TREATMENT

Pharmacologic therapy for TS and chronic tic disorders has been available for more than 30
years, and clinical management revolves around identifying target symptoms. While tics may be
the most flagrant manifestation, they may not be the most disabling one. Concurrent ADHD,
impulse control disorders, OCD, and depression may be more problematic for many individuals
than are tics. Tics respond most consistently to low doses of dopamine antagonists such as
haloperidol or pimozide. Clonidine has also been shown to be beneficial, although probably less
effective than dopamine antagonists. Some patients improve on benzodiazepine agents. (4,5)
Particularly as they get older, many patients learn to suppress their tics in social situations without
medication. Family counseling and psychotherapy may be useful to help cope with adjustment
problems associated with the social stigma common in more severe cases. In addition, the
physician may have to interact with the school system in order to explain the nature of the tic
disorder, and occasionally to clarify the special needs
of such children, such as help with timed testing. Psychiatric comorbidity can be more disabling
than the tics themselves. In those cases, directed pharmacotherapy, such as the use of serotonin
reuptake inhibitors (eg, clomipramine) for OCD or tricyclic antidepressants for depression, can be
an important intervention. For most patients with TS or tic disorders, the clinical course is benign
and the outcome is good.

Treatment:
The goal of therapy in patients with TS is to reduce motor and vocal tics and alleviate associated
behavioral problems, such as obsessive-compulsive behaviors, ADHD, and impulsivity. Many
patients do not have significant functional impairment because their symptoms are mild and
therefore may not require medication. However, for those with symptoms that are functionally
disabling and affect academic, occupational, or social performance, there are a number of
medications that may alleviate particular symptoms.

Drug therapy may include low doses of certain antipsychotic (dopamine receptor antagonist)
medications (neuroleptics), such as haloperidol (Haldol), pimozide (Orap), fluphenazine
(Prolixin),and risperidone (Risperdal), which have been found to be effective in reducing the
frequency and intensity of tics. These medications should be prescribed with caution since their
use may be associated with certain severe side effects. Adverse effects associated with neuroleptic
therapy include the development of tardive dyskinesia (TD), a movement disorder characterized
by persistent, repetitive (stereotypic) involuntary movements usually involving the lower face and
mouth. Although TD often resolves with the discontinuation of drug therapy, particularly in
children, the condition is not always reversible. Therefore, those who receive long-term
neuroleptic therapy should be periodically evaluated to determine whether dosage level may be
decreased or therapy may be discontinued. Neuroleptic therapy may also be associated with
certain short-term side effects, such as drooling, contraction of the facial and neck muscles, slow
movement (bradykinesia), restlessness (akathisia), and other symptoms.

Injections of botulinum toxin (BTX) into the muscles involved in tics may markedly alleviate not
only the abnormal movements but also the premonitory sensations or urges that precede the tics.
The administration of the antianxiety medication clonazepam (Klonopin) or certain
antidepressant medications may be helpful in the management of some of the associated
behavioral symptoms. Therapy with clonidine (Catapres) or guanfacine (Tenex), alpha 2-
adrenergic agonists, may relieve symptoms of ADHD and impulsivity, but these drugs are
generally not very effective in controlling tics. In addition, in patients with obsessive-compulsive
behaviors, treatment with certain antidepressant agents known as selective serotonin reuptake
inhibitors (SSRIs) may be beneficial. Such medications include fluvoxamine (Luvox),
fluoxetine (Prozac), clomipramine (Anafranil), and many others.

Biofeedback, relaxation methods, or other behavioral techniques may occasionally be helpful in

alleviating stress that potentially aggravates tics. In addition, for those with associated behavioral
difficulties, individualized academic, vocational, social, or other supportive services are often
beneficial.

How is TS treated?

Because symptoms do not impair most patients and development usually proceeds normally, the
majority of people with TS require no medication. However, medications are available to help
when symptoms interfere with functioning. Unfortunately, there is no one medication that is
helpful to all persons with TS, nor does any medication completely eliminate symptoms; in
addition, all medications have side effects. Instead, the available TS medications are only able to
help reduce specific symptoms.

Some patients who require medication to reduce the frequency and intensity of the tic symptoms
may be treated with neuroleptic drugs such as haloperidol and pimozide. These medications are
usually given in very small doses that are increased slowly until the best possible balance
between symptoms and side effects is achieved.

Recently scientists have discovered that long-term use of neuroleptic drugs may cause an
involuntary movement disorder called tardive dyskinesia. However, this condition usually
disappears when medication is discontinued. Short-term side effects of haloperidol and pimozide
include muscular rigidity, drooling, tremor, lack of facial expression, slow movement, and
restlessness. These side effects can be reduced by drugs commonly used to treat Parkinson's
disease. Other side effects such as fatigue, depression, anxiety, weight gain, and difficulties in
thinking clearly may be more troublesome.

Clonidine, an antihypertensive drug, is also used in the treatment of tics. Studies show that it is
more effective in reducing motor tics than reducing vocal tics. Fatigue, dry mouth, irritability,
dizziness, headache, and insomnia are common side effects associated with clonidine use.
Fluphenazine and clonazepam may also be prescribed to help control tic symptoms.

Medications are also available to treat some of the associated behavioral disorders. Stimulants
such as methyphenidate, pemoline, and dextroamphetamine, usually prescribed for attention
deficit-hyperactivity disorders, although somewhat effective, have also been reported to increase
tics; therefore their use is controversial. For obsessive compulsive behaviors that significantly
disrupt daily functioning, fluoxetine, clomipramine, sertraline, and paroxetine may be prescribed.

Other types of therapy may also be helpful. Although psychological problems do not cause TS,
psychotherapy may help the person better cope with the disorder and deal with the secondary
social and emotional problems that sometimes occur. Psychotherapy does not help suppress the
patient's tics.

Relaxation techniques and biofeedback may be useful in alleviating stress which can lead to an
increase in tic symptoms.
Medical Treatment of Tics and Movements in TS

1. Neuroleptics (Haldol, Orap, Risperdal)

2. Clonidine
3. Serotonin Drugs (Prozac-like); Klonopin (benzodiazapine with 5HT action)

Medical Treatment of OCD in TS

1. Serotonin Reuptake Inhibitors (SSRI): Prozac, Luvox, Paxil, Zoloft

2. Anafranil (more side-effects)
3. Augment with dopamine agents (Orap) or Klonopin

Medical Treatment of Attention Deficit (ADHD) in TS

1. Ritalin
2. Tenex, clonidine
3. Tricyclics: imipramine, desipramine, Anafranil (clomimpramine)

Other Medication Issues

Sensory symptoms
Biochemistry of TS
Environmental factors
Alerts for medication side effects at school
Goals of treatment

Medications for Tic Treatment

Neuroleptics (Haldol-like drugs)

o haloperidol (Haldol), 0.5 mg - 5.0 mg/day
o pimozide (Orap), 0.5 mg - 10 mg/day
o risperidone (Risperdal), 1.0 - 6.0 mg/day
o neuroleptic medication side effects: sedation; weight gain; EPS: muscle spasms,
tremors, restlessness; risk of tardive dyskinesia; skin sensitivity; eyesight
changes; anxiety; monitor liver, EKG (esp. Orap), EEG
Alpha-adrenergic drugs
o gaunfacine (Tenex), 0.5 - 2.0 mg/day
o clonidine (Catepres), 0.05 - 0.2 mg/day
 o Alpha-adrenergic medication side effects: lethargy; drowsiness; deceased blood
pressure; EKG changes

Medications for obsessive-compulsive (OCD) symptoms in TS

Serotonin Reuptake Inhibitors (SRIs, SSRIs)

o Prozac, Zoloft, Paxil, Luvox
o Very good for OCD & depression
o SSRI side effects: gastrointestinal symptoms; restlessness; insomnia; genital-
urinary side effects
Anafranil (clomipramine, a tricyclic compound)
o may improve obsessive-compulsive components of TS
o (also anti-depressant & anti-anxiety medication)
o side effects: dry mouth, constipation, urinary problems; skin changes; lower
blood pressure; monitor EKG, EEG, and liver

Medications for Attention Deficit

Ritalin
o May not increase tics if used in reasonable dosages; may decrease vocal tics
o Improve concentration, impulsivity, hyperactivity
o Ritalin side effects: anorexia, insomnia, irritability; gastro-intestinal upset
Tricyclics (Anafranil, imipramine etc.)
o Improve attention, impulsivity, hyperactivity
o Also anti-depressant, anti-anxiety
o Tricyclic side effects: dry mouth, constipation, urinary problems; skin changes;
lower blood pressure; monitor EKG, EEG, and liver
Alpha-drugs
o clonidine, Tenex
o improves attention
o Alpha-adrenergic medication side effects: lethargy; drowsiness; deceased blood
pressure; EKG changes

Sensory Symptoms

"Just right" feeling

Premonitory urge (sensation or pressure immediately before a tic)
Restless Legs Syndrome
Because of these sensations the movements are more like compulsions,
Therefore, many movements are voluntary-like
Biochemistry

Norepinephrine involved in pathobiology of Tourette's Syndrome

Altered balance of NE, 5HT, and DA likely involved in OCD

Environmental Factors in Tourette's Syndrome

11 factors resulted in decreased symptoms: visits to doctor's office, relaxed reading,

talking to friends
17 factors increased the tics: anxiety, emotional trauma, social gatherings
Other factors were neutral

School

Poor attention in achool may be due to:

1. Tic severity
2. Medication
3. Executive dysfunction (cognitive dysfunction)
4. Social consequences of a stigmatizing disorder
5. Coexistent ADHD, OCD or other disorders

Current Pharmacology of Tourette Syndrome

by:Roger Kurlan, MD

Introduction

Chronic, multiple motor and vocal tics are the most prominent clinical features of Tourette
Syndrome (TS) and represent the signs upon which the diagnosis of the disorder is currently
based. Tic severity encompasses a wide spectrum. Although a number of patients with TS
experience severe and disabling tics, recent family studies indicate that for most individuals with
the disorder, tic severity is relatively mild and medical attention is not required.

Tics may also be accompanied by a variety of associated behavioral disorders. For example,
recent genetic work suggests that obsessions (recurrent, persistent ideas, thoughts, images,
impulses) and compulsions (repetitive behaviors performed as rituals or in a stereotyped fashion)
may be clinical manifestations of TS. Others have suggested that attention deficit disorder (short
attention span, daydreaming, poor concentration) with hyperactivity (ADHD) also may be
associated with TS. For some individuals, such behavioral disturbances may represent the
predominant clinical manifestations of the disorder. In addition, patients with TS may display a
variety of other psychopathological conditions (e.g., depression, anxiety, conduct disorder) and
personality traits (e.g., irritability, argumentativeness, stubbornness, impulsivity) that may be part
of the disorder or, alternatively, may represent psychological responses to living with a chronic
illness.
Taken together, current evidence indicates that the clinical manifestations of Tourette Syndrome
can be quite variable. It is, therefore, important to evaluate each individual closely to determine
which aspects are most disabling. For example, school performance may be impaired by frequent
tics, obsessional thinking, attention deficit, personality disorder, or various combinations of those
difficulties. For most patients, one or two of the clinical aspects will predominate and can serve as
specific target symptoms for therapy.

Ideally, patients with mild cases of TS who have made a good adaptation in their lives can avoid
the use of any medications. Our impression is that the majority of patients with TS can manage
well without drug therapy. Educating patients, family members, and school personnel concerning
the nature of TS; restructuring the school environment (e.g., small group teaching, one-on-one
tutoring; allowing TS students to work at their own pace); and providing supportive counseling,
are measures that may be sufficient to avoid medications.

Medication therapy should be considered if it is determined that the symptoms of TS are

functionally disabling and not remediable to non-drug interventions. A variety of therapeutic
agents are now available to treat the symptoms of TS. Each medication should be chosen on the
basis of specific target symptoms and potential side effects. For example, in one patient, tic-
suppression may be the important goal, while treatment of obsessive-compulsive features may
take precedence in another. Dosages should be titrated slowly in order to achieve the lowest
satisfactory dosage. The maximum dosage utilized depends on achieving a "tolerable"
suppression of symptoms. "Tolerable" is determined by the nature of the symptoms (for example,
coprolalia is usually less tolerable than eye tics) and the ability of an individual to exercise
voluntary modulation of his/her vocalizations and motor tics. Some children may have relatively
few tics in school but a great many at home, thus allowing less overall use of medication. In our
view, home is a haven where a child can have some relief from holding symptoms in check. It is
vital that the patient and the family understand the ever changing nature of TS, so that
medications can be adjusted in a rational fashion, increasing when the symptoms upsurge and
decreasing during periods of relative remission. It is essential for effective dosage adjustment that
"target symptoms" are monitored at all times. For example, if an individual is treated with so
much medication that all movements are suppressed, it can never be known when tics, which tend
to wax and wane in severity during the course of the illness, decrease spontaneously. In the long
run, our goal is to use as little medication as possible (i.e., "less is best").

Pharmacotherapy of Tourette Syndrome

I. Tics

A. Clonidine (Catapres)
B. Neuroleptics
1. Haloperidol (Haldol)
2. Pimozide (Orap)
3. Fluphenazine (Prolixin)
4. Others
C. Other Drugs

D. Botulinum Toxin *
II. Obsessive Compulsive Disorder

A. Clomipramine (Anafranil)
B. Fluoxetine (Prozac)

C. Sertraline (Zoloft)
III. Attention Deficit Hyperactivity Disorder

A. Clonidine (Catapres)
B. Stimulants
1. Methylphenidate (Ritalin)
2. Pemoline (Cylert)
3. Dextroamphetamine (Dexedrine)

C. Tricyclic antidepressants

* Recent research has shown that for a small number of patients who prove resistant to the motor
medications, injections of botulinum toxin might be helpfu
Tourette Syndrome & Associated Disorders Medication
Reference

This medication reference covers the most commonly

prescribed medications for the treatment of TS, OCD,
and ADHD. It is presented in a Physician's Desk
Reference like format featuring expected therapeutic
effects, drug interactions and information about
interactions with other drugs. A comprehensive glossary
is included.

Index of medications: Full

information
Neuroleptics on
Haldol [Haloperidol medications
Orap [Pimozide]
Prolixin [Fluphenazine]
Navane [Thiothixene]
Thorazine [Chlorpromazine]