Treatment Of Tourette Syndrome

The decision about whether to treat and, if so, what form the treatment should take, will depend on the degree to which the tics or TS is interfering with the child's normal development or the adult patient's ability to function productively. When treating a child, the primary emphasis must be on helping the youngster to navigate the normal developmental tasks - to feel competent in school, develop friendships, experience trust in his or her parents, and enjoy life's adventures. Many children with multiple tics and TS do well in moving onward with their lives. For them, treatment to ameliorate the tics generally is not indicated. Natural parental upset about the tics requires lengthy, calm discussion and education about available treatments. If treatment is decided upon by the child, family, and physician, developmental issues must constantly be reassessed.

There are several approaches to treatment.

Monitoring

Unless there is a state of emergency, the clinician usually can follow a patient for several months before a specific treatment plan is organized. The goals of the first stage of treatment are to establish a baseline of symptoms; define associated difficulties in school, family, and peer relationships; obtain necessary medical tests; and monitor, through check lists and interviews, the range and fluctuations in symptoms and the specific contexts of greatest difficulties; and establish a relationship.

Reassurance

It may become apparent that the child's tics are of minimal functional significance. Even if a youngster satisfies the criteria for TS, no treatment may be necessary because of good peer relations, school achievement, and self image. If parents have read about TS, they may be worried about the child's future. In the majority of cases, the severity of TS becomes apparent within two to three years of its first appearance. For milder cases, we tend to tell families that while their child can be diagnosed as having TS, it is not the same severity as they might hear about in relation to TS, and that "in the old times" their child probably would have been called simply "a nervous child." We also explain to families that, in many instances, TS symptoms are spontaneously ameliorated in the late teens. However, families deserve to know about the clearly emerging knowledge of genetic factors even if they are assured about the nature of their child's disorder.

Treatment of adult TS patients requires much of the same kind of reassurance and education. A well informed patient is much better able to make a wise decision about the need for drugs and to be cooperative in adjusting the dosage if medication is decided upon.

Pharmacologic Treatment of Tourette Syndrome

Pharmacologic treatment is the only proven effective treatment for simple and complex motor and vocal tics. in a recent survey done by the Ohio Tourette Syndrome Association, 70% of patients reported a history of treatment with some medication.

The basic principles governing treatment of TS with medication are:

- Start patients on the smallest dose of medication that is possible and reasonable.

- Increase the dosage gradually paying close attention to the development of side effects as well as diminution of symptoms. A slow increase will usually result in fewer and milder side effects.

- Assure an adequate duration of any drug trial on sufficient dosage. An adequate length of drug trial may be difficult for the clinician who is faced with his patient's urgent need for effective symptom control. However, it is important since premature discontinuation of a medication trial will only result in failure and a series of such "failures" will make the patient feel that he or she is incurable.

- Maintain the lowest effective dosage.

- Make changes in regimens as sequences of single steps.

- When discontinuing medication be careful not to confuse withdrawal reactions with the need for more potent medication.

Haloperidol

Since the 1960's, haloperidol (Haldol) has been the mainstay of treatment for TS. During the first years of its use, dosage was rapidly increased to very high levels followed by gradual reduction. However, it is now accepted that haloperidol is most effective at quite low doses, and patients generally are started at 0.25 to 0.50 mg/day and slowly increased every 4 to 5 days up to an average of 3 to 4 mg/day. Impressive benefits are seen at those low doses, and patients may have almost complete remissions with few side effects. Some may benefit from as little as 1 mg/day or less. Those who do not respond to low doses of haloperidol may sustain a reduction of symptoms at higher doses (10-15 mg), but results are never as satisfying and side effects intervene to limit the drug's usefulness.

Up to 80% of patients with TS initially benefit from haloperidol, sometimes dramatically. However, our long-term follow-up suggests that only a smaller number, perhaps 20-30%, continue haloperidol for an extended period of time. Patients often discontinue the drug because of the emergence of side effects (including excessive fatigue, weight gain, dysphoria, parkinsonian symptoms, intellectual dulling, memory problems, personality changes, feeling like a "zombie," akathisia, school or social phobias, loss of libido, sexual dysfunctions, and, especially after chronic use of high doses, tardive dyskinesia [TD]). There is a diversity of opinion about the use of anti-parkinsonian agents with haloperidol.

Some clinicians prefer to initiate treatment with both haloperidol and low doses of anti-parkinsonian medication (e.g., 0.5 mg/day of benztropine). Others will not use anti-parkinsonian medication until side effects warrant them. Most parkinsonian and acute dystonic reactions can be controlled with 1-2 mg/day of benztropine or an equivalent medication. Akathisia may be harder to manage.

School phobias generally appear during the first weeks of treatment with low doses of haloperidol even while the tic symptoms are improving. Social phobias and dysphoria in adults may involve acute anxiety about going to work or performing at work and can be extremely disabling. When such phobias are not recognized as drug side effects, they can continue for months; they remit within weeks of haloperidol discontinuation. Intellectual dulling leads to marked worsening of school and work performance. Children who are "A" students and have friends may become "C" students, dysphoric, and isolated.

The long term use of medication often complicates the understanding of the emergence of social and personality difficulties. Side effects of neuroleptics may have considerable impact on a child's sense of self-control, autonomy, self-esteem, and cognitive and social competence. In addition to the way that psychoactive medication may alter how a child's body feels to him or her and how he or she experiences the working of his or her mind, the use of any medication may single out a child in school, alter the daily schedule, focus parental and other adult concern on small changes in symptoms and side effects, and tie down the child to the care and attention of many adults.

Education of the patient and/or family about the possibility of developing TD is essential, as are periodic assessments for dyskinetic movements that the patient or family may mistake for TS symptoms. Because of the frequency and potential gravity of side effects associated with haloperidol, many clinicians experienced in the treatment of TS prefer to try other medications first and reserve haloperidol for more severe and refractory cases.

It should be emphasized that withdrawal from haloperidol and other neuroleptics may produce confusing symptoms (see pages 19-20).

Pimozide

Pimozide (Orap) was approved in this country for treatment of TS in 1984, and is now in fairly common use. Pimozide is a diphenylbutylpiperidine, chemically distinctive from haloperidol or phenothiazines, with potent dopamine blocking properties. Its side effects are similar to haloperidol, but may be less severe and appear in fewer patients. In general, it is better tolerated than haloperidol and probably is of equal efficacy. Concern about cardiotoxicity was raised by initial reports of EKG abnormalities (U waves, inverted T waves, and Q-T prolongation) in early studies. Further investigations with larger numbers of patients have not justified those concerns. Nevertheless, routine EKG studies before and periodically during treatment are still advised.

Treatment with pimozide is initiated at 1 mg/day, and dosage is gradually increased, on clinical indications, to a maximum of 6-10 mg/day for children and 20 mg/day for adults. (The Physicians' Desk Reference indicates that doses greater than 0.2 mg/kg or 10 mg/day are not recommended.) Because of its long half-life (55 hours), a single daily dosage may be feasible. Major side effects are similar to haloperidol and, as with haloperidol, tardive dyskinesia is a possibility.

Other Neuroleptics

Phenothiazines, particularly fluphenazine, may be effective alternatives to haloperidol and pimozide. Fluphenazine's side effects are potentially the same as those associated with haloperidol, but, as with pimozide, some patients tolerate them better. The recommended dose range is similar to haloperidol and the same principles (lowest possible starting dose and gradual increases) are applicable. Other neuroleptics that have been reported to be effective in a few patients include thiothixene, chlorpromazine, and trifluoperazine.

Clonidine

Clonidine (Cataprese) is an imidazoline compound with alpha-adrenergic agonist activity. In low doses it "down-regulates" alpha-adrenergic neurons in the locus ceruleus, decreasing the release of central norepinephrine. Since 1979 it has been considered to be of benefit for the treatment of TS although the response rate is lower than that of either haloperidol or pimozide. In general it is of advantage because of the low incidence of side effects associated with its use. Perhaps of greatest importance is that it does not have the potential of causing tardive dyskinesia. Clonidine has been approved by the FDA only for use in hypertension, but clinicians can prescribe it for TS without special government approval as long as they understand its indications and share the basis for their decision with the family and child.

In addition to reducing the simple motor and phonic symptoms in TS, clonidine seems especially useful in improving attentional problems and ameliorating complex motor and phonic symptoms.

In general, clonidine is started at low doses of 0.05 mg/day and slowly titrated over several weeks to 0.15-0.30 mg/day. Since clonidine has a 6 hour half-life it is important that patients take small doses 3 to 4 times each day. (An alternative to multiple doses is the transdermal patch that needs to be changed only once a week.) Doses of 0.4 mg daily are not infrequent, but doses above 0.5 to 0.6 mg/day are more likely to lead to side effects. When the medication is working effectively, patients may experience the need for their next dose by sensing an increasing anxiety, frequency of symptoms, or irritability. Unlike haloperidol, which may lead to clear improvement within a few days, clonidine tends to have a slower onset of action. When larger doses are used earlier, improvement may occur sooner, but there may be more sedation. With slower titration to therapeutic levels, clonidine may take three weeks or longer to show a beneficial effect.

The patient may experience a reduction in tension, a feeling of being calm, or a sense of having a "long fuse" before tics are reduced. A gradual decrease in complex motor tics and compulsions also may precede clear improvement in simple tics. In the most successful cases, attentional, behavioral, and complex phenomena seem more responsive than the simpler tics. Evaluation of the medication's effectiveness may not be possible before three to four months. When there is a positive response, improvement may progressively appear over many months and up to a year or more later. Patients gain confidence in themselves, adjust better to school, feel less irritable, and have fewer tic symptoms. Those therapeutic benefits reinforce each other.

The major side effect of clonidine is sedation, which appears early in the course of treatment and especially if the dose is increased quickly, but which tends to abate after several weeks. A few patients have dry mouth, although it is experienced less often by children than by adults. There are occasional reports that patients feel that things are "too bright," perhaps because of the impairment of pupillary contraction. At high doses, there may be hypotension and dizziness, particularly if clonidine is given at high doses quite early or if it is increased to over 0.4 or 0.5 mg/day. At lower doses, blood pressure is not clinically affected, although a fall of several mm mercury in diastolic and systolic pressure can be detected. Slight prolongation of the PR interval on the electrocardiogram has been noted, but this has not been considered to be of significance. Increased irritability, nightmares, and insomnia have also been reported.

Treatment of Obsessions and Compulsions in TS

It is now recognized that obsessive-compulsive symptoms occur in about half of patients with Tourette Syndrome. Current evidence suggests a genetic relationship between obsessive-compulsive disorder (OCD) and TS. Symptoms of OCD may be even more disabling than motor and vocal tics for some patients, resulting in impaired school or job performance, abnormal psychosocial development, or disrupted family life. Furthermore, obsessive thought patterns and/or compulsive activities may contribute to impaired attention - another behavioral problem of TS.

Clomipramine

Among pharmacological interventions for OCD, antidepressant medications have shown the greatest clinical efficacy. The most widely studied antidepressant drug for the treatment of primary OCD in psychiatric populations is clomipramine (Anafranil), a potent serotonin reuptake inhibitor now available in the United States. Several controlled clinical trials have confirmed superior efficacy of clomipramine over other tricyclic antidepressants in adult patients with primary OCD. Recent experience indicates that the drug can be effective for OCD associated with TS as well.

Clomipramine is administered in capsules of either 25 mg, 50 mg or 75 mg. The drug is initiated at 25 mg daily and can be titrated to a maximum daily dosage of 250 mg in adults (3 mg/kg in children) in divided doses, as needed. Each patient is brought to his or her optimal dosage level as determined by clinical response and side effects encountered. Clomipramine should be administered with meals to reduce gastrointestinal side effects or at bedtime to minimize daytime sedation. The maintenance dose for all patients should be the lowest effective dose, usually 50-150 mg per day. The clinical response to clomipramine may be delayed by several weeks. Side effects observed during clomipramine therapy are those typical of tricyclic antidepressant drugs, such as sedation, dry mouth, dizziness, tremor, constipation and sexual dysfunction. As with other tricyclic antidepressant drugs, clomipramine may lower seizure threshold.

Fluoxetine

Fluoxetine (Prozac), another antidepressant now marketed, inhibits serotonin reuptake but has been less well-studied for treating OCD. Preliminary experience suggests that this drug may be effective for OCD associated with TS. The medication is initiated at 20 mg each morning and may be adjusted as required to 60-80 mg per day divided into 2 or 3 doses. Clinical response to fluoxetine may also be delayed by several weeks.

Fluoxetine appears to produce fewer and less toxic side effects than clomipramine. In addition to those side effects typical of antidepressant medications, dyspepsia, nausea, skin rash, and hypomanic behavior may occur. The drug appears to suppress appetite for some patients. Fluoxetine has been used safely in a small number of children with TS. Some TS patients have reported a reduction of tics, and some parents have reported improvement in their child's school performance during fluoxetine therapy. However, these effects have not been formally assessed.

Combinations of Medications

Some clinicians prefer to use combinations of medications when a single agent is only partially effective. There is some clinical evidence to indicate that haloperidol (or another of the neuroleptics mentioned previously) plus clonidine may have synergistic effects. There is also some evidence that clonidine may reduce akathisia caused by neuroleptics. The combination of haloperidol and clonidine has been used in two clinical situations: (1) for patients whose symptoms are not fully controlled on haloperidol, or who are having serious side effects when medication is increased, yet who cannot have their haloperidol fully discontinued because of the severity of symptoms or the emergence of an exacerbation with tapering; and (2) for patients who are on clonidine but are still having motor and phonic symptoms. It appears that patients can be managed with smaller doses of haloperidol if clonidine is added to the regimen, and, on the other hand, that haloperidol may improve the tic control for some patients on clonidine. In general, quite small doses of both medications have been used when the drugs are combined, and no serious side effects have been reported in addition to what is seen when each drug is used individually.

Other combinations such as a neuroleptic plus fluoxetine or a tricyclic antidepressant may be helpful for patients with tics and OC symptoms in which both are severe. Clonazepam has been used in combination with either clonidine or neuroleptics, but there is little evidence of the improved efficacy of those combinations. While there may be justification for using various combinations of medications in individual patients, the best recommendation would be to thoroughly explore the use of single pharmacologic agents before resorting to polypharmacy.

Clonazepam has been found to be effective in some cases for mild tic symptoms. It may also be used in conjunction with another of the previously discussed medications. However, it has the disadvantage of being a habit-forming drug.

Choice of Medication

The clinician's choice of a first drug is a difficult decision. Haloperidol has the longest "track record," and its therapeutic benefits and side effects are well defined. Another major contender as a first drug is clonidine, which is less well defined and less likely to be dramatically effective. Clinicians who lean toward clonidine as a first drug do so because of its limited side effects and positive effect on attention; however, where a rapid response is needed, haloperidol or pimozide may be more effective.

When treating a child with both ADHD and TS, it is advisable to avoid the use of stimulant medications (see page 15). Alternative treatments for ADHD include imipramine, clonidine, and neuroleptics.

When used alone, antidepressant medications are not useful in the treatment of tics. However, TS patients may develop serious depressions, and then the use of antidepressant medication should be considered. In such situations, antidepressants have been added to ongoing TS treatment (haloperidol and clonidine) with good results. Complicating the assessment of depression in TS is the fact that pimozide, haloperidol, and clonidine may elicit lowered spirits or dysphoria. Therefore a trial of no medication might be considered before the addition of an antidepressant, especially if the depression emerges soon after the use of another medication and with no apparent psychosocial precipitant.

Various minor tranquilizers have been used in the treatment of TS with no apparent benefit on the tic symptomatology. However, individual patients seem to have benefitted from medications such as benzodiazepines (e.g., diazepam and alprazolam) when used to help alleviate anxiety or to improve sleep. As such, their use for TS patients should follow the usual guidelines.

Psychodynamic Psychotherapy

Although psychotherapy will not eliminate tics, it may be beneficial to some TS patients who require treatment of the psychological sequelae of this difficult illness. The inability to control one's own body and even one's own thoughts, which is taken for granted by most people, often is a great source of anxiety, guilt, fear, helplessness, anger, and depression. Some patients react by withdrawal, others by aggressivity, and still others by perfectionism and excessive efforts to be in control. Since virtually all TS patients are subjected to some form of negative social reactions, self-esteem problems are common. In addition, the person with TS experiences all the difficulties associated with growing up with a chronic illness. For those reasons rather than for the primary symptoms of TS, psychodynamic psychotherapeutic treatment may well be indicated.

Family Treatment

As with any chronic illness, TS causes a great strain on the family as well as on the individual patient. Parents often have a harder time accepting their children's symptoms than the children themselves. Part of the trouble may lie in the guilt associated with the genetic nature of the disorder. Another major problem for parents is understanding which behaviors are beyond the control of the TS child and which can be - and should be - controlled. Also, preoccupation with the "sick" child may lead to a situation where scant attention is paid to the impact on the siblings without TS. Often spouses do not appreciate the complex problems of TS and its effects on a loving relationship until some time after they are married.

Family therapy for TS should focus on the role that the TS patient plays in the family. Is he or she overprotected, treated punitively, misunderstood, or a source of embarrassment? Does the illness dominate the family's interrelationships or is it taken more "in stride?" If the family can learn to accept the member with TS along with the symptoms - not despite them, it can provide the sense of security necessary for a healthy approach to the "outside world."

Usually, the first task of family therapy is to educate family members about various aspects of the disorder. It is often found that the family and even the TS patient do not thoroughly understand the range of symptomatology nor how they might be expected to handle it. Following an understanding of the symptoms, an effort should be made to understand how the symptoms impact on each member of the family. The ultimate goals for the family member with TS include: the promotion of self-esteem and competency and support in the challenges of work or school and in peer group relationships. The goal for family members is to develop the flexibility to give special help when needed but not to overprotect.

Genetic Counseling

With the recognition that TS is familial and genetic, families naturally have become interested in the possibility of genetic counseling. Such counseling must be provided by knowledgeable clinicians who can impart accurate information about the mode of transmission and work with families in dealing with the complex feelings which are aroused.

Academic and Occupational Interventions

Children with attentional and learning problems require educational intervention similar to the approaches used in the treatment of other forms of ADHD and learning disabilities. Depending on the severity of the school and associated behavioral problems, TS patients may require special tutoring, a learning laboratory, a self-contained classroom, a special school, or a residential school. It may be difficult to convince a school district of the need for special school provisions for a bright TS patient who does not have specific learning disabilities, but whose attentional problems limit optimal functioning.

Since TS is an uncommon disorder, schools need to be informed about the nature of TS and the ways it affects attention and learning. Sometimes the physician must actively serve as a child's advocate.

Children with TS sometimes are kept as homebound students because their symptoms are thought to be too disruptive for the classroom. Most difficult for teachers are phonic/vocal symptoms. A homebound child is deprived of his or her legal rights for the least restrictive educational environment and adequate education .

When children stay at home, their TS symptoms are likely to be exacerbated as they exert less control and are exposed to the tedium of no outside diversions and intense, often negative or ambivalent interactions with parents. A chain reaction may be set up in which bad symptoms lead to worse symptoms and increased isolation.

Some further specific recommendations for teachers may be found in a pamphlet entitled, The Teacher's Guide to Tourette Syndrome, published by the Tourette Syndrome Association.

Many adults with TS require special modifications in their working situations. Often an explanation to the employer about special needs will receive a positive response. Flexibility, compassion, and productivity in the workplace can be increased to everyone's benefit with appropriate interventions for a very symptomatic patient or for a patient who is having difficulty adjusting to a new medication.