clozapine and Huntington-Disease

Psychosis may be seen with several movement disorders. As pharmacological treatments can sometimes worsen movement disorders, psychosis in these situations can be complex for clinicians to manage. This review covers the management of psychosis in three different movement disorders: Parkinson's disease, dementia with Lewy bodies and Huntington's disease.

Topics: Antipsychotic Agents; Clozapine; Haloperidol; Humans; Huntington Disease; Lewy Body Disease; Parkinson Disease; Patient Education as Topic; Psychotic Disorders; Risperidone

Clozapine, the only commercially available atypical neuroleptic, is approved for the treatment of schizophrenic patients who are unresponsive to or intolerant of typical neuroleptics. It has an unusual pharmacologic profile compared with standard neuroleptics, and it follows that clinical response to this drug is also different. It has shattered the notion that a drug must be capable of inducing or worsening parkinsonism to be a potent antipsychotic. Based on these findings, it is being used increasingly by neurologists for psychiatric and nonpsychiatric problems in patients with movement disorders. The most common use for clozapine among neurologists is in the management of drug-induced psychosis in Parkinson's disease (PD). This problem has been a source of increased morbidity and mortality in PD because of a lack of adequate therapeutic intervention. At this time, because of success in numerous open trials, with improvement of > 80% of patients, clozapine therapy for psychosis in PD is becoming the standard of care. It also appears to be of value in the management of some motor features of PD, including tremors and dyskinesia and possibly even sensory symptoms such as akathisia and pain. The literature also suggests that clozapine may be of potential benefit in hyperkinetic movement disorders including essential tremor, Huntington's disease, and tardive dyskinesia. We review the current data concerning the use of clozapine in patients with these movement disorders and others.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Dyskinesia, Drug-Induced; Humans; Huntington Disease; Movement Disorders; Parkinson Disease; Psychotic Disorders; Tremor

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

To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.. Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.. Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.. Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatigue; Female; Humans; Huntington Disease; Male; Middle Aged; Placebos; Severity of Illness Index; Sleep Stages; Treatment Outcome

In an open-label trial, we evaluated the efficacy of clozapine on abnormal involuntary movements in five patients with Huntington's chorea. We administered clozapine at increasing doses of 25, 50, and 150 mg/d for 3 weeks. Subjective self-evaluation of all patients reported reduction of chorea and improvement of daily living activities. At the end of the trial, all patients requested to continue with clozapine. Objective evaluation with the Abnormal Involuntary Movements Scale demonstrated in all patients moderate-to-marked reduction of abnormal involuntary movements without any significant side effects; the improvement was dose-dependent and markedly decreased 1 week after drug withdrawal.

Topics: Clozapine; Female; Humans; Huntington Disease; Male; Middle Aged

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: Clozapine; Humans; Huntington Disease; Psychotic Disorders

Topics: Clozapine; Humans; Huntington Disease

Topics: Affective Symptoms; Clozapine; Electroconvulsive Therapy; Humans; Huntington Disease; Male; Middle Aged; Psychotic Disorders; Treatment Outcome

We report on the successful use of a combined psychopharmacological treatment in a patient with Huntington's disease, at age 39, suffering from severe psychotic and behavioral symptoms. He presented with a schizophreniform psychosis accompanied by aggressive behavior leading to admission to the locked ward of our hospital. After unsatisfactory control of the psychiatric symptoms with olanzapine, risperidone, and amisulpride, we introduced aripiprazole. This did not affect the psychotic symptoms; however, led to an improvement in aggressive behavior, motivation, and even chorea. Accordingly, we choose not to switch medication but to add clozapine. Nevertheless, his delusions improved slightly, and further add-on treatment with reboxetine brought a further beneficial effect on motivation and activities of daily living. As chorea was not disabling in our patient, tetrabenazine has not yet been tried. Treatment was safe without any relevant side effects.

Topics: Adult; Aggression; Antipsychotic Agents; Aripiprazole; Clozapine; Drug Therapy, Combination; Humans; Huntington Disease; Male; Morpholines; Piperazines; Psychotic Disorders; Quinolones; Reboxetine; Treatment Outcome

We present the case of a patient with advanced Huntington's disease treated with minocycline. Minocycline (but not tetracycline which does not cross the blood-brain barrier) appears to increase longevity in an animal model for Huntington's disease. The patient has been maintained on minocycline for more than 1 year with positive effects. Cessation of minocyclin for 3 weeks resulted in an exacerbation of symptoms. The animal studies have suggested that minocycline may prevent progression of Huntington's disease and other neurological disorders. By contrast, this present result suggests that minocycline may benefit those with advanced Huntington's disease and can be used safely in these patients.

Topics: Adult; Anti-Bacterial Agents; Antipsychotic Agents; Apoptosis; Clozapine; Female; Humans; Huntington Disease; Minocycline

Topics: Clozapine; Dopamine Antagonists; Female; Humans; Huntington Disease; Middle Aged; Risperidone; Serotonin Antagonists

Topics: Clozapine; Humans; Huntington Disease

Topics: Adult; Antipsychotic Agents; Clozapine; Depression; Drug Resistance; Female; Humans; Huntington Disease

Topics: Animals; Carbachol; Catheterization; Clozapine; Corpus Striatum; Disease Models, Animal; Dyskinesia, Drug-Induced; Haloperidol; Huntington Disease; Hydrazines; Levodopa; Male; Phentolamine; Rats; Trifluoperazine; Tyramine