Синдром Туретта

[Кэт]

Буду рад, если ответит специалист, имеющий опыт лечения этого синдрома.

[October]

MEDICATIONS AND TOURETTE’S DISORDER:

COMBINED PHARMACOTHERAPY AND DRUG INTERACTIONS



Barbara Coffey, M.D., Cheston Berlin, M.D., Alan Naarden, M.D.



Introduction

Tourette Syndrome (TS) or Tourette’s Disorder (DSM IV) is a complex neuropsychiatric

disorder characterized by a changing pattern of motor and vocal tics that begin in childhood.

Many individuals with Tourette Syndrome have associated non-tic symptoms such as

hyperactivity, distractibility, impulsivity, obsessions and compulsions, anxiety, depression, and

anger control. These associated symptoms may occur in patterns of frequency or intensity

characteristic of an additional comorbid (coexisting) disorder such as Attention Deficit

Hyperactivity Disorder (ADHD), Obsessive Compulsive Disorder (OCD), or Oppositional

Defiant Disorder (ODD). Whether these problems are an integral part of Tourette Disorder or

are separate problems is under investigation. They may result in difficulties in school, in the

work place and with social adjustment. Frequently these associated problems or comorbid

disorders are a source of more distress or impairment to the individual with TS than the tics. Not

all patients with tics meet the formal diagnostic criteria for Tourette Syndrome but the tics may

still have significant intensity to warrant treatment.

Medication Treatment: General Indications

Medication treatment can be beneficial in both reducing the tics and the behavioral and

emotional problems in the individual with Tourette’s Disorder or other tic disorders. When

symptoms are mild, treatment may include only support, education and monitoring. For

symptoms that produce significant distress or impairment, medication treatment may be

indicated. Currently there are a variety of medications available for the treatment of tics and the

non-tic symptoms. There is no single medication, which is helpful to all individuals with tics or

Tourette Syndrome. Tics are often mild and will frequently at least partially remit in many

individuals, particularly as they go through adolescence. Often it is the behavioral and

emotional features that cause the most difficulty for the child.

Tic symptoms that cause interference in the child’s functioning or cause significant distress are

targets for medication treatment with the goal of reducing tic severity and frequency. For

individuals with mild to moderate tics, specific medications effective for tic reduction include

clonidine (Catapres) or guanfacine (Tenex). For individuals with moderate to severe tics, the

newer atypical neuroleptics such as risperidone (Risperdal) or older traditional neuroleptics such

as haloperidol (Haldol) may be indicated. The decision to use medication should take into

account a variety of factors in addition to tic severity such as the child’s age, medical history and

past history of response to medication. Typically one medication can be used over period of

several months or longer until the tics have abated.



For many individuals, the primary symptoms requiring treatment may be behavioral or

emotional, such as hyperactivity, impulsivity or obsessions and compulsions. Medications that

target the non-tic symptoms such as antiobsessionals (selective serotonin reuptake inhibitors or SSRIs) or medications for Attention Deficit Hyperactivity Disorder such as methylphenidate

(Ritalin), dextroamphetamine (Dexedrine, Addreall), or atomoxetine (Strattera) may be

indicated. These medications may or may not have direct effects on the tics, in addition to the

effects on the behavioral or emotional symptoms.

Monotherapy or Targeted Combined Pharmacotherapy

If the major symptoms include both tics and behavioral or emotional difficulties, medication

may be effective to address both sets of symptoms. The first option is called monotherapy when

just one medication is used to address two or more problems; this strategy is recommended if

possible as a first choice since it is easiest to use and may have the best compliance. The

physician may start with one agent that can address both the tics and the non-tic symptoms such

as clonidine for tics and ADHD or clonazepam (Klonopin) for tics and moderate to severe

anxiety.

If monotherapy is not possible or has not been effective individuals may require the use of two

(or more) medications simultaneously to control both tics and behavioral or emotional

symptoms. This approach is called targeted combined pharmacotherapy, referring to the careful,

judicious use of more than one medication simultaneously. Although this is a more complicated

approach, it has several advantages including 1) using lower doses of each medication, reducing

the likelihood of side effects associated with higher doses of single agents and 2) potential

augmentation or synergism (booster effects) of combination therapy. Given the increasing

recognition of the prevalence and clinical significance of the comorbid problems in individuals

with TS, this approach is becoming more frequent in its use.

The combined use of haloperidol (Haldol) and fluoxetine (Prozac) would be an example of a

combination used to control both tics and obsessive-compulsive behaviors. Another example is

the combination of clonidine (Catapres) and dextroamphetamine (Dexedrine) to reduce both tics

and symptoms of Attention Deficit Hyperactivity Disorder.

Less frequently, more than two medications can be used in the treatment of tics and the

comorbid problems. This is a more complicated approach since the likelihood of interactions

between the medications increases as the number of medications used together increases.

[Смирик]

Medication Interactions: Prescribed Agents

Potential interactions between two or more medications prescribed simultaneously need to be

taken into account when the decision is made to use targeted combined pharmacotherapy. These

interactions include those between the prescribed medications and those that may occur when

non-prescribed (“over the counter”) medications are used. All medications are metabolized or

broken down by a system of enzymes in the liver and distributed to the brain where they have

their active effects. This process if also necessary to prepare the drug for elimination from the

body. There is a considerable amount of information about these enzymes, known as the

cytochrome oxidase P450 system. Medications such as the selective serotonin reuptake

inhibitors (SSRIs) can alter activity in this liver enzyme system, resulting in reduced metabolism

and reduced clearance of medication. This may result in increased blood levels of medication

and/or increased side effects.



There is a large variation between individuals in their response to drugs. The response may

depend on genetic and environmental factors. There may be considerable variation in the

response of a single person to different members of the same drug class.

Medication Interactions: Non-Prescribed Agents (“Over the Counter”)

Many children with Tourette’s Syndrome and other tic disorders may receive over the counter

medications to reduce symptoms of upper respiratory illness such as nasal decongestants and

cough suppressants. Others may take acetaminophen (Tylenol) for muscle paints or for fever, or

nonsteroidal anti-inflammatory agents (NSAIDS) such as Ibuprofen (Motrin, Advil) for

headaches or muscle pain. Antibiotics are frequently prescribed for children for ear infections or

strep throats. While these medications are generally safe for pediatric usage, some may have

significant interactions with medications prescribed for children with TS.

Specific Medications

The medications commonly used to treat symptoms of Tourette Syndrome are reviewed in the

tables at the end of this brochure. They are listed by their general purpose, typical starting doses,

common maximum dosages and common side effects. Children generally require lower dosages

of the same medications used for adults. The neuroleptic medications (e.g. Haldol [haloperidol]

and Orap (Pimozide) may have uncommon side effects such as restlessness, muscle stiffness or

slowness or a rare side effect known as tardive dyskinesia (TD). Symptoms of TD may begin

with twitching movements of the face and mouth, which may not disappear when the medication

is discontinued.

Some medications prescribed for TS have primary indications other than the treatment of

Tourette Syndrome. Catapres (clonidine), and a close relative guafacine (Tenex), have been

used to control high blood pressure. Clonazepam (Klonopin) is used in the treatment of seizures

as well as for the control of tics.

Whether generic medications are as effective as brand name medication needs to be studied.

Some reports have suggested that bioavailability (availability of the medication and its

breakdown products after oral dosing is reduced slightly for generic neuroleptics such as

haloperidol when compared to the brand Haldol. Some individuals switching to generic from

brand name products have reported experiencing no problems, but some have noted that the

generics proved less beneficial than the brand name products. It is important that individuals

review this issue with their physicians when a medication program is being started.

The more commonly used medications for ADHD are the stimulants such as Ritalin

(methylphenidate), and Dexedrine (dextroamphetamine) and Adderall (mixed amphetamines).

These medications may cause an increase in tics in some TS patients. Other reports have been

unable to find an effect on tic frequency. Experience has shown, however, that these

medications can be safely taken by some individuals with TS. For those individuals with

significant ADHD symptoms, a cautious trial of stimulant medication may be helpful. A new

medication for ADHD is Strattera (atomoxetine), which is reported not to increase tics.

There is no single TS “drug of choice”. A careful matching of the medication to the specific

needs of the individual is critical. There are no medical tests, which can predict which

medication will work best. More than one medication, even within the same family of drugs

may need to be tried before the best treatment program is found. Unfortunately, there are some

individuals who may not respond to any of the available medications, or may experience

intolerable side effects. These individuals may be candidates for other types of treatment.

Additional medications for TS are also available although they are used less commonly.

Research programs are working actively to discover new and better treatment programs. Until

that time, the currently available medications can be of help to many individuals with Tourette

disorder and other tic disorders.



Health care providers should carefully monitor patients receiving antidepressants for

possible worsening of depression or suicidality, especially at the beginning of therapy or

when the dose either increases or decreases. Although FDA has not concluded that these

drugs cause worsening depression or suicidality, health care providers should be aware that

worsening of symptoms could be due to the underlying disease or might be a result of drug

therapy.

Heath care providers should carefully evaluate patients in whom depression persistently

worsens, or emergent suicidality is severe, abrupt in onset, or was not part of the presenting

symptoms, to determine what intervention, including discontinuing or modifying the

current drug therapy, is indicated.

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia

(severe restlessness), hypomania, and mania have been reported in adult and pediatric

patients being treated with antidepressants for major depressive disorder as well as for

other indications, both psychiatric and nonpsychiatric. Although FDA has not concluded

that these symptoms are a precursor to either worsening of depression or the emergence of

suicidal impulses, there is concern that patients who experience one or more of these

symptoms may be at increased risk for worsening depression or suicidality. Therefore,

therapy should be evaluated, and medications may need to be discontinued, when

symptoms are severe, abrupt in onset, or were not part of the patients presenting symptoms.

If a decision is made to discontinue treatment, certain of these medications should be

tapered rather than stopped abruptly (see labeling for individual drug products for details)

.

Because antidepressants are believed to have the potential for inducing manic episodes in

patients with bipolar disorder, there is a concern about using antidepressants alone in this

population. Therefore, patients should be adequately screened to determine if they are at

risk for bipolar disorder before initiating antidepressant treatment so that they can be

appropriately monitored during treatment. Such screening should include a detailed



Use of Drugs in the Pediatric Population

Some of the drug information that families may receive when the use of medication for tic

disorder is discussed may indicate that a drug is not “approved” for children in the pediatric age group (usually under age 18 years). This information comes from what is called the “pediatric label” or “package insert”. This is information jointly agreed to by both the company and the Food and Drug Administration (FDA) to support the use of the drug as indicated. It is not unusual once a drug is on the market for it to be used in either a pediatric population or for an indication that is not in the label. An example of this is the drug clonidine, which is labeled for use in the treatment of high blood pressure in adults. However it has found widespread use for other disorders including tic disorders and ADHD. The Committee on Drugs in the American Academy of Pediatrics is very aware of this issue and has published a useful statement entitled “The Uses of Drugs Not Described in the Package Insert” in the July 2002 issue of Pediatrics (pp. 181-183). This statement points out that any labeling of a drug is not intended to preclude a physician from using his or her best judgment in the use of this medication. Because of rapidly advancing knowledge in pediatric therapeutics there can be widespread acceptance of the use of a drug not labeled for children before the label may be changed. There has been a very active effort in expanding the labeled drugs for the pediatric population in the last ten years so that children, their families and practitioners will have the benefit of the most up to date indications. When a certain drug is suggested for the treatment of a tic disorder or a co-morbid disorder.

There is almost always significant published research to support such a recommendation. The child’s physician would be in the best position to discuss this with the family.



http://www.tsa-usa.org/medsci.html

[tony19@yandex]

Potential interactions between two or more medications prescribed simultaneoMedication Interactions: Prescribed Agentsusly need to be

taken into account when the decision is made to use targeted combined pharmacotherapy. These

interactions include those between the prescribed medications and those that may occur when

non-prescribed (“over the counter”) medications are used. All medications are metabolized or

broken down by a system of enzymes in the liver and distributed to the brain where they have

their active effects. This process if also necessary to prepare the drug for elimination from the

body. There is a considerable amount of information about these enzymes, known as the

cytochrome oxidase P450 system. Medications such as the selective serotonin reuptake

inhibitors (SSRIs) can alter activity in this liver enzyme system, resulting in reduced metabolism

and reduced clearance of medication. This may result in increased blood levels of medication

and/or increased side effects.



There is a large variation between individuals in their response to drugs. The response may

depend on genetic and environmental factors. There may be considerable variation in the

response of a single person to different members of the same drug class.

Medication Interactions: Non-Prescribed Agents (“Over the Counter”)

Many children with Tourette’s Syndrome and other tic disorders may receive over the counter

medications to reduce symptoms of upper respiratory illness such as nasal decongestants and

cough suppressants. Others may take acetaminophen (Tylenol) for muscle paints or for fever, or

nonsteroidal anti-inflammatory agents (NSAIDS) such as Ibuprofen (Motrin, Advil) for

headaches or muscle pain. Antibiotics are frequently prescribed for children for ear infections or

strep throats. While these medications are generally safe for pediatric usage, some may have

significant interactions with medications prescribed for children with TS.

Specific Medications

The medications commonly used to treat symptoms of Tourette Syndrome are reviewed in the

tables at the end of this brochure. They are listed by their general purpose, typical starting doses,

common maximum dosages and common side effects. Children generally require lower dosages

of the same medications used for adults. The neuroleptic medications (e.g. Haldol [haloperidol]

and Orap (Pimozide) may have uncommon side effects such as restlessness, muscle stiffness or

slowness or a rare side effect known as tardive dyskinesia (TD). Symptoms of TD may begin

with twitching movements of the face and mouth, which may not disappear when the medication

is discontinued.

Some medications prescribed for TS have primary indications other than the treatment of

Tourette Syndrome. Catapres (clonidine), and a close relative guafacine (Tenex), have been

used to control high blood pressure. Clonazepam (Klonopin) is used in the treatment of seizures

as well as for the control of tics.

Whether generic medications are as effective as brand name medication needs to be studied.

Some reports have suggested that bioavailability (availability of the medication and its

breakdown products after oral dosing is reduced slightly for generic neuroleptics such as

haloperidol when compared to the brand Haldol. Some individuals switching to generic from

brand name products have reported experiencing no problems, but some have noted that the

generics proved less beneficial than the brand name products. It is important that individuals

review this issue with their physicians when a medication program is being started.

The more commonly used medications for ADHD are the stimulants such as Ritalin

(methylphenidate), and Dexedrine (dextroamphetamine) and Adderall (mixed amphetamines).

These medications may cause an increase in tics in some TS patients. Other reports have been

unable to find an effect on tic frequency. Experience has shown, however, that these

medications can be safely taken by some individuals with TS. For those individuals with

significant ADHD symptoms, a cautious trial of stimulant medication may be helpful. A new

medication for ADHD is Strattera (atomoxetine), which is reported not to increase tics.

There is no single TS “drug of choice”. A careful matching of the medication to the specific

needs of the individual is critical. There are no medical tests, which can predict which

medication will work best. More than one medication, even within the same family of drugs

may need to be tried before the best treatment program is found. Unfortunately, there are some

individuals who may not respond to any of the available medications, or may experience

intolerable side effects. These individuals may be candidates for other types of treatment.

Additional medications for TS are also available although they are used less commonly.

Research programs are working actively to discover new and better treatment programs. Until

that time, the currently available medications can be of help to many individuals with Tourette

disorder and other tic disorders.



Health care providers should carefully monitor patients receiving antidepressants for

possible worsening of depression or suicidality, especially at the beginning of therapy or

when the dose either increases or decreases. Although FDA has not concluded that these

drugs cause worsening depression or suicidality, health care providers should be aware that

worsening of symptoms could be due to the underlying disease or might be a result of drug

therapy.

Heath care providers should carefully evaluate patients in whom depression persistently

worsens, or emergent suicidality is severe, abrupt in onset, or was not part of the presenting

symptoms, to determine what intervention, including discontinuing or modifying the

current drug therapy, is indicated.

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia

(severe restlessness), hypomania, and mania have been reported in adult and pediatric

patients being treated with antidepressants for major depressive disorder as well as for

other indications, both psychiatric and nonpsychiatric. Although FDA has not concluded

that these symptoms are a precursor to either worsening of depression or the emergence of

suicidal impulses, there is concern that patients who experience one or more of these

symptoms may be at increased risk for worsening depression or suicidality. Therefore,

therapy should be evaluated, and medications may need to be discontinued, when

symptoms are severe, abrupt in onset, or were not part of the patients presenting symptoms.

If a decision is made to discontinue treatment, certain of these medications should be

tapered rather than stopped abruptly (see labeling for individual drug products for details)

.

Because antidepressants are believed to have the potential for inducing manic episodes in

patients with bipolar disorder, there is a concern about using antidepressants alone in this

population. Therefore, patients should be adequately screened to determine if they are at

risk for bipolar disorder before initiating antidepressant treatment so that they can be

appropriately monitored during treatment. Such screening should include a detailed



Use of Drugs in the Pediatric Population

Some of the drug information that families may receive when the use of medication for tic

disorder is discussed may indicate that a drug is not “approved” for children in the pediatric age group (usually under age 18 years). This information comes from what is called the “pediatric label” or “package insert”. This is information jointly agreed to by both the company and the Food and Drug Administration (FDA) to support the use of the drug as indicated. It is not unusual once a drug is on the market for it to be used in either a pediatric population or for an indication that is not in the label. An example of this is the drug clonidine, which is labeled for use in the treatment of high blood pressure in adults. However it has found widespread use for other disorders including tic disorders and ADHD. The Committee on Drugs in the American Academy of Pediatrics is very aware of this issue and has published a useful statement entitled “The Uses of Drugs Not Described in the Package Insert” in the July 2002 issue of Pediatrics (pp. 181-183). This statement points out that any labeling of a drug is not intended to preclude a physician from using his or her best judgment in the use of this medication. Because of rapidly advancing knowledge in pediatric therapeutics there can be widespread acceptance of the use of a drug not labeled for children before the label may be changed. There has been a very active effort in expanding the labeled drugs for the pediatric population in the last ten years so that children, their families and practitioners will have the benefit of the most up to date indications. When a certain drug is suggested for the treatment of a tic disorder or a co-morbid disorder.

There is almost always significant published research to support such a recommendation. The child’s physician would be in the best position to discuss this with the family.



http://www.tsa-usa.org/medsci.html

Большое спасибо за ответ.Но к сожалению я английским не владею.О сущесвовании Американской ассоциации я знаю.Не могу понять почему в русскоязычном мире ничего подобного не существует.А может что-то есть?

[Стопангин]

Уважаемый,Игорь Николаевич,спасибо за ответ.

Скажите,у вас были пациенты с этим синдромом?

[Li3a]

Были.

[Джамбул]

Вкратце, смысл в том, что синдром Туретта может сопровождаться рядом поведенческих и эмоциональных проблем, таких как синдром гиперактивности/дефицита внимания, обсессивно-компульсивное расстройство, тревожное, депрессивное расстройство и др. Самостоятельные ли это заболевания или часть проявлений синдрома Туретта изучается. Иногда данные расстройства вызывают гораздо большую проблему для социальной адаптации ребенка, чем собственно тики. Также указывается, что больные, у которых тики не ярко выражены и не мешают социальной адаптации, не нуждаются в медикаментозном лечении. Другим же из лекарственных средств, используемых для лечения непосредственно синдрома Туретта, могут быть назначены клонидин (Catapres) или guanfacine (Tenex) при умеренной выраженности тиков и нейролептики типа risperidone (Risperdal) или галоперидол (Haldol) при выраженных проявлениях заболевания.

При наличии сопутствующих поведенческих и эмоциональных нарушений назначается комбинированное лечение, чаще с использованием двух препаратов, один из которых снижает выраженность тиков, другой устраняет психоэмоциональные нарушения, например: комбинация галоперидола (Haldol) и fluoxetine (Prozac) при тиках и обсессивно-компульсивном расстройстве. Другой пример комбинация клонидина (Catapres) и dextroamphetamine (Dexedrine), чтобы уменьшить тики и симптомы гиперактивности/дефицита внимания.