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Chapter: Essentials of Psychiatry: Childhood Disorders: Tic Disorders

Tic Disorders: Standard Approaches to Treatment

Educate the Patient and Family

Standard Approaches to Treatment

 

Educate the Patient and Family

 

The initiation of treatment can be a delicate process, given the difficulties patients and their families experience before finding appropriate care. Most families are frightened about their child’s having a neuropsychiatric disorder and envision a grim progno-sis. After the evaluation is completed, often in the first session, general education of the patient and family about the course of the tic disorder is essential (Table 30.1). Most patients and fami-lies are relieved to hear that the majority of persons with tics have consistent improvement in tic severity as they move through their teenage years and into adulthood. They are also pleased to hear that tic symptoms are not inherently impairing.


 

Identify Cooccurring Disorders

 

Identifying whether ADHD, LD and OCD are present is espe-cially important because they are often the more common im-pairing conditions in these children. One of the major pitfalls of treatment of patients with Tourette’s disorder is to pursue tic sup-pression to the exclusion of the treatment of other cooccurring conditions that are present and possibly more impairing.

 

Create a Hierarchy of the Clinically Impairing Conditions

 

Most psychiatrists, as part of their formulation, create some clini-cal hierarchy; yet in Tourette’s disorder, with the multitude of often complex problems, it is essential that a conscious effort be made to formulate, organize and create hierarchies for treatment. For example children with moderate tics and separation anxiety with school refusal should be considered for a treatment with selective serotonin reuptake inhibitor (SSRI) for their separation anxiety rather than neuroleptics for tic suppression (The Research Unit on Pediatric Psychopharmacology Anxiety Study Group, 2001). It is possible with successful treatment of the anxiety disorder that patient may also experience a reduction in tic severity also.

 

Treat the Impairing Conditions

 

Tic Suppression: Pharmacological

 

The goal of pharmacological treatment is the reduction of tic severity, not necessarily the elimination of tics. Haloperidol has been used effectively to suppress motor and phonic tics for more than 30 years. Since that time, a number of other neuroleptic agents have also been identified as useful in tic suppression, in-cluding fluphenazine and pimozide. In Europe, the substituted benzamides, sulpiride and tiapride, and the nonneuroleptic tetrabenazine have also been shown to be useful. As new neu-roleptic agents become available, clinical trials for tic suppres-sion invariably occur. Preliminary results with risperidone have been mixed, whereas trials with clozapine are more uniformly negative. The major drawback with neuroleptic agents is the fre-quent and significant side effects, which often preclude continued use of the medication.

 

Haloperidol

 

Haloperidol is a high-potency neuroleptic that preferentially blocks dopamine D2 receptors. Historically, haloperidol has been the most frequently used medication for tic suppression. It is ef-fective in a clear majority of patients, although relatively few pa-tients are willing to tolerate the side effects to obtain the tic-sup-pressing benefits. Neuroleptics are often effective at low doses, and low doses minimize side effects. For haloperidol, doses in the range of 0.5 to 2.0 mg/day are usually adequate. Starting dosages are low (0.25–0.5 mg/day), with small increases in dose (0.25–0.5 mg/day) every 5 to 7 days. Most often the medication is given at bedtime, but with low doses, some patients may require twice-a-day dosing for good tic control.

 

Side effects with all neuroleptics are common and include sedation, acute dystonic reactions, extrapyramidal symptoms including akathisia, weight gain, cognitive dulling and the com-mon anticholinergic side effects. There have also been reports of subtle, difficult to recognize side effects with neuroleptics, in-cluding clinical depression, separation anxiety, panic attacks and school avoidance.

 

Dosage reduction is the most prudent response to side ef-fects, although the addition of medications such as benztropine for the extrapyramidal symptoms can be useful. Dosage reduc-tion in those children with Tourette’s disorder who have been administered neuroleptics long term may be complicated by withdrawal dyskinesias and significant tic worsening or rebound. Withdrawal dyskinesias are choreoathetoid movements of the orofacial region, trunk and extremities that appear after neu-roleptic discontinuation or dosage reduction and tend to resolve in 1 to 3 months. Tic worsening even above pretreatment baseline level (i.e., rebound) can last up to 1 to 3 months after discontinu-ation or dosage reduction. Tardive dyskinesia, which is similar in character to withdrawal dyskinesia, most often develops during the course of treatment or is “unmasked” with dosage reductions. Rarely have cases of tardive dyskinesia been reported to occur in patients with Tourette’s disorder.

 

Fluphenazine

 

Whereas fluphenazine has never undergone controlled trials, clinical experience suggests that it has somewhat fewer side effects than haloperidol. Fluphenazine has both dopamine D1 and D2 receptor-blocking activity, and the side effect profile is similar to that of haloperidol. Fluphenazine is slightly less potent than haloperidol so that starting doses are somewhat higher (0.5–1 mg/day), as are treatment doses (3–5 mg/day).

 

Pimozide

Pimozide is a potent and specific blocker of dopamine D2 recep-tors. Its side-effect profile is generally similar to that of the other neuroleptics, although it has fewer sedative and extrapyramidal side effects than haloperidol. In contrast to either haloperidol or fluphenazine, pimozide has calcium channel blocking properties that affect cardiac conduction, as evidenced by changes in the electrocardiogram. The coadministration of other medications that affect cardiac conduction, such as the tricyclic antidepres-sants (TCAs), is generally contraindicated. Baseline and follow-up electrocardiograms are important for adequate management of patients.

 

Beginning treatment with a dose of 1 mg/day is prudent, although with pimozide’s long half-life, every-other-day dos-ing can be used to decrease the effective daily dose. Increases of up to 1 mg/day can occur every 5 to 7 days until symptoms are controlled. Most patients experience clinical benefit with few side effects with doses of 1 to 4 mg/day. Higher doses can be associated with more side effects. In a comparison of pimozide, haloperidol and no drug in patients with Tourette’s disorder and ADHD, pimozide at 1 to 4 mg/day was useful in decreasing tics and improving some aspects of cognition that are commonly im-paired in ADHD (Sallee and Rock 1994). The potential to have impact on both Tourette’s disorder and ADHD symptoms with a single drug is a clear advantage that pimozide may have over other neuroleptics.

 

Atypical Neuroleptics

 

The atypical neuroleptics appear to have replaced the standard neuroleptics as the mainstay of treatment for the psychotic dis-orders. Given the potentially lower risk for tardive dyskinesia with these agents, their efficacy has been assessed for tic sup-pression in patients with Tourette’s disorder. To date there are only small controlled or open trials to guide the clinician in the use of these agents. Clozapine does not appear to be effective as a tic-suppressing agent and its hematological side effects preclude its use. Risperidone has been effective in reducing tic symptoms severity in one controlled trial (Dion et al., 2002) and may have the added benefit of augmenting SSRIs in treating tic-related OCD.

 

Olanzapine in low doses does not appear to have the same tic-suppressing power as the typical neuroleptics which may be related to olanzapine’s relatively weak dopamine D2 blocking activity. Side effects, especially weight gain, have dampened the enthusiasm for the atypicals risperidone, olanzapine and quetiapine. In one of the larger placebo-controlled trials (N 5 56) of the new neuroleptics, ziprasidone was found to be effective in reducing tic symptoms. The mean dose was low 28 ± 10 mg/day. There were few side effects including a low incidence of weight gain (Gilbert et al., 2000).

 

Clonidine and Guanfacine

 

Whereas controlled trials have shown that some patients ben-efit with symptom reduction, the overall effect of clonidine for tic suppression and ADHD is more modest than that achieved with the “gold standards” (haloperidol and the stimulants, re-spectively) for these conditions (Goetz, 1993). Given clonidine’s mild side-effect profile, it is often the first drug used for tic suppression, especially in those children with Tourette’s disor-der and ADHD. Treatment is initiated at 0.025 mg/day and in-creased in increments of 0.025 to 0.05 mg/day every 3 to 5 days or as side effects (sedation) allow. Usual effective treatment doses are in the range of 0.1 to 0.3 mg/day and are given in di-vided doses (4–6 hours apart). Higher doses are associated with side effects, primarily sedation, and are not necessarily more effective. The onset of action is slower for tic suppression (3–6 weeks) than for ADHD symptoms. Side effects, in addition tosedation, include irritability, headaches, decreased salivation, and hypotension and dizziness at higher doses. Interestingly, owing to clonidine’s short half-life, some patients experience mild withdrawal symptoms between doses. More severe re-bound in autonomic activity and tics can occur if the medica-tion is discontinued abruptly. Some patients find that clonidine in the transdermal patch form provides a more stable clinical effect and avoids multiple doses each day. Children are usually stabilized on oral doses before they are switched to the patch. A rash at the site of the patch is a common, but manageable, complication of treatment.

 

Guanfacine is an alpha-2-adrenergic agonist that poten-tially offers greater benefit than clonidine because of differ-ences in site of action, side effects and duration of action. In nonhuman primates, guanfacine appears to bind preferentially with alpha-2-adrenergic receptors in prefrontal cortical re-gions associated with attentional and organizational functions. Guanfacine’s long half-life offers the advantage of twice-a-day dosing, which is more convenient than the multiple dosing required with clonidine. In a randomized, placebo-controlled trial (N 5 31) of children with tics and ADHD, guanfacine in doses up to 0.3 mg/day had an average 31% reduction in tic severity compared with no reduction on placebo. Clinically the effect on tics is less than would be expected on neuroleptics (Scahill et al., 2001).

 

Benzodiazepines

 

Benzodiazepines can be useful in decreasing comorbid anxiety in patients with Tourette’s disorder. In addition, clonazepam ap-pears also to be useful in selected patients for tic reduction. Of-ten, doses of 3 to 6 mg/day may be necessary for tic reduction. Because sedation is a significant side effect at these dosages, an extended titration phase of 3 to 6 months may be necessary. Simi-larly, a slow taper is required to avoid withdrawal symptoms.

 

Pergolide

 

Agonist activity on presynaptic dopamine neurons results in decrease dopamine release and may therefore result in decreased tic severity in people with Tourette’s disorder. To exploit this finding a number of small open trials of dopamine agonists and a small controlled trial of pergolide (N 5 24) have been conducted. Pergolide, a mixed D1–D2–D3 dopamine agonist often used for restless leg syndrome, was found to be superior to placebo in reducing tic severity and was associated with few adverse events (Gilbert et al., 2000). Doses used were low as higher doses may be associated with dopamine agonist effects postsynaptically.

 

Baclofen

 

Baclofen, a muscle relaxant, is GABA-B receptor agonist that acts presynaptically to inhibit the release of excitatory amino acids such as glutamate. In a small placebo controlled crossover trial (N 5 10) baclofen 20 mg t.i.d. was not found to be effective in reducing tic severity but did appear to have an effect on tic-related impairment (Singer et al., 2001).

 

Infection and Autoimmune-based Treatments

 

Several treatment studies have been undertaken based on the hy-pothesis that some forms of Tourette’s disorder or OCD may be related to streptococcal infection. Based on the beneficial effects of penicillin prophylaxis in preventing recurrences of rheumatic fever, a similar strategy was employed in subjects meeting cri-teria for PANDAS (Garvey et al., 1999). The study was limited by a number of flaws and although the concept of prophylaxis is compelling, special design considerations will be required in future studies.

 

After small open trials with the immunomodulatory treat-ments such as plasma exchange or intravenous immunoglobulin (IVIG), a larger trial comparing these methods to sham IVIG was undertaken. Children meeting criteria for PANDAS (N 5 30) were randomly assigned (1 : 1 : 1) to treatment with plasma exchange (five single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on two consecutive days), or placebo (saline solution given in the same manner as IVIG) and subjects were reported as doing well at 1 year (Lougee et al., 2000). Although this study is encour-aging there are a number of methodological problems including lack of a placebo control for plasma exchange and inclusion of uncontrolled subjects in outcome analysis after the first month. These findings do support ongoing investigation of these treat-ment methods but given the cost, risk and highly experimental nature of these treatments it is recommended that patients obtain these treatments only in the context of ongoing clinical inves-tigations of these treatments at major medical research centers (for further information, see http://intramural.nimh.nih.gov/re-search/pdn/web.htm).

 

Tic Suppression: Nonpharmacological

 

The behavioral technique shown to be most effective is habit reversal training. For Tourette’s disorder, habit reversal training is the use of a competing muscle contraction or behavioral re-sponse that opposes the tic movement. This method is usually combined with relaxation training, self-monitoring, awareness training and positive reinforcement. In the few published studies of habit reversal training, there were marked overall reductions in tic frequency. Treatment averaged 20 training sessions during an 8- to 11-month period. Marked tic reduction was noted at 3 to 4 months. Interestingly, urges or sensations experienced before the tic movements also decreased with behavioral treatment (Azrin and Peterson, 1990).

 

Psychosocial Treatments

 

There are no published systematic studies of psychosocial in-terventions for patients with Tourette’s disorder. Most treatment efforts are based on a combination of traditional psychosocial in-terventions and clinical judgment.

 

Education

 

Perhaps the most useful psychosocial and educational interven-tion is to make the patient aware of the Tourette Syndrome Asso-ciation, both national and local c-hapters. This and other self-help groups can be useful as a source of support and education for patients, families and psychiatrists.

 

Therapy

 

Individual psychotherapy can be useful for support, develop-ment of awareness, or addressing personal and interpersonal problems more effectively. Family therapy can be useful when families have problems adjusting, functioning and communicat-ing. Although most families do well, some families have difficul-ties understanding the involuntary nature of tics and may punish their children for their tics, even after diagnosis and education. Alternatively, some families have more behavior difficulties with their children after diagnosis than before. Many parents of chil-dren with Tourette’s disorder inadvertently lower general behav-ior expectations because of confusion about what behaviors areand are not tics, or because of the parents’ desire not to add any additional stress to the youngster’s life. Also, with confusion in the field regarding the scope of problems in Tourette’s disorder, some parents see all maladaptive behaviors as involuntary and do not hold their children responsible for their behaviors. For chil-dren with Tourette’s disorder to do well, they need support from their family to develop effective self-control in areas not affected by Tourette’s disorder so that optimal adaptation can occur.

 

In newly diagnosed adults, psychotherapy oriented toward adequate adjustment to the diagnosis is important but not always easy. Adult patients frequently experience a mixture of relief to be finally diagnosed, with anger and resentment related to their past experiences with discrimination or inadequate medical care. Severely affected adults may also need psychotherapy to deal with the psychological and psychosocial difficulties related to having a chronic illness.

 

Other Psychosocial Interventions

 

For children, active intervention at school is essential to create a supportive yet challenging academic and social environment. Ef-forts to educate teachers, principals and other students can result in increased awareness of Tourette’s disorder and tolerance for the child’s symptoms.

 

Many young adults are finding Tourette’s disorder support and social groups important for interpersonal contact and con-tinued adult development. Efforts to keep people with Tourette’s disorder working are important, as are rehabilitation efforts for those who are not working. Finding housing and obtaining disa-bility or public assistance may be necessary for the most disabled patients with Tourette’s disorder.

 

Genetic Counseling

 

One question commonly asked by young adults with Tourette’s disorder is their risk for having a child with Tourette’s disorder. Given the fact that many who present for clinical attention with Tourette’s disorder have comorbid conditions, genetic counseling of people with Tourette’s syndrome should include not only the risk for Tourette’s disorder but also the risk for other neuropsy-chiatric problems such as ADHD or OCD that may be part of the young person’s history. In addition, because the base rate of neu-ropsychiatric disorders is high, it is not uncommon for spouses of people with Tourette’s disorder to have a neuropsychiatric disorder. In providing counseling to these couples it is impor-tant that genetic counseling be conducted not just about Tourette syndrome, but about the other conditions that occur as part of the young couple’s history.

 

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