clozapine and Tourette-Syndrome

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Brain; Cardiomyopathies; Child; Clozapine; Dyskinesia, Drug-Induced; Energy Metabolism; Feeding Behavior; Female; Gene Expression; Genetic Association Studies; Humans; Male; Myocarditis; Olanzapine; Pericarditis; Risperidone; Tourette Syndrome; Twin Studies as Topic; Weight Gain

We reviewed articles in English dealing with research into the effect of atypical antipsychotic drugs on tic reduction in Tourette's syndrome. In Denmark, there are four registered atypical antipsychotic drugs; clozapine, sulpiride, olanzapine, and risperidone. The topic of interest is the effectiveness and side effects of these drugs as compared to the conventional antipsychotic, pimozide, which is today the preferred pharmacological treatment of Tourette's syndrome among the antipsychotics. The conclusion is that risperidone would be a good first-line antipsychotic drug for the treatment of Tourette's syndrome. It is as effective as pimozide, its side effect profile is overall much more favourable, and unlike pimozide it does not contain the risk of causing heart arrhythmia.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dopamine Antagonists; Humans; Olanzapine; Pirenzepine; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Sulpiride; Tics; Tourette Syndrome

The increasing recognition of Tourette's syndrome is probably responsible for the broadening range of symptom severities seen in clinic patients. Greater clinical diversity also brings greater treatment challenges, particularly for children in whom the risks and benefits of medication for the developing central nervous system must be weighed against the long-term risks associated with the disorder itself. Knowledge of the natural history and pathophysiology of Tourette's syndrome is vitally important for informed clinical decision making.. A MEDLINE literature search was undertaken to identify studies of the natural history and pathophysiology of Tourette's syndrome that would be relevant to clinical psychopharmacology.. Although impossible to predict with certainty for any given patient, the natural history of Tourette's syndrome is typically characterized by an early childhood onset, a prepubertal exacerbation, postpubertal attenuation, and an adult stabilization of symptoms. Symptoms fluctuate in all phases of the illness, often in response to stress. The natural history and clinical phenotype of Tourette's syndrome are thought to have both genetic and nongenetic determinants that are mediated through their effects on basal ganglia nuclei and related neural systems. Medications used in the treatment of Tourette's syndrome are thought to modulate the functioning of these neural systems.. Although medication decisions must consider tic symptom severity, expectations of the disorder's natural history, and the child's adaptive capacities-his or her comorbid illnesses, coping mechanisms, interpersonal relatedness, impulse control, affect regulation, and family and social supports-are the most important determinants of well-being and outcome. These therefore are the most important considerations when making treatment decisions, as well.

Topics: Adolescent; Adult; Age of Onset; Antipsychotic Agents; Child; Clozapine; Disease Progression; Diseases in Twins; Dopamine; Haloperidol; Humans; Obsessive-Compulsive Disorder; Phenotype; Pimozide; Risperidone; Tourette Syndrome; Treatment Outcome

Serotonin uptake inhibitors (SUIs) have been established as the first-line pharmacotherapy of obsessive compulsive disorder (OCD). However, approximately one half of patients who receive an adequate trial with these agents remain clinically unchanged. The addition of drugs that enhance serotonin (5-HT) neurotransmission, such as lithium and buspirone, to ongoing treatment in SUI-refractory patients has generally proved to be an ineffective strategy. The addition of dopamine antagonists to the regimens of SUI-resistant patients appears to be a useful approach for OCD patients with a comorbid chronic tic disorder (e.g., Tourette's syndrome) and possibly for those with concurrent psychotic spectrum disorders. These drug response data suggest that both the 5-HT and dopamine systems may be involved in the treatment, and possibly the pathophysiology, of specific subtypes of OCD.

Topics: Adult; Antipsychotic Agents; Clinical Trials as Topic; Clomipramine; Clozapine; Dopamine Antagonists; Drug Therapy, Combination; Female; Fluvoxamine; Haloperidol; Humans; Isoxazoles; Male; Obsessive-Compulsive Disorder; Piperidines; Risperidone; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Tic Disorders; Tourette Syndrome

Recent research on the role of clozapine in the treatment of Parkinson's disease and other movement disorders is discussed. Most clinical trials have shown resolution of or improvement in psychotic symptoms accompanying Parkinson's disease without worsening of parkinsonian symptoms. Adverse effects appear to be mild at dosages of < 100 mg/day; sedation is the most frequent problem. Most of these studies have serious limitations, however; until better studies have been completed, the decision to use clozapine for Parkinson's disease-related psychosis should be made on a case-by-case basis, with thorough evaluation of risks, benefits, and other therapeutic options. Some patients with Parkinson's disease have shown improvement in tremor and other abnormal movements when given clozapine. Clozapine cannot be recommended for treating tardive dyskinesia on the basis of the research done so far; some trials show dramatic resolution of symptoms, others no benefit. Anticholinergics or dopamine-reuptake inhibitors should be considered before clozapine is given to patients with tardive dyskinesia because of clozapine's potential for serious adverse effects. A few patients with Huntington's disease have responded to clozapine, but again no conclusions can be drawn. Clozapine appears to offer no real advantage over haloperidol for treating choreiform movements in Huntington's disease. The frequency of tics in Tourette's syndrome does not seem to be reduced by clozapine. Clozapine has shown some efficacy as a treatment for psychosis and abnormal movements in Parkinson's disease. Results have been less promising for other movement disorders. Further study in larger populations is needed before any definitive conclusions about clozapine's place in movement disorder therapy can be made.

Topics: Clinical Trials as Topic; Clozapine; Dyskinesia, Drug-Induced; Humans; Huntington Disease; Movement Disorders; Neurocognitive Disorders; Parkinson Disease; Tourette Syndrome

Twelve patients with abnormal involuntary movement disorders were treated with clozapine in a double-blind, placebo-controlled trial. The cohort consisted of individuals with Gilles de la Tourette's syndrome, Huntington's disease, and atypical persistent dyskinesia that was drug induced. Two subjects were dropped from the protocol due to complications. Two patients with Huntington's disease showed a marked decrease in movements; other individuals obtained no significant therapeutic benefits. Seven of the 10 patients completing the trial experienced moderate or marked side effects.

Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Clozapine; Dibenzazepines; Double-Blind Method; Drug Evaluation; Dyskinesia, Drug-Induced; Female; Humans; Huntington Disease; Male; Middle Aged; Movement Disorders; Placebos; Tourette Syndrome

Topics: Adolescent; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Humans; Male; Quetiapine Fumarate; Receptors, Dopamine D4; Tourette Syndrome; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Humans; Male; Piperazines; Quinolones; Tourette Syndrome

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Disease Progression; Dose-Response Relationship, Drug; Haloperidol; Humans; Male; Schizophrenia; Tourette Syndrome; Young Adult

The selective serotonin (5-HT) reuptake inhibitors (SSRIs) represent the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), and atypical antipsychotic drugs, which block 5-HT2A receptors, are used in augmentation strategies. Opiate drugs are also effective in treatment-refractory OCD and Tourette syndrome. The 5-HT2A-related behavior (i.e., head twitch) has been related with tics, stereotypes, and compulsive symptoms observed in Tourette syndrome and OCD.. The aim of this study was to explore whether 5-HT2A-related behavior is affected by atypical opiate drugs.. Head-twitch response was induced in mice by administration of either 5-hydroxytryptophan (5-HTP) or the 5-HT2A/C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Dose-effect curves of atypical opiate drugs [(+/-)-tramadol, (-)-methadone and levorphanol], morphine, and other psychoactive drugs (fluvoxamine, desipramine, nefazodone, and clozapine) were performed. Opioid mechanisms were investigated by administration of naloxone.. All the opiates tested reduced both 5-HTP and DOI-induced behavior in a naloxone-reversible fashion, atypical opiates being more effective. The effects of the other drugs depended on the protocol, clozapine being the most effective.. Combined 5-HT and opioid properties result in a greater efficacy in antagonizing 5-HT2A-related behavior. These results provide behavioral evidence to support convergent effects of the 5-HT and opioid systems in discrete brain areas, offering the potential for therapeutic advances in the management of refractory stereotypes and compulsive behaviors.

Topics: 5-Hydroxytryptophan; Analgesics, Opioid; Animals; Clozapine; Desipramine; Disease Models, Animal; Dose-Response Relationship, Drug; Fluvoxamine; Indophenol; Levorphanol; Male; Methadone; Mice; Morphine; Naloxone; Narcotic Antagonists; Obsessive-Compulsive Disorder; Piperazines; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Stereotyped Behavior; Tics; Tourette Syndrome; Tramadol; Triazoles

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Psychotic Disorders; Tourette Syndrome

To describe two patients with tics status, propose a definition of this syndrome and draw attention to its clinical significance.. Two patients suffering from Tourette's Syndrome who had developed episodes of continual motor tics that lasted from minutes to hours, were non-suppressible and intruded into normal functioning, were treated with an increase in the dose of haloperidol, in one case with the addition of clonazepam.. The offset of the episodes was gradual and the tic disorder was worse after the episodes. One patient had further spontaneous episodes of tics status.. The recognition of tics status has implications for the management as well as our understanding of the pathobiology of tics and Tourette's Syndrome. The definition of tics status should be standardised.

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Haloperidol; Humans; Neurologic Examination; Recurrence; Tic Disorders; Tourette Syndrome

Topics: Adult; Antipsychotic Agents; Clozapine; Dyskinesia, Drug-Induced; Haloperidol; Humans; Injections, Intramuscular; Male; Neurologic Examination; Schizophrenia; Schizophrenic Psychology; Social Behavior; Substance Withdrawal Syndrome; Tourette Syndrome