Rebound phenomena in Tourette's syndrome after abrupt withdrawal of clonidine. Behavioral, cardiovascular, and neurochemical effects

Following an open trial of clonidine hydrochloride (3 to 8 micrograms/kg/day for 12 weeks), we studied the behavioral, cardiovascular, and neurochemical effects of abrupt clonidine withdrawal in seven patients with Tourette's syndrome aged 9 to 13 years. Five patients showed marked worsening of tics. After reinitiation of clonidine therapy, the time required for patients to return to prewithdrawal levels of tic symptoms ranged from two weeks to four months. Increases in motor restlessness, blood pressure, and pulse rate were also observed over the 72-hour period following abrupt withdrawal of clonidine. Plasma levels of free 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and urinary excretion of norepinephrine and epinephrine increased during the withdrawal period. Clonidine's effectiveness in Tourette's syndrome may be dependent on changes in dopaminergic as well as adrenergic mechanisms.     

Clonidine treatment of Gilles de la Tourette's syndrome

The safety and effectiveness of clonidine hydrochloride (3 to 5 micrograms/kg per day) were evaluated in 47 subjects with Gilles de la Tourette's syndrome, aged 7 to 48 years. Twenty-four subjects were randomly assigned to clonidine treatment and 23 to placebo. Forty subjects (21 given clonidine and 19 placebo) successfully completed the 12-week, double-blind clinical trial. Clinical ratings of tic severity improved for both groups. The magnitude of response was greater in the group receiving clonidine. Clinician-rated measures of motor tic severity, the degree to which the tics are "noticeable to others," motor tic counts from videotaped interviews, and parent-rated measures of impulsivity and hyperactivity were the most responsive to clonidine treatment. These results indicate that clonidine is more effective than placebo in reducing some of the tic and other behavioral symptoms associated with Gilles de la Tourette's syndrome.     

Tics in Tourette syndrome: new treatment options.

Tourette Syndrome is a familial neurobehavioral disorder characterized by fluctuating involuntary motor and/or vocal tics. The most commonly used medications to treat Tourette's syndrome are haloperidol, pimozide, fluphenazine, and clonidine, all of which may have considerable side effects. We enrolled 450 patients with tics/Tourette's syndrome to be treated with baclofen/botolinum toxin type A for their symptoms. Global severity of tic symptoms was rated by the Yale Global Tic Severity Scale and a quantified videotaped micro-structured analysis of tics. We found that baclofen/botolinum toxin type A are very effective, safe, and reliable in the treatment of tics/Tourette's syndrome. It is worthwhile considering this treatment approach in patients with tics/Tourette's syndrome in order to reduce or avoid the side effects of other medications. Further studies, however, are required.     

Treatment of Gilles de la Tourette's syndrome with clonidine and neuroleptics

In an open clinical trial of clonidine hydrochloride and neuroleptics in patients with Gilles de la Tourette's syndrome, neuroleptics resulted in greater improvement across the range of symptoms in a larger proportion of patients than did clonidine. A small subgroup of patients may have benefited from treatment with clonidine. Carefully controlled, randomized, and double-blind studies are necessary to resolve the divergent views about the effectiveness of clonidine in the treatment of Gilles de la Tourette's syndrome.     

Clonidine in neuropsychiatric disorders: a review

We describe the basic pharmacological principles underlying the activity of the alpha 2-adrenergic receptor agonist clonidine, including its interactions with the cholinergic, histaminergic, serotoninergic, endorphinergic and possibly dopaminergic systems. The use of clonidine for the therapy of various neuropsychiatric indications in which it appears to be beneficial is described. These conditions include migraine, Korsakoff's psychosis, Tourette's syndrome, withdrawal states, tardive dyskinesia, essential tremor, neuroleptic-induced akathisia, neurogenic bladder, idiopathic orthostatic hypotension, paroxysmal localised hyperhydrosis, diabetic neuropathy and stiff-man syndrome. The need for long term evaluation of this agent in some of these diseases is stressed.     

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.     

Tourette syndrome: successful treatment with clonidine and oxycodone

Summary A 15-year-old boy with Tourette's syndrome exhibited severe involuntary self-mutilatory behavior. While clonidine effectively controlled the motor and phonic tics, it failed to ameliorate the self-mutilatory behavior. Administration of oxycodone (50 mg/day) combined with clonidine produced a dramatic reduction in the frequency and severity of the self-mutilatory acts within 12 h. This report indicates that disturbances in the functional interplay between the noradrenergic and opiatergic systems may be important in the pathophysiology of Tourette's syndrome.     

Comparison of acetorphan with clonidine for opiate withdrawal symptoms

OBJECTIVE AND METHOD: The authors compared the effects of acetorphan, an enkephalinase inhibitor, with those of clonidine for the treatment of the opioid withdrawal syndrome. Nineteen patients addicted to heroin or synthetic opiates who were undergoing drug withdrawal and displayed a withdrawal syndrome according to DSM-III criteria were studied for 5 days in a hospital setting. In a double-blind trial, 10 subjects were given acetorphan intravenously and nine were given clonidine; objective signs and subjective symptoms of withdrawal were recorded. RESULTS: On several objective signs, the effect of acetorphan was more marked than that of clonidine, whereas the two drugs exhibited similar efficacy with respect to the subjective components of withdrawal. No side effect was noted in the subjects who received acetorphan. CONCLUSIONS: Enkephalinase inhibition may constitute a novel and safe therapeutic approach to the opioid withdrawal syndrome.     

Pharmacotherapy of Tourette's syndrome and associated disorders.

Tourette's syndrome (TS) is a chronic neuropsychiatric disorder characterized by multiform motor and phonic tics. Conditions that are commonly associated with TS include attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Medications used to treat tics include haloperidol, pimozide, and clonidine. Symptoms of ADHD may respond to clonidine or desipramine. Specific serotonin uptake inhibitors, such as fluoxetine or clomipramine, are used in the treatment of OCD symptoms. The decision to use medication and the monitoring of its impact require careful assessment of the child's overall development and not only the presence of tic symptoms.     

Self-injurious behavior associated with clonidine withdrawal in a child with Tourette's disorder

A 7-year-old boy with Tourette's disorder, atypical pervasive developmental disorder, borderline mental retardation, and a history of self-injurious behavior was treated for 21 months with clonidine transdermal patches at doses ranging from 0.1 to 0.5 mg weekly. When withdrawn from clonidine over 4 weeks to assess the need for continued therapy, the patient developed multiple self-destructive behaviors involving the theme of suffocation. The importance of careful clinical monitoring of the behavior of patients undergoing withdrawal from prolonged treatment with high doses of clonidine is emphasized.     

Naltrexone suppresses abnormal sexual behavior in Tourette's syndrome

Abnormal sexual behavior occurs in 30-40% of patients with Tourette's syndrome (TS). Two patients with TS who exhibited distressing abnormal sexual behavior experienced amelioration of symptoms with administration of the oral opiate receptor antagonist naltrexone (TrexanR). Conventional anti-TS drugs including haloperidol and clonidine were ineffective. Abnormal sexual behavior may be another feature of the disease responding to opiate blockers.     

Ineffectiveness of clonidine in the treatment of the benzodiazepine withdrawal syndrome: report of three cases

The effectiveness of clonidine hydrochloride in the treatment of abrupt withdrawal from long-term, therapeutic doses of benzodiazepines was studied in three patients under double-blind, placebo-controlled conditions. The intensity, severity, and duration of the abstinence syndrome were not altered by clonidine at a dose sufficient to markedly reduce blood pressure and plasma free 3-methoxy-4-hydroxyphenylglycol. These results contrast with the established efficacy of clonidine in the opiate withdrawal syndrome and suggest that many of the symptoms of benzodiazepine withdrawal may not be caused by hyperactivity of the noradrenergic system.     

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome

OBJECTIVE: To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourette's syndrome (TS). METHOD: Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS: Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS: In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.     

Clonidine suppresses the opioid abstinence syndrome without clonidine-withdrawal symptoms: A blind inpatient study

Nine hospitalized opioid-addicted patients were blindly given clonidine within 36 hours of the abrupt and blind discontinuation of methadone. All nine patients were successfully withdrawn from methadone and were asymptomatic upon discharge. Clonidine-treated patients had significantly fewer symptoms than a comparable group of opioid addicts abruptly withdrawn from methadone. No exacerbation of symptomatology developed after the cessation of clonidine. The clinical implications of clonidine's suppression of opioid withdrawal and the α-2 adrenergic mediation of the abstinence syndrome are discussed.     

A case of Tourette's syndrome with symptoms of attention deficit disorder treated with desipramine

Therapy for Tourette's syndrome with tricyclic antidepressants has had varied results. Previous reports have not addressed the frequent association of symptoms of attention deficit disorder (ADD) with Tourette's syndrome or the plasma levels of tricyclic antidepressants. A boy with Tourette's syndrome and ADD-like symptoms was treated with desipramine, and all the symptoms improved. This drug may be effective therapy for patients with Tourette's syndrome and ADD-like symptoms.     

On the use of clonidine and thioproperazine in a woman with Gilles de la Tourette's disease

A 25-year-old woman with Gilles de la Tourette's disease was successfully treated with clonidine (an inhibitor of noradrenaline release). However, the drug was stopped because of side effects. Thioproperazine, a phenothiazine derivative which blocks subcortical dopaminergic receptors, suppressed Gilles de la Tourette's symptoms totally. The patient has tolerated the drug well for over a year since its introduction. The pharmacomanometric investigation performed in this patient showed hyperactivity of her noradrenergic system.     

Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County

We have done an epidemiological study in an elementary school with 2000 Taiwanese children aged from 6 to 12 years, and found 11 of them with Tourette's syndrome. The prevalence rate of Tourette's syndrome was around 0.56%. The ratio of male to female was 9 to 2. The comorbid rate of attention-deficit/hyperactivity disorder was 36%, self-injurious behaviors 27%, and obsessive-compulsive behaviors 18%. The familial rate of Tourette's syndrome was 27%. We also found that another 98 children had transient tic disorders. For 73% of patients with mild tics, understanding and acceptance from family, teachers, and friends are the most important things. When tics are so severe that medication is necessary, haloperidol is no longer the first or only choice. We tried clonidine, atypical neuroleptics such as risperidone or olanzapine, or pergolide. The first support group was established in 1999 for children with tics in Taiwan and transformed to Taiwan Tourette Family association in June 2001 to provide further service for Tourette's syndrome.     

Imipramine treatment of panic disorder in a boy with Tourette's syndrome

Tourette's syndrome patients may suffer associated behavior and emotional problems that require treatment intervention even when tic symptoms are mild. A case is reported of a boy with Tourette's syndrome whose panic attacks were successfully treated with imipramine. The results suggest that trials of imipramine might prove beneficial for Tourette's syndrome patients who experience panic attacks.     

Clinical features and long-term treatment with pimozide in 65 patients with Gilles de la Tourette''s syndrome.

During the last seven years 65 patients with Gilles de la Tourette's syndrome have been treated. Pimozide was used as the preferred drug because of our experience of treating other hyperkinesias which indicated fewer side-effects than with haloperidol. Of the 65 patients with Gilles de la Tourette's syndrome, 59 were treated with pimozide alone or in combination with tetrabenazine or clonidine. The dose ranges of pimozide were 0.5-9 mg per day. Eighty-one percent experienced a good clinical response without side-effects. The side-effects seen in our patients were sedation, gain in weight, depression, pseudoparkinsonism and akathisia; acute dystonic reactions, blurred vision, slurred speech and xerostomia did not occur. No cases of tardive dyskinesia were seen.