Clonidine ameliorates Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (TS) is a severe, familial neuropsychiatric disorder of childhood onset that is characterized by multiform motor, phonic, behavioral, and psychological symptoms. Clonidine hydrochloride, a centrally active alpha-adrenergic agonist, was observed to ameliorate the disorder in the majority of 25 patients who could not tolerate or did not benefit from treatment with haloperidol. Clonidine had a gradual onset of action. Compulsive behavior, frustration intolerance, speech difficulties, behavioral blocking, attentional problems, and tics were responsive to treatment. The noradrenergic system may be involved, primarily or secondarily, in the expression of the genetic predisposition to TS. These observations will require testing by suitably controlled efficacy studies.

Familial pattern and transmission of Gilles de la Tourette syndrome and multiple tics.

Fifty-two patients with Gilles de la Tourette syndrome (TS) diagnosed according to DSM-lll criteria and/or their parents were interviewed regarding symptoms among family members. Occurrences of TS and multiple tics (MT) among first-degree relatives were distinguished to determine the familial patterns of the two diagnoses. comparing these data with family data collected on a random national sample of patients with TS, we found no differences between the two samples. Each separately and both combined showed that (1) MT seems to be a mild form of TS; (2) both MT and TS are transmitted in the same families; (3) the sex difference is real and not an artifact of ascertainment; and (4) the sex difference is related the the transmitted susceptibility as a threshold effect. A specific genetic mechanism has not been identified.

School avoidance and social phobia triggered by haloperidol in patients with Tourette's disorder.

Fifteen patients with Tourette's disorder developed school and work avoidance syndromes when treated with low doses (mean 2.5 mg/day) of haloperidol for short periods of time (mean, 8 weeks). The phobic syndromes disappeared completely with discontinuation or reduction of the haloperidol dose. Haloperidol's effects on dopaminergic functioning support a role for catecholamines in the pathogenesis of phobic syndromes. It is not known whether phobias are precipitated by haloperidol only in patients with Tourette's disorder as a consequence of the specific metabolic alterations in this disorder or are a medication side effect in other psychiatric disorders as well.

Short- and long-term treatment of Tourette's syndrome with clonidine: a clinical perspective.

Thirteen patients with Gilles de la Tourette's syndrome were treated with clonidine (0.125 to 0.3 mg/d) for at least 60 weeks. In a single-blind, placebo-controlled trial, 6 of the 13 patients were judged to be unequivocal responders to clonidine, and 6 other patients had an equivocal response. There was significant improvement in motor and phonic tics, as well as in associated behavior problems, and there were no serious side effects. Tolerance to clonidine did not develop. Further placebo-controlled, randomized, double-blind studies of clonidine in Tourette's syndrome are needed to establish the drug's efficacy.

Assessment of brain function in clinical pediatric research: behavioral and biological strategies.

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established. In this setting, participation in research can facilitate better treatment for a child. The use of novel biological strategies, such as pharmacological challenge tests, permits evaluation of the relation of specific neuronal systems to behavioral dimensions in clinical disorders. The development of a new treatment for Tourette's syndrome illustrates the integration of basic and clinical research methods.

Clonidine in the treatment of Tourette syndrome: a review of data.

There are conflicting data concerning the efficacy of clonidine in TS. Some TS patients, probably 50% or more, experience substantial, long-term symptomatic improvement with minimal side effects. However, their profile of response is often variable, with behavioral symptoms appearing to show the most consistent improvement. Maximal benefit may not be evident for 4 to 6 months. A minority of patients do not respond, and a few worsen on clonidine. The need for additional double-blind trials is clear. Additional metabolic and pharmacologic investigations are needed to understand the determinants of the response of TS patients to clonidine. The response to acute doses of clonidine on sedation, growth hormone release, blood pressure, and plasma MHPG levels may be predictive of eventual therapeutic response. The variable response to clonidine, however, suggests that noradrenergic mechanisms in TS may not be of primary pathogenic importance. The study of interactions between neurochemical systems may help illuminate the pathophysiology of TS and lead the way to improved treatment of this disabling condition.

Stimulant medications precipitate Tourette's syndrome.

Following treatment with stimulant medications for symptoms of attention deficit disorder, Gilles de la Tourette's syndrome occurred in 15 patients. Early signs of Tourette's syndrome may be difficult to distinguish from hyperactive and attention disordered symptoms, leading the clinician to consider, treatment with stimulants. In these Tourette's-susceptible patients, stimulants may exacerbate severe motor and phonic tics, requiring discontinuation of administration of stimulants and institution of haloperidol therapy for tic control. Clinical evaluation for tics and Tourette's syndrome in children and their families should precede and dictate use of stimulant medications in children.

Stimulant medications precipitate Tourette's syndrome.

Following treatment with stimulant medications for symptoms of attention deficit disorder, Gilles de la Tourette's syndrome occurred in 15 patients. Early signs of Tourette's syndrome may be difficult to distinguish from hyperactive and attention disordered symptoms, leading the clinician to consider treatment with stimulants. In these Tourette's-susceptible patients, stimulants may exacerbate severe motor and phonic tics, requiring discontinuation of administration of stimulants and institution of haloperidol therapy for tic control. Clinical evaluation for tics and Tourette's syndrome in children and their families should precede and dictate use of stimulant medications in children.