia

Sniffing -gt Allergy

Scratching -gt Scabies lice skin disorders

Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias

Extremely exaggerated tics -gt Functional movement disorder

Other movement disorders (myoclonus tremor chorea dystonia)

Compulsions

PANDAS

Pediatric Autoimmune Neuropsychiatric Disorder

Associated with Streptococcal Infections (Swedo

et al 1998)

OCD and or tics

Prepubertal onset

Episodic (saw-tooth) course

Associated with Group A beta-hemolytic Strep

infections

Association with neurological signs

17

18

7262019

10

PANS

Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)

Abrupt dramatic onset

OCD or severely restricted food intake

Two or more of

Anxiety

Emotional lability or depression

Irritability aggression andor severely oppositional behavior

Behavioral regression

Deterioration in school

Sensory or motor abnormalities

Somatic symptoms including sleep disturbances enuresis and urinary frequency

Symptoms not better explained by another neurological or medical disorder

Cunningham Panel

Antibody Moleculara Upper

Limit of Normal

Hesselmark Upper

Limit of Normal

Calcium

Calmodulin Kinase II

130 197

Anti-Dopamine

Receptor 1

8000 15200

Anti-Dopamine

Receptor 2

16000 18400

Lysoganglioside

GM01 Antibody

640 1280

Beta-Tubulin

Antibody

1000 8000

19

20

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

8

Copyright copy1998 American Academy of Pediatrics

Leckman J F et al Pediatrics 199810214-19

Take Home Point 1

15

16

7262019

9

Differential Diagnosis

Eye rolling -gt Absence seizures

Blinking -gt Allergy poor vision blepharospasm

Facial grimacing -gt Dystonia

Sniffing -gt Allergy

Scratching -gt Scabies lice skin disorders

Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias

Extremely exaggerated tics -gt Functional movement disorder

Other movement disorders (myoclonus tremor chorea dystonia)

Compulsions

PANDAS

Pediatric Autoimmune Neuropsychiatric Disorder

Associated with Streptococcal Infections (Swedo

et al 1998)

OCD and or tics

Prepubertal onset

Episodic (saw-tooth) course

Associated with Group A beta-hemolytic Strep

infections

Association with neurological signs

17

18

7262019

10

PANS

Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)

Abrupt dramatic onset

OCD or severely restricted food intake

Two or more of

Anxiety

Emotional lability or depression

Irritability aggression andor severely oppositional behavior

Behavioral regression

Deterioration in school

Sensory or motor abnormalities

Somatic symptoms including sleep disturbances enuresis and urinary frequency

Symptoms not better explained by another neurological or medical disorder

Cunningham Panel

Antibody Moleculara Upper

Limit of Normal

Hesselmark Upper

Limit of Normal

Calcium

Calmodulin Kinase II

130 197

Anti-Dopamine

Receptor 1

8000 15200

Anti-Dopamine

Receptor 2

16000 18400

Lysoganglioside

GM01 Antibody

640 1280

Beta-Tubulin

Antibody

1000 8000

19

20

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

9

Differential Diagnosis

Eye rolling -gt Absence seizures

Blinking -gt Allergy poor vision blepharospasm

Facial grimacing -gt Dystonia

Sniffing -gt Allergy

Scratching -gt Scabies lice skin disorders

Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias

Extremely exaggerated tics -gt Functional movement disorder

Other movement disorders (myoclonus tremor chorea dystonia)

Compulsions

PANDAS

Pediatric Autoimmune Neuropsychiatric Disorder

Associated with Streptococcal Infections (Swedo

et al 1998)

OCD and or tics

Prepubertal onset

Episodic (saw-tooth) course

Associated with Group A beta-hemolytic Strep

infections

Association with neurological signs

17

18

7262019

10

PANS

Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)

Abrupt dramatic onset

OCD or severely restricted food intake

Two or more of

Anxiety

Emotional lability or depression

Irritability aggression andor severely oppositional behavior

Behavioral regression

Deterioration in school

Sensory or motor abnormalities

Somatic symptoms including sleep disturbances enuresis and urinary frequency

Symptoms not better explained by another neurological or medical disorder

Cunningham Panel

Antibody Moleculara Upper

Limit of Normal

Hesselmark Upper

Limit of Normal

Calcium

Calmodulin Kinase II

130 197

Anti-Dopamine

Receptor 1

8000 15200

Anti-Dopamine

Receptor 2

16000 18400

Lysoganglioside

GM01 Antibody

640 1280

Beta-Tubulin

Antibody

1000 8000

19

20

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

10

PANS

Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)

Abrupt dramatic onset

OCD or severely restricted food intake

Two or more of

Anxiety

Emotional lability or depression

Irritability aggression andor severely oppositional behavior

Behavioral regression

Deterioration in school

Sensory or motor abnormalities

Somatic symptoms including sleep disturbances enuresis and urinary frequency

Symptoms not better explained by another neurological or medical disorder

Cunningham Panel

Antibody Moleculara Upper

Limit of Normal

Hesselmark Upper

Limit of Normal

Calcium

Calmodulin Kinase II

130 197

Anti-Dopamine

Receptor 1

8000 15200

Anti-Dopamine

Receptor 2

16000 18400

Lysoganglioside

GM01 Antibody

640 1280

Beta-Tubulin

Antibody

1000 8000

19

20

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

11

Current State of Evidence

Guidelines are based on expert consensus

Insufficient high-quality data to support the use of

long-term antibiotics immunomodulation andor

tonsillectomy

Treatment studies have small numbers of subjects

Controlled studies have been negative

No studies of more specific immunomodulators

21

22

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

12

EMTICSEuropean Multicentre Tics in Children Studies

Longitudinal observational prospective study

involving 16 sites in Europe

Goal

To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD

To characterize the immune response to microbial

antigens and the hosts immune response regulation in association with onset and exacerbations of tics

To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders

To develop prediction models for the risk of onset and exacerbations of tic disorders

httpscordiseuropaeuprojectrcn102102reportingen

EMTICS Design

ONSET cohort

At-risk individuals

N = 260 children aged 3-10 years who are tic-free at

study entry and have a first-degree relative with a

chronic tic disorder

COURSE cohort

Affected individuals

N = 715 youth aged 3-16 years with a tic disorder

23

24

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

13

EMTICS Conclusions

No indication for a role of new GAS exposures in

relation to exacerbations of tic disorders

GAS infections are frequent and exposure at some

point in childhood is nearly universal

Co-occurrence of tic exacerbations and recent

new GAS exposures is most likely due to chance

Anti-GAS responses in patients with tics did not

increase after tic exacerbations

Assessing GAS exposure in children with tic disorders

is not clinically meaningful

Possible altered post-infectious immune response

in patients with TD OCD

25

26

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

14

Take Home Point 2

Co-morbid Conditions

bull ADHD

bull Anxiety OCD

bull Learning difficulties

bull Mood disorders

bull Impulse control

disorders

bull Dysgraphia fine

motor impairment

27

28

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

15

Treatment of Tics

Take Home Point 3 Not all patients require treatment

Current treatments do not ldquocurerdquo tics

Think about treating patients whose tics are causing

Paininjury

Social distress

Significant disturbance to others in classroom environment

No scientific evidence to support the use of dietary interventions

Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first

Take Home Point 5

29

30

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

16

Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate

(Tourette Syndrome Study Group 2002)

31

32

7262019

17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

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17

Take Home Point 6

Patients with TD CTD are

at increased risk of

suicide

Clinicians must inquire

about suicidal thoughts

and suicide attempts in

people with TS and refer

to appropriate resources

if present

Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118

Treatment Options

33

34

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

18

Comprehensive

Behavioral Intervention in

Tics (CBIT)

Components of CBIT

Habit Reversal Training

Tic-awareness

Self-monitoring of current tics

Focus on premonitory urge or other early sign that tic is going to occur

Competing response training

Engagement in a voluntary behavior that is physically incompatible with the tic

Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic

PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics

35

36

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

19

Piacentini et al JAMA 2010303(19)1929-1937

CBIT Study Design

Baseline Week 5 and

Week 10 Scores

37

38

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

20

bull Durable response at 3 and 6 months

bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)

NNT=3

ARR=34

Alpha-2 Agonists

Act presynaptically to inhibit NE release

Examples

Clonidine (Catapres)

Clonidine ER (Kapvay)

Guanfacine (Tenex)

Guanfacine XR (Intuniv)

Side effects

Sedation

Drowsiness

Hypotension

Bradycardia

QTc prolongation (guanfacine XR)

39

40

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

21

Alpha-2 Agonist Safety

Issues

1) Counsel about side effects

2) Monitor pulse and blood pressure

3) Monitor QTc interval if patient is taking guanfacine

XR and has a history of cardiac conditions are on

other QTc prolonging agents andor have a family

history of long QTc syndrome

4) Taper alpha-2 agonists gradually to avoid rebound

hypertension

D2 AntagonistsAtypical and Typical Antipsychotics

41

42

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

22

D2 Antagonists

Medication Initial dose Dose range

Typical

Haloperidol 025-05 mgd 025-6 mgd

Pimozide 1 mgd 1-10 mgd

Atypical

Risperidone 025-05 mgd 025-6 mgd

Ziprasidone 5-20 mgd 5-100 mgd

Aripiprazole 25-5 mgd 5-30 mgd

General Principles of

Prescribing D2 Antagonists

Insufficient evidence to determine the relative

efficacy of the antipsychotic drugs

Atypical antipsychotics are not inherently safer

than typical antipsychotics

Use the lowest effective dose

Reevaluate need for treatment on an ongoing

basis

43

44

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

7262019

23

D2 Antagonist Safety

Issues Side Effects

Drug-induced movement disorders

Weight gain

Somnolence

Adverse metabolic side effects

Increased prolactin

QTc prolongation

Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)

Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval

Taper antipsychotics gradually to avoid withdrawal dyskinesias

Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589

45

46

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24

The Other Playershellip

Benzodiazepines

Clonazepam

Substituted benzamides

Sulpiride

Tiapride

Metoclopromide

Monoamine-depleting

Tetrabenazine

Botulinum toxin

Limited Evidence

Baclofen

Anticonvulsants

Topiramate (Topamax)

Levetiracetam (Keppra)

Dopamine agonists

Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)

Ropinirole (Requip) (Anca et al 2004)

Levodopa

Apomorphine (Feinberg and Carroll 1979)

Cannabinoids

Nicotine

47

48

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25

Experimental Therapies

Ineffective

Discontinued

N-Acetylcysteine

Fatty acid amide

hydrolase

Pramipexole

Valbenazine (T-Force

Gold Platinum

Neurocrine)

Under Investigation

D1 dopamine receptor antagonist

Ecopipam (D1amond Emalex)

VMAT inhibitors

Deutetrabenazine(Artists2 Teva)

Cannabis-related cannabinoid compounds

D-cycloserine (Abide)

Oral appliance

Deep brain stimulation

Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C

49

50

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26

Oral Orthotic

Proof of Concept Study of an Oral Orthotic

to Reduce Tic Severity in Chronic Tic

Disorder and Tourette Syndrome

51

52

7262019

27

Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094

DBS Targets for TS

(Hariz MI and Robertson MM EJNR 2010)

53

54

7262019

28

Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY

SUPPORT

55

56

7262019

29

Tourette Association of

America (wwwtouretteorg)

Family Guide Care Providers Guide

Tourette Association

YouTube

57

58

7262019

25

Experimental Therapies

Ineffective

Discontinued

N-Acetylcysteine

Fatty acid amide

hydrolase

Pramipexole

Valbenazine (T-Force

Gold Platinum

Neurocrine)

Under Investigation

D1 dopamine receptor antagonist

Ecopipam (D1amond Emalex)

VMAT inhibitors

Deutetrabenazine(Artists2 Teva)

Cannabis-related cannabinoid compounds

D-cycloserine (Abide)

Oral appliance

Deep brain stimulation

Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C

49

50

7262019

26

Oral Orthotic

Proof of Concept Study of an Oral Orthotic

to Reduce Tic Severity in Chronic Tic

Disorder and Tourette Syndrome

51

52

7262019

27

Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094

DBS Targets for TS

(Hariz MI and Robertson MM EJNR 2010)

53

54

7262019

28

Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY

SUPPORT

55

56

7262019

29

Tourette Association of

America (wwwtouretteorg)

Family Guide Care Providers Guide

Tourette Association

YouTube

57

58

7262019

26

Oral Orthotic

Proof of Concept Study of an Oral Orthotic

to Reduce Tic Severity in Chronic Tic

Disorder and Tourette Syndrome

51

52

7262019

27

Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094

DBS Targets for TS

(Hariz MI and Robertson MM EJNR 2010)

53

54

7262019

28

Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY

SUPPORT

55

56

7262019

29

Tourette Association of

America (wwwtouretteorg)

Family Guide Care Providers Guide

Tourette Association

YouTube

57

58

7262019

27

Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094

DBS Targets for TS

(Hariz MI and Robertson MM EJNR 2010)

53

54

7262019

28

Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY

SUPPORT

55

56

7262019

29

Tourette Association of

America (wwwtouretteorg)

Family Guide Care Providers Guide

Tourette Association

YouTube

57

58

7262019

28

Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY

SUPPORT

55

56

7262019

29

Tourette Association of

America (wwwtouretteorg)

Family Guide Care Providers Guide

Tourette Association

YouTube

57

58

7262019

29

Tourette Association of

America (wwwtouretteorg)

Family Guide Care Providers Guide

Tourette Association

YouTube

57

58

7262019

30

Helpful Books amp ResourcesFamily Information for Tourette

A Families Guide to TS

10 Secrets to a Happier Life with TS

TS- What Families Should Know

The Keeper (Tim Howardrsquos Book for Adults and Children)

Natural Remedies for Tics and Tourettersquos Syndrome

Tourette Education for Children

Quit It

A Test of Will

Matthew Sally and Simon Story Series

Twitch and Shout

Front of The Class (Movie)

I Have Tourettersquos but It Doesnrsquot Have Me

OCD

Anxiety Workbook for Teens

Up and Down the Worry Hill

Freeing Your Child from OCD

Talking Back to OCD

Taming the Tiger

Executive Functioning

See It Say It Do It

Smart but Scattered

Smart but Scattered Planner

CPRI Brake Shop

Brake Shop ClinicLeaky Brake Toolkit

httpwwwcpricacontentpageaspxsection=26

59

60

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31

Tic Helper

61

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31

Tic Helper

61